American Cancer Society

Atlas of
Clinical Oncology

Published
Blumgart, Fong, Jarnagin Hepatobiliary Cancer (2001)
Cameron Pancreatic Cancer (2001)
Char Tumors of the Eye and Ocular Adnexa (2001)
Eifel, Levenback Cancer of the Female Lower Genital Tract (2001)
Shah Head and Neck Cancer (2001)
Silverman Oral Cancer (1998)
Sober, Haluska Skin Cancer (2001)
Wiernik Adult Leukemias (2001)
Willett Cancer of the Lower Gastrointestinal Tract (2001)
Winchester, Winchester Breast Cancer (2000)

Forthcoming
Carroll, Grossfeld, Reese Prostate Cancer (2001)
Clark, Duh, Jahan, Perrier Endocrine Tumors (2002)
Droller Urothelial Cancer (2002)
Fuller Uterine and Endometrial Cancer (2003)
Ginsberg Lung Cancer (2001)
Grossbard Malignant Lymphomas (2001)
Ozols Ovarian Cancer (2002)
Pollock Soft Tissue Sarcomas (2001)
Posner, Vokes, Weichselbaum Cancer of the Upper Gastrointestinal Tract (2001)
Prados Brain Cancer (2001)
Raghavan Germ Cell Tumors (2002)
Steele, Richie Kidney Tumors (2003)
Volberding Viral and Immunological Malignancies (2003)
Yasko Bone Tumors (2002)
 American Cancer Society
Atlas of
Clinical Oncology

Editors

GLENN D. STEELE JR, MD

Geisinger Health System
THEODORE L. PHILLIPS, MD
University of California
BRUCE A. CHABNER, MD
Harvard Medical School

Managing Editor

TED S. GANSLER, MD, MBA

Director of Health Content, American Cancer Society
 American Cancer Society
Atlas of
Clinical Oncology
Cancer of the
Head and Neck
Editor
Jatin P. Shah, MD, MS (Surg.), FACS,
Hon. FRCS (Edin), Hon. FDSRCS (Lond)
Chief, Head and Neck Service
E.W. Strong Chair in Head and Neck Oncology
Memorial Sloan-Kettering Cancer Center
Professor of Surgery, Weill Medical College, Cornell University
New York, New York

Assistant Editor
Snehal G. Patel, MD, MS (Surg.), FRCS
Clinical Research Associate
Head and Neck Service
Memorial Sloan-Kettering Cancer Center
New York, New York

Illustrator
Alice Y. Chen

2001
BC Decker Inc
Hamilton • London

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Contributors

PETER E. ANDERSEN, MD, FACS PETER G. CORDEIRO, MD, FACS

Associate Professor Associate Attending Surgeon
Department of Otolaryngology, Head and Plastic and Reconstructive Surgery Service
Neck Surgery Memorial Sloan-Kettering Cancer Center;
Oregon Health Sciences University Associate Professor of Surgery
Portland, Oregon Department of Surgery
Management of Cervical Metastasis Weill Medical College of Cornell University
New York, New York
JAY O. BOYLE, MD General Principles of Reconstructive Surgery
Assistant Attending Surgeon for Head and Neck Cancer
Head and Neck Service Mandible Reconstruction
Memorial Sloan-Kettering Cancer Center;
Assistant Professor BRUCE J. DAVIDSON, MD, FACS
Department of Otorhinolaryngology Assistant Professor
—Head and Neck Surgery Deartment of Otolaryngology
Weill Medical College of Cornell University —Head and Neck Surgery
New York, New York Georgetown University Medical Center
Oral Cavity Cancer Washington, District of Columbia
Epidemiology and Etiology
JOHN F. CAREW, MD
Assistant Attending Surgeon JOSEPH J. DISA, MD
Department of Otorhinolaryngology Assistant Attending Surgeon
—Head and Neck Surgery Plastic and Reconstructive Surgery Service
New York Presbyterian Hospital; Memorial Sloan-Kettering Cancer Center;
Assistant Professor Assistant Professor
Department of Otorhinolaryngology Department of Surgery
—Head and Neck Surgery Weill Medical College of Cornell University
The Weill Medical College of Cornell University New York, New York
New York, New York General Principles of Reconstructive Surgery
The Larynx: Advanced Stage Disease for Head and Neck Cancer
Mandible Reconstruction
LANCEFORD M. CHONG, M.D.
Associate Attending Radiation Oncologist ANDREW G. HUVOS, MD
Department of Radiation Oncology Attending Pathologist
Memorial Sloan-Kettering Cancer Center Memorial Sloan-Kettering Cancer Center;
New York, New York Professor of Pathology
Head and Neck Radiation Oncology Weill Medical College of Cornell University
New York, New York
Pathology of Head and Neck Tumors

v
vi CONTRIBUTORS

PAUL A. KEDESHIAN, MD FERNANDO C. MALUF, MD

Visiting Assistant Professor Associate Professor
Division of Head and Neck Surgery Division of Solid Tumor, Department of Medicine
University of California Medical Center Sirio Libanes Hospital
Los Angeles, California Sao Paolo, Brazil
Skull Base: Anterior and Middle Cranial Fossa Chemotherapy and Chemoprevention in
Neurogenic and Vascular Tumors of the Head Head and Neck Cancer
and Neck
BERNARD B. O’MALLEY, MD
DANIEL J. KELLEY, MD Attending Radiologist
Director, Head and Neck Oncology The Princeton Medical Center
and Skull Base Surgery Princeton, New Jersey
Department of Otolaryngology— Head and Neck Imaging
Bronchoesophagology
Assistant Professor SNEHAL G. PATEL, MD, MS, FRCS
Temple University School of Medicine Clinical Research Associate
Philadelphia, Pennsylvania Head and Neck Service
Cancer of the Hypopharynx and Cervical Memorial Sloan-Kettering Cancer Center
Esophagus New York, New York
Tumors of the Oropharynx
DENNIS H. KRAUS, MD, FACS Soft Tissue and Bone Tumors
Associate Attending Surgeon Thyroid and Parathyroid Tumors
Head and Neck Service
Memorial Sloan-Kettering Cancer Center; DAVID G. PFISTER, MD
Associate Professor Associate Attending Physician
Department of Otorhinolaryngology Division of Solid Tumor
—Head and Neck Surgery Memorial Sloan-Kettering Cancer Center;
Weill Medical College of Cornell University Associate Professor, Department of Medicine
New York, New York Weill Medical College of Cornell University
Cancer of the Nasal Cavity and Paranasal Sinuses New York, New York
Skull Base: Anterior and Middle Cranial Fossa Chemotherapy and Chemoprevention in
Head and Neck Cancer
DANIEL D. LYDIATT, DDS, MD, FACS
Associate Professor MANJU L. PRASAD, MD
Department of Otolaryngology/Head and Neck Assistant Professor
Surgery Department of Pathology
University of Nebraska Medical Center Ohio State University Hospital
Omaha, Nebraska Columbus, Ohio
The Larynx: Early Stage Disease Pathology of Head and Neck Tumors

WILLIAM M. LYDIATT, MD, FACS SCOTT SAFFOLD, MD

Associate Professor Resident, Department of Otolaryngology
Department of Otolaryngology/Head and Neck —Head and Neck Surgery
Surgery Oregon Health Sciences University
University of Nebraska Medical Center Portland, Oregon
Omaha, Nebraska Management of Cervical Metastasis
The Larynx: Early Stage Disease
 CONTRIBUTORS vii

ERIC SANTAMARIA, MD Department of Otorhinolaryngology

Associate Professor —Head and Neck Surgery
Department of Surgery Weill Medical College of Cornell University
Hospital General Dr. Manuel Gea Gonzalez New York, New York
Mexico City, Mexico Skin Cancers of the Head and Neck
General Principles of Reconstructive Surgery Rehabilitation and Quality of Life Assessment in
for Head and Neck Cancer Head and Neck Cancer
Mandible Reconstruction
JEFFREY D. SPIRO, MD, FACS
JATIN P. SHAH, MD, FACS Professor of Surgery
Chief and Attending Surgeon University of Connecticut Health Science Center
Elliot W. Strong Chair in Head and Neck Oncology Farmington, Connecticut
Head and Neck Service Salivary Tumors
Memorial Sloan-Kettering Cancer Center;
Professor, Department of Surgery RONALD H. SPIRO, MD, FACS
Weill Medical College of Cornell University Professor of Surgery
New York, New York Head and Neck Service
Skin Cancers of the Head and Neck Memorial Sloan-Kettering Cancer Center
Tumors of the Oropharynx New York, New York
Skull Base: Anterior and Middle Cranial Fossa Salivary Tumors
Neurogenic and Vascular Tumors of the
Head and Neck ELLIOT W. STRONG, MD, FACS
Soft Tissue and Bone Tumors Professor Emeritus
Head and Neck Service
ASHOK R. SHAHA, MD, FACS Memorial Sloan-Kettering Cancer Center
Attending Surgeon New York, New York
Head and Neck Service Oral Cavity Cancer
Memorial Sloan-Kettering Cancer Center;
Professor, Department of Surgery SUZANNE L. WOLDEN, MD
Weill Medical College of Cornell University Assistant Attending Radiation Oncologist
New York, New York Memorial Sloan-Kettering Cancer Center;
Thyroid and Parathyroid Tumors Assistant Professor of Radiation Oncology
Weill Medical College of Cornell University
ERIC J. SHERMAN, MD New York, New York
Assistant Member Cancer of the Nasopharynx
Division of Population Science
Department of Medical Oncology RICHARD J. WONG, MD
Fox Chase Cancer Center Fellow, Head and Neck Service
Philadelphia, Pennsylvania Memorial Sloan-Kettering Cancer Center
Chemotherapy and Chemoprevention in New York, New York
Head and Neck Cancer Cancer of the Nasal Cavity and Paranasal Sinuses

BHUVANESH SINGH, MD IAN M. ZLOTOLOW, DMD

Assistant Attending Surgeon Chief and Attending Dental Surgeon
Head and Neck Service Dental Service
Memorial Sloan-Kettering Cancer Center; Memorial Sloan-Kettering Cancer Center
Assistant Professor New York, New York
Dental Oncology and Maxillofacial Prosthetics
Contents

1 Epidemiology and Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Bruce J. Davidson, MD, FACS

2 Pathology of Head and Neck Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Manju L. Prasad, MD, Andrew G. Huvos, MD

3 Head and Neck Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

Bernard B. O’Malley, MD

4 Skin Cancers of the Head and Neck . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

Bhuvanesh Singh, MD, Jatin P. Shah, MD, FACS

5 Oral Cavity Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

Jay O. Boyle, MD, Elliot W. Strong, MD, FACS

6 Tumors of the Oropharynx . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127

Snehal G. Patel, MD, MS, FRCS, Jatin P. Shah, MD, FACS

7 Cancer of the Nasopharynx . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146

Suzanne L. Wolden, MD

8 The Larynx: Advanced Stage Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156

John F. Carew, MD

9 The Larynx: Early Stage Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169

William M. Lydiatt, MD, FACS, Daniel D. Lydiatt, DDS, MD, FACS

10 Cancer of the Hypopharynx and Cervical Esophagus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185

Daniel J. Kelley, MD

11 Cancer of the Nasal Cavity and Paranasal Sinuses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204

Richard J. Wong, MD, Dennis H. Kraus, MD, FACS

viii
 CONTENTS ix

12 Skull Base: Anterior and Middle Cranial Fossa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225

Paul A. Kedeshian, MD, Dennis H. Kraus, MD, FACS, Jatin P. Shah, MD, FACS

13 Salivary Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240

Jeffrey D. Spiro, MD, FACS, Ronald H. Spiro, MD, FACS

14 Thyroid and Parathyroid Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251

Ashok R. Shaha, MD, FACS, Snehal G. Patel, MD, MS, FRCS

15 Management of Cervical Metastasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274

Peter E. Andersen, MD, FACS, Scott Saffold, MD

16 Neurogenic and Vascular Tumors of the Head and Neck . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288

Paul A. Kedeshian, MD, Jatin P. Shah, MD, FACS

17 Soft Tissue and Bone Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309

Snehal G. Patel, MD, MS, FRCS, Jatin P. Shah, MD, FACS

18 General Principles of Reconstructive Surgery for Head and Neck Cancer . . . . . . . . . . . . . . . . . . . 330
Joseph J. Disa, MD, Eric Santamaria, MD, Peter G. Cordeiro, MD, FACS

19 Mandible Reconstruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 358

Peter G. Cordeiro, MD, FACS, Eric Santamaria, MD, Joseph J. Disa, MD

20 Dental Oncology and Maxillofacial Prosthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376

Ian M. Zlotolow, DMD

21 Head and Neck Radiation Oncology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395

Lanceford M. Chong, MD

22 Chemotherapy and Chemoprevention in Head and Neck Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . 444

Fernando C. Maluf, MD, Eric Sherman, MD, David G. Pfister, MD

23 Rehabilitation and Quality of Life Assessment in Head and Neck Cancer . . . . . . . . . . . . . . . . . . . 467
Bhuvanesh Singh, MD

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478
Preface
Although oral cancer is the sixth most common cancer worldwide, cancer of the head and neck is a rare dis-
ease in the western world. A higher incidence is reported in Southeast Asia as well as certain parts of Europe
and Latin America. Tobacco and alcohol remain the most important etiologic factors; however, the primary
site incidence of head and neck cancer varies throughout the world depending on the type of substance abuse
and the extent of consumption.
Management of these patients requires a team effort with expertise in various disciplines. As our under-
standing of the biology and natural history of cancers of the head and neck increases, efforts at preservation
or restoration of form and function become increasingly important. These efforts are not only important in
the surgical treatment of these tumors but are also important in the multidisciplinary, integrated treatment
programs delivered by comprehensive treatment teams. Most major cancer centers, not only in the United
States but also worldwide, now deliver optimal care for patients with cancers of the head and neck through
the integrated efforts of multidisciplinary “disease-management” teams. Such disease-management teams
work to develop treatment algorithms and establish guidelines for a unified treatment approach in order to
maintain internal consistency, initiate investigative protocols, and push the frontiers in the battle against can-
cer. Such guidelines are also developed by the American Head and Neck Society (AHNS) and the National
Cancer Center Network (NCCN). The focus has clearly been on outcome analysis and (whenever feasible),
implementation of evidence-based medicine. These have provided excellent practice guidelines for the prac-
titioner in the community and are rapidly becoming standards of care.
The contributing authors in this book are or have been members of the head and neck disease-management
team at Memorial Sloan-Kettering Cancer Center in New York. As a result, the treatment programs practiced
at Memorial Sloan-Kettering Cancer Center tend to be reflected in the philosophies expressed in this book,
though every attempt has been made to be comprehensive and to give a balanced view of other treatment
approaches and report results. Thus, in spite of being a multi-authored book, the strength of this work is its
internal consistency of diagnostic approaches, therapeutic decisions, multidisciplinary treatment programs,
and surgical techniques. It is obviously impossible for a work of this nature to be either complete or perma-
nently up-to-date; new technology will offer newer diagnostic approaches that will impact on the development
of newer treatment strategies and therapeutic protocols. However, this book represents the art and science of
head and neck surgery and oncology as well as the current approach to the multidisciplinary management of
tumors of the head and neck. Accurate clinical staging of head and neck tumors is crucial to treatment plan-
ning and for comparison of outcomes. However, we have deliberately not included the AJCC/UICC staging
system in the book due to the anticipated revision of the AJCC/UICC staging system this year. It is expected
that the sixth edition of the AJCC/UICC staging manual will be published in the year 2002 and we recommend
that the reader refer to this manual for information on details of staging criteria. This book will not only be a
valuable resource to aspiring head and neck surgeons and oncologists but also to surgeons, medical oncolo-
gists, radiation oncologists, and physicians in other specialties as it will act as a reference volume for current
concepts in the management of cancer of the head and neck.

Jatin P. Shah, MD
August 2001

x
Dedication
This work is dedicated to our patients who have endured the ravages of head and neck cancer and who have
demonstrated extraordinary strength in their struggle to preserve life. These exceptional human beings, who
join hands with us in the dogged pursuit of a cure for their cancer and a better quality of life, have a special
place in our hearts. We salute their courage, understanding, and perseverance. We are thankful to them for
putting their trust and lives in our hands, for giving us the opportunity to understand the disease, and for
inspiring us to put this work together.
Acknowledgments
I would like to express my sincere appreciation to the American Cancer Society for asking me to edit this
volume in their series of clinical atlases. I am equally grateful for the contributions of each of the authors
who so willingly and promptly provided up-to-date, generously illustrated, comprehensive but concise chap-
ters on their assigned topics. But for their diligence and promptness, it would not have been possible to com-
pile this work on schedule.
My special thanks are owed to Ms. Alice Chen for the artwork in this book, Ms. Nancy Bennett for the
graphics and editorial responsibilities, and Ms. Arlene Cooper for transcription of the text.

Jatin P. Shah, MD
 1
Epidemiology and Etiology
BRUCE J. DAVIDSON, MD, FACS

INCIDENCE vious increases. From 1940 to 1985, there was an

increase in laryngeal cancer incidence in men and
Current Incidence Data women reflecting the increase in cigarette use in this
century.3 Oral and pharyngeal cancer incidence was
The global incidence of cancers of the oral cavity, stable in men and increased in women over this time
pharynx and larynx is about 500,000 cases per year period.3 Between 1973 and 1997, a decrease in oral
with mortality of 270,000 cases per year.1 Excluding and pharyngeal cancer and in laryngeal cancer
skin cancers, this represents about 6 percent of the appeared.4 This decrease was primarily determined
incidence and 5 percent of the mortality of all can- by large rate decreases in men. During this same
cers.1 About three-fourths of these are cancers of the period, females showed an increase in laryngeal can-
oral cavity and pharynx and the remainder are laryn- cer rates and no change in oral cancer.4 Most
geal cancers. Figure 1–1 describes the incidence of recently, 1990s United States cancer registry data
oral and pharyngeal cancers by world region. As shows a significant drop in the incidence rates of
demonstrated here, the areas of the world with the oral cavity and pharyngeal cancers for both sexes.5
greatest incidence are Melanesia (Papua, New A steady drop in oral and pharyngeal cancer mortal-
Guinea and adjacent islands), Western Europe and ity has also been noted.6 Mortality trends differ by
South Central Asia (India and the Central Asian race, which will be explored later in this chapter.
republics of the former Soviet Union).1
Figure 1–2 details the oral and pharyngeal cancer Europe
mortality rates for selected countries. In 2001, oral,
pharyngeal and laryngeal cancers are expected to While United States’ rates (incidence and mortality)
occur in approximately 40,100 individuals in the for oral and pharyngeal cancer have recently been
United States and result in death in 11,860.2 In falling, European mortality rates for these cancers
United States males, oral and pharyngeal cancer among males rose between 1983 and 1993.7 Laryn-
comprise the seventh most common cancer and lar- geal cancer mortality increased in Eastern Europe.7
ynx cancer ranks fifteenth.2 In females, the incidence Studies from individual European countries tend to
of oral and pharyngeal cancers ranks fourteenth and reflect a rising mortality from oral,8,9 pharyngeal,9,10
laryngeal cancer and anal cancer (2,000 each) share and laryngeal9,10 cancers from the early 1950s
the twenty-seventh and twenty-eighth positions.2 through about 1980. One exception to this is a Swiss
study showing a decrease in laryngeal cancer mor-
Trends Over Time tality in males, but an increase in females.11 More
recent studies, spanning the mid 1970s into the
United States 1990s, show decreases in oral cancer mortality in
France12 and laryngeal cancer mortality in France,12
Head and neck cancer incidence in the United States Italy,13 Switzerland,11 and Sweden.14 These reduc-
has shown declines in the past 2 decades after pre- tions may be secondary to decreased cigarette con-

1
2 CANCER OF THE HEAD AND NECK

Figure 1–1. Incidence (cases/100,000) of cancer of the lip, oral cavity and pharynx in males by geographic
area. (Data from: Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin 1999;49:33–64.)

sumption or a change to less carcinogenic tobacco Variations in alcohol use may also explain some
products (eg, filtered cigarettes or less carcinogenic cancer incidence changes over time. A Scottish study
blond tobacco products). showed an increased incidence of oropharyngeal and

Figure 1–2. World map with death rates for oral and pharyngeal cancer in males indicated for selected
countries. Units are age-adjusted death rates per 100,000 population. Countries shown are: Canada (4.0),
United States (3.4), Chile (2.2), Norway (2.8), United Kingdom (3.0), France (12.0), Spain (7.0), Hungary
(18.5), Russian Federation (9.2), Israel (1.5), China (2.6), Japan (2.5), and Australia (4.4). Source docu-
ment does not include data from several high-incidence areas such as Melanesia, India and Brazil. (Data
from: Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1998. CA Cancer J Clin 1998;48:6–29.)
 Epidemiology and Etiology 3

hypopharyngeal cancers with stable incidence of Soviet Union. From the figure, wide variations in
nasopharyngeal cancer between 1960 and 1989.15 As a mortality are indicated.
possible predictor of future trends, young adult males
(ages 20 to 44) have shown an increase in oral and pha- Asia
ryngeal cancer mortality between the 1950s and the
Japanese males showed an increase in oral and pha-
late 1980s in a Swiss study16 as well as in studies across
ryngeal cancers mortality between 1950 and 1994,
Europe.17 Increased incidence and mortality rates from
although no change was seen in females. Analysis
hypopharyngeal cancers in individuals under 60 years
specified by tumor site showed a decrease in oral
of age have also been shown since 1960 in an Austrian
tongue and tongue-base cancer mortality, with
study.18 These data are thought to be a reflection of
increases in mortality from other oral and oropha-
increased alcohol consumption over time.15
ryngeal sites. It was suggested that these changes
were reflective of increased tobacco consumption
Former Soviet Union
for pharyngeal cancers, increased alcohol consump-
A long-term study of cancer mortality in the former tion for oral cancers and were unrelated to tobacco
Soviet Union showed an increase in oral, pharyngeal or alcohol for tongue cancers.21
and laryngeal cancer mortalities between 1965 and The incidence of head and neck cancer in India is
1990.19 Estonia (former Eastern European Soviet variable, with some areas showing rates of cancer
Union member) showed increased mortality rates for among the highest in the world and other areas with
cancers of the oral cavity, pharynx and larynx in men rates comparable to the United States. Oral and pha-
and oral cavity and pharynx in women, between 1965 ryngeal cancers are highest in the area of Ahmedabad
and 1989.20 Trends in the former Soviet Union and in in West India. Between the 1960s and 1980s, a drop in
Eastern Europe appear to reflect continued high rates head and neck cancer incidence was seen across India.
of tobacco consumption. Figure 1–3 shows oral and This decrease has been attributed to decreased con-
pharyngeal mortality rates for several countries in sumption of oral tobacco and an increase in cigarette
Western Europe, Eastern Europe and the former and bidi (tobacco rolled in a tendu leaf) smoking.22

Figure 1–3. Death rates for oral and pharyngeal cancer in males indicated for Europe and
Russia. Units are age-adjusted death rates per 100,000 population. (Data from: Landis SH,
Murray T, Bolden S, Wingo PA. Cancer statistics, 1998. CA Cancer J Clin 1998;48:6–29.)
4 CANCER OF THE HEAD AND NECK

EPIDEMIOLOGY (all 10–15/100,000).4 The rates for females were

highest in Singapore, Hong Kong, and Kuwait
Geographic Variation (2–5/100,000).4 In the more recent period, four of
the five countries with the highest mortality in males
Incidence and Tumor Site Differences are in Eastern Europe.117 Hungary has shown a rise
As indicated in Figure 1–1, the incidence of head in mortality rates from 12.5 to 18.5 in less than a
and neck cancer varies throughout the world. For decade. In females, two of the top five are in Eastern
instance, mouth cancers are 45 times more common Europe and the other three are in the Central Asian
in certain areas of France than in The Gambia.4 The republics of the former Soviet Union.117 The com-
Basque region of Spain has an incidence of laryn- parison between 1986 to 1988 and 1992 to 1995
geal carcinoma (20/100,000) that is about 200 times shows the effect of geopolitical changes on cancer
greater than the incidence of laryngeal cancer in statistics with several newly independent countries
Qidong, China (0.1/100,000).4 reporting high mortality rates from these cancers.
Mortality also differs throughout the world. Mor-
tality differences are influenced by incidence of dis- Race
ease as well as survival rates after diagnosis. The 5- Significant racial differences are seen in cancer
year survival rate for cancers of the oral cavity and demographics in the United States. According to
pharynx is 46 percent worldwide, but differs SEER statistics from 1973 to 1997, the incidence of
between developed (59%) and developing (39%) oral and pharyngeal cancer was shown to be higher
countries. The larynx cancer 5-year survival rate is in blacks than in whites from 1975 onward. Simi-
46 percent with similar differences between devel- larly, the incidence of laryngeal cancer has been
oped (51%) and developing (41%) countries.1 higher in blacks since 1973.118 While oral/
Table 1–1 lists the countries with the highest pharyngeal cancer is the sixth most common cancer
rates of oral and pharyngeal cancer mortality over in the United States, this represents the fourth most
two periods in the past 20 years. Unfortunately, the common cancer in blacks.119 An exploration of this
source documents fail to report mortality data on observation has found that most of the increased inci-
several high-incidence areas such as India, Melane- dence in blacks can be attributed to higher tobacco
sia and Brazil. In the mid 1980s, the highest rates of and alcohol consumption among this group. Control-
oral and pharyngeal cancer mortality for males were ling for these exposures results in almost equivalent
seen in Hong Kong, France, Singapore and Hungary risk of oral and pharyngeal cancers by race.120

Table 1–1. COUNTRIES WITH THE HIGHEST MORTALITY RATES FOR ORAL AND PHARYNGEAL CANCER
(AGE-ADJUSTED DEATH RATES / 100,000)

1986–1988 1992–1995

Male Female Male Female

Country Rate Country Rate Country Rate Country Rate

Hong Kong 14.8 Singapore 4.8 Hungary 18.5 Hungary 2.4

France 14.3 Hong Kong 4.8 France 12 Kazakhstan 1.9
Singapore 12.8 Kuwait 2.4 Croatia 11.7 Turkmenistan 1.7
Hungary 12.5 Cuba 1.8 Slovenia 11.2 Albania 1.6
Puerto Rico 9 Malta 1.7 Romania 11.1 Uzbekistan 1.5
Czechoslovakia 8.2 Panama 1.7 Ukraine 9.6 Denmark 1.4
Luxembourg 7.6 Hungary 1.6 Russian Federation 9.2 France 1.3
Uruguay 6.9 Australia 1.4 Estonia 9 Australia 1.3
Soviet Union 6.6 Denmark 1.4 Belarus 8.8 United States 1.2
Switzerland 6.5 Venezuela 1.4 Lithuania 8.3 Canada 1.2

Adapted from Ries LAG. Rates. In: Harras A, editor. Cancer: Rates and risks. Washington, DC, National Institutes of Health; 1996. p.9–55. and from Li FP,
Correa P, Fraumeni JF. Testing for germ line p53 mutations in cancer families. Cancer Epidemiol Biomarkers Prev 1991;1:91–4.
 Epidemiology and Etiology 5

Trends in oral and pharyngeal cancer and laryn- male-to-female ratio of laryngeal cancer over two peri-
geal cancer incidence are favorable when evaluated ods in the past four decades. The proportion of male-
by race. For oral and pharyngeal cancers, the trend to-female cases dropped from 5.6:1 to 4.5:1 between
in cancer incidence is downward since about 1984 in the periods 1959 to 1973 and 1974 to 1988.121 Other
whites and since 1980 in blacks. For laryngeal can- studies have reflected similar trends.122,123 Significant
cer the negative trend began in 1988 in whites and differences in the site of laryngeal cancer development
1990 in blacks.118 has been suggested, with a ratio of glottic to supra-
Mortality rates are also significantly higher for glottic sites of 22.1:1 in men and 0.6:1 in women.124
blacks than for whites for both oral/pharyngeal and Among nonsmokers who develop oral and pha-
laryngeal cancers. For both types of cancer, between ryngeal cancer, a higher proportion of women than
1973 and 1997, mortality was higher in blacks every men is seen in patients over the age of 50.29 Analyz-
year, and from 1993 to 1997, mortality rates in ing oral cancers by site relative to gender reveals that
blacks were approximately double that seen in the ratio of males to females is highest for floor-of-
whites. Oral and pharyngeal cancer mortality has mouth cancers (ratio=3.4:1), and lowest for gingival
been trending downward since 1973 for whites, but cancers (ratio=0.5:1).125
for blacks, mortality rates rose from 1973 to 1980 SEER data suggests a downward trend for oral and
and since then have been falling. For laryngeal can- pharyngeal cancer incidence for both males and
cer, mortality has also fallen since 1973 in whites, females since the early 1980s. Mortality has also been
but rose in blacks from 1973 to 1992. Mortality rates declining for both males and females since 1979. For
in blacks have more recently been trending down- laryngeal cancer, incidence has declined since the
ward (trend not statistically significant).118 mid to late 1980s for both males and females. Mor-
The differences in oral and pharyngeal cancer tality has been falling since 1973 for males, but rose
mortality between African Americans and Cau- until 1992 in females. Recently a downward trend in
casians have been attributed in part to differences in laryngeal cancer mortality rate (not statistically sig-
survival rates. Five-year survival rates for these can- nificant) has been seen in females.118
cers from 1989 to 1996 were 56 percent for Cau-
casians and 35 percent for African Americans.118 ETIOLOGY
Data shows that African Americans are more likely
to be diagnosed at a higher tumor stage, but that It has been estimated that in the United States, well
even after adjustment for stage, the mortality is over three-fourths of all head and neck cancers can
greater in African Americans (see Figure 1–8).2 be attributed to tobacco and alcohol use.23 This sec-
Access to health care may play a role as 21 percent tion will explore these risk factors for head and neck
of African American adults lack a health care plan squamous cell carcinoma and will describe other fac-
while only 13 percent of Caucasians are without tors that may play a role in the etiology of these can-
coverage.119 Racial differences in prevention appear cers. As with most cancers, age itself may be a risk
to exist, in that a higher proportion of African factor for the development of head and neck cancer.
Americans over Caucasians continue to smoke—34 In nonsmokers and nondrinkers, the average age of
percent versus 28 percent respectively.119 onset of laryngeal cancer is about 10 years later than
in patients with a history of tobacco or alcohol use.24
Gender
Tobacco
Gender differences in head and neck cancer incidence
and mortality appear to reflect differences in risk fac- Cigarettes
tor exposure. The rise in tobacco consumption by
women since the 1950s has resulted in an increased Cigarette smoking is the single most important risk
proportion of female cancer incidence and mortality factor in head and neck cancer. For oral cancers in
for these cancers. A study from Houston compared the men, 90 percent of cancer risk can be attributed to
6 CANCER OF THE HEAD AND NECK

tobacco. The attributable risk of tobacco for oral can- that cigar or pipe smoking without a history of cig-
cer development is lower in females at 59 percent.4 arette smoking was associated with a relative risk of
The smoking attributable risk for laryngeal cancer in oral and pharyngeal cancer of 3.3. When mixed
males and females is more similar at 79 and 87 per- exposures (ie, pipe and cigarette or cigar and ciga-
cent respectively.4 The relative risk of laryngeal can- rette) were analyzed, the relative risk of oral and
cer between smokers and nonsmokers is 15.5 in men pharyngeal cancer was 2.6 for cigar smokers and
and 12.4 in women.14 In support of the association 3.2 for pipe smokers.27
between tobacco and head and neck cancer is infor-
mation associating cigarette consumption with oral Smokeless Tobacco
dysplasia (Odds Ratio [OR] = 4.1), a premalignant
oral lesion.25 Smokeless tobacco use has gained popularity in the
Discontinuation of smoking reduces the risk of United States over the past 25 years. The habit was
head and neck premalignant and malignant lesions. traditionally practiced by women in the rural south
Smoking cessation results in a decreased risk of as an alternative to cigarette smoking. In this popu-
oral dysplasia that reaches that of “never-smokers” lation, a four- to six-fold increase in risk of oral can-
after 15 years.25 The risk of oral cancer has been cer has been shown.23,33 Cancers are typically well-
suggested to be reduced by 30 percent for those differentiated and occur on the alveolar ridge or
who have discontinued tobacco for 1 to 9 years and buccal mucosa.34 Snuff-related oral cancer appears
by 50 percent for those who have abstained for over to require prolonged exposure. Patients developing
9 years.26 No excess risk of oral and pharyngeal oral cancers who have a history of snuff use without
cancer has been shown among individuals who other risk factors typically are in their 60s and have
have abstained for over 10 years.23,27 These results been using oral tobacco for 40 years.34
emphasize the importance of smoking cessation Recent attempts to define the risk of oral can-
efforts. cer related to this increasingly popular practice has
Tobacco contains over thirty known carcinogens. been difficult. The state with the highest per capita
The majority of these are polycyclic aromatic hydro- consumption of smokeless tobacco, West Virginia,
carbons and nitrosamines.28 Increasing tar consump- has not shown an increased incidence of or mor-
tion has been associated with oral and pharyngeal tality from oral or pharyngeal cancer when com-
cancer in a dose-dependent manner. Interestingly, pared with national averages.35 These results are
when this is evaluated by gender, the risks of cancer possibly reflective of the low prevalence of alcohol
associated with tar exposure increase more sharply abuse in West Virginia. In addition, a Swedish
for women than men.29 Specific tobacco use habits case-control study showed no increased risk for
appear to alter the risk of head and neck cancer. oral cancer in current or former snuff users.36
Exclusive use of filtered cigarettes is protective when These results may be a reflection of the prolonged
compared to unfiltered cigarette use.27,30 Inhalation exposure to oral tobacco required for the develop-
increases the risk of cancer of the endolarynx, ment of oral cancer.
although it does not alter the risk of hypopharyngeal
or epilaryngeal (suprahyoid epiglottis and aryepiglot- Types of Tobacco
tic folds) cancer.31
Two major types of tobacco exist. Black or dark (air-
Cigars, Pipe Smoking cured) tobacco is used in the manufacture of cigars,
pipe-blends and certain cigarettes. Blond (flue-
An increased risk of incidence for cancers of the cured) tobacco is used more commonly for ciga-
oral cavity, pharynx and larynx has been shown for rettes. A major difference in these two tobacco types
pipe and cigar smokers.28 Risk of cancer from pipe is that the alkalinity of black tobacco causes it to be
smoking tends to be higher for oral cavity sites than irritating to the respiratory mucosa. Deep inhalation
pharyngeal or laryngeal sites.32 Mashberg found is less well-tolerated than with blond tobacco prod-
 Epidemiology and Etiology 7

ucts. For this reason, it is theorized that black where blond tobacco cigarettes are typical and
tobacco products might exert a greater effect on the laryngeal glottic cancer is more common.
upper aerodigestive mucosa while blond products
have a greater effect on the lower respiratory Alcohol
mucosa. This is supported by data showing a greater
risk of larynx cancer than lung cancer in persons Head and neck squamous cell carcinoma is a disease
using black tobacco products.32 occurring most often in individuals with heavy
Experimental studies have shown the extract of tobacco and alcohol use. Tobacco has gained the
black tobacco cigarettes to be more carcinogenic majority of attention in terms of public health edu-
than blond tobacco cigarettes.37 As a reflection of cation and many lay persons are unaware of the
this, epidemiologic studies have shown that the association of alcohol with upper aerodigestive
type of tobacco consumed is associated with the squamous cell carcinoma. The cancer risk associated
risk of aerodigestive tract cancer. Dark (air-cured) with alcohol consumption varies among upper
tobacco use was associated with a 59-fold aerodigestive tract sites.
increased risk of laryngeal cancer while blond The association between alcohol and head and
(flue-cured) tobacco was associated with a 25-fold neck cancer is stronger for pharyngeal cancer than
risk.38 After control for socioeconomic factors, for other head and neck sites. A dose-response effect
alcohol consumption, length of smoking exposure, has been shown between alcohol and pharyngeal
and filter use, the user of black tobacco cigarettes cancer in a German study. After adjustment for
has a threefold relative risk of oral cavity and pha- tobacco consumption, the relative risk of pharyngeal
ryngeal cancer when compared with the user of cancer is seen to rise progressively from 1.0 for
blond tobacco cigarettes.39 those consuming < 25 g/day (> 2 drinks) to 125 for
When studies compare the use of blond tobacco those consuming > 100 g/day (> 7 drinks).41 High
only, with black tobacco only, with mixed expo- alcohol consumption (> 100 g/day) represents less
sures, a dose-response effect is demonstrated. A of a risk for oral cancers (RR=11)42 and laryngeal
multi-institutional case-control study from Europe cancers (RR=15) (unpublished data described in41).
showed such an effect with an increased relative Figure 1–5 describes the difference in relative risk of
risk of cancer of the endolarynx, epilarynx and cancer for several head and neck sites when com-
hypopharynx associated with increasing use of pared to various levels of alcohol consumption.43
black tobacco relative to blond tobacco.31 Analo- These data support a strong association between
gous data from Thailand has shown that certain alcohol use and pharyngeal cancer.
Thai tobacco preparations, specifically the more This variation in the risk of alcohol on the devel-
alkaline and less easily inhaled varieties, are associ- opment of head and neck cancer has also been
ated with an increased risk of laryngeal cancer over shown to differ for subsites of the larynx. Patients
other Thai preparations.40 with glottic cancer are more likely than those with
The difference in popularity of black and blond supraglottic cancer to be nondrinkers.43 When com-
tobacco cigarettes is likely to influence the geo- parison is made between drinkers and nondrinkers,
graphic variations in laryngeal cancer incidence and the nondrinkers more often develop glottic cancer
subsite distribution throughout the world (Figure than supraglottic cancer. By comparison, the distri-
1–4, A and B). Countries with the highest death rates bution is about equal for drinkers. Similarly, the
from laryngeal cancer are France, Uruguay, Spain association between alcohol and cancer varies
and Italy. Each of these countries, along with Cuba, between oral cavity sites, with a higher risk of buc-
Argentina, Brazil, Columbia and Greece has a rela- cal cancer than floor-of-mouth cancer in the non-
tively high prevalence of black tobacco cigarette drinkers and a higher risk of lateral tongue cancer
consumption. Several of these countries also show a than other tongue cancers in the nondrinkers. In
greater prevalence of supraglottic cancers than glot- drinkers, lateral tongue cancer is less common than
tic cancers.38 This is in contrast to the United States other tongue cancers (includes base of tongue), and
8 CANCER OF THE HEAD AND NECK

floor-of-mouth cancer is twice as common as buc- considered using an additive risk model.47 Other stud-
cal mucosa cancer.43 ies have also supported a synergistic effect of tobacco
and alcohol on head and neck cancer risk.38,44
Multiplicative Effect of Alcohol and Tobacco
Types of Alcohol and Risk
The synergistic effects of tobacco and alcohol have
been shown in head and neck cancer in multiple stud- There are significant differences of content between
ies.38,44–46 Figure 1–6 shows data from a multicenter various alcoholic beverages. Beer contains the car-
case-control study for oral and pharyngeal cancers in cinogen nitrosodimethylamine, while distilled wines
the United States. The combined use of tobacco and have a high content of tannin, another carcinogen.
alcohol increases the risk of laryngeal cancer by about When comparing various hard liquors, dark liquors
50 percent over the estimated risk if these factors are (eg, whiskey, dark rum, cognac) contain greater

B
Figure 1–4. A, Worldwide incidence of supraglottic cancer. B, Worldwide incidence
of glottic cancer.
 Epidemiology and Etiology 9

Figure 1–5. Relative risk of cancer for various head and neck sites relative to history of daily alco-
hol consumption adjusted for tobacco use. (Data from: Brugere J, Guenel P, Leclerc A, Rodriguez
J. Differential effects of tobacco and alcohol in cancer of the larynx, pharynx and mouth. Cancer
1986;57:391–5.)

amounts of organic compounds than light liquors liquor intake. The risk is greater for hypopharyngeal
(eg, vodka, gin, light rum). These include higher cancer than for laryngeal cancers.48
alcohols, esters and acetaldehyde.48 The risk of The relationship between type of liquor consumed
laryngeal and hypopharyngeal cancers is increased and cancer risk has not been consistent. Mashberg
with dark liquor intake when compared with light reported on a series of oral cavity cancers and found

Figure 1–6. Relative risk of oral and pharyngeal cancer relative to tobacco and alcohol intake.
The synergistic effect of tobacco and alcohol exposure is shown. One pack-year is equivalent to
smoking 20 cigarettes perday per one year. (Data from: Blot WJ, McLaughlin JK, Winn DM, et al.
Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 1988;48:3282–7.).
10 CANCER OF THE HEAD AND NECK

that after controlling for total alcohol consumption, Alcohol and Carcinogenesis
beer and wine intake were more strongly associated
with oral cancer risk than was whiskey consump- The mechanisms by which alcohol use contributes to
tion.49 On the other hand, Blot showed increased risk the risk of head and neck cancer is not clearly
of oral and pharyngeal cancer for beer and whiskey defined, while systemic and local effects have been
intake, but no excess risk for wine consumption.23 proposed. While alcohol itself is not a known car-
The type of alcohol consumed may influence the cinogen, it may act as a solvent, allowing increased
site of aerodigestive cancer development. A study cellular permeability of other carcinogens through
from the Institut Curie in France attempted to evaluate mucosa of the upper aerodigestive tract. As noted
these differences, but was limited by the fact that > 90 above, the non-alcohol constituents of various alco-
percent of patients were wine drinkers, and the major- holic beverages may have carcinogenic activities.48
ity drank other liquors as well.43 However, tongue can- As summarized in Maier,41 chronic alcohol use
cer was associated with wine drinking while supra- may upregulate enzymes of the cytochrome P-450
glottic cancer was associated with aniseed liquor system. This enzyme system can contribute to acti-
consumption. vation of procarcinogens to carcinogens. This up-
The synergistic effect of tobacco and alcohol regulation may be critical to activation of many car-
consumption has been shown to vary with the type cinogens, as the vast majority of environmental
of tobacco used as well as the type of alcohol. Upon carcinogens exist in their procarcinogenic form.
comparing the level of consumption of blond and Alcohol has also been shown to decrease the activ-
black tobacco as well as the level of wine intake ver- ity of DNA-repair enzymes, and increased chromo-
sus spirits, heavy use of black tobacco and heavy somal damage has been documented in chronic alco-
wine consumption showed the greatest synergistic hol users. Other possible effects of alcohol include
effect. Blond tobacco and spirit consumption impaired immunity resulting from a reduction in T
showed a lesser, but still considerable synergistic cell number, decreased mitogenic activity and/or
effect (Figure 1–7).50 reduced macrophage activity.

Figure 1–7. Graph demonstrating the odds ratio for exposure to alcohol and tobacco exposure
in pharyngeal and laryngeal cancer patients. Odds ratio highest with heavy wine and black
tobacco consumption. (Data from: Sancho-Garnier H, Theobald S. Black (air-cured) tobacco and
blond (flue-cured) tobacco and cancer risk II: Pharynx and larynx cancer. Eur J Cancer 1993;
29A:273–6.).
 Epidemiology and Etiology 11

The greater significance of the solvent activity of squamous cell carcinoma in southern South America
alcohol, as opposed to its systemic effect, is supported may be linked to maté ingestion.54 The odds ratio for
by data comparing dark and light liquor intake and the maté ingestion has been reported as 3.0 for glottic
risk of hypopharyngeal cancer. Only dark liquor con- cancer and 3.3 for cancer of the supraglottis.38 Oth-
sumption was related to the risk of hypopharyngeal ers have demonstrated a significant association with
cancer. After controlling for total alcohol use and oral cancers.54 Maté consumption is more strongly
tobacco use, heavy dark liquor consumption was associated with the risk of laryngeal cancer in
associated with an increased risk of cancer while no patients with a history of heavy tobacco or alcohol
such risk was seen with light liquor intake.48 These use. Maté itself has not been shown to be carcino-
data argue against a systemic effect of alcohol on genic but, similar to alcohol, may act as a solvent for
hypopharyngeal cancer risk and instead argue for the other carcinogens or as a promoter.38
solvent effect of alcohol along with the carcinogenic-
ity of the nonalcoholic components of dark liquors. Dental Considerations
Injury to mucosa of the upper aerodigestive tract
may relate to a toxic metabolite of alcohol,
Hygiene
acetaldehyde. The enzyme aldehyde dehydroge-
nase-2 (ALDH-2) is a strong determinant of blood Poor oral hygiene is associated with oral cancer, but
acetaldehyde concentration following alcohol no causal relationship has been established. A case-
ingestion. A small group of Japanese patients was control study of patients with upper aerodigestive
studied, and those with an inactive ALDH-2 pheno- tract squamous cell carcinoma matched 100 patients
type more often had multiple primary esophageal with 214 age- and sex-matched controls and found
cancers (77%) versus those with an active ALDH-2 significantly worse oral hygiene and dental status in
phenotype (31%).51 the tumor patients. Chronic inflammation of the gin-
giva was more often seen in the cancer patients.55
Other Carcinogens Similarly, oral cancers have been significantly asso-
ciated with a history of chronic oral infections
Betel Quid (OR = 3.8).56
Other studies have also supported the relationship
In India and parts of Asia, oral tobacco is commonly between poor oral hygiene and increased risk of oral
consumed in a preparation known as “pan,” which cancer.57 Less-than-daily brushing has been associ-
combines tobacco with betel leaf, slaked lime and ated with an approximate twofold increased risk of
areca nut. These betel quid are associated with the tongue and other oral cancers in a Brazilian popula-
risk of oral cancer. Oral cancer risk increases in a tion,58 but no association was seen in a United States
dose-dependent manner when classified by years of study.59 The absence of multiple teeth may represent
betel quid use and by numbers of betel quid per a surrogate marker of dental hygiene and has been
day.52 Like the relationship between tobacco and associated with oral cancer in multiple studies.60,61
alcohol exposure, the use of betel quid has been However, a history of multiple broken teeth has not
shown to act synergistically with tobacco and alco- been associated with oral cancer risk.59,62
hol to promote oral cancer.53 The frequent use of mouthwash has been dis-
couraged due to the fact that several preparations
Maté contain ethanol. The association between mouth-
wash use and risk of oral or pharyngeal cancer has
Maté is a hot drink made from the herb Ilex been the subject of previous studies with mixed
paraguariensis and is commonly consumed in South results.59,63,64 When controlled for total tobacco and
America. It has been associated with an increased alcohol intake, users of alcohol-containing mouth-
risk of cancer of the esophagus and larynx. It has washes appear to be at increased risk.64 Women,
been estimated that up to 20 percent of head and neck especially those who are not tobacco users, appear to
12 CANCER OF THE HEAD AND NECK

be most consistently associated with this risk fac- trolling for tobacco use.75 Laryngeal cancers have
tor.65 However, it is possible that the cancer risk of been associated with nickel and mustard gas expo-
mouthwash use may be confounded by other unmea- sure.4 An association between asbestos exposure and
sured factors. In one study of oral cancer in women, laryngeal cancer has been suggested, but contradic-
the reasons for mouthwash use were explored. While tory results have been reported.4,71,76,77
mouthwash use per se was not associated with a risk
of cancer in this particular study, the use to “disguise Social and Economic Factors
the smell of tobacco” or “disguise the smell of alco-
hol” was seen more commonly in cancer cases.60 Associations between oral, pharyngeal and laryngeal
cancers and marital status (cancer patients more
Dentures
often unmarried or divorced) and educational status
(cancer patient less often with college education)
A large Brazilian case-control study has demon- have been described.78 However, a study in the
strated an association between oral sores from loose- United States failed to show any relationship
fitting dentures and risk of oral cancer. 58 Painful or between oropharyngeal cancer and education or
ill-fitting dentures have also been associated with occupational status. This United States study did
oral or oropharyngeal cancer in a study from Wis- show an inverse relationship between the percentage
consin.59 However, in these and other studies, long- of potential working life spent in employment and
term use of dentures has not been shown to increase the risk of cancer.79 While this study attempted to
the risk of oral cancers.62,66,67 These results and those adjust for tobacco and alcohol consumption, alcohol
relating hygiene to oral cancer may describe the role consumption may confound the employment mea-
of chronic inflammation as a risk for oral cancer. sure used. Regularity and consistency of employment
may be reduced by excessive alcohol use which, in
Occupational Exposure turn, contributes to cancer risk.
Occupational risks for head and neck squamous cell
cancer development have been suggested in epi- Infections
demiologic data. Wood dust exposure is associated
Human Papillomavirus
with the risk of oral cancer68 as well as pharyngeal
and laryngeal cancer.69 Other occupations associated Evidence of human papillomavirus (HPV) genetic
with increased risk of head and neck squamous cell material has been identified in a proportion of head
carcinoma include machinists70–72 and automobile and neck squamous cell cancers.80 Verrucous carcino-
mechanics.70 Occupations which involve exposure mas have the squamous histology with the strongest
to organic chemicals, coal products, cement, and association with HPV, as HPV genomic material is
paint, laquer or varnish are also associated with found in 30 to 100 percent of these tumors.80 For squa-
increased risk of head and neck cancer.69 A risk of mous cell cancers in general, the proportion of cancers
cancer of the upper aerodigestive tract has also been with evidence of HPV genomic material appears to
shown in cases of long-term exposure to high con- vary, depending upon the upper aerodigestive tract site
centrations of sulfuric or hydrochloric acid as found analyzed. As reviewed and compiled by Steinberg,80
in battery plant workers.73 While it has been sug- the tumor site most often revealing HPV infection is
gested that an increased risk of oral and pharyngeal tonsil (74%), with lesser evidence of HPV in larynx
cancer is seen in bartenders,27 no excess risk has (30%), tongue (22%), nasopharynx (21%) and floor-
been found when analysis includes adjustment for of-mouth (5%) carcinomas. The role of HPV in these
alcohol and tobacco consumption.74 cancers is confounded by the fact that HPV genomic
Premalignant laryngeal lesions have also been material may also be found in normal head and neck
associated with occupational exposures, with a rela- mucosa in up to 64 percent of samples.80,81
tive risk of 10 for laryngeal dysplasia for blue-collar Cofactors for HPV induction of oral cancers have
compared with white-collar workers even after con- been investigated in a handful of studies. Tobacco
 Epidemiology and Etiology 13

Figure 1–8. Incidence and survival of oral and pharyngeal cancer for Caucasian and African
American males, 1986 to 1993. Circle position indicates percent 5-year survival for each stage.
Circle size indicates stage distribution for each race. Numbers correspond to circle size and
indicate percent of tumors presenting at each stage. Figure indicates a higher stage at diag-
nosis for African Americans and poorer survival at each stage. (Data from: Landis SH, Murray
T, Bolden S, Wingo PA. Cancer statistics, 1998. CA Cancer J Clin 1998;48:6–29.)

and alcohol habits have not been associated with the cancer (OR=1.9). A stronger association was seen
likelihood of detecting HPV in tumor tissue.82 How- with a history of a suspected HSV-1 infection
ever, use of betel quid has been associated with HPV (OR=3.3).56 While this study raises concerns about
detection in 9 of 11 (82%) cases of tongue cancer.83 reporting bias, support for this association is pro-
vided by a finding of HSV type 1 protein in 42 per-
Human Immunodeficiency Virus cent of patients with oral cancer and no positive
results in control patients.86
Human immunodeficiency virus (HIV) has shown
an emerging association with head and neck squa- Epstein-Barr Virus
mous cell carcinoma. In a recent study from New
York, HIV infection was present in almost 5 percent Epstein-Barr virus (EBV) has been associated with
of patients with head and neck cancer.84 Patients nasopharyngeal carcinoma. The association appears
with HIV were younger than non-HIV patients and strongest with World Health Organization (WHO)
HIV infection was present in over 20 percent of types II and III while a minority of WHO type I car-
head and neck cancer patients who were under 45 cinomas have revealed EBV.87 Type I tumors make up
year of age. The site of tumor presentation did not one-third of cancers in non-endemic populations.
vary with respect to HIV status, but tumors were The presence of EBV DNA in upper aerodigestive
larger and more advanced in the HIV group. As in mucosa samples seems to vary geographically. An 81
most cases of head and neck squamous cell carci- percent prevalence has been found in Greenland
noma, a history of tobacco and alcohol use is preva- Eskimos, a population with a high incidence of
lent in the HIV population.85 undifferentiated nasopharyngeal cancer. Among the
Danish population, the prevalence is only 35 per-
cent.88 Despite the fact that over 90 percent of the
Herpes Simplex Virus
world’s population shows serologic evidence of prior
Herpes simplex virus (HSV) has been associated EBV infection, evidence of persistent EBV DNA
with cancer of the oral cavity. In a study utilizing was seen in less than 1 percent of normal upper
patient questionnaires for data collection, a history aerodigestive mucosa samples in a large North
of proven HSV-1 infections was associated with oral American series.89 These results suggest that an EBV
14 CANCER OF THE HEAD AND NECK

chronic carrier state exists in endemic populations. Other studies have suggested an increased risk of
However, the detection of EBV in nasopharyngeal head and neck squamous cell cancer with red meat
samples is not a specific enough assessment to intake.94,104 Salted meat intake has been associated
require nasopharyngeal cancer screening.88 with oropharyngeal cancer risk,105 and processed
meat consumption associated with oral and oropha-
Inflammatory ryngeal cancer.94 On the other hand, a multi-institu-
tional European study showed an inverse association
Gastroesophageal Reflux Disease between preserved meat intake and risk of laryngeal
Chronic irritation from gastric reflux into the phar- and hypopharyngeal cancers.96
ynx and larynx has been suggested to be a risk fac- Heavy tobacco use appears to double the risk
tor for cancers of these sites.90,91 The presence of associated with low fruit consumption.38 On the
reflux has been documented by 24-hour pH probe other hand, a high intake of vegetables and fish has
study in 36 to 54 percent of patients with laryngeal been shown to modify the risk of aerodigestive tract
and pharyngeal carcinomas.92,93 While this preva- cancer in smokers.106 It has been estimated that
lence is significant, it is not dissimilar to the preva- among smokers/drinkers, the low intake of fruits and
lence in patients undergoing pH probe study for vegetables may contribute to between 25 and 50 per-
nonmalignant conditions.93 While causation has cent of laryngeal cancers.107
been difficult to establish, previous case series have
described the development of laryngeal and pharyn- GENETIC AND IMMUNOLOGIC
geal cancers in nonsmoking and nondrinking PREDISPOSITION
patients with documented reflux.90,91
The strong influence of tobacco and alcohol on the
Nutritional Considerations development of cancers of the upper aerodigestive
tract obscure underlying genetic predispositions that
Diet and Cancer Risk may exist. However, a subset of patients may have
Several studies have repeatedly associated high fruit factors that increase their cancer susceptibility. The
and vegetable intake with a decreased risk of head and Li-Fraumeni syndrome, inherited as an autosomal
neck squamous cell carcinoma.38,94–98 The association dominant trait, involves mutation of one allele of the
between fruit and vegetable consumption and a p53 tumor suppressor gene. This has been associated
reduced cancer risk may reflect increased intake of with head and neck cancer in some patients with min-
such micronutrients as vitamins C and E and beta imal tobacco exposure, and may indicate increased
carotene. In a nested case-control study correlating susceptibility to environmental carcinogens in these
serum micronutrient levels to later risk of developing patients.108 Fanconi’s anemia, Bloom syndrome and
upper aerodigestive tract carcinoma (up to 20 years ataxia-telangiectasia are autosomal recessive disor-
after serum collection), an association between low ders that are associated with increased chromosomal
alpha and beta carotene levels and subsequent devel- fragility and cancer susceptibility. Patients with head
opment of cancer was shown.99 When other elemental and neck squamous cell carcinoma have been
dietary components are compared to head and neck reported to be diagnosed with each syndrome.109–111
and esophageal cancer risk, an association with pro- Patients previously treated with bone marrow and
tein intake and an inverse association with vitamin C organ transplantation appear to have an increased
and flavonoid intake is shown.100 Other studies have risk of skin and oral cavity squamous cell carcinoma.
shown that increased iron and zinc intake are associ- The risk of oral cancer is well under 5 percent in
ated with a reduced risk of laryngeal or esophageal long-term bone marrow transplant recipients.112 The
cancers.101 Significant reduction in risk of oral, pha- risk may be associated with chronic graft versus host
ryngeal and esophageal cancers has been associated disease and long-term use of immunosuppressive
with high intake of tomatoes, an important source of medications.112 Viral etiologies have been suggested,
vitamin C in some parts of the world.102,103 but a clear cause has not yet been demonstrated.113
 Epidemiology and Etiology 15

Field Cancerization 2. Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer

Statistics, 2001. CA Cancer J Clin 2001;51:15–36.
While the etiologic factors described above may 3. Devesa SS, Silverman DT, Young JL Jr, et al. Cancer inci-
dence and mortality trends among whites in the United
allow one to make an estimation of head and neck States, 1947–84. J Natl Cancer Inst 1987;79:701–70.
cancer risk, one of the strongest predictors of cancer 4. Ries LAG. Rates. In: Harras A, editor. Cancer: Rates and
risk is a history of previous head and neck cancer. risks. Washington, DC, National Institutes of Health;
1996. p.9–55.
Patients with head and neck squamous cell carcino- 5. Wingo PA, Ries LA, Giovino GA, et al. Annual report to the
mas have long been shown to have an increased risk nation on the status of cancer, 1973–1996, with a special
of multiple aerodigestive tract tumors. When fol- section on lung cancer and tobacco smoking [see com-
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lowed over time, patients previously treated for these 6. Goldberg HI, Lockwood SA, Wyatt SW, Crossett LS. Trends
cancers have a risk of developing second cancers of and differentials in mortality from cancers of the oral cav-
the head and neck, esophagus, and lung that approx- ity and pharynx in the United States, 1973–1987. Cancer
imates 4 percent per year.114 The risk does not 1994;74:565–72.
7. La Vecchia C, Boyle P. Trends in the tobacco-related cancer
appear to taper off with long-term follow-up.114 epidemic in Europe. Cancer Detect Prev 1993;17:
The risk of second cancers appears to relate to 495–506.
tobacco and alcohol exposure.115 Long-term expo- 8. Sanchez V, Borras JM, Mingot M. [Cancer mortality trends
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sure to these carcinogens appears to place large 606–12.
areas of aerodigestive tract mucosa at increased risk 9. Hill C, Benhamou E, Doyon F. Trends in cancer mortality,
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63:587–90.
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detectable abnormalities in tumor suppressor genes 1955–1978. Tumori 1985;71:201–18.
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Switzerland, 1990–1994. Soz Praventivmed 1997;42:
37–54.
CONCLUSION 12. Menegoz F, Black RJ, Arveux P, et al. Cancer incidence and
mortality in France in 1975–95. Eur J Cancer Prev
The epidemiology of head and neck squamous cell 1997;6:442–66.
carcinoma has changed considerably in this century. 13. Capocaccia R, Micheli A, Berrino F, et al. Time trends of
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215–7.
these risk exposures is complex. This chapter has 15. MacFarlane GJ, Evstifeeva TV, Scully C, Boyle P. The
described variations in risk related to tobacco types descriptive epidemiology of pharyngeal cancer in Scot-
and delivery methods and has also detailed informa- land. Eur J Epidemiol 1993;9:587–90.
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dence and mortality in young adults in Vaud, Switzerland,
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development in the United States has been decreas- since 1960. The epidemiologic context in Austria]. HNO
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attention in cancer prevention and treatment. :31–9.
20. Leinsalu M, Rahu M. Time trends in cancer mortality in
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 2
Pathology of Head
and Neck Tumors
MANJU L. PRASAD, MD
ANDREW G. HUVOS, MD

TUMORS OF THE UPPER pressure. Synchronous or metachronous association

AERODIGESTIVE TRACT MUCOSA with squamous cell carcinoma as well as progres-
sion to it may occur in some patients with inverted
Neoplasias of the upper aerodigestive tract histolog-
ically tend to mimic the normal constituent cells in
this region. The most common neoplasias show dif-
ferentiation toward lining epithelium.

Benign Papillary Lesions

Squamous papilloma is a solitary papillary lesion of

the squamous epithelium which has a white, frond-
like gross appearance. Microscopically, it consists of
multiple papillae of benign, stratified squamous
cells arranged around central fibrovascular cores.
They usually occur in adults. Although a viral etiol-
ogy is suspected, human papillomavirus (HPV)
types 6 and/or 11 have been detected in only some of
the cases. Juvenile laryngeal papillomatosis are his-
tologically similar to squamous papilloma but occur
in children and are characteristically multiple. They
tend to recur and sometimes can be florid enough to
cause asphyxiation. Sometimes the recurrences
cease at puberty. Squamous cell carcinoma may fol-
low radiation therapy for treatment of juvenile papil-
lomatosis (Figure 2–1).
Schneiderian papillomas arise in the sinonasal
region and may be fungiform (exophytic), inverted
(endophytic) or oncocytic (Figure 2–2). The role of
Figure 2–1. Infiltrating squamous cell carcinoma developing in a
HPV in their development is controversial. The solitary tracheal papilloma in a 31-year-old male. The papillary lesion
patients are middle-aged. Although benign, the occupied the anterior half of the tracheal lumen. The carcinoma infil-
recurrence rate with local excision is almost 70 per- trated the anterior wall of the trachea. The patient had a benign soli-
tary tracheal papilloma since the age of 2 and had suffered many
cent. The inverted papilloma may erode bone by recurrences.

19
20 CANCER OF THE HEAD AND NECK

and oncocytic papillomas. The histologic appear- mous epithelium. Suprabasal mitosis heralds moder-
ance does not help in predicting the occurrence of ate dysplasia, the diagnosis of which may be aided by
recurrence or carcinomatous change.1 immunohistochemical staining for cell proliferation
Verruca vulgaris and condyloma can be seen in markers, eg, Ki-67 (MIB1) and proliferating cell
the oral mucosa and their appearance is similar to nuclear antigen (PCNA). Overexpression of p53,
that occurring elsewhere in the body. although uncommon, signifies malignant transfor-
mation of moderate dysplasia to carcinoma in situ.6
Malignant and Premalignant
Squamous Cell Lesions Carcinoma in Situ

Carcinoma in situ (CIS)/severe dysplasia of the oral

Squamous cell carcinoma (SCC) is the most com-
mucosa is usually of the keratinizing type, in which
mon malignant tumor of the upper aerodigestive
the abundant eosinophilic cytoplasm continues to
mucosa, and shows a distinct male predilection.
show some degree of differentiation as the atypical
Tobacco and alcohol consumption are significant
epithelial cells migrate from basal to more superficial
risk factors. Several HPV DNA subtypes have been
layers while still retaining their mitotic activity. The
found in association with SCC; however, their role
basaloid type, in which atypical, undifferentiated,
in carcinogenesis remains conjectural.
basaloid cells with high nuclear cytoplasmic ratio
Precancerous Lesions

Leukoplakia is a whiter patch on the oral mucosa

which cannot be scraped off; nor can it be attributed
to any other disease entity. Histologically, it is repre-
sented by hyperkeratosis with acanthosis with or
without dysplasia. Erythroplakia is a red, velvety
mucosal patch that represents epithelial atrophy,
inflammation and subepithelial telangiectasia. Ery-
throplakia or erythroleukoplakia (speckled white
and red patches) confer a greater risk of being asso-
ciated with dysplasia with 91 percent being in situ or
invasive SCC.2,3 Proliferative verrucous leukoplakia
(PVL) is an idiopathic condition occurring typically
in the oral mucosa of elderly women which pursues
a recurrent and progressive clinical course. Histo-
logically, it appears with innocuous hyperkeratosis
of the squamous epithelium and progresses to verru-
cous hyperplasia and dysplasia with the ultimate
development of verrucous or conventional SCC over
a protracted period of time.4 This has led some to
advocate that verrucous hyperplasia, the earliest his-
tologically definable event in PVL, should be treated
like verrucous carcinoma.5
Dysplasia is architecturally disordered prolifera-
tion of epithelial cells displaying abnormal cytologic
appearance and maturation. Graded along a 3-tier Figure 2–2. Fungiform schneiderian papilloma. The lesion is exo-
system, mild dysplasia manifests as an increase in phytic, lined with multiple layers of cells with a morphology transi-
tional between squamous and columnar cells. Mucous cells contain-
mitotic activity in the basal layer. It is difficult to dis- ing blue mucin are scattered throughout. Acute and chronic
tinguish it from reactive/repair activity of the squa- inflammation is characteristically present.
 Pathology of Head and Neck Tumors 21

Figure 2–3. Carcinoma in situ/severe dysplasia in atrophic laryngeal mucosa. Dysplastic cells with
hyperchromatic nuclei and increased nuclear cytoplasmic ratio are present even in the superficial
layer of the squamous mucosa. The basement membrane is intact.

occupy all layers of the epithelium, is usually seen in prognosis and lower rate of lymph node metastasis
the oropharynx and the larynx (Figure 2–3). than when it is jagged, irregularly infiltrative in the
Field cancerization is the appearance of multiple form of short cords and even single cells (grade 3 to
synchronous or metachronous primary carcinomas 4) (Figure 2–5).10,11 Assessment of surgical margins
in a mucosal field exposed to the same local car- by intraoperative pathology consultation helps
cinogen. The synchronous lesions are separated by ensure complete removal of tumor. In situ or inva-
so-called skip areas of histologically normal sive carcinoma at or close (less than 5 mm) to the
mucosa. Metachronous second primary lesions are inked margin of resection increases the risk of recur-
accompanied by CIS. rence and may require postsurgical radiotherapy.
Tumors of the lower alveolar ridge infiltrate the
Invasive Squamous Cell Carcinoma mandible by direct extension and either spread
between the medullary bony trabeculae or perineu-
Squamous cell carcinoma (SCC) consists of malig- rally around the inferior alveolar nerve. The latter is
nant cells with squamous differentiation as evinced significantly more common in edentulous patients
by the presence of intercellular bridges and keratin than in the dentate ones. The mandibular extension
formation. The conventional SCC is histologically
graded on a scale of 3: well-, moderately- and
poorly-differentiated SCC, depending upon the pres- Table 2–1. PATHOLOGIC PROGNOSTIC FACTORS
IN UPPER AERODIGESTIVE SQUAMOUS
ence of intra- and extracellular keratin. However,
CELL CARCINOMA
this scheme has little bearing on prognosis. Better
Factors Related Factors Related to
prognostic indicators and predictors of lymph node to Primary Tumor Regional Lymph Nodes
metastasis are enumerated in Table 2–1. Excellent
Size Positive/negative
prognosis is expected for so-called thin tumors ver- Thickness Number of positive nodes
sus thick ones, ie, less than 1.5 mm in the floor of Invasive front Size of largest positive node
Vascular and perineural invasion Laterality of positive nodes
the mouth,7 2 mm in the tongue,8 and 3 mm in the Margins of resection Presence/absence of
buccal mucosa.9 Tumor thickness is an independent Morphology extracapsular extension
predictor of recurrence, lymph node metastasis and Well/poorly differentiated
Exophytic/endophytic
survival. It has been shown that when the invasive Mitotic index
front is well demarcated, blunt and of pushing type Presence of carcinoma in situ
and multifocality
(grade 1) (Figure 2–4), the tumors have a better
22 CANCER OF THE HEAD AND NECK

is, however, limited and corresponds to the extent of diagnosis, as it may not include the invasive base of
the tumor in the overlying mucosa.12 the tumor which is essential for a histologic diagno-
In node-positive carcinomas, the number of pos- sis. The prognosis is excellent, marred only by local
itive nodes, their location and the size of the largest recurrences. Pure verrucous carcinoma does not have
positive lymph node are important predictors of sur- metastatic potential. However, approximately 20 per-
vival. The presence of extracapsular extension of cent of verrucous carcinomas are hybrid, having an
tumor is a poor prognostic feature requiring postsur- additional component of conventional SCC that con-
gical radiotherapy (see Table 2–1). Some conven- fers metastatic potential to it.13
tional SCC may show cystic degeneration, pseudog- Papillary SCC is also exophytic but has a frond-
lands and extracellular mucinous substance, but like appearance with a central fibrovascular core
intracytoplasmic mucin is not seen in SCC. Several usually lined by layers of poorly-differentiated
variants of SCC are recognized. tumor cells. Infiltration of the stroma and/or the
Verrucous carcinoma is an exophytic, warty, low- base of the neoplasm is necessary to establish inva-
grade, well-differentiated SCC predominantly occur- sion (Figure 2–7).
ring in men in their seventh decade of life. It has a Basaloid SCC usually arises in the posterior oral
well-defined, broad, pushing invasive front. The cavity and is highly aggressive. These patients fare
cytomorphology of tumor cells is bland (Figure 2–6). much worse as compared to even the poorly-differen-
Therefore, a superficial biopsy may not establish the tiated SCC in terms of metastasis and survival. Nodal

Figure 2–5. Moderately-differentiated squamous cell carcinoma

Figure 2–4. Moderately-differentiated squamous cell carcinoma of of the tongue infiltrating the lamina propria. The invasive front
the tongue with a pushing type (grade 1) of infiltrating pattern at the shows a grade 3 infiltrating pattern by small clusters and cords of
tumor’s growing edge. malignant cells.
 Pathology of Head and Neck Tumors 23

Figure 2–7. Papillary squamous cell carcinoma of the tongue. The

Figure 2–6. Verrucous carcinoma of the vocal cord. The malignant tumor is exophytic with a focus of infiltration in the lamina propria.
squamous cells are extremely well-differentiated with maturation and The papillae have fibrovascular cores and are lined by non-kera-
abundant keratinization toward the surface. The deep edge of the tinizing moderately-differentiated squamous carcinoma cells in con-
tumor is broad and of the pushing type. Grossly, the carcinoma was trast with verrucous carcinoma. The prognosis is worse than the ver-
exophytic and warty. rucous carcinoma as this tumor has metastatic capabilities.

metastasis is detected at initial presentation in almost have been demonstrated in the spindle cells. Expres-
two-thirds of the patients, and one-half of them sion of smooth muscle actin and occasionally
develop distant metastasis with the lung being the desmin points to myofibroblastic differentiation of
most common site. This mandates a metastatic survey the spindle cells.16
at initial diagnosis.14 Median survival is 18 months.15 Adenocarcinoma and adenosquamous carcinoma
Sarcomatoid (spindle cell) SCC is usually exo- of the upper aerodigestive tract are believed to arise
phytic and polypoid with the same clinical profile as in the submucosal glands. They may resemble sali-
conventional SCC. Histologically, the tumor has vary gland tumors and are discussed in that section.
remarkable resemblance to malignant fibrous histio-
cytoma. Lymph node metastasis can show either or Undifferentiated Carcinoma
both epithelial and sarcomatous components.
Immunohistochemically, cytokeratin can be demon- Lymphoepithelial carcinoma occurs most commonly
strated in the epithelial as well as spindle cell com- in the nasopharynx where it is also designated as
ponents. Ultrastructurally, tonofilaments and des- World Health Organization (WHO) type 3 nasopha-
mosomes, two of the hallmarks of squamous cells, ryngeal carcinoma (Table 2–2). Cervical lymph
24 CANCER OF THE HEAD AND NECK

Table 2–2. CLASSIFICATION OF NASOPHARYNGEAL icopathologic characteristics similar to anywhere

CARCINOMA WORLD HEALTH ORGANIZATION, 1991 else in the body. The nasal NK/T-cell lymphomas
1. Squamous cell carcinoma, keratinizing (synonyms: polymorphic reticulosis, angiocentric
2. Non-keratinizing carcinoma lymphoma, lethal midline granuloma) is a distinct
A. Differentiated non-keratinizing carcinoma
B. Undifferentiated carcinoma
clinicopathologic entity affecting Asians and Native
Americans. It is a destructive sinonasal disease pre-
senting usually in the midline. It is a tumor of the
node metastasis from an occult primary is a frequent natural killer cells and T cells, and is frequently
presentation. There is a bimodal age distribution associated with EBV infection. The prognosis is
with peaks in the second and sixth decades. There is extremely poor in Asians and Native Americans in
a predilection for people of southern China and a contrast to Caucasians.
well-established association with Epstein-Barr virus Plasmacytoma, either solitary or in association
(EBV) infection.17 The tumor is heavily infiltrated with multiple myeloma, may occur in relation to the
by lymphocytes and sometimes eosinophils and may upper aerodigestive tract. It may be associated with
mimic Hodgkin’s or non-Hodgkin’s lymphoma (Fig- amyloid.
ure 2–8). The sinonasal undifferentiated carcinoma Neuroendocrine carcinoma and malignant mel-
(SNUC) usually occurs in middle-aged patients and anoma are discussed in a separate section on tumors
has a slight female preponderance. The tumor is of neurogenic origin.
characterized by numerous mitoses, necroses and
extensive vascular invasion—features supportive of TUMORS OF THE SALIVARY GLANDS
its high-grade nature (Figure 2–9).
The distribution of tumors among different salivary
glands studied at the Memorial Sloan-Kettering
Lymphoma
Cancer Center is given in Figure 2–10.18 Benign
The sinonasal region is the most frequent site for tumors occur more frequently in the parotid glands
lymphomas of the upper aerodigestive tract, most of of women in their fourth to fifth decades of life (Fig-
which are diffuse large B-cell lymphomas with clin- ure 2–11). Tumors in the minor salivary glands are

Figure 2–8. Lymphoepithelial carcinoma of the nasopharynx. The tumor cells have large, vesicular
nuclei with prominent nucleoli and indistinct cytoplasm. They appear to be in a syncytium with an inti-
mate admixture of lymphocytes (Schmincke pattern). Another pattern (not seen here) consists of cells
arranged in loosely cohesive groups (Régaud pattern).
 Pathology of Head and Neck Tumors 25

Figure 2–11. Relative distribution of benign versus malignant

tumors among 1,875 parotid tumors at the Memorial Sloan-Kettering
Cancer Center, New York.

Pleomorphic Adenoma

Pleomorphic adenoma or benign mixed tumor is the

most frequent of parotid tumors. It occurs usually in
the third to fifth decades with a female preponder-
ance. The usual history is that of a slow growing
tumor present for a long time. Grossly, the tumor is
usually located in the superficial lobe of the parotid
gland, and is well circumscribed with a gray-white,
lobulated cut surface (Figure 2–13A). Histologically,
it is composed of a varied mixture of epithelial and
stromal components giving rise to its name “pleo-
morphic” or “mixed” tumor (Figure 2–13B). The
tumor is believed to arise in the myoepithelial cells
Figure 2–9. Sinonasal undifferentiated carcinoma (SNUC).
Poorly-differentiated tumor cells with central comedo-type necrosis
infiltrating bone.

more likely to be malignant than parotid tumors (see

Figure 2–11). Salivary gland tumors tend to recapit-
ulate the normal histology of the salivary glands
(Figure 2–12).

Figure 2–12. Schematic diagram of the histology of the normal

Figure 2–10. Relative distribution of 2,743 salivary gland tumors salivary gland. A uniform layer of myoepithelial cells invests the ter-
at the Memorial Sloan-Kettering Cancer Center, New York. minal secretory unit—the acinus and the intercalated duct.
26 CANCER OF THE HEAD AND NECK

B
Figure 2–13. A, Pleomorphic adenoma. The tumor has a nodular external surface and a
gray-white cut surface which may display focal chondroid differentiation. B, Histology
shows prominent blue mucinous/myxoid component with small cuboidal bland cells form-
ing cords and duct-like structures.

which retain their capacity for dual differentiation. former is much more frequent, giving rise to the
Although these tumors are well-circumscribed, multi- designation “carcinoma ex mixed tumor” and “car-
ple microscopic pseudopods of the tumor can be left cinoma ex pleomorphic adenoma.” They represent
behind if resected by “shelling out” which can lead to about 11 percent of all malignant salivary gland
multifocal recurrences. A cellular mixed tumor has an neoplasms.19 The patients are usually in their fifth
excess of epithelial and myoepithelial cells with decade with a slight female predilection. Most
sparse chondromucinous stroma. tumors are more than 3 cm in size. Important histo-
Malignant transformation occurs in 5 to 10 per- logic prognostic factors are morphology of carci-
cent of cases and is much more common than the de noma (low vs. high grade) and degree of infiltration
novo malignant mixed tumor. Clinically, recent (in situ or minimally vs. extensively invasive).20
rapid growth and nerve palsy, while microscopi- Almost all patients have local treatment failure.
cally, cellular atypia, mitosis, invasion of the sur- Distant metastasis can occur in 33 percent of cases,
rounding tissue, nerves and vessels constitute fea- with lungs and bones being common sites. The less
tures of malignancy. Although both the epithelial commonly occurring biphasic carcinosarcoma or
and the mesenchymal components of the mixed “true” malignant mixed tumor has a very aggressive
tumor can undergo malignant transformation, the and lethal behavior.21
 Pathology of Head and Neck Tumors 27

Monomorphic Adenoma number of cases. The extremely rare oncocytic carci-

noma has an infiltrative growth pattern and an
Monomorphic adenomas are relatively uncommon aggressive clinical behavior.
benign epithelial tumors predominantly occurring in Malignant salivary gland tumors account for
the parotid glands. They lack the myxoid stroma of approximately 7 percent of all carcinomas arising in
the pleomorphic adenoma. Various morphologic the upper aerodigestive tract.22 Risk factors include
types are described. The canalicular adenoma occurs exposure to radiation, tobacco, chemicals, and
most frequently in the upper lip. The basal cell ade- viruses, and genetic predisposition. About 15 per-
noma is composed of basal cells surrounded by a cent of all parotid, 35 percent of submandibular, 45
thick, hyaline basement membrane material contain- percent of minor salivary and 80 percent of sublin-
ing stroma. The malignant counterpart, basal cell gual gland tumors are malignant.23 Men and women
adenocarcinoma, is characterized by an infiltrative are almost equally affected. In most instances, the
growth pattern. clinical stage of the disease has greater influence on
prognosis than the histologic grade, except in
Oncocytic Tumors mucoepidermoid and adenocarcinoma, not other-
wise specified.
The parotid gland is the most common site for onco-
cytic tumors which tend to occur in the fifth to sixth
Mucoepidermoid Carcinoma
decades and which have shown a relationship to pre-
vious radiation exposure. Oncocytomas are solid The most frequent site for a mucoepidermoid carci-
tumors composed of cells with abundant mitochon- noma is the parotid, followed by intraoral minor sali-
dria-rich cytoplasm which is intensely eosinophilic vary glands. Most patients are in their early fifties.
and granular in texture (Figure 2–14). The much Grossly, the tumor is poorly circumscribed and mea-
more common papillary and cystic Warthin’s tumor sures from 3 to 5 cm. The cut surface is solid but
has a male predilection and a strong association with may be cystic. The tumor is composed of glandular
smoking. A characteristic non-neoplastic lympho- and epidermoid cells, the latter characteristically of
cytic component with activated follicles containing intermediate basaloid type (Figure 2–16). The histo-
germinal centers is present, justifying the synonym logic grading scheme is prognostically significant.
papillary cystadenoma lymphomatosum (Figure Low-grade tumors form cysts lined by a single layer
2–15). It may be bilateral in a small but significant of glandular mucinous cells with an admixture of

Figure 2–14. Oncocytoma. The tumor is solid with sheets of cells with abundant aci-
dophilic cytoplasm. The nuclei have characteristic prominent nucleoli.
28 CANCER OF THE HEAD AND NECK

Figure 2–15. Warthin’s tumor. The lesion is predominantly cystic with an exuberant lymphoid
follicular reaction. The cyst is lined by oncocytic cells which are arranged in papillary structures.

epidermoid cells. The epidermoid and intermediate recurrence rate of 47 percent. Perineural invasion is
basaloid-type cells tend to form solid areas in inter- frequent and extensive, requiring intraoperative
mediate grade, and predominate in high-grade assessment of the neural margin of resection. Dis-
lesions along with scant evidence of glandular dif- tant metastasis has been reported in 38 percent of
ferentiation, increased cytologic atypia, mitosis, cases with lung and bones being common sites. The
necrosis and perineural invasion. Using these grad- microscopic grading system does not appear to be
ing criteria, 90 percent of the low-grade as compared useful. Clinical stage is the most important factor in
to 42 percent of the high-grade mucoepidermoid determining prognosis.25
carcinoma patients were found to be alive at 10 years
after treatment.24 An important differential diagnosis Polymorphous Low-Grade Adenocarcinoma
is primary or metastatic squamous cell carcinoma,
which is rare in the parotid and lacks intracellular This tumor is increasingly being recognized as one of
mucin. Sebaceous and clear cell neoplasms are addi- the more frequent salivary gland adenocarcinomas
tional differential diagnostic concerns. ever since it was described under synonyms such as
lobular, terminal duct or trabecular carcinoma.26,27
Adenoid Cystic Carcinoma The patients usually are in their fifth decade. The
tumors involve the minor salivary glands almost
The most frequent site of origin of adenoid cystic exclusively, and rarely, the nasal cavity or nasophar-
carcinoma is in the minor salivary glands, especially ynx. The lesion may be relatively well-circumscribed
in the palate, followed by the sinuses and nasal cav- but can extensively invade the adjacent bone. Micro-
ity and the parotid glands. The patients are usually in scopically, there is great architectural diversity (Fig-
their fifties and may be of either sex. On micro- ure 2–18). A single file arrangement may be seen as
scopic examination, the tumor has a characteristic in the infiltrating lobular carcinoma of breast. In
cribriform appearance formed by the interruption of spite of their low-grade, usually indolent biologic
sheets of tumor cells by cylindrical pseudo-spaces or behavior, 76 percent show perineural invasion and up
pseudo-lumina, giving rise to the designation cylin- to 29 percent may metastasize to the cervical lymph
droma (Figure 2–17). Although clinically indolent, nodes.28 Differential diagnosis includes adenoid cys-
these tumors are relentlessly infiltrative with a local tic carcinoma and pleomorphic adenoma.
 Pathology of Head and Neck Tumors 29

Acinic Cell Carcinoma stromal hyalinization. Although the histologic grad-

ing system is not always useful, the conventional
Acinic cell carcinoma (ACC) comprises 17 percent ACC should be separated from the papillocystic
of primary malignant salivary gland tumors.25 variant (Figure 2–19B) believed to have a particu-
Almost 90 percent of them arise in the parotid gland, larly bad prognosis, and a highly aggressive dedif-
making it the second most common malignant ferentiated variant.29,30 The conventional ACC is a
tumor at this site. The age varies widely with a small low-grade malignant tumor characterized by pro-
peak in the fourth decade. Grossly, the tumor usually longed disease-free survival, late recurrences and
measures less than 3 cm, and is well-defined with a late distant metastasis to bone, lung and brain.31
friable, tan cut surface. The most characteristic
tumor cells are the acinic cells which contain peri-
Adenocarcinoma, Not Otherwise Specified
odic acid Schiff’s reagent (PAS)-positive cytoplas-
mic glycogen granules resembling the serous cells These are adenocarcinomas lacking any characteris-
of salivary glands (Figure 2–19A). Histologic fea- tic feature that helps in classifying them as other
tures used for grading are increased mitosis, necro- specific types of epithelial tumors of salivary origin.
sis, neural invasion, infiltration, pleomorphism and Thus, it is a diagnosis by exclusion. There is a slight

Figure 2–16. A, A partly cystic mucoepider-

moid carcinoma involving a dilated minor sali-
vary gland duct. Although the tumor forms
numerous cysts, the solid areas indicate its inter-
mediate grade. B, The intracytoplasmic, as well
as extracytoplasmic, neutral mucin stains bright
pink with mucicarmine stain. The former is diag-
nostic of mucoepidermoid carcinoma.

B
30 CANCER OF THE HEAD AND NECK

Figure 2–17. Adenoid cystic carcinoma showing tumor cell nests with a cribriform/cylindromatous
pattern. The pseudolumina may contain acidic mucin (as in this figure) or basement membrane-like
material which may also surround tumor nests. The pseudolumina shows two layers of tumor cells
with small, cuboidal cells towards the center and clear myoepithelial cells at the periphery.

male preponderance with a median age of 58 years.

The minor salivary glands are more frequently
involved followed by the parotid glands. Microscop-
ically, the cells may display a glandular, papillary or
mucinous growth pattern, and sometimes even
resemble colonic adenocarcinoma. The histologic
grading which takes into account cytologic atypia,
pleomorphism, mitosis and necrosis, identifies low,
intermediate and high grades. Prognosis depends on
site (better in oral cavity tumors), histologic grade
and clinical stage.32

Rare Tumors

Myoepithelioma and myoepithelial carcinoma are

rare neoplasms composed almost entirely of myoep-
ithelial cells. The parotid is the most common site.
Multiple recurrences, distant metastasis and death
due to disease occur in one-third of the patients suf-
fering from myoepithelial carcinoma, suggesting an
intermediate- to high-grade malignant potential.31
Epithelial-myoepithelial carcinoma is an uncommon,
low-grade, multilobular, malignant neoplasm that
shows both epithelial and myoepithelial differentia-
tion and occurs most commonly in the parotid glands Figure 2–18. Polymorphous low-grade adenocarcinoma. The
squamous mucosa of the oral cavity is visible above. The tumor cells
of elderly women. Clear cell adenocarcinoma occurs are squamoid near the surface and become clear and form glandu-
in the fifth to seventh decade and is comprised of lar structures below.
 Pathology of Head and Neck Tumors 31

glycogen-rich cells. It affects both sexes equally. sis is ruling out mucoepidermoid carcinoma and
Lymphoepithelial carcinoma may arise in the sali- metastatic squamous cell carcinoma. Cystadenoma
vary glands, usually de novo but sometimes in asso- and cystadenocarcinoma are rare tumors character-
ciation with Sjögren’s syndrome. A female predilec- ized by cysts lined by columnar cells and resemble
tion and a higher incidence among the Inuit is their counterparts in the pancreas and ovary.31
noted.33 The parotid is the most frequently involved
salivary gland. The morphology is similar to the TUMORS OF THYROID AND
nasopharyngeal variant—metastasis from which PARATHYROID GLANDS
should be ruled out before considering a primary
parotid tumor. Salivary duct carcinoma is a very Thyroid tumors affect females more often than men.
aggressive neoplasm that resembles intraductal carci- Radiation is an important predisposing factor, espe-
noma of the breast replete with comedo-necrosis, cially for papillary thyroid carcinoma. A close associ-
“Roman bridges” and cribriform pattern. Most ation of Hashimoto’s thyroiditis to many thyroid
tumors occur in the parotid glands of elderly men.31 malignancies, eg, lymphoma, papillary and Hürthle
Perineural and vascular invasion and dense fibrosis cell carcinoma, sclerosing mucoepidermoid thyroid
are commonly present. Primary squamous cell carci- carcinoma and squamous cell carcinoma has been
noma of the salivary gland is a rarity. It probably noted. Malignant cells arising in the follicular epithe-
arises in the part of the excretory salivary duct which lium express thyroglobulin, a feature that may be used
is closer to the oral cavity. A prerequisite for diagno- to support their thyroid origin at metastatic sites.

Figure 2–19. A, Acinic cell carcinoma—conventional type. The tumor

is predominently solid with microcyst formation. Several tumor cells
have the typical granular cytoplasm of serous acinic cells. B, Acinic cell
carcinoma—papillocystic variant. The tumor is predominantly cystic with
papillary proliferation in the cyst lumen. This variant is believed to have
a poorer prognosis than the conventional type.

A
32 CANCER OF THE HEAD AND NECK

Papillary Carcinoma architecture of the thyroid gland, have similar bio-

logic behavior and a good prognosis (see Figure
This is the most common thyroid carcinoma affect- 2–20). The size of the papillary microcarcinoma is
ing patients at a young age. The size of the tumor by definition less than 1 cm. It is usually incidentally
varies widely from microscopic to massive tumors discovered in association with a fibrous scar and has
that may completely replace the thyroid and extend an excellent prognosis as has the encapsulated vari-
outside of it. Incidental or occult presentation and ant. The diffuse sclerosing variant is characterized
multifocality is well known. The characteristic by the patient’s younger age, extensive involvement
nuclear features (Figure 2–20A), when present, are of the thyroid gland with a predominantly fibrosing,
sufficient for the diagnosis of papillary carcinoma, psammomatous papillary carcinoma with frequent
even in the presence of a capsule and in the absence squamous metaplasia, lymphocytic infiltration and
of invasion. Psammoma bodies may be present in vascular invasion. More than half of the patients
nearly half of the cases. The nuclear morphology, develop regional lymph node involvement, and
papillary tissue fragments and psammoma bodies metastasis to lungs are frequent. In spite of the
can also be appreciated in fine-needle aspiration higher incidence of distant metastasis, death rate due
cytology facilitating correct diagnosis. Several his- to tumor is extremely low.34 The tall cell (Figure
tologic variants have been described. The conven- 2–21) and columnar cell variants have extremely
tional papillary carcinoma with true papillae, and poor prognosis.35,36 The former occurs in older
the follicular variant recapitulating the follicular patients and presents with large tumor size while the

Figure 2–20. A, Papillary thyroid carcinoma—conventional type with

well-formed papillae with fibrovascular cores. A psammoma body is
seen in the upper right corner. The surrounding non-neoplastic tissue
shows lymphocytic thyroiditis with which it is commonly associated.
Inset shows the characteristic nuclear clearing, overlapping nuclei
(“eggs in a basket”) and nuclear grooves. B, Papillary carcinoma—fol-
licular variant. The diagnosis is based on the similarity of nuclear fea-
tures to conventional papillary carcinoma. A psammoma body is seen in
the upper left corner.

B
 Pathology of Head and Neck Tumors 33

latter is reported in young men who die of disease lesions should be completely excised with their cap-
within 2 years of presentation. Other morphologic sule and the adjacent thyroid, so as to permit histo-
indicators of poor prognosis are extra-thyroidal logic evaluation of the entire capsule for infiltration.
extension and vascular invasion. A cribriform-moru- For this reason, distinction between follicular ade-
lar variant has been described in young women in noma and carcinoma cannot be made on fine-needle
association with familial adenomatous polyposis.37 aspiration cytology. Mitosis and nuclear atypia may
be present in adenomas which are then designated
Follicular Neoplasm atypical follicular neoplasms, the overwhelming
majority of which behave in a benign fashion. Most
Follicular adenoma is a benign, solitary, encapsu- patients with follicular carcinoma are in their fifth
lated tumor of the thyroid follicular epithelium. Fol- decade of life and present with a solitary neck mass.
licular carcinoma is a malignant neoplasm which is Blood-borne metastasis to lungs and bones is more
distinguished from its benign counterpart by the common than lymphatic spread to regional nodes. A
presence of vascular and full-thickness capsular minimally invasive (encapsulated) follicular carci-
invasion into the surrounding non-neoplastic thyroid noma needs to be distinguished from an extensively
parenchyma (Figure 2–22). Thus, all follicular invasive one, as fewer than 5 percent of the former

Figure 2–21. Papillary carcinoma—tall cell variant. The cells are Figure 2–22. Hürthle cell carcinoma—minimally invasive. The
twice as tall as broad while the nuclear features remain the same as tumor cell cytoplasm is deeply acidophilic. Although the fibrous cap-
in papillary carcinoma. This morphologic variant is believed to have a sule is present all around the tumor, at this focus the tumor shows
worse prognosis than the conventional papillary thyroid carcinoma. vascular invasion.
34 CANCER OF THE HEAD AND NECK

metastasize.38,39 In the encapsulated variant, capsu-

lar invasion in the absence of vascular invasion has
little value in predicting outcome. Figure 2–23
schematically enumerates all follicular neoplasms in
order of their malignant potential.

Hürthle Cell Neoplasms

Hürthle cell or oncocytic neoplasms are composed

of cells with abundant pink (oxyphilic) cytoplasm
containing ample abnormal mitochondria on ultra-
structural examination. The majority of these tumors
are benign. The lesion is often divided into lobules
by thick fibrous septa. As in follicular carcinoma,
presence of capsular or vascular invasion is a pre- Figure 2–23. Follicular neoplasms arranged in order of worsening
prognosis from above down.
requisite for the diagnosis of malignancy (see Figure
2–22). As a result, fine-needle aspiration cytology
can at best suggest a Hürthle cell neoplasm, but can-
not distinguish between a benign or malignant
lesion. These tumors tend to occur in an older age
group with only a slight female preponderance.
They are more aggressive than the conventional pap-
illary or follicular carcinomas, suggesting an inter-
mediate-grade malignant behavior.40

Poorly-Differentiated (Insular) Carcinoma

This tumor is viewed as a poorly-differentiated vari-

ant of the well-differentiated papillary or follicular
thyroid carcinoma and occurs in a relatively older
age group. The tumor cells are uniformly small with
mild atypia and variable mitosis. Focal necrosis may
be present. The cells are arranged in a solid or
micro-follicular, nested or insular pattern. They
express thyroglobulin which is useful in distinguish-
ing them from medullary carcinoma. The biologic
behavior is aggressive, resulting in recurrences and
distant metastases (Figure 2–24).

Undifferentiated/Anaplastic Carcinoma

This is a high-grade malignant neoplasm which usu-

ally affects older patients and has a female prepon-
derance. Patients present with a recent-onset
rapidly-enlarging mass frequently associated with Figure 2–24. Poorly-differentiated carcinoma of thyroid with an
dyspnea, dysphagia and/or hoarseness, indicating insular and barely discernible micro-follicular growth pattern. This
tumor showed nuclear features of papillary carcinoma at higher
extra-thyroidal extension at presentation. Histologi- magnification, suggesting that it may have progressed from a well-
cally, the tumor may be composed of three types of differentiated papillary carcinoma.
 Pathology of Head and Neck Tumors 35

Figure 2–25. Anaplastic carcinoma

of the thyroid. The tumor cells are spin-
dle-shaped with markedly anaplastic
nuclei resembling a high-grade sar-
coma. Due to their extreme degree of
dedifferentiation, the tumor cells do not
(or only focally) express thyroglobulin,
requiring a combined clinicopathologic
effort to make a definite diagnosis of
primary thyroid carcinoma.

cells: anaplastic spindle cells resembling a sarcoma, have been found to be associated with all familial
bizarre pleomorphic multinucleate giant cells and and some sporadic cases.41 The tumor usually
squamoid cells (Figure 2–25). Severe nuclear atypia, involves the upper two-thirds of the thyroid, the area
cellular pleomorphism, brisk mitosis, large foci of of maximum concentration of C cells in the normal
necrosis and extensive invasion are characteristic gland. The sporadic cases are unifocal and discrete
features. Rarely, metaplastic bone or cartilage may while the familial cases are more likely to be multi-
be present. Immunohistochemically, thyroglobulin focal and involve both lobes. Less than 50 percent of
expression is variable—usually weak or even nega- tumors contain the characteristic stromal amyloid
tive. The undifferentiated carcinomas may arise which may be focally calcified (Figure 2–27).
from dedifferentiation in a well-differentiated papil- Immunohistochemistry shows that the tumor cells
lary or follicular carcinoma (Figure 2–26). The and sometimes the stromal amyloid are positive for
tumor metastasizes widely using both blood and calcitonin (Figure 2–28). The tumor cells also
lymphatic vessels. All patients die, mostly due to
respiratory compromise caused by the tumor.

Well-Differentiated Thyroid Carcinoma

Medullary Thyroid Carcinoma
Papillary Carcinoma Follicular Carcinoma

Medullary thyroid carcinoma (MTC) is a malignant

Dedifferentiation
tumor of the calcitonin-secreting parafollicular C
cells of the thyroid. It accounts for less than 10 per-
cent of all thyroid malignancies. Characteristically, Poorly-differentiated Carcinoma
MTCs secrete calcitonin, produce amyloid and, in
about 20 percent of cases, are familial. In the latter
situation, it may be inherited in an autosomal domi- Dedifferentiation
nant manner either in association with multiple
endocrine neoplasia (MENIIa and MENIIb) syn- Anaplastic Carcinoma
dromes or as familial MTC, and affects children and
adolescents with an equal gender distribution. Muta- Figure 2–26. Schematic diagram showing possible progression of
tions in the RET proto-oncogene on chromosome 10 well-differentiated thyroid carcinoma to anaplastic carcinoma.
36 CANCER OF THE HEAD AND NECK

express calcitonin gene-related peptide and carci- of the lung. It is mitotically more active, less likely to
noembryonic antigen, and are negative for thyroglob- produce calcitonin and amyloid, and is believed to
ulin. However, immuno-stain for chromogranin, a have a slightly worse prognosis than the conventional
marker for neuroendocrine differentiation, is more MTC. Mixed medullary-follicular and medullary-
sensitive than calcitonin for MTC. Ultrastructurally, papillary carcinomas have also been described.
multiple intracytoplasmic membrane-bound secre-
tory granules are demonstrated. It is possible to diag- Uncommon Tumors of the Thyroid
nose MTC by fine-needle aspiration because of the
typical plasmacytic tumor cell morphology and Primary squamous cell carcinoma is extremely rare
demonstration of amyloid and calcitonin. The tumor in the thyroid. Direct extension from the larynx,
tends to be indolent in familial MTC, and aggressive metastasis, or a nonsquamous thyroid carcinoma, eg,
in sporadic MTC and MENIIb, leading to metastasis papillary or undifferentiated carcinoma with exten-
due to lymphatic and vascular invasion of cervical sive squamous metaplasia should be ruled out.
nodes, lung, liver and bone. Death is usually due to Mucoepidermoid carcinoma in the thyroid is a rare,
uncontrolled local disease. It is important to recog- low-grade neoplasm postulated to arise as a meta-
nize a small cell (anaplastic) variant of MTC which plastic change in the thyroid follicular epithelium. A
resembles small (oat) cell neuroendocrine carcinoma sclerosing variant with eosinophilia has been
described.42 Carcinoma showing thymus-like differ-
entiation is a rare, low-grade tumor believed to arise
in branchial pouch remnants capable of thymic dif-
ferentiation with resemblance to a thymic carci-
noma.43 Lymphomas of the thyroid are usually non-
Hodgkin’s lymphomas of B-cell type spanning the
spectrum of low-grade to high-grade diffuse large
cell type. The low-grade lymphomas are similar to
the mucosa-associated lymphoid tissue lymphomas
elsewhere in the body. Frequent association with
Hashimoto’s thyroiditis is noted. Transformation of
low- to high-grade lymphoma is well documented.

Parathyroid Adenoma and Carcinoma

Parathyroid adenoma is a solitary, well-defined,

hyperfunctional benign neoplasm which accounts
for the majority of cases of primary hyperparathy-
roidism. Its distinction with hyperplasia is important
for correct surgical management, as the former is
treated by removal of only the adenomatous gland
while the latter requires resection of all four glands.
The distinction between normal and hyperplastic
glands is made by weight as the histologic appear-
ance may be similar. Most adenomas are composed
of chief cells which completely replace the
intraglandular fat that is present in normal and
hyperplastic glands. Ectopic adenomas may be
found in association with the thymus in the medi-
Figure 2–27. Medullary carcinoma of the thyroid showing an insu-
lar pattern of growth interrupted by hyalinized fibrous septa which
astinum and in intrathyroidal locations. Extremely
may contain amyloid. high serum calcium levels are generally indicative of
 Pathology of Head and Neck Tumors 37

Figure 2–28. Immunohistochemistry for calcitonin highlights a metastatic focus of medullary car-
cinoma in a lymph node.

parathyroid carcinoma. This is an infiltrative tumor

characterized by vascular and capsular invasion,
dense fibrosis, nuclear atypia, increased mitosis and
regional and distant metastasis (Figure 2–29).

NEURONAL, NEUROENDOCRINE AND

NEUROECTODERMAL TUMORS

Paraganglioma

Extra-adrenal paragangliomas can occur in the head

and neck. They secrete norepinephrine and are func-
tional. Patients (most of whom are adults) present
with hypertensive headaches, tachycardia and sweat-
ing. The carotid body tumors occur at the bifurcation
of the carotid artery. The jugulotympanic paragan-
glioma (glomus jugulare tumor) may present as
mass in temporal bone extending to the middle ear
or external auditory canal or involve the jugular bulb
in the jugular foramen. There is a female predilec-
tion. Angiographic findings are characteristic as the
tumor is very vascular. Because of poor accessibility
in the jugulotympanic region, the tumors are
removed in a piece-meal fashion destroying the typ-
ical “zellballen” arrangement of the tumor cells, Figure 2–29. Parathyroid carcinoma in a 51-year-old man with hyper-
making histologic diagnosis difficult (Figure parathyroidism. The cells have uniform morphology and frequent cyto-
plasmic clearing. The tumor invaded blood vessels, adjacent soft tis-
2–30A). The cells express several neuroendocrine sue, and thyroid gland in other sections. Immunostaining with
markers by immunohistochemistry and contain anti-parathyroid hormone antibody is characteristically positive (inset).
38 CANCER OF THE HEAD AND NECK

dense core neurosecretory granules on ultrastruc- superior one-third of the nasal septum, superior
tural examination (Figure 2–30B). Ten percent of turbinate and the cribriform plate, which may be
these tumors metastasize. Histologic criteria such as broken with intracranial extradural extension of the
nuclear atypia, pleomorphism and mitosis are not tumor. The usual presentation is as a polypoid nasal
reliable in predicting malignant behavior. The vagal mass with epistaxis and nasal obstruction, usually of
paraganglioma may be seen in association with the long duration. Microscopically, the tumor is submu-
vagus nerve in the anterolateral portion of the neck. cosal and is composed of nests of monomorphous
cells in a fibrillary background of neuropil (Figure
Olfactory Neuroblastoma 2–31A). Immunohistochemically, the tumor cells
are positive for neural and neuroendocrine markers,
Olfactory neuroblastoma or esthesioneuroblastoma eg, synaptophysin, neurofilament protein, and chro-
is a rare malignancy with a bimodal age distribution mogranin among others (Figure 2–31B). Ultrastruc-
in adolescents and adults and without any gender tural examination can help in the differential diag-
predilection. It is believed to arise in the specialized nosis by demonstrating neurosecretory granules,
neurosecretory cells of the olfactory mucosa in the microtubules and neuritic processes. We believe that

Figure 2–30. A, Paraganglioma—carotid

body tumor. The cells have moderate-to-abun-
dant cytoplasm, and are arranged in well-
defined nests (“zellballen”). There is occasional
binucleation and nuclear atypia. Cytologic crite-
ria are of no help in predicting biologic behavior.
B, Intense and diffuse cytoplasmic staining of
tumor cells with anti-chromogranin antibody by
immunohistochemistry supporting their neu-
roendocrine nature.

B
 Pathology of Head and Neck Tumors 39

the olfactory neuroblastoma is different from rare in the head and neck. It is characterized by the
Ewing’s sarcoma/primitive neuroectodermal tumors chromosomal translocation t(11:22)(q24;q12) lead-
at both the molecular and immunohistochemical ing to the EWS/FLI1 fusion protein MIC2 which
level.44 Higher incidence of S100 protein expression can be detected immunohistochemically by O13
and low expression of Ki 67, a cell proliferation (CD99) antibody.44 Metastasis should be ruled out
marker, have been linked to better survival.45 Most before considering the lesion as a primary tumor in
tumors are slow growing, locally destructive and the head and neck.
have a favorable prognosis although regional and
distant metastasis can occur at prolonged follow-up. Neuroendocrine Carcinoma

Ewing’s Sarcoma/Primitive Small cell neuroendocrine carcinoma is extremely

Neuroectodermal Tumor rare in the head and neck and may be seen in the nasal
cavity, paranasal sinuses, salivary or thyroid glands. It
Skeletal or extraskeletal Ewing’s sarcoma/primitive resembles the small (oat) cell carcinoma of the respi-
neuroectodermal tumor (ES/PNET) is extremely ratory tract. The tumor cells are positive for markers

Figure 2–31. A, Olfactory neuroblastoma

showing a cellular small blue cell neoplasm in a
fibrillary background of neuropil. Homer-Wright
rosettes formed by the arrangement of tumor
cells around central neurofibrillary collections
are seen. B, Immunohistochemistry with S100
protein shows staining of sustentacular cells
around the periphery of tumor cell nests, an
important feature in the differential diagnosis
with other relatively high-grade neuroendocrine/
neuroectodermal neoplasms in this area.

B
40 CANCER OF THE HEAD AND NECK

of neuroendocrine differentiation and cytokeratin. In diffusely for S100 protein, and markers for
the nose, it needs to be distinguished from an olfac- melanocytic differentiation gp-100 (HMB 45) and
tory neuroblastoma because of different prognosis Melan-A/ MART-1.47 The clinical outcome depends
and management. In the thyroid, lack of calcitonin upon several clinical criteria, eg, age, sex (younger
expression and amyloid production are helpful hints and female patients have a better outcome than older
to distinguish it from medullary carcinoma. and males), location (neck and ear better than scalp
Merkel cell carcinoma (MCC) is a variant of neu- and face) and several histopathologic criteria enu-
roendocrine carcinoma of the dermis and subcuta- merated in Table 2–3. Of these, the thickness of the
neous tissue. There is a male predilection with a lesion and Clark’s level are the most powerful pre-
median age of 70 years. Most MCCs arise in the skin dictors of outcome (Figure 2–35).49 In the radial
of the head and neck. They differ from the small cell growth phase, regressive changes have a negative
neuroendocrine carcinoma in having a distinct pale effect on survival. The desmoplastic melanoma is a
nucleus with fine speckled chromatin, a characteris- spindle cell, collagen producing, usually amelanotic
tic perinuclear dot-like reaction with cytokeratin 20 melanoma which is usually a vertical growth phase
and neurofilament protein46 on immunohistochem- tumor but may be associated with a radial growth
istry (Figures 2–32 and 2–33.). This is a high-grade phase (Figure 2–36). The prognosis is good despite a
tumor and has rarely been reported in the salivary tendency to neurotropism (nerve invasion).
gland and oral mucosa.

Malignant Melanoma

Head and neck melanomas can be categorized into

cutaneous and mucosal types. Cutaneous melanomas
occur most commonly in the face, followed by scalp,
neck and external ear in decreasing order of fre-
quency. They have a slightly worse prognosis than
similar lesions outside of the head and neck. The
tumor may be in the radial growth phase which is
completely excisable and therefore curable, and/or in
the vertical growth phase. In the latter, the malignant
cells invade and grow within the dermis and acquire
metastatic potential The two phases are clinically
definable. The superficial spreading melanoma is an
in situ, and usually microinvasive, radial growth
phase malignant melanoma etiologically associated
with recreational sun exposure (Figure 2–34A).
Lentigo maligna is usually in situ and occurs in the
background of epidermal atrophy and severe sun
damage as a result of chronic exposure in an elderly
person. If invasion is also present, the diagnosis is
lentigo maligna melanoma (Figure 2–34B). In con-
trast, the nodular melanoma is completely within the
dermis without any associated radial growth phase
and needs to be differentiated from metastatic
melanoma. The cells may be epithelioid or spindle-
shaped giving the tumor a biphasic appearance. Figure 2–32. Merkel cell carcinoma in the skin showing nests of
Immunohistochemically, malignant melanoma stains small blue cells.
 Pathology of Head and Neck Tumors 41

Figure 2–33. A, Merkel cell carcinoma—

higher magnification shows the typical hyper-
chromatic endocrine type of nucleus, necrosis
and brisk mitosis. B, Immunostain with neurofil-
ament shows characteristic dot-like positivity in
the paranuclear golgi area. Similar positivity is
A B also seen with cytokeratin (CK20).

Figure 2–34. A, Cutaneous superficially-

spreading malignant melanoma in situ (Clark
level 1). Single cell proliferation of malignant
melanocytes is seen in contact with the basal
layer of the epidermis while single atypical
melanocytes are identified migrating into upper
dermis-like “buckshots.” The tumor does not
acquire metastatic potential even when microin-
vasion is present. B, Malignant melanoma in
situ—lentiginous type involving the buccal
mucosa. The malignant melanocytes spread
along the basal layer of the squamous epithelium.

B
42 CANCER OF THE HEAD AND NECK

Table 2–3. HISTOPATHOLOGIC CRITERIA AFFECTING THE an in situ radial phase lesion where the tumor cells are
PROGNOSIS OF CUTANEOUS MALIGNANT MELANOMA arranged basally in the mucosa (see Figure 2–34B).
Radial versus vertical growth pattern Nodular and desmoplastic melanomas can also pre-
Breslow’s thickness
sent in the mucosa. Presence of an in situ component
Clark’s level
Nodular morphology or junctional activity helps to differentiate primary
Regressive changes from metastatic mucosal melanoma. A significant
Mitosis
Ulceration number of mucosal melanomas are amelanotic. The
Lymphocytic response typical immunohistochemical profile helps in the dif-
Microsatellitosis
ferential diagnosis of amelanotic melanoma from
other undifferentiated tumors of the head and neck.
The prognosis is generally poor although patients with
Primary mucosal melanoma of the upper aerodi- melanomas less than 1 mm thick appear to do better.51
gestive mucosa is a rarity. It may arise from pre-exist-
ing melanocytes in the squamous or respiratory TUMORS OF THE
mucosa and usually presents as polypoid growths. In a SOFT TISSUES AND BONES
series of 259 patients from the United Kingdom, 69
percent of mucosal melanoma occurred in the nasal Almost any soft-tissue tumor (Table 2–4) occurring
cavities and sinuses (Figure 2–37), 22 percent in the elsewhere in the body may be seen in the head and
oral cavity and 9 percent in the pharynx, larynx and neck region. Only the more frequent ones will be
upper esophagus.50 In contrast to skin melanomas, no described here.
race distribution or relationship to exposure to sunlight The most frequent benign mesenchymal tumors
has been noted. The mucosal-lentiginous melanoma is of the head and neck are vascular in nature and

Figure 2–35. Microstaging vertical growth phase of malignant melanoma—Clark levels II to IV. The tumor has acquired
metastatic potential.
 Pathology of Head and Neck Tumors 43

Figure 2–36. Desmoplastic malignant melanoma. The spindle-shaped tumor cells are identified in a
very collagenous stroma.

Figure 2–37. A, Mucosal malignant melanoma in the nasal sep-

tum. The tumor forms a raised, darkly pigmented nodule. B, Another
sinonasal melanoma. This tumor is composed of amelanotic epithe-
lioid cells which form a polypoid nodule underneath columnar cili-
ated respiratory mucosa.
B
44 CANCER OF THE HEAD AND NECK

include hemangioma and lymphangioma. Their fre- of the vessel wall (larger lumina and thicker walls in
quent presence in childhood suggests a hamartoma- cavernous angiomas) (Figure 2–38). Lymphan-
tous nature with congenital origin. The distinction giomas or cystic hygromas usually are congenital
between capillary and cavernous hemangiomas lies and occur in the neck. Angiosarcoma may be seen in
in the size of the vascular lumina and the thickness the skin of the scalp and face in elderly individuals
(Figure 2–39). The tumor may be indolent with a
better prognosis than post-radiation and deep soft
Table 2–4. MESENCHYMAL TUMORS tissue angiosarcomas.
Fatty Tumors Lipoma are common, superficial, benign tumors
Benign: Lipoma
Variants:
of mature adipose tissue derivation (Figure 2–40). A
Spindle cell special variant, the spindle cell lipoma has a propen-
Intra- and intermuscular sity to occur in the back of the neck.
Pleomorphic
Myolipoma Granular cell tumor is a benign solitary subep-
Angiolipoma ithelial tumor characterized by large pink cells with
Malignant: Liposarcoma
Variants:
abundant granular cytoplasm, bland nuclear mor-
Atypical lipomatous tumor (well-differentiated phology and diffuse positive reaction to S100 pro-
liposarcoma) teins on immunohistochemistry. Although a myoge-
Myxoid
Pleomorphic nous origin was once favored, hence the older term
Fibrous Tumors
Benign: Fibromatosis
Malignant: Fibrosarcoma
Sclerosing epithelioid fibrosarcoma
Fibromyxoid sarcoma
(nodular and cranial fascitis—pseudotumor)

Fibrohistiocytic Tumors
Benign: Xanthoma
Benign fibrous histiocytoma/ dermatofibroma
Borderline: Dermatofibrosarcoma protuberans
Malignant: Atypical fibroxanthoma (superficial MFH)
Malignant fibrous histiocytoma (MFH)
Variants:
Pleomorphic
Myxofibrosarcoma

Vascular Tumors
Benign: Hemangioma
Variants:
Capillary
Cavernous
Intramuscular
Glomus tumor
Lymphangioma
Lymphangiomyoma
Borderline: Atypical vascular proliferation
Hemangioendothelioma
Hemangiopericytoma
Malignant: Angiosarcoma
Kaposi’s sarcoma

Neural Tumors
Benign: Schwannoma
Cellular
Ancient
Neurofibroma
Traumatic neuroma
Plexiform neurofibroma
Neurofibromatosis
Figure 2–38. Cavernous hemangioma. The tumor is encapsulated
Malignant: Malignant peripheral nerve sheath tumor
and contains cavernous vascular spaces.
 Pathology of Head and Neck Tumors 45

granular cell “myoblastoma,” it is now believed to be the head and neck in middle-aged patients. There is
of nerve sheath origin. The tongue and skin are fre- a slight male preponderance. Microscopically, the
quent sites. tumor is composed of uniform, benign-appearing
The desmoid tumor or fibromatosis usually spindle cells arranged in a “storiform” pattern infil-
presents in the neck of a young woman as a slow- trating into the dermis and subcutaneous tissue. A
growing mass. Grossly, the tumor is related to skele- pigmented variant, the so-called Bednar tumor is
tal muscle and fascia, and is firm and white on cut also known. A dermatofibroma (benign fibrous his-
surface. Microscopically, the tumor cells are bland, tiocytoma), on the other hand, is a non-infiltrative
uniform, spindle-shaped with myofibroblastic differ- benign dermal tumor, usually less than 3 cm in size
entiation (Figure 2–41). The tumor is locally infiltra- which can be cured by local excision alone.
tive with frequent involvement of several resection Atypical fibroxanthoma (superficial malignant
margins and has a great tendency for multiple recur- fibrous histiocytoma) is a dermal tumor character-
rences. It should be distinguished from a fibrosar- ized by markedly atypical mitotically-active spindle
coma, as the latter has metastatic capabilities even cells with paradoxically low-grade behavior. The typ-
when it is low grade. ical patient is elderly and the lesion may affect the
Dermatofibrosarcoma protuberans is an uncom- face or scalp. The tumor has low metastatic potential
mon, locally aggressive fibrohistiocytic neoplasm of which may be heralded by multiple recurrences, deep
trunk and lower extremity which may rarely occur in soft tissue and vascular invasion and necrosis.

A B

Figure 2–39. A, Epithelioid angiosarcoma in the skin of the forehead of an 85-year-old man. The bizarre, pleomorphic tumor cells are lining
clefts and spaces, recapitulating the tendency of the endothelial cells to line blood vessels. B, Immunohistochemistry for CD31, an endothe-
lial cell marker, shows strong, diffuse positive cytoplasmic reaction.
46 CANCER OF THE HEAD AND NECK

Figure 2–40. Intramuscular infiltrating lipoma of the retropharynx. Mature adipose tissue is seen dis-
secting skeletal muscle fibers. Although benign, this tumor is difficult to excise completely and may recur.

Malignant fibrous histiocytoma (MFH), a usually

high-grade spindle cell sarcoma of fibrohistiocytic
origin rarely presents in the deep soft tissue of the
head and neck. Most patients are elderly males. This
is the most common post-radiation sarcoma. The
most frequent variant, pleomorphic MFH, is com-
posed of highly atypical cells arranged in a storiform
pattern and shows brisk mitosis, tumor necrosis and
giant cells (Figure 2–42). The myxoid variant, myx-
ofibrosarcoma is relatively low grade.

Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most frequent

soft-tissue sarcoma in the head and neck. It occurs
most commonly in the pediatric age group and rarely
in older people. The common sites are orbit, nose and
paranasal sinuses, the middle ear and the mastoid. In
the nose, they may present as polypoid, grape-like
masses giving rise to the name sarcoma botryoides.
Microscopically , the majority of tumors are alveolar
RMS (Figure 2–43). Immunohistochemical demon-
stration of myoid differentiation such as positive
staining for desmin, actin, and myosin among many
others helps distinguish them from other small Figure 2–41. Fibromatosis of the neck in a young woman. The
tumor is highly collagenous (desmoid) and composed of spindle
“blue” cell tumors, eg, non-Hodgkin’s lymphoma, cells with bland uniform nuclei which have infiltrated the adjacent
olfactory neuroblastoma, Ewing’s sarcoma/primitive skeletal muscle.
 Pathology of Head and Neck Tumors 47

Figure 2–42. Malignant fibrous histiocytoma—pleomorphic variant. This is a high-grade spindle cell
neoplasm demonstrating marked pleomorphism and multinucleated tumor giant cells.

neuroectodermal tumor, other neuroectodermal, neu- composed of fibrous tissue and woven bone trabec-
roendocrine and in adults amelanotic melanoma. The ulae which have osteoblastic rimming. Radiologi-
embryonal RMS is hypocellular and myxoid with no cally, OF is well defined whereas fibrous dysplasia
fibrosis and has a better prognosis than the alveolar has merging outlines. Cemento-ossifying fibroma
RMS. The sarcoma botryoides, a variant of embry- has, in addition to bone, cementum formation (Fig-
onal RMS, is characterized by a thin, submucosal ure 2–44). A juvenile aggressive form of ossifying
“cambium” layer of hypercellularity overlying areas fibroma occurs in patients in their early teens.
of loose, edematous, hypocellular tumor. This variant Eosinophilic granuloma of the bone has been
has an excellent prognosis. A characteristic finding noted in the skull or skull base where it can involve
of all RMSs is the presence of at least a few tumor the sella turcica and present with symptoms attribut-
cells with abundant pink cytoplasm. Although the able to pituitary dysfunction. The tumor is com-
older literature shows a distinct survival disadvan- posed of Langerhans’ cells which demonstrate S100
tage in RMS, with the new multimodal therapy, sur- protein and CD1 immunoreactivity and contain an
vival appears to depend on the clinical stage.52 admixture of other inflammatory cells including
Osteoma is a common benign bone tumor of the eosinophils. Birbeck granules are ultrastructural
head and neck microscopically composed of lamellar hallmarks of the Langerhans’ cells.
bone which may be arranged into outer cortical and
inner cancellous bone with marrow elements (ivory Osteosarcoma
osteomas). They are common in the paranasal sinuses,
frontal being most frequently affected. Multiple This is the most frequent malignant bone tumor of the
osteomas are associated with Gardner’s syndrome. head and neck. About 6 percent of all osteosarcoma
Benign fibro-osseous lesions run the gamut from occur in the jaw.53 They are usually spontaneous, but
fibrous dysplasia to ossifying fibroma to cemento- risk factors include radiation, Paget’s disease and
ossifying fibroma. Fibrous dysplasia is an ill- retinoblastoma, among others.54 There is an almost
defined solid lesion consisting of thin trabeculae of equal distribution in the maxilla and mandible. A
irregular, curvilinear woven bone directly formed by male preponderance with a peak incidence in the
fibrous tissue. Ossifying fibroma (OF) is rare and is early fourth decade is noted. Histologically, most
48 CANCER OF THE HEAD AND NECK

A B
Figure 2–43. A, Solid alveolar rhabdomyosarcoma of left periparotid soft tissue in a 47-year-old male consisting of predominantly round
tumor cells with hyperchromatic nuclei and scant cytoplasm. Presence of occasional cells with abundant deep pink, glassy cytoplasm is a clue
to rhabdoid differentiation. The alveolar pattern is produced by thin fibrous septa intersecting the tumor. B, Immunohistochemistry with anti-
desmin antibody shows several cells expressing this cytoplasmic protein and further supporting the skeletal muscle differentiation.

Figure 2–44. Cementifying fibroma.

The tumor occurred in the maxilla of a
15-year-old boy and shows cementi-
cles within fibrous tumor tissue.
 Pathology of Head and Neck Tumors 49

gnathic osteosarcomas are well-differentiated low- Chordomas arising in the spheno-occipital area
grade tumors and may show osteoblastic, fibroblastic and the upper cervical vertebrae can present as naso-
and chondroblastic differentiation (Figure 2–45). The pharyngeal tumors. These are low-grade, locally
direction of differentiation does not have prognostic aggressive tumors believed to derive from embryonal
significance. The prognosis is better than extra- notochordal remnants and are comprised of lobules of
gnathic osteosarcoma and distant metastasis is infre- cells with abundant foamy cytoplasm and the charac-
quent. Radical surgical resection with negative mar- teristic physaliphorous cells. Immunohistochemically,
gins as initial therapy is more effective than combined the cells are positive for cytokeratin and S100 protein.
modality treatment. There is no well-documented
relationship between response to chemotherapy and TUMORS OF THE SKIN
degree of tumor necrosis in gnathic osteosarcomas in
contrast to the extra-gnathic osteosarcomas. Several benign tumors of the skin appendages fre-
Chondrosarcoma may occur in the base of the quently affect the head and neck. The classic cylin-
skull, in the craniofacial bones, larynx, trachea or the droma (turban tumor) is a tumor of eccrine origin
cervical vertebrae. Most are low-grade conventional which is usually solitary but can be multiple. It pro-
chondrosarcomas (Figure 2–46), although mesenchy- duces abundant basement membrane material and
mal, skeletal and extra-skeletal myxoid and dediffer- shows myoepithelial differentiation. Syringomas are
entiated chondrosarcomas are also described.55–57 eccrine tumors usually occurring in the lower eyelid

Figure 2–45. A, Osteosarcoma of the right maxilla in a 37-year-old

woman. The tumor is gray-white and bone-hard, and replaces the
maxillary sinus entirely. B, At low magnification, the tumor is lobu-
lated and shows a zonation from extremely cellular to chondroblas-
tic to osteogenic areas, which is characteristic of osteosarcomas in
the maxilla.

B
50 CANCER OF THE HEAD AND NECK

in women and which may be multiple. Chondroid by multifocality and skip lesions. The sclerosing or
syringoma (mixed tumor) is the cutaneous counter- morpheaform BCC is accompanied by a pseudosar-
part of the pleomorphic adenoma of the salivary comatous stroma with very few infiltrating carci-
glands and shows myoepithelial differentiation. It is noma cells. In a surgical excision, it is difficult to
believed to be eccrine in origin. Pilomatrixoma (syn- assess the margins without the help of immunohis-
onym: pilomatricoma, calcifying epithelioma of Mal- tochemistry. This usually indolent tumor can be
herbe) is a benign tumor of the pilar apparatus and locally destructive and may metastasize if neglected.
occurs in children and young adults. Another benign Basal cell nevus syndrome is discussed in tumors of
tumor of the hair follicle cells is the pilar tumor which the dentoalveolar structures (Figure 2–47).
usually affects women; it occurs in the scalp and at the Sebaceous carcinoma is a rare high-grade tumor
base of neck and can grow quite large. showing sebaceous differentiation (Figure 2–48).
The majority of these carcinomas arise in the eyelid
Squamous Cell Carcinoma in association with meibomian glands.58 It may be
associated with multiple visceral malignancies
The squamous cell carcinoma is the most common (Muir-Torre syndrome). Rarely, it has been reported
malignant tumor of the skin, particularly in the head in the parotid glands.
and neck. A relationship with cumulative sun expo-
sure, actinic keratosis and SCC has been noted; p53
mutation by ultraviolet light is a postulated mecha-
nism. Actinic keratosis is characterized by atrophy
of the epidermis with dysplasia of the basal layer in
a background of solar elastosis. All morphologic
variants of SCC have been identified in the skin of
the head and neck. In addition, an excessively kera-
tinized variant, SCC with horn formation, may also
be seen. Verrucous SCC needs to be differentiated
from keratoacanthoma which is a rapidly-growing
benign lesion affecting males more frequently than
females. The diagnosis is made on the characteristic
architecture which shows a keratin-filled epidermal
crater with overhanging edges. Most lesions regress
spontaneously after a few weeks, suggesting a viral
etiology. Because of the cytologic overlap with SCC
and the reports of metastasizing keratoacanthomas,
it has been suggested that all keratoacanthomas
should be considered variant SCC.

Basal Cell Carcinoma

Basal cell carcinoma (BCC) is a malignant tumor of

the basal layer of the epidermis arising in a back-
ground of prolonged cumulative exposure to sun and
therefore is seen in older people. Although many
morphologic forms are described, the superficial
and sclerosing BCCs require special mention
because of a high propensity for local recurrence.
Figure 2–46. Chondrosarcoma of the larynx in an 84-year-old
The superficial BCC is a clinically subtle in situ man. Lobules of tumor cartilage push the respiratory epithelium of
change in the basal layer of epidermis characterized the larynx.
 Pathology of Head and Neck Tumors 51

Sweat gland carcinoma is another rare skin- or the odontogenic ectomesenchymal line and are
appendage carcinoma that can occur in the face and classified accordingly (Table 2–5). They are pre-
the scalp. The adenoid cystic carcinoma, sclerosing dominantly benign with rare exceptions.
sweat duct carcinoma and mucinous carcinoma are Ameloblastoma is a locally aggressive, usually
some of the variants. intraosseous tumor of odontogenic epithelium most
Merkel cell carcinoma and malignant melanoma commonly involving the posterior part of mandible
are discussed in the section on neuroendocrine and and sometimes the posterior maxilla. The tumor
neuroectodermal tumors. affects both sexes at all ages, with a higher incidence
in the third to fifth decades. The tumors are usually
TUMORS AND CYSTS OF THE multicystic with solid areas (Figure 2–49). Various
DENTOALVEOLAR STRUCTURES histologic types are described, the most common
being follicular and plexiform. The uncommon uni-
About 9 percent of all tumors in the oral cavity are cystic variant may be radiologically misinterpreted
odontogenic and may differentiate toward epithelial as an odontogenic cyst. The peripheral ameloblas-

Figure 2–47. A, A neglected basal

cell carcinoma of the skin of face. The
patient was a 73-year-old woman who
had the lesion for many years. The
eye is identified in the right side of
the photograph. B, Microphotograph
shows nests of cellular blue basaloid
cells with peripheral pallisading, cen-
tral small cyst formation and a single
keratin pearl. The tumor is connected
A to the overlying epidermis.

B
52 CANCER OF THE HEAD AND NECK

Table 2–5. BENIGN TUMORS OF THE ODONTOGENIC TISSUE

Tumors related to Odontogenic Epithelium
Ameloblastoma: central and peripheral
Squamous odontogenic tumor
Clear cell odontogenic tumor
Calcifying epithelial odontogenic tumor
Tumors related to Odontogenic Mesenchyme
Odontogenic fibroma: central and peripheral
Odontogenic myxoma/fibromyxoma
Cementifying tumors
Cementoblastoma (cementoma)
Cementifying and cemento-ossifying fibroma
Mixed Tumors related to Odontogenic Epithelium
and Mesenchyme
Ameloblastic fibroma
Ameloblastic fibrodentinoma
Ameloblastic fibro-odontoma
Odontoameloblastoma
Odontoma: complex and compound
Adenomatoid odontogenic tumor
Calcifying odontogenic cyst

demonstrates additional formation of dentine, and

the latter both dentine and enamel. The tumors show
variable radio-opacity depending upon the amount
of dentine and enamel formation.
Squamous odontogenic tumor is an intraosseous
infiltrative tumor composed of islands of well-differen-
tiated squamous cells, sometimes with central cystic
change. Most behave in a benign fashion requiring
curettage only. The clear cell odontogenic tumor con-
Figure 2–48. Sebaceous carcinoma. The tumor shows sebaceous
differentiation with large cells with multiple small vacuoles. The sists of islands of clear epithelial cells. Most tumors are
smaller cells with hyperchromatic nuclei can show brisk mitosis. Ker- benign though locally aggressive, and clinical behavior
atinization is identified.
appears to be slightly worse than ameloblastoma.
Rarely, primary intraosseous squamous cell carcinoma
toma is extraosseous, located in the gingiva or buc-
cal mucosa. The unicystic peripheral and desmo-
plastic ameloblastoma have lower recurrence rates
than the conventional multicystic ameloblastoma.
Rare metastasis after prolonged illness punctuated
by multiple surgeries and/or radiotherapy is known
(malignant ameloblastoma). Odontoameloblastoma
is an extremely rare, composite, true neoplasm con-
sisting of an ameloblastoma and hard dental tissue
eg, dentine, cementum or enamel. The clinical
behavior is similar to ameloblastoma.
The ameloblastic fibroma is essentially a solid
intraosseous fibrous lesion with scattered foci of
attenuated ameloblastic epithelium. Ameloblastic Figure 2–49. Ameloblastoma. The central cystic portion of the
tumor contains a loose reticulum of stellate cells. There is a periph-
fibrodentinoma (dentinoma) and fibro-odontoma eral layer of tall columnar cells with dark nuclei resembling the inner
are similar to ameloblastic fibroma, but the former dental epithelium.
 Pathology of Head and Neck Tumors 53

and clear cell adenocarcinoma (odontogenic carci- cementum and odontogenic epithelium whereas the
noma) occur and are believed to arise in intraosseous same components are more orderly with tooth-like
remnants of the odontogenic epithelium. They may be formations in the compound odontoma.
seen in association with an odontogenic cyst (type 1), Mesenchymal odontogenic tumors are usually
ameloblastoma (type 2) or may arise de novo (type 3), tumors of young people affecting the mandible. The
and may be keratinizing or non-keratinizing. odontogenic fibroma may be intraosseous (central)
The calcifying epithelial odontogenic tumor or in the gingiva (peripheral) and contains odonto-
(Pindborg tumor) presents as a painless slow-growing genic epithelium. Myxoma is locally destructive and
mass of variable radiolucency, most commonly in the extends through the bone into the soft tissue, making
posterior lower jaw, in adults between the ages of 20 to complete surgical resection difficult. Cementoblas-
60 years. It may be associated with an unerupted tooth. toma (cementoma) consists of large fusing globules
One-third of cases may present in the maxilla. Micro- and masses of cementum associated with the root of
scopically, the tumor shows sheets of polyhedral, a tooth. A special variant, the gigantiform cemen-
sometimes pleomorphic epithelial and clear cells in a toma is a bilateral deposition of cementum in both
fibrous stroma. Characteristically, large globular jaws of young black women with an autosomal dom-
masses of acidophilic amyloid-like material and vari- inant inheritance pattern.
able degrees of calcification may be seen. The clinical Most cysts of the jaw are not true neoplasms.
behavior is similar to ameloblastoma. The adenoma- They may arise in the odontogenic epithelium or in
toid odontogenic tumor occurs commonly in the ante- developmental fissures. A diagrammatic representa-
rior maxilla in the second decade of life. The presence tion of the different odontogenic cysts is depicted in
of a capsule, duct-like structures and dentine are char- Figure 2–50.
acteristic. Enucleation may be adequate treatment. The most common cyst is the periapical or radic-
Calcifying odontogenic cyst has a cystic component ular cyst, an incidental radiologic discovery. The
lined by odontogenic epithelium containing character- cyst is usually less than 1 cm in size with stratified
istic “ghost” epithelial cells, and a mesenchymal com- squamous lining associated with inflammation.
ponent which may contain dental hard tissue. It usu- The dentigerous cyst is a destructive cyst associ-
ally presents as an intraosseous lesion in the second ated with the crown of an unerupted and displaced
decade of life and may not be a true neoplasm. permanent tooth (Figure 2–51). Rarely, neoplastic
Odontoma is a developmental anomaly occurring transformation to ameloblastoma can occur.
in association with the crown of a developing tooth Odontogenic keratocyst is another destructive
in young individuals. The complex odontoma con- uni- or multiloculated cystic lesion in the posterior
sists of a disordered mixture of dentine, enamel, mandible and maxilla (Figure 2–52). These cysts

Figure 2–50. Schematic diagram of odontogenic cysts by location.

54 CANCER OF THE HEAD AND NECK

Figure 2–51. Dentigerous cyst. The cyst is lined by stratified squamous epithelium with an admix-
ture of mucus-secreting cells. The lumen contains hemorrhagic debris showing cholesterol clefts.

have a high propensity for destructive growth and Fissural or developmental cysts are believed to
recurrence. They may be associated with the arise in the epithelium entrapped between the bony
nevoid basal cell carcinoma syndrome, an autoso- parts of the jaw bones during embryologic develop-
mal dominant condition with high penetrance ment. The different types are depicted in the diagram
described by Gorlin and Goltz.59 Other components (Figure 2–53). The most common is the midline
of the syndrome include skeletal abnormalities, nasopalatine cyst which may be within the bone or in
ectopic calcification and dyskeratotic pitting of the the soft tissue. The lateral nasolabial cyst is also a soft-
hands and feet. tissue cyst. The other types of cysts are intraosseous.

Figure 2–52. Odontogenic keratocyst. The cyst is lined by stratified squamous cells showing kera-
tinization toward the surface.
 Pathology of Head and Neck Tumors 55

13. Medina JE, Dichtel W, Luna MA. Verrucous squamous car-

cinomas of the oral cavity. A clinicopathologic study of
104 cases. Arch Otolaryngol 1984;110:437–40.
14. Winzenburg SM, Nichans GA, George E, et al. Basaloid
squamous cell carcinoma: a clinical comparison of two
histologic types with poorly differentiated squamous cell
Nasolabial
Globulomaxillary carcinoma. 1998;119:471–5.
15. Banks ER, Frierson HF Jr, Mills SE, et al. Basaloid squa-
Nasopalatine mous cell carcinoma of the head and neck: a clinico-
Median pathologic and immunohistochemical study of 40 cases.
palatal Am J Surg Pathol 1992;16:939–46.
16. Nakhleh RE, et al. Myogenic differentiation in spindle cell
(sarcomatoid) carcinomas of the upper aerodigestive
tract. Appl Immunohistochem 1993;1:58–68.
17. Gaffey MJ, Weiss LM. Association of Epstein-Barr virus
with human neoplasia. Pathol Annu 1992;27(Pt 1):55–74.
18. Spiro RH. Salivary neoplasms, overview of a 35 year experi-
ence with 2,807 patients. Head Neck Surg 1986;8:
177–84.
19. Spiro RH, Huvos AG, Strong EW. Malignant mixed tumor of
Figure 2–53. Schematic diagram of the fissural cysts. salivary origin, a clinicopathologic study of 146 cases.
Cancer 1977;39:388–96.
20. Tortoledo ME, Luna MA, Batsakis JG. Carcinoma ex pleo-
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 3
Head and Neck Imaging
BERNARD B. O’MALLEY, MD

Imaging the neck is unlike imaging any region of the mented to improve upon the accuracy of clinical
torso or brain since maximal contrast resolution is lymph node staging. This is true of either computed
necessary to differentiate lesions in cross-sectional tomography (CT), magnetic resonance imaging
exams of those solid organs. Because of the various (MRI) or sonography and nuclear imaging including
organ systems, the neck has very good native con- fluorodeoxyglucose-positron emission tomography
trast resolution between lesions and adjacent normal (FDG-PET). Intravenous contrast is necessary to
structures and at the interface with the skull base characterize internal lymph node architecture on CT,
and thoracic inlet. Intravenous contrast is necessary, but less important on MRI. Careful attention to
however, to differentiate veins (and arteries) from lymph node sub-sites is needed at the lateral
adenopathy and masses (Figure 3–1). Once a base- retropharyngeal (Figure 3–3) and tracheo-esophageal
line scan has been obtained, contrast is less impor- groove (Figure 3–4) when appropriate. The added
tant for this particular consideration. Intravenous value of sonography is the capacity to perform fine-
contrast also helps characterize internal lymph node needle aspiration (FNA) of suspicious lymph
architecture for necrosis. Bolus timing parameters nodes,5 which might otherwise look unremarkable
are dependent on the equipment used1 and the med- on other imaging modalities or feel unimportant to
ical condition of the patient. Oral contrast in the the examiner. With proper attention to technique,
form of barium paste is helpful for lesions of the
hypopharyngo-esophageal complex. The throat,
being a semi-collapsed tube, is difficult to evaluate
on cross-sectional images. The importance of cross-
sectional imaging is in evaluating the submucosal 2
component of lesions (Figure 3–2), complementing
the clinical and endoscopic exam. Imaging is there-
fore not valuable for detection of mucosal disease 1
and cannot be a substitute for clinical inspection.
Evaluating a palpable neck mass2 and staging a
known mucosal or sinonasal lesion is the primary
role for imaging of the neck and head. Lesions of the
nasopharynx, parapharyngeal space, sinonasal tract
and subglottic space are better staged by the cross-
sectional exam, however. Familiarity with the imag-
ing of lymphomas and benign3 or inflammatory
lesions of the neck can prevent unnecessary surgical
Figure 3–1. Enhanced axial CT image through the oropharynx. (1)
explorations in this functionally and cosmetically Partially necrotic pathologic lymph node (level II). (2) Normal sub-
sensitive region.4 Imaging exams have been docu- mandibular node (level I-b) with fatty hilum.

57
58 CANCER OF THE HEAD AND NECK

1
1
2

Figure 3–2. Enhanced axial CT images through the oropharynx. (1) Base of tongue
squamous cancer extending to lateral pharyngeal wall. (2) Early extra-pharyngeal exten-
sion into parapharyngeal space.

both the neck and the primary lesion can be ade- CT and MRI improve upon the clinical accuracy of
quately scanned at one imaging visit. Whether or not 71 percent.7 Conventional MR is not adequate10 and
there is a known primary tumor, the contrast bolus has no benefit over CT.11 The neck can be adequately
should be peak for the axial survey of the neck. The staged if MR is chosen for staging of the primary
primary site, if it is known, can be scanned in what- site. FDG-PET is very accurate in the post-treatment
ever plane necessary in the post-bolus phase of the setting compared to either CT or MRI.12,13
scan. These issues are less important in MRI. As As in other body regions, a diagnosis has often
many as one-third of all N0 neck dissections show been established and the imaging is performed to
histologically positive metastatic adenopathy.6 round out the TNM staging. While radiology is com-
Imaging may demonstrate some of these occult plementary to the clinical staging, it is responsible
metastases and thus improves upon the clinical for so-called stage creep,14,15 increasing the T, N, or
exam.7 In the N0 neck, FDG-PET (Figure 3–5) has M component of the diagnosis. The radiologist and
been reported to be more sensitive than CT or MRI8 clinical oncologist need to establish a rapport and
and to have a sensitivity and specificity of approxi- select the modality most appropriate for their collec-
mately 90 percent.9 However, true micro-metastases tive expertise and imaging armamentarium. Scan
will remain below the resolution of cross-sectional protocols must be established for consistency within
exams and current FDG-PET technology, but a practice and at the very least among sequential fol-
enlarged lymph nodes should not be overlooked. low-up surveillance-type scans on a given patient.
One half of all missed lymph nodes are less than or Consistent imaging parameters from contrast injec-
equal to one centimeter in size. Careful analysis of tion rates through scan technique16 to photography
high quality scans is necessary to maintain a facilitate detection of subtle changes lending confi-
respectable accuracy rate for staging the neck. Both dence to the diagnosis of often clinically occult
 Head and Neck Imaging 59

flap reconstruction (Figure 3–8) and/or radiation ther-

apy can be very distracting and misleading.21 Inflam-
matory changes related to chemotherapy-induced
mucositis and superimposed radiation changes22 limit
2 our ability to diagnose mucosal recurrences. Lymph
node metastases take unconventional pathways after
neck dissection.23 Different phases of contrast are
beneficial for different modalities. Early phases are
better for MRI1 and later phases are better for CT.24
Metabolic imaging in the form of FDG-PET will find
a more important role for this stage of patient evalua-
tion.13,25,26 This tool, while not perfect,27 will help
1 triage previously operated patients into categories
such as intervention or continued surveillance. In the
“unresectable” or organ preservation groups, deter-
mining the relative degree of metabolic activity of a
tumor prior to being treated will help determine the
Figure 3–3. Axial T2-weighted MR image through the maxilla. (1) effects of radiation treatment28 or combined thera-
Metastatic left lateral retropharyngeal lymph node. (2) Palate tumor pies.29 These images are best interpreted with some
(hard and soft palate).
form of co-registration with a cross-sectional scan.30
Less expensive methods of imaging FDG-PET with-
changes. Consistency also allows the other members out a dedicated PET scanner (Figure 3–9) can be
of the clinical oncology team to work with reliable competitive.31 If the PET radionuclides are not avail-
images for treatment planning. able, SPECT imaging with Tl-201 can be used as an
Staging the index lesion involves evaluating for adjunct to the clinical exam.32,33
the possibility of clinical underestimation of the
submucosal extent of disease17 (Figure 3–6), inva- The Paranasal Sinuses
sion of adjacent vital structures18 (Figure 3–7), and
non-palpable adenopathy. Imaging for determination Tumors of the nasal cavity and paranasal sinuses are
of the M stage of disease begins (and usually ends) the most challenging lesions to stage. The cosmetic
with the chest radiograph. Cross-sectional imaging
of the chest should be productive given the preva-
lence of smoking exposure in the head and neck can-
cer population. This would also serve as a baseline
against which any developing apical pulmonary
radiation changes or aspiration infiltrates could be
compared. A well-designed scan of the neck that
covers the superior mediastinum should provide
adequate evaluation of the apical pulmonary region. 1 2
Detection and staging of neck lesions are very
important for accurate assignment of initial treatment
pathways for individual patients. High quality CT is
usually adequate for most upper aerodigestive sub-
sites. MRI is useful for skull base, larynx19 and equiv-
ocal CT findings.20 Follow-up imaging is very chal-
Figure 3–4. Enhanced axial CT through thoracic inlet. (1) Thick-
lenging, especially for the uninitiated. Distortion of ened esophagus related to squamous cancer. (2) Necrotic lymph
tissue planes by biopsy, resection, neck dissection, node in the left tracheo-esophageal groove.
60 CANCER OF THE HEAD AND NECK

ties each provide vital but incomplete information.

Nowhere else than the skull-base margin is per-
ineural extension more problematic.37 Some very
2 small and very peripheral lesions track deep into the
skull base foramina (Figure 3–11) while other larger,
1
more centrally located masses grow in a simple cen-
trifugal manner. The interpretation must be made
with a high index of suspicion while the oncologist
must have a great deal of confidence in the interpre-
tation. A brain imaging protocol is often applied but
is inadequate in its standard form. A standard neck
imaging protocol will not provide adequate spatial
resolution at the skull base. A well-designed CT or
MR imaging protocol with appropriate plane, range
and section thickness is necessary for accurate diag-
nosis. Coronal, axial and sometimes sagittal views
Figure 3–5. Corongal FDG-PET image of torso. (1) Activity related
to unsuspected lymph node metastasis. (2) Activity related to glottic track the deep margin to best advantage. The cav-
squamous cancer. ernous sinus is the most difficult compartment to
confidently pronounce clear of disease with imag-
and functional impact of these tumors is immedi- ing. The vascular channels intermixed with fat are
ately apparent. They rarely present at an early stage. alternately bright and dark on MR imaging and
There are few, if any, discriminating imaging fea- inhomogeneously bright on CT. Tumor extension
tures among the various subtypes of tumors in this within the cavernous sinus can actually be identified
region. The challenge is to accurately predict the tis- on non-contrast images (Figure 3–12). Contrast
sue compartments that have been violated without images are necessary, however, to exclude disease
overestimating the boundaries of the tumor. Unlike
the neck, this region requires multiplanar imaging.
Radiographs and tomographic radiographs no
longer have a role in this work-up. The coronal view
is the single most important imaging plane (Figure
3–10) for the orbital margin and for the cribriform
plate for high naso-ethmoidal lesions.34 Prior to
MRI, high resolution CT was used to evaluate these 2 1
thin osseous barriers. Any distortion of the bone tex-
ture raised the suspicion of involvement of the adja-
cent soft-tissue space. With the advent of MRI, not
only is the coronal plane easier to acquire but also
the soft tissue within any compartment is directly 3
evaluated,35 not inferred from bony change. MRI is
probably the single best baseline-imaging exam for
paranasal neoplasms.36 Certain vagaries of physics
disturb tissue signal at these bone tissue air inter-
faces, but this is less problematic when tumor or
fluid replaces the air of the sinus cavity. The critical
determination of whether or not an orbit should be Figure 3–6. Axial T1-weighted MR image through maxilla in a
patient with squamous cancer of the soft palate. (1) Neurotropic
exenterated demands the application of both modal- extension to the left pterygopalatine fossa (PPF). (2) Normal appear-
ities (CT and MRI). These complementary modali- ance of right PPF. (3) Vidian canals, diseased on the left.
 Head and Neck Imaging 61

beyond the cavernous sinus, within the basal cisterns pharyngeal spaces. The lateral retropharyngeal
(Figure 3–13). Axial views are familiar to most lymph node station can also be cleared in this view.
observers and easily outline the deep posterolateral Extra-paranasal extension into the clinically sus-
extracranial extension to the masticator and para- pected buccal and pre-maxillary spaces is confirmed
in this plane as well. Involvement of the palate must
be determined to allow appropriate preoperative
2 consultation with the maxillofacial prosthodontist.
Epithelial tumors of the hard palate are best
staged by cross-sectional imaging protocols that
evaluate deep extension such as a paranasal sinus
4
protocol. The larger lesions are staged for the deep
3 margin that is neither visible nor palpable. Both
advanced and apparently early/small lesions are at
1
risk for central neurotropic extension to and through
the foramina at the skull base (Figure 3–14). Distant
perineural extension is more typical of the minor
salivary histologies but can be seen in squamous
neoplasms, particularly those with desmoplastic fea-
tures. MRI has the distinct advantage over CT by
revealing abnormal perineural enhancement before
A evidence of widening of the corresponding fissure
or foramen. These images help determine the extent
and appropriateness of skull base resection and por-
tal planning for radiation therapy in anticipation of a
3 positive margin.

Oral Cavity

Oral cavity lesions rarely require imaging without

clinical suspicion of deep infiltration. Patients with
floor of mouth, retromolar gum and endophytic
2
lesions of the tongue are imaged to rule out deeper
involvement. Key landmarks are the midline lin-
gual septum, mylohyoid sling, extrinsic muscles
and cortical margin of mandible. Although axial
images are most familiar, the coronal view is cru-
1 cial for the above determination. The sagittal view
is important to exclude extension of anterior
tongue lesions into the root of the tongue base (Fig-
ure 3–15). As with surgical margins, the confi-
dence in diagnosing involvement of the intrinsic
B
tongue is limited by the heterogeneous signal of the
interlacing muscle and fat. Pre-contrast and fat-
Figure 3–7. A, Enhanced axial CT through lower neck. (1) Left
common carotid artery (CCA). (2) Recurrent squamous cancer sur- suppressed post-contrast views must be carefully
rounding the CCA. (3) Normal right CCA. (4) Normal right internal matched to improve confidence. Involvement of
jugular vein. B, Nonselective cervical catheter angiogram. (1) Proxi-
mal left CCA. (2) Extrinsic compromise of distal left CCA. (3) Normal
the extrinsic muscles must also be carefully
caliber proximal left internal carotid artery. excluded. Determining T stage by measuring size
62 CANCER OF THE HEAD AND NECK

status of bone as well as perineural involvement.38

2
Confirming that disease is limited to the mucosal
1 compartment allows treatment of nasopharyngeal
lesions with a standard radiation portal while spar-
ing the cranial nerves (particularly cranial nerve II)
and the temporal lobes is the main goal of imaging.
While one modality may be adequate and efficient
for follow-up surveillance, it is the combination of
CT and MRI that is crucial at the baseline for this
disease. MRI is more sensitive than CT for invasion
of the cancellous bone of the central skull base. CT
is more sensitive to early involvement of the overly-
ing cortical bone of the sphenoid and basi occiput.
The minor change in the bone cortex that is not well
shown with MRI may have prognostic implications,
but will not likely change the treatment portal. MRI
may be the single best staging exam (Figure 3–16)
given the greater sensitivity to perineural exten-
Figure 3–8. Enhanced axial CT image through reconstructed
sion,39 cavernous sinus extension4 and the more
hypopharynx. (1) Composite free tissue graft at hypopharynx produces accurate estimation of cancellous bone involvement.
a pseudo-mass. (2) Partial airway compromise at supraglottic airway. MRI is adequate for nodal staging. Treatment plan-
ning is widely performed with CT although MRI-
may be difficult to determine by any means and based planning continues to develop.
any radiographic description must be considered an Imaging follow-up is best performed with the
estimated margin. modality that is most compatible with the patients’
Retromolar lesions sit within one of the most condition. CT remains an efficient method for fol-
asymmetrically shaped structures, the trigone. Fur-
thermore, imaging artifacts most often degrade this
area, especially CT. Upward posterior extension 3
along the lateral pterygoid fascia and neurotropic
extension along the mandibular segment of the Vth
nerve can be clinically silent but should be excluded 2

in all cases.
Buccal mucosal lesions are not usually imaged 1
until they become problematic due to multiple recur-
rences and limitations to clinical evaluation due to
trismus. Submucosal, periosteal and perineural
extension is difficult to evaluate and close correla-
tion with the clinical findings is necessary to avoid
over- or underestimating disease which becomes dif-
ficult to stage given the loss of tissue planes after
multiple treatments.

Nasopharynx
Figure 3–9. Coronal coincidence FDG image of the upper body.
(1) Clinically symptomatic metastatic lower left cervical lymph node.
Imaging of nasopharyngeal tumor requires the (2) Primary base of tongue lesion, occult on cross-sectional imaging.
greatest expenditure of techniques to confirm the (3) Normal intensity brain activity.
 Head and Neck Imaging 63

1
1

3 3

1
1

2 2

Figure 3–10. MRI images of sinus tumor. Sagittal upper and coronal lower
images with T1 and T2 weighting. (1) Penetration through fovea ethmoidalis into
extradural space. No brain invasion. (2) Displaced lamina papyracea without inva-
sion of orbital fat or muscle cone. (3) Obstructed sphenoid sinus secretions, not
tumor extension.

low-up surveillance imaging of the primary site does require intravenous contrast for detailed
and the neck. It is very reproducible between restaging, however. Patients receiving nephrotoxic
patients’ visits and among different institutions. CT chemotherapeutic agents should be followed with

Figure 3–11. Enhanced coronal T1-weighted MR image

1 through mid-orbits. (1) Thickened first division of left trigem-
inal nerve due to neurotropic skin tumor at forehead. (2)
2
Normal appearing first division of left trigeminal nerve.
64 CANCER OF THE HEAD AND NECK

2 1
3

Figure 3–12. Coronal T2-weighted MR image

through cavernous sinuses. (1) Tumor extension into
left cavernous sinus. (2) Intact dura stretched by
expanding tumor. (3) Normal heterogeneous
appearance of non-contrast MR of cavernous sinus.

MRI if their mucositis doesn’t produce too much contralateral to the original primary tumor. Misin-
swallowing motion artifact. Scanning of both the terpretation of this phenomenon could falsely sug-
primary site and comprehensive evaluation of the gest locoregional failure. Imaging artifact can be
neck does result in a lengthy exam, however. A avoided in the oropharynx with direct coronal views
bonus for the MRI cohort is evaluation of the CNS behind the dental work that would otherwise obscure
white matter injury of the spinal cord, brainstem the lesion in the axial plane.
and optic nerves.

Oropharynx

Most of the oropharyngeal sub-sites are easily eval-

uated in the axial plane with cross-sectional imag-
ing. Pharyngeal wall lesions rarely penetrate the 3

tough pharyngo-basilar fascia in their early stages.

Retropharyngeal extension and adenopathy are clin-
ically occult and must be excluded radiographically.
Invasion of the masticator space by tonsillar lesions
(Figure 3–17) can be detected with a good contrast-
enhanced scan. The index of suspicion must be high
particularly when trismus is present. Axial views
also outline base of tongue lesions across the glosso-
1
tonsillar sulcus, which may be difficult to appreciate
clinically. Base of tongue lesions are best supple-
2
mented by sagittal views to outline the status of the
preepiglottic space. This also determines the extent
of involvement anteriorly into the intrinsic muscles
of the tongue for accurate T staging.
Follow-up images need careful correlation with
pretreatment scans because of the variability of Figure 3–13. Axial contrast T1-weighted MR image through skull
base. (1) Neurotropic intracranial extension along cisternal segment of
native lymphoid tissue during treatment. Often Vth nerve. (2) Leptomeningeal growth along cerebellar folia. (3) Oper-
regrowth of lymphoid tissue produces pseudotumor ative bed of original ethmoid sinus tumor remains free of disease.
 Head and Neck Imaging 65

2
1

2
1 3
Figure 3–14. CT images of palate tumor with centripetal neurotrophic extension.
Upper panel: axial bone (L) and tissue (R) windows through palate. Lower panel:
coronal (L) and para-sagittal (R) tissue windows. (1) Palate tumor involving hard
and soft segments. (2) Extension upward through widened left greater palatine
foramen. (3) Normal bilateral palatine canals.

Soft palate lesions are difficult to discriminate without intravenous contrast. That benefit is not nec-
with conventional imaging because of the curved essary in early larynx cancer but has a bearing on
contour of the structure, the poor conspicuity of prognosis for local recurrence for more locally
these lesions and motion artifact from the soft palate advanced lesions.41 A negative CT is adequate for
resting on the tongue. This organ is best imaged in
the semi-coronal plane (Figure 3–18) with special
attention to the tonsillar margin.

Larynx and Hypopharynx

Imaging findings in the larynx have, in the past,

helped confirm the limited extent of early larynx
cancer allowing patients to decide between radiation
and surgery for primary management. Imaging for
advanced larynx and hypopharynx lesions helps
confirm the need for surgery and single out the 1
patients appropriate for organ preservation. Post- 2
3 4 5
biopsy changes distort the narrow tissue planes Figure 3–15. Midline sagittal MR tongue with undifferentiated
within the larynx and patients should not be scanned carcinoma. (1) Intact bone cortex of buccal plate at symphysis.
(2) Tumor originating at oral tongue. (3) Intact geniohyoid muscle.
prior to any endoscopic manipulation or biopsy. (4) Tumor extension toward base of tongue. (5) Preserved pre-
MRI provides exquisite soft tissue resolution40 even epiglottic space.
66 CANCER OF THE HEAD AND NECK

3 3

5 4

Figure 3–16. Nasopharynx cancer. Clockwise from upper left: semi-coronal T1-
weighted, contrast T1-weighted, and fat-suppressed T2-weighted MR images and
para-sagittal contrast T1-weighted MR images. (1) Mucosal mass. (2) Levator veli
palatini muscles (invaded on the left). (3) Intact skull base (clivus) with normal mar-
row signal. (4) Early invasion of parapharyngeal space. (5) Benign reactive
enhancement at foramen ovale, intracranial extension.

clearance of the paraglottic space and preepiglottic

space42 (Figure 3–19). MRI better evaluates the sub-
glottic extent and is more sensitive to early cartilage
involvement.43 Neither of these features is common
with early glottic cancer. Either modality can con-
firm a locally advanced lesion being restricted to the
supraglottis or hemilarynx permitting a primary sur-
1
gical approach.44,45 Advanced cancers of the larynx 2
cause pain and difficulty managing secretions—lim-
iting the success of MRI for staging. Tracheostomy
alleviates some of these problems. Rapid CT scan-
ners coupled with “slip ring” (helical/spiral) tech-
nology help produce images with less patient motion
artifact.46 Reformatted images can be produced in 3
the sagittal and coronal planes from the original
axial scan plane (Figure 3–20). Either modality pro-
vides adequate surgical planning or baseline infor-
mation prior to treatment. MRI is more sensitive but
Figure 3–17. Squamous cancer tonsillar pillar. (1) Large mass
less specific than CT for cartilage invasion.47 Imag- arising in right palatine tonsil. (2) Right medial pterygoid invaded. (3)
ing of primary tumors of the hypopharynx is per- Right base of tongue extension.
 Head and Neck Imaging 67

2 1

1
3 2

Figure 3–18. CT images of soft palate squamous cancer. Axial (L) and semi-
coronal (R) tissue windows. (1) Soft palate component. (2) Tonsillar pillar exten-
sion. (3) Medial pterygoid muscle (normal).

formed with larynx style protocols. Local extension One method to reduce the need for re-biopsy and
to the laryngeal framework is the most important avoid the difficulties of follow-up cross-sectional
component of extra-pharyngeal extension. Imaging imaging is PET imaging.13,26 Non-surgical or organ
detects cartilage invasion that can be clinically preservation patients treated by chemo/radiotherapy
occult.48 CT can detect inferior extension of pyri- frequently have persistent morphologic abnormali-
form sinus tumor (Figure 3–21) that cannot be ties on follow-up clinical evaluation and imaging
assessed clinically.49 Surveillance follow-up imag- despite maximal therapy. Often this represents ster-
ing should take into account the risk for patient ilized tumor and fibrosis. Pain or dysfunction influ-
motion with MRI and the ability of the patient to tol- ence the decision to re-biopsy the primary site. In an
erate intravenous contrast for CT. effort to avoid the post-biopsy injury, a baseline

2
1

Figure 3–19. CT images of left transglottic squamous cancer. Clockwise from

upper left panel: axial images through epiglottic, false cord and true cord levels of
larynx and coronal reformatted image of same. (1) Supraglottic lesion. (2) Para-
glottic component at false cord level. (3) Paraglottic extension to true cord level.
68 CANCER OF THE HEAD AND NECK

FDG-PET scan should be obtained and repeated head and neck best evaluated with fluoroscopy (Figure
after treatment.50 If the degree of metabolic activity 3–22). Mural and exophytic lesions can be detected
has improved, biopsy could be deferred unless cross- prior to advanced dysphagia, which is usually the
sectional imaging shows a distinct progression and accompanying chief complaint. Like other segments
resection deferred unless the correlation of modali- of the esophagus, complete staging is best performed
ties indicates severe tissue necrosis. Another sec- with a combination of endo-sonography,54 and cross-
ondary benefit of the FDG-PET scan would be sur- sectional imaging. These techniques are complemen-
veillance for second primaries. Nuclear scans with tary, with the endoscopic exam providing information
thallium-201 on more conventional equipment with about the depth of invasion relative to the muscularis,
single photon emission computed tomography the linear extent of the lesion and characterization of
(SPECT) capacity has been shown to be competitive internal architecture of posterior mediastinal lymph
with CT in the post-treatment larynx population.51 nodes. Synchronous lesions can be excluded at other
This method had an accuracy of 90 percent and does levels of the esophagus at baseline. Cross-sectional
not require investment in PET technology. exams provide a more complete locoregional N stag-
Follow-up imaging of the reconstructed and irra- ing and can be extended for regional M staging. Nei-
diated laryngopharyngectomy is very important ther CT nor MRI has sufficient negative predictive
given the difficulty of examining the irradiated/ value for adenopathy, however.
operated neck. Familiarity with the type of resec-
tions, flap reconstructions and patterns of recurrence Salivary Glands
is essential for accurate interpretation.52,53 Careful
attention should be directed to the anastomotic level Imaging of cancer of the minor salivary glands is
and peristomal region. covered in the corresponding sub-sites. Imaging of
the major salivary gland masses is usually per-
Esophagus formed when the clinical exam does not provide
accurate assessment of the anatomic extent of the
The cervical segment of the esophagus is difficult to tumor or when surgical excision is likely to have a
evaluate clinically. It remains one of the sites in the positive margin on a vital structure. Imaging

Figure 3–20. Large supraglottic cancer. Upper

panel: sagittal (L) and coronal (R) reformatted CT 1
images. Lower panel: glottic (L) and epiglottic (R) 1
axial CT source images. (1) Mucosal lesion at laryn-
geal surface of epiglottis. (2) Inferior preepiglottic
extension. 2
2

1
 Head and Neck Imaging 69

1 1

2 2

Figure 3–21. Contrast CT images of left pyriform squa-

mous cell carcinoma. Clockwise from upper left: serial
images through the laryngo-pharynx. (1) Diseased left
pyriform aperture. (2) Preserved left pyriform apex.

should also be considered in the setting of cranial

nerve palsy.55
Parotid lesions are easily outlined with CT when
high quality multiplanar images can be acquired and
intravenous contrast used. Contrast helps outline the
lesion relative to the gland and provides better char-
acterization of the vascular margin at the carotid 1
sheath. The benefits of MRI over CT are better dis-
crimination of the lesion relative to background
parotid tissue (Figure 3–23) and slightly better dis-
crimination of proximal neurotropic extension of 2
disease along the VIIth nerve.
Image-guided biopsy is helpful when there is a
need to establish the diagnosis prior to treatment.
Follow-up imaging is best performed with the
modality that revealed the lesion prior to treatment.
Radiation changes produce extensive regional
hyperintensity22 of the parotid bed and mastoid, lim-
iting the value of T2-weighted images. Contrast-
enhanced fat-suppressed T1-weighted images are
important at this stage.1
Submandibular lesions are often managed without
imaging prior to resection. Imaging of the neck can be
Figure 3–22. Anterior esophagram of squamous cell carcinoma
performed to confirm the completeness of the resec- upper esophagus. (1) Varicoid appearance of squamous cancer cer-
tion and determine whether a limited neck dissection vicothoracic esophagus. (2) Trachea.
70 CANCER OF THE HEAD AND NECK

is appropriate. Both sublingual and submandibular tracheoesophageal lymph nodes at risk. Correlation
salivary gland lesions are imaged with an oral cavity- of the cross-sectional views with the radioiodine
type imaging protocol with careful attention to the scans is more productive than either scan alone.
floor of mouth and the status of Wharton’s duct. Lesions that accumulate iodine less well can be
imaged with thallium57 or FDG-PET.58,59 This
Thyroid agent accumulates in metabolically active tissue,
and to a greater degree in tumor. Although costly
Imaging of the thyroid gland and neck for thyroid and less specific, FDG-PET can be used without
cancer varies because of the variety of disciplines interruption of thyroid replacement. Another defi-
that manage this disorder. Imaging of the gland is nite advantage of PET is the ability to co-register
only part of a comprehensive clinical and labora- the images in any plane with cross-sectional exams
tory evaluation. Whether the imaging is cross-sec- in a way that cannot be done with I-131.
tional, functional (radioiodine), or metabolic
(FDG-PET) should be determined by the evalua- Unknown Primary
tion and the chief complaint. Persons with meta-
bolic complaints should be imaged with radioio- No discussion of head and neck imaging would be
dine to supplement their work-up, if necessary. complete without a discussion of the occult primary
Persons with palpable abnormalities don’t neces- presumed to be within the upper aerodigestive tract.
sarily need radioiodine scanning initially. Sonogra- If one looks at the larger picture of patients with
phy is often used to confirm multiplicity and con- metastatic adenopathy above the clavicles, the role
sistency of lesions, favoring a benign condition. of imaging has increasing value. CT of the neck,
Neither CT, MRI, sonography nor radioiodine chest, abdomen and pelvis usually follows the tradi-
scans can confirm or exclude cancer, however. tional method of panendoscopy and exam under
FNA is essential for lesions considered at risk for anesthesia after an unproductive office exam. The
cancer by clinical or imaging grounds. Sonography advent of FDG-PET can obviate the need for such
preceding or as an adjunct to the FNA may reveal a comprehensive searching60 and might even be
cyst, which could be aspirated or followed, as clin- sequenced between the office exam and any subse-
ically indicated. When cancer has been confirmed,
sonography (Figure 3–24) can establish the size of
the lesion(s), the status of any pseudo-capsule, and
the condition of the capsule of the gland.56 Sono-
graphic staging of the lymph nodes is limited5 and
CT or MRI is better at covering the high level II
nodes and the lower tracheo-esophageal nodes. 1
Cross-sectional imaging of the neck is not neces- 3
2
sary prior to thyroid surgery in the absence of clin-
ical features suspicious for extra-thyroidal or medi-
astinal extension. Since iodinated intravenous
contrast alters the accuracy of radioiodine scans,
CT is a less useful modality for baseline staging.
Imaging artifacts at the thoracic inlet and upper
mediastinum are difficult to sort out in the absence
of contrast with CT. MRI is not prone to these arti- 4

facts (Figure 3–25) and can be performed with con-

trast without interference with radioiodine scans.
Figure 3–23. Parotid tumor. (1) Parotid tumor along expected course
Neck scans by either modality should be extended of facial nerve. (2) Superficial lobe involvement. (3) Deep lobe exten-
to the level of the tracheal carina to cover the lower sion to paraphayngeal space. (4) Preserved stylomastoid foramen.
 Head and Neck Imaging 71

sectional exam of the neck. The majority of patients

3
with positive FDG-PET scans are found to have a
2 corresponding tumor and most of those with nega-
tive scans never manifest a head or neck primary on
1
follow-up (after treatment).61,62 At the very least,
patients with no identifiable primary or one local-
ized to the head and neck have a better prognosis
than those discovered to have a visceral primary
below the clavicles.63

Sarcomas
4
Soft tissue sarcomas and other tumors usually pre-
sent within the lateral neck or paraspinal compart-
ments. These are imaged equally well with MRI64 or
Figure 3–24. Throid cancer sonogram. Transverse sonogram contrast enhanced CT. CT tends to overestimate the
through right thyroid bed. (1) Solid component of complex mass. (2) overall size of neck masses65 compared with MRI—
Cystic component of complex mass. (3) Artifact. (4) Intact pseudo-
capsule of lesion.
probably because of its multiplanar capacity. Vascu-
lar integrity and margins can also be surveyed at the
initial MRI visit with the help of magnetic resonance
quent procedure requiring anesthesia. The results of angiography (MRA). Many patients can be spared
the PET scan can show other sites of adenopathy and catheter angiography. Sarcomas developing within
locate the primary tumor25 (see Figure 3–9). PET sub-sites of the aerodigestive tract are imaged
images are best reviewed in correlation with a cross- according to those protocols. Combining informa-

Figure 3–25. Throid cancer MRI. Clockwise from

upper left: Coronal and sagittal T1-weighted non-
contrast images and axial T2-weighted images
4 through base of neck and thoracic inlet. Note the lack
1 of imaging artifacts. (1) Left lobe thyroid mass. (2)
Extracapsular extension. (3) Tracheoesophageal
lymph node metastasis. (4) Trachea. (5) Invasion of
prevertebral muscles. (6) Plane of brachiocephalic
vein. (7) Left common carotid artery.

6
2 3

7
7
1

4 5
72 CANCER OF THE HEAD AND NECK

tion from pretreatment MRI with CT based treat- tion. Ideally the technique would provide anatomic
ment planning lends confidence to those plans. staging of the primary site, comprehensive lymph
node staging and functional information regarding
FUTURE DIRECTIONS nerves and blood vessels. One of the original goals
of MRI was to provide in vivo tissue characteriza-
Cross-sectional imaging will continue to develop tion on human subjects. Twenty years after its intro-
computer assisted interactive methods for opera- duction, MR shows promise for “one-stop shop-
tive guidance66 and treatment based on pre-proce- ping” for all vital information: MR imaging, MR
dure scans. These procedures are best performed angiography, and now MR spectroscopy.74 Improve-
by practitioners with prior experience without the ments in software have followed necessary
aid of imaging support. Further development of improvements in hardware and magnetic field
interactive types of software should allow trainees strength. Sampling a small volume of tissue from a
to develop skills on so-called virtual patients, pro- cross-sectional image and analyzing for relative
viding that experience base. Performing proce- amounts of known metabolites can predict the like-
dures under imaging guidance is advancing from lihood of neoplasm.75 As with other modalities, a
simple biopsies and ablations to realtime guidance physician is responsible for determining the pres-
on “fluoroscopic-CT” and “open architecture” ence of a target on the image for sampling. Like
MRI equipment. FDG-PET, this noninvasive technique allows one to
Developments in sonography with color flow follow a trend during treatment in order to confirm
imaging of lymph nodes and power Doppler imag- treatment response.
ing of masses and lymph nodes is being explored to
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simply for correlation.73 node metastases of squamous-cell cancer of the head and
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research has been to find an efficient pathway of 211–6.
10. Yucel T, Saatci I, Sennaroglu L, et al. MR imaging in squa-
patient management where selection of an imaging mous cell carcinoma of the head and neck with no palpa-
modality provides pertinent and accurate informa- ble lymph nodes. Acta Radiol 1997;38(5):810–4.
 Head and Neck Imaging 73

11. Anzai Y, Brunberg JA, Lufkin RB. Imaging of nodal metas- 28. Greven KM, Williams DW III, Keyes JW Jr, et al. Positron
tases in the head and neck. J Magn Reson Imaging emission tomography of patients with head and neck car-
1997;7(5):774–83. cinoma before and after high dose irradiation [see com-
12. Adams S, Baum RP, Stuckensen T, et al. Prospective com- ments]. Cancer 1994;74(4):1355–9.
parison of 18F-FDG PET with conventional imaging 29. Haberkorn U, Strauss LG, Dimitrakopoulou A, et al. Fluo-
modalities (CT, MRI, US) in lymph node staging of head rodeoxyglucose imaging of advanced head and neck can-
and neck cancer. Eur J Nucl Med 1998;25(9):1255–60. cer after chemotherapy. J Nucl Med 1993;34(1):12–7.
13. Fischbein NJ, AAssar OS, Caputo GR, et al. Clinical utility 30. Sercarz JA, Bailet JW, Abemayor E, et al. Computer coregis-
of positron emission tomography with 18F-fluo- tration of positron emission tomography and magnetic
rodeoxyglucose in detecting residual/recurrent squamous resonance images in head and neck cancer. Am J Oto-
cell carcinoma of the head and neck [see comments]. laryngol 1998;19(2):130–5.
AJNR Am J Neuroradiol 1998;19(7):1189–96. 31. Zimny M, Kaiser HJ, Cremerius U, et al. F-18-FDG positron
14. Stevens MH, Harnsberger HR, Mancuso AA, et al. Com- imaging in oncological patients: gamma camera coinci-
puted tomography of cervical lymph nodes. Staging and dence detection versus dedicated PET. Nuklearmedizin
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1985;111(11):735–9. 32. Valdes Olmos RA, Balm AJ, Hilgers FJ, et al. Thallium-201
15. Prehn RB, Pasic TR, Harari PM, et al. Influence of computed SPECT in the diagnosis of head and neck cancer. J Nucl
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to the prevertebral compartment by squamous cell carci- masses. [review] [17 refs]. Radiographics 1995;15(6):
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1998;170(5):1389–94. 36. Held P, Breit A. [Comparison of CT and MRI in diagnosis of
18. Yousem DM, Hatabu H, Hurst RW, et al. Carotid artery inva- tumors of the nasopharynx, the inner nose and the
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ing. Radiology 1995;195(3):715–20. in der Diagnostik von Tumoren des Nasopharynx, der
19. Curtin HD. Importance of imaging demonstration of neo- inneren Nase und der Nebenhohlen. Bildgebung 1994;
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ment]. Radiology 1995;194(3):643–4. 37. Nemzek WR, Hecht S, Gandour-Edwards R, et al. Perineural
20. Lemort M. Computed tomography (CT) in head and neck spread of head and neck tumors: how accurate is MR
tumors: technique and indications. [review] [14 refs]. imaging? AJNR Am J Neuroradiol 1998;19(4):701–6.
Journal Belge de Radiologie 1994;77(2):60–6. 38. Su CY, Lui CC. Perineural invasion of the trigeminal nerve in
21. Som PM, Urken ML, Biller H, Lidov M. Imaging the post- patients with nasopharyngeal carcinoma. Imaging and
operative neck. [review] [30 refs]. Radiology 1993; clinical correlations. Cancer 1996;78(10):2063–9.
187(3):593–603. 39. Majoie CB, Hulsmans FJ, Verbeeten B Jr, et al. Perineural
22. Becker M, Schroth G, Zbaren P, et al. Long-term changes tumor extension along the trigeminal nerve: magnetic res-
induced by high-dose irradiation of the head and neck onance imaging findings. Eur J Radiol 1997;24(3):
region: imaging findings. Radiographics 1997;17(1):5–26. 191–205.
23. Koch WM. Axillary nodal metastases in head and neck can- 40. Zbaren P, Becker M, Lang H. Pretherapeutic staging of
cer. Head Neck 1999;21(3):269–72. hypopharyngeal carcinoma. Clinical findings, computed
24. Harris EW, LaMarca AJ, Kondroski EM, et al. Enhanced CT tomography, and magnetic resonance imaging compared
of the neck: improved visualization of lesions with delayed with histopathologic evaluation [published erratum
imaging. AJR Am J Roentgenol 1996;167(4):1057–8. appears in Arch Otolaryngol Head Neck Surg 1998
25. Bailet JW, Abemayor E, Jabour BA, et al. Positron emission Feb;124(2):231]. Arch Otolaryngol Head Neck Surg
tomography: a new, precise imaging modality for detec- 1997;123(9):908–13.
tion of primary head and neck tumors and assessment of 41. Castelijns JA, van den Brekel MW, Smit EM, et al. Predictive
cervical adenopathy. Laryngoscope 1992;102(3):281–8. value of MR imaging-dependent and non-MR imaging-
26. Wong WL, Chevretton EB, McGurk M, et al. A prospective dependent parameters for recurrence of laryngeal cancer
study of PET-FDG imaging for the assessment of head after radiation therapy. Radiology 1995;196(3):735–9.
and neck squamous cell carcinoma. Clin Otolaryngol 42. Thabet HM, Sessions DG, Gado MH, et al. Comparison of
1997;22(3):209–14. clinical evaluation and computed tomographic diagnostic
27. Paulus P, Sambon A, Vivegnis D, et al. 18FDG-PET for the accuracy for tumors of the larynx and hypopharynx.
assessment of primary head and neck tumors: clinical, Laryngoscope 1996;106(5 Pt 1):589–94.
computed tomography, and histopathological correlation 43. Zbaren P, Becker M, Lang H. Pretherapeutic staging of laryn-
in 38 patients. Laryngoscope 1998;108(10):1578–83. geal carcinoma. Clinical findings, computed tomography,
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and magnetic resonance imaging compared with [18F]fluorodeoxyglucose positron emission tomography.
histopathology. Cancer 1996;77(7):1263–73. Nucl Med Commun 1998;19(6):547–54.
44. Williams DW III. Imaging of laryngeal cancer [review] [51 60. Mendenhall WM, Mancuso AA, Parsons JT, et al. Diagnostic
refs]. Otolaryngol Clin N Am 1997;30(1):35–58. evaluation of squamous cell carcinoma metastatic to cer-
45. Weinstein GS, Laccourreye O, Brasnu D, Yousem DM. The vical lymph nodes from an unknown head and neck pri-
role of computed tomography and magnetic resonance mary site. Head Neck 1998;20(8):739–44.
imaging in planning for conservation laryngeal surgery 61. AAssar OS, Fischbein NJ, Caputo GR, et al. Metastatic head
[review] [25 refs]. Neuroimaging Clin N Am 1996;6(2): and neck cancer: role and usefulness of FDG PET in locat-
497–504. ing occult primary tumors. Radiology 1999;210(1):177–81.
46. Korkmaz H, Cerezci NG, Akmansu H, Dursun E. A compar- 62. Schipper JH, Schrader M, Arweiler D, et al. [Positron emis-
ison of spiral and conventional computerized tomography sion tomography for primary tumor detection in lymph
methods in diagnosing various laryngeal lesions. Eur node metastases with unknown primary tumor]. HNO
Arch Otorhinolaryngol 1998;255(3):149–54. 1996;44(5):254–7.
47. Becker M, Zbaren P, Laeng H, et al. Neoplastic invasion of 63. Jones AS, Roland NJ, Hamilton J, et al. Non-squamous
the laryngeal cartilage: comparison of MR imaging and malignancy in lymph nodes: the occult primary. Clin Oto-
CT with histopathologic correlation [see comments]. laryngol 1996;21(1):49–53.
Radiology 1995;194(3):661–9. 64. Hirsch RJ, Yousem DM, Loevner LA, et al. Synovial sarco-
48 . Zbaren P, Becker M, Lang H. Staging of laryngeal cancer: mas of the head and neck: MR findings. AJR Am J
endoscopy, computed tomography and magnetic reso- Roentgenol 1997;169(4):1185–8.
nance versus histopathology. Eur Arch Otorhinolaryngol 65. Rasch C, Keus R, Pameijer FA, et al. The potential impact of
Suppl. 1997;1:S117–S22. CT-MRI matching on tumor volume delineation in
49. Saleh EM, Mancuso AA, Stringer SP. Relative roles of com- advanced head and neck cancer. Int J Radiol 1997;39(4):
puted tomography and endoscopy for determining the 841–8.
inferior extent of pyriform sinus carcinoma: correlative 66. Davis SP, Anand VK, Dhillon G. Magnetic resonance navi-
histopathologic study. Head Neck 1993;15(1):44–52. gation for head and neck lesions. Laryngoscope 1999;
50. Kitagawa Y, Sadato N, Azuma H, et al. FDG-PET to evaluate 109(6):862–7.
combined intra-arterial chemotherapy and radiotherapy of 67. Shen YY, Kao CH, Changlai SP, et al. Detection of nasopha-
head and neck neoplasms. J Nucl Med 1999;40(7):1132–7. ryngeal carcinoma with head and neck Tc-99m tetrofos-
51. Mukherji SK, Gapany M, Phillips D, et al. Thallium-201 sin- min SPECT imaging. Clin Nucl Med 1998;23(5):305–8.
gle-photon emission CT versus CT for the detection of 68. Flamen P, Bernheim N, Deron P, et al. Iodine-123 alpha-
recurrent squamous cell carcinoma of the head and neck methyl-l-tyrosine single-photon emission tomography for
[see comments]. AJNR Am J Neuroradiol 1999;20(7): the visualization of head and neck squamous cell carcino-
1215–20. mas. Eur J Nucl Med 1998;25(2):177–81.
52. Misiti A, Macori F, Caimi M, et al. Computerized tomogra- 69. Lindholm P, Leskinen S, Lapela M. Carbon-11-methionine
phy in the evaluation of the larynx after surgical treatment uptake in squamous cell head and neck cancer. J Nucl
and irradiation. Radiol Med (Torino) 1997;94(6):600–6. Med 1998;39(8):1393–7.
53. Hudgins PA, Burson JG, Gussack GS, Grist WJ. CT and MR 70. De Rossi G, Maurizi M, Almadori G, et al. The contribution
appearance of recurrent malignant head and neck neo- of immunoscintigraphy to the diagnosis of head and neck
plasms after resection and flap reconstruction. AJNR Am tumours. Nucl Med Commun 1997;18(1):10–6.
J Neuroradiol 1994;15(9):1689–94. 71. de Bree R, Roos JC, Quak JJ, et al. Radioimmuno-
54. Doldi SB, Lattuada E, Zappa MA, et al. Ultrasonographic scintigraphy and biodistribution of technetium-99m-
imaging of neoplasms of the cervical esophagus. Hepato- labeled monoclonal antibody U36 in patients with head
gastroenterology 1997;44(15):724–6. and neck cancer. Clin Cancer Res 1995;1(6):591–8.
55. Ariyoshi Y, Shimahara M. Determining whether a parotid 72. Ramos-Suzarte M, Rodriguez N, Oliva JP, et al. 99mTc-
tumor is in the superficial or deep lobe using magnetic res- labeled antihuman epidermal growth factor receptor anti-
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56. Shimamoto K, Satake H, Sawaki A, et al. Preoperative stag- Clinical trials safety and diagnostic efficacy. J Nucl Med
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Eur J Radiol 1998;29(1):4–10. 73. Leitha T, Glaser C, Pruckmayer M, et al. Technetium-99m-
57. Lin JD, Kao PF, Weng HF, et al. Relative value of thallium- MIBI in primary and recurrent head and neck tumors:
201 and iodine-131 scans in the detection of recurrence or contribution of bone SPECT image fusion. J Nucl Med
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noma. Eur J Nucl Med 1998;25(7):695–700. 74. Adalsteinsson E, Spielman DM, Pauly JM, et al. Feasibility
58. Wang W, Macapinlac H, Larson SM, et al. [18F]-2-fluoro-2- study of lactate imaging of head and neck tumors. NMR
deoxy-D-glucose positron emission tomography localizes Biomed 1998;11(7):360–9.
residual thyroid cancer in patients with negative diagnostic 75. Star-Lack J, Spielman D, Adalsteinsson E, et al. In vivo lac-
(131)I whole body scans and elevated serum thyroglobulin tate editing with simultaneous detection of choline, crea-
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59. Jadvar H, McDougall IR, Segall GM. Evaluation of sus- tation with applications to the study of brain and head and
pected recurrent papillary thyroid carcinoma with neck tumors. J Magn Reson 1998;133(2):243–54.
 4
Skin Cancers of the Head and Neck
BHUVANESH SINGH, MD
JATIN P. SHAH, MD, FACS

derm, and correspondingly supports the development

SKIN PATHOLOGY of a myriad of benign and malignant processes.
Approximately 1 million new cases of basal or squa-
Benign epidermal tumors
mous cell carcinoma, 51,400 melanomas, and 5,000
Fibroepithelial polyp
non-epithelial skin cancers occur yearly in the United
Keratoacanthoma
States, with the head and neck region as the site of
Actinic keratosis
origin in over 80 percent of these cases.1
Adnexal tumors
Benign tumors
Benign Epidermal Tumors
Malignancies
Dermal tumors Fibroepithelial Polyp
Malignant fibrous histiocytoma
Dermatofibrosarcoma protuberans Also known as skin tags, fibroepithelial polyps typi-
Kaposi’s sarcoma cally develop in middle-aged persons and are of lim-
Hemangioma ited consequence. These lesions are usually removed
Xanthoma for cosmetic reasons, although they may become
quite large and symptomatic due to irritation or
Malignant epidermal tumors
trauma. The pedunculated lesions are usually fleshy
Basal cell carcinoma
and are composed of an epithelial covering and a
Squamous cell carcinoma
fibrovascular core. Occasional case reports have
Other cancers demonstrated the presence of coexistent carcinoma;
Merkel cell carcinoma but this is rare, with one series showing only 5 of
Dermatofibrosarcoma protuberans 1,335 fibroepithelial polyps containing malignancy.2,3
Malignant fibrous histiocytoma The neck is the most common site of involvement.
Melanocytic lesions Local excision is sufficient for management of symp-
Malignant melanoma tomatic lesions or for cosmetic concerns.

Keratoacanthoma
The skin is by far the largest organ in humans. It has
several functions, but mainly acts as a barrier against These are lesions of middle-aged people that typi-
the outside environment. Given its chronic exposure cally begin as a keratosis, firm papule, or wart-like
to environmental carcinogens, it is not surprising that lesion. Keratoacanthomas often display rapid
cancers of cutaneous origin are the most common enlargement into a dome-shaped lesion with a central
human malignancies. Embryologically, the skin is crater filled with keratin. These lesions typically
derived from ectoderm, neuroectoderm and meso- grow over a period of 2 to 4 weeks, to a size of 1 to

75
76 CANCER OF THE HEAD AND NECK

2 cm, although giant, >5 cm lesions rarely do namic therapy with topical δ-aminolevulinic acid to
develop. The natural course of these lesions after the be as effective as 5-fluorouracil treatment.16, 17
rapid growth phase is involution, leaving a scar or
hypopigmented region on the skin. Clinically and Adnexal Tumors
histologically, these lesions can resemble squamous
cell carcinoma, with cytologic atypia often present.4
Benign Tumors
An evaluation of the overall architecture of the
lesion, with accompanying hyperkeratosis, paraker- These tumors arise from the skin appendages and
atosis, acanthosis, and hypergranulosis, is diagnostic. can show pilosebaceous, eccrine, or apocrine differ-
The lesions typically occur on the central portion of entiation. Common benign adnexal tumors include
the face, usually involving the cheek and nose. Soli- nevus sebaceous, trichoepithelioma, pilomatricoma,
tary lesions are present in the majority of cases, but cylindroma, syringocystadenoma papilliferum,
multiple lesions may occur infrequently. Observation syringoma, and eccrine spiradenoma.
and local care usually suffice for management, Nevus sebaceous tumors are congenital hamar-
although vigilance for the presence of squamous cell tomas of the skin that probably arise from basal cells.
carcinoma must remain.5 These lesions typically involve the face and scalp
regions of children, ranging in appearance from
Actinic Keratosis slightly raised flesh-colored plaques to verrucous
nodular lesions. Although it is controversial, excision
Actinic keratoses are common premalignant lesions is usually recommended due to the risk of transfor-
of the skin that are associated with chronic sun expo- mation to basal cell carcinoma. A study by Cribier
sure. Although lesions are reported to progress into and colleagues showed that of 596 excised cases of
squamous cell carcinoma in up to 25 percent of nevus sebaceous tumor, 0.8 percent contained coex-
cases, most studies suggest that the true progression istent basal cell carcinoma, while 13.6 percent of
rate is closer to 0.01 to 0.24 percent.6–11 Clinically cases contained benign pathology, mainly syringo-
these lesions have an erythematous papular or cystadenoma papilliferum (37%) and trichoblastoma
plaque-like appearance, a rough texture, and can (35%).18 Similarly, a study by Chun and colleagues
form conical projections called cutaneous horns. also observed low transformation rates, suggesting
Histologically, these tumors contain anaplastic ker- that excision of sebaceous nevi should be performed
atinocytes in the basal layers of aplastic or hyper- only in cases where transformation of benign to
plastic epidermis. The lesions are typically multiple malignant pathology is suspected.19
and most often involve the sun-exposed regions of Trichoepithelioma is a tumor displaying hair fol-
the head, neck and arms. Some authors advocate licle differentiation that occurs in two forms: a spo-
intervention in all cases, given the high rates of trans- radic form that typically presents as a solitary lesion,
formation to carcinoma and an inability to identify and a familial form with multifocal lesions. Multiple
high-risk lesions.12 Treatment typically consists of familial trichoepithelioma (MFT) has an autosomal
cryosurgery and curettage, topical chemotherapy dominant inheritance pattern with the gene located
with 5-fluorouracil (5-FU), or surgical excision.13,14 on chromosome 9p21.29 MFT may degenerate into
Topical 5-FU is usually applied as a 5 percent cream basal cell carcinoma in a small number of cases. The
twice daily for 2 weeks. An intense local reaction lesions appear as flesh-colored papules and nodules
results, followed by resolution of the lesion, with no of the facial or scalp skin, and less commonly that of
effects to the remaining skin. More recently, novel the neck and trunk.
therapies have shown promise in treating these Pilomatricomas or Malherbe’s calcifying epithe-
lesions. A double-blind controlled study demon- liomas are tumors of hair follicle origin, derived from
strated an enhanced efficacy of 5-FU with the addi- the adnexal keratinocytes. Although these tumors can
tion of tretinoin cream.15 Another randomized paired occur at any age, they typically occur in the first and
comparison showed a single treatment with photody- sixth decades of life.20 The lesions involve the face or
 Skin Cancers of the Head and Neck 77

arms and can range from subcutaneous nodules to behavior with a tendency toward regional and distant
superficial lesions with rare ulceration. A familial metastasis.36,37 Multimodality treatment with
association to myotonic dystrophy has been sug- aggressive surgical resection, adjuvant radiation
gested.21,22 Fifty-five cases of degeneration into therapy, and consideration for chemotherapy has
malignant pilomatricomas have been reported in the been recommended for malignant syringomas.36,37
literature.23 Surgical excision is usually sufficient for Eccrine spiradenoma are derived from eccrine
management.24 A malignant variant of this lesion has glandular structures. These tumors typically present
been reported, which has locally aggressive features as painful subcutaneous nodules in young adults.38
and rare metastasis. Recurrence of malignant pilo- No anatomical predilection has been reported.
matricoma is common after simple excision, requir- Degeneration of eccrine spiradenoma to a malignant
ing aggressive local surgical treatment and adjuvant variant has been reported, which usually presents as
radiation as required.25–27 an expanding solitary painful nodule. Malignant
Cylindroma, also known as turban tumor, can tumors are rare, have no site predilection, and dis-
either be apocrine or eccrine in origin. These lesions play locally aggressive behavior with a propensity
arise in the scalp and facial region in early adult- for regional and distant metastasis.39,40 These tumors
hood. The lesions can be single, but are more often occur in older patients and manifest as rapidly
multiple. A familial syndrome of multiple cylindro- enlarging lesions which incite a local inflammatory
mas is inherited via an autosomal dominant pattern response and an accompanying change in the color
of inheritance with a linkage to chromosome 16q12- of the overlying skin.41
13.28 Briggs and colleagues, using loss of heterozy-
gosity (LOH) analysis, suggested that CYLD1, a Malignant Tumors
tumor suppressor gene, is involved in both familial
and sporadic types.28 Malignant transformation may Malignant sweat gland tumors can be divided into
occur in both the sporadic and familial varieties, but those of apocrine or eccrine origin and typically
is rare. Typically, the presence of rapid growth and occur in older patients in their fifth to sixth decades
frequent recurrence after excision should raise sus- of life. Unlike most other skin cancers, these lesions
picion for malignant transformation. These tumors do not have a racial predilection, although apocrine
are locally aggressive with frequent regional and tumors may be more common in African Ameri-
distant metastasis.25, 29, 30 cans.25,42 Surgical excision is recommended for all
Syringocystadenoma papilliferum is a lesion types of sweat gland carcinomas, with regional node
occurring in the scalp and facial region of patients dissection advocated for patients with clinically pal-
entering puberty. It can have either eccrine or apoc- pable lymphadenopathy and electively in selected
rine differentiation and clinically presents as a high risk cases.43 Taken as a whole, recurrence in
plaque or nodule of the scalp or face.31 It is usually sweat gland cancers occurs in the majority of cases,
associated with a pre-existing nevus sebaceous.32 with up to 56 percent having more than one recur-
Syringomas are derived from the eccrine duct rence. 25 Although these tumors tend to be radiation-
and typically occur in adulthood. The majority of resistant, adjuvant radiation treatment should be con-
patients present with generalized syringomas, sidered in selected cases.43, 44 Apocrine gland
although solitary lesions can occur. These lesions carcinomas are less common, occurring most often
typically occur on the face (especially the lower eye- in the axilla of elderly individuals.42 In the head and
lid), abdomen and vulva.33 The lesions are multiple neck, the eyelid region is the one most often
flesh top yellowish-colored, 1 to 2 mm subcutaneous involved. In the eyelid, the origin of these tumors are
nodules. Reports have suggested a higher rate of Moll’s glands, which are modified apocrine glands.25
palpebral syringomas in patients with Down’s syn- The mortality associated with these tumors is
drome.34 A malignant variant of this lesion has been approximately 39 percent.42 Eccrine gland carcino-
reported, but is more common in the trunk and mas, the most common type of sweat gland carci-
extremity.35 These lesions show locally aggressive noma, can arise either de novo or from pre-existing
78 CANCER OF THE HEAD AND NECK

benign lesions. Primary eccrine gland cancers typi- predominance, reflecting the effects of chronic sun
cally present as asymptomatic subcutaneous nodules exposure. The majority of lesions present with an
in elderly individuals. Histologic variants include ulceration, surrounded by a pearly rolled border,
syringoid, mucinous, microcystic eccrine carcino- thereby earning the appellation of “rodent ulcer.”
mas, and adenocarcinomas. Lesions most often The head and neck region is involved in over 85 per-
involve the extremity and head and neck, with the cent of cases.49–51 Within the head and neck region,
eyelid as the most common site.45 Secondary eccrine the nasal tip is the most common site followed by
gland carcinomas are more common, arising from other areas of the face, scalp and neck. These lesions
pre-existing benign lesions. Overall, malignant trans- generally display a locally infiltrative behavior pat-
formation should be suspected when rapid change in tern but can occasionally metastasize to regional
size, color, or appearance manifest in a long-standing lymph nodes and distant sites. The location of the
benign lesion. Details of the most common sec- lesion has been purported to have some influence on
ondary eccrine gland carcinomas are discussed above behavior, with those occurring in the center of the
as part of the precursor benign lesions. face having a greater risk for recurrence than other
Sebaceous gland carcinomas typically arise in sites.55 This probably reflects the difficulty of exci-
older females, from the ocular adnexa, including the sion to obtain satisfactory margins in central facial
meibomian glands, Zeis’ glands, and the piloseba- lesions. One study showed that the relative risk of
ceous glands. The facial region is the most common recurrence was highest for lesions of the nose, fol-
site for extraocular involvement, with rare cases of lowed by ears, periorbital areas, remainder of the
tumor arising from upper aerodigestive tract mucosa face, neck and scalp and finally, the lowest risk at
and salivary glands. Prior irradiation may increase the the trunk and upper extremity. Size greater than
risk for the development of sebaceous carcinoma.46–48 2 cm increased the recurrence rate from 13 percent
Local invasion and regional lymphatic metastasis fol- to 46 percent in one series of 1,620 cases of basal
lowed by distant metastasis often occurs. cell carcinoma.49–51,56
Metastasis occurs in less than 1 percent of cases
Basal Cell Carcinoma and is associated with a dismal outcome.56 The
average survival after the development of a lymph
Basal cell carcinomas (BCC) account for the vast node metastasis is 3.6 years but the metastasis can
majority of non-melanoma skin cancers (75%) and present as late as 15 years after initial treatment of
well over 25 percent of all cancers diagnosed in the the primary lesion.57 Accordingly, long-term fol-
United States each year.49–51 Five clinical low-up of a patient with this histopathology is
histopathologic subtypes of basal cell carcinoma required. The rate of metastasis to cervical nodes
have been described of which nodular ulcerative is from basal cell carcinoma is reported to range from
most common, followed by pigmented, superficial, 0.0028 to 0.4 percent.58 Other sites of metastasis
morphea-like, and fibroepithelioma. 51 BCC has a include the bones and lungs. The 1-year and 5-year
predilection for fair-skinned individuals but can survival rates for metastatic basal carcinoma are
occur in Latin American and African American reported to be approximately 10 percent and 20 per-
patients.52 A causative association with chronic cent respectively.58
ultraviolet radiation exposure has been established.53 Treatment of this tumor revolves around surgical
Other factors linked with the development of BCC excision or radiation therapy.59 Surgical excision can
include immunosuppression and several genetic be accomplished using a variety of techniques
syndromes. The genetic syndromes include basal including curettage and electrodesiccation, Mohs’
cell nevus syndrome, Basex’s syndrome and surgery, and wide surgical excision. The recurrence
Rambo’s syndrome, all of which are associated with rates are purported to be lower for the Mohs’ surgery
the development of multiple basal cell carcinomas.54 approach, however this likely represents a signifi-
BCC typically occurs in older individuals in their cant selection bias in the studies reporting these
fourth to eighth decades of life, with a slight male results.60 The rate of recurrence increases with the
 Skin Cancers of the Head and Neck 79

margin status, with a recurrence rate of 1.2 percent 34 percent.70 The overall 2- and 5-year survival rates
in absence of tumor at the margin, 12 percent when drop to 33 percent and 22 percent respectively. Clin-
the tumor is within one high power field, and 33 per- ical staging of the neck is the most important prog-
cent when gross tumor is present at the margin. Sur- nostic factor once metastasis develops.49,63,64,69
gical margins of 2 to 3 mm are adequate with 85 per-
cent of cases adequately treated in this manner based Melanocytic Lesions
on results from Mohs’ surgical excision.61,62 Larger
lesions and morphea-like lesions require larger mar-
Malignant Melanoma
gins up to 1 cm.
The incidence of malignant melanoma in the United
Squamous Cell Carcinoma States increased by approximately 69 cases per year
during the 1970s and by approximately 39 cases per
After basal cell carcinoma, squamous cell carci- year during the 1980s and 1990s.70 The death rate
noma (SCC) is the next most common type of skin from melanoma, however, has not changed during
cancer accounting for 20 percent of all cutaneous that period, suggesting the impact of more aggres-
malignancies and occurring in approximately 40 sive efforts at early detection. Approximately 20 per-
people per 100,000 population annually.49,63,64 Well cent of these tumors involve the head and neck
over 90 percent of cutaneous squamous cell carcino- region and occur in patients in their fifth and sixth
mas arise in the head and neck and most commonly decades of life.71–73
involve the ears and upper face.49,64 Like basal cell Like non-melanomatous skin cancers, melan-
carcinoma, these lesions have been associated with oma is more common in fair-skinned individuals
chronic exposure to UVB radiation.53 There is a sig- but also occurs in darker-skinned populations,
nificant increase in the rate of development of squa- albeit at a lower rate. An association with chronic,
mous cell carcinomas in immunosuppressed patients intense sun exposure has been implicated in the
including patients undergoing medical immunosup- development of melanomas.71-73 Clinical syndromes
pression for organ transplantation, as well as such as xeroderma pigmentosum and basal cell
patients with lymphoma and acquired immunodefi- nevus syndrome have also been associated with a
ciency syndrome.65–68 Although an increasing pro- high rate of melanoma development.54 A family his-
portion of squamous cell carcinoma is seen with tory of melanoma is associated with a two to eight
age, age is felt to be a coexistent rather than inde- times increased risk for developing melanoma.54
pendent variable with respect to causation. Patients undergoing immunosuppression for renal
SCC can be effectively treated with either transplantation and those with hematologic malig-
surgery or radiation therapy with equal efficacy.59,63 nancies also appear to have a higher risk for
Factors associated with poor outcome include size melanoma development.
greater than 3 cm, prior treatment, immunosuppres- The treatment and prognosis of melanoma is
sion, tumor thickness, perineural invasion, and pos- most consistently associated with depth of invasion.
sibly anatomic site of the lesion—with lesions of the Patients with thin lesions less than 0.75 mm tend to
external ear, lip and temple having the worst out- have an excellent prognosis and require only local
come within the head and neck region.49,63,64,69 The excision. Patients with intermediate thickness
development of locoregional or distant metastasis melanoma ranging in size from 0.76 to 3.99 mm
has a grave implication for patients with head and have a significantly increased risk for development
neck squamous cell carcinoma and occurs in of lymphatic metastasis and therefore require not
approximately 0.3 to 13.7 percent of all cases.70 only adequate surgical resection but also considera-
These metastases can develop in a delayed fashion tion for treatment of regional metastasis.71–73
as seen for basal cell carcinomas. Once local or Patients with lesions greater than 4 mm in thickness
regional metastasis develops, the 5-year disease free have a dismal prognosis with distant metastasis
rate drops from approximately 90 percent down to being the most common source for failure.
80 CANCER OF THE HEAD AND NECK

Adjuvant therapy should be considered in patients The failure rate is reported to be as high as 75 percent
with locally advanced melanoma as well as those in cases where regional lymphatics are not electively
with regional or distant metastasis. Adjuvant radia- treated. In addition, MCC is a radiosensitive tumor.
tion therapy has been supported by studies from Har- Therefore, the use of adjuvant radiation may improve
wood and colleagues, reporting a 75 percent 4-year local and regional control. Morrison and colleagues
locoregional control rate in 89 patients with stage III recommend the addition of adjuvant radiation in cases
melanoma who were treated with 3 doses of 800 cGy with primary lesions over 1.5 cm, narrow resection
over a 3-week period.74–76 Ang and colleagues from margins (< 2 cm), or those showing evidence of lym-
M.D. Anderson reported similar control rates for phatic penetration. Dose recommendations for adju-
patients with high-risk melanoma using a treatment vant treatment are 46 to 50 Gy in 2 Gy fractions and
regimen of 600 cGy fraction × 4 over 2 weeks or × 5 56 to 60 Gy for unresectable disease.98
over 2.5 weeks postoperatively.77–79 Systemic adju- Even with radical treatment, MCC has an aggres-
vant therapy is not as well established as yet. Inter- sive course. Local recurrence occurs in 40 percent of
feron has been approved by the FDA for adjuvant cases, regional nodal involvement in 46 percent, and
treatment of high-risk patients with melanoma. How- distant metastasis in upward of 36 percent of cases.
ever, more recent randomized trials have shown dis- For head and neck primaries, disease control above
appointing results for interferon use with respect to the clavicles is associated with a lower rate of distant
overall survival.80–91 Studies looking at gene therapy, metastasis (69% in patients who fall locoregionally
immunotherapy, chemotherapy and combinations versus 17% in thoses who are free of locoregional dis-
thereof have been similarly disappointing.80–91 ease).25,92–97 Although a wide variety of locations can
be involved, distant metastasis usually occurs to the
Other Cancers liver, bone, brain, lung, or skin. Survival is reported to
be 88 percent at one year, 72 percent at 2 years, 55
Merkel Cell Carcinoma percent at 3 years, and 30 percent at 5 years.25, 92–97
Merkel cell carcinomas (MCC) are rare tumors orig-
Dermatofibrosarcoma Protuberans
inating from neuro-tactile cells in the epidermis.92
These lesions present as 0.5 to 5 cm smooth, dome- Dermatofibrosarcoma protuberans (DFSP) is a low-
shaped lesions, with telangiectasias and red to viola- to intermediate-grade sarcoma that involves the
ceous color. MCCs tend to be indolent, slow-grow- head and neck region in 14 percent of cases,
ing tumors, which often display sudden rapid accounting for 1.4 percent of all head and neck sar-
enlargement.93–97 These tumors typically occur in comas.99–102. In the head and neck region, the scalp
elderly Caucasian individuals, involving the head and supraclavicular fossae are most often
and neck region in 49 percent of cases. The distrib- involved.102,103 There is a 3:2 male to female ratio
ution of MCC leads to speculation of a relationship and a predominance in the fourth to fifth decade of
to sun exposure, but no definitive association has life. These tumors typically display a locally aggres-
been established. A study by Goepfert and col- sive course, with local recurrence rates as high as 60
leagues reported a 19 percent incidence of excessive percent.99,100,102,103 This reflects the propensity of
sun exposure in patients with head and neck MCC.93 tumor cells to invade the local tissue with tentacle-
MCC occurs in decreasing order of frequency on like projections within clinically normal-appearing
the skin of the cheek, upper neck, and nose. Treatment skin. Recurrence rates appear to be higher for head
requires excision with wide surgical margins and and neck lesions (up to 75% of cases) than those at
regional nodal dissection in patients with metastasis.93- other sites, probably due to limitations99,100,102,103 in
97
Elective nodal dissection should be considered in the extent of surgical resection. Regional and distant
tumors occurring in close proximity to draining lym- metastasis is uncommon, occurring in 1 percent and
phatics, having >10 mitotic figures per high power 4 percent of cases respectively.99, 100
field, displaying histologic evidence of lymphatic The treatment of these neoplasms is wide surgi-
involvement, or containing predominantly small cells. cal resection, with resection margins of ≥ 3 cm. The
 Skin Cancers of the Head and Neck 81

rates of recurrence are directly associated with by Fanburg-Smith and colleagues showed that 83
extent of resection. In a review of series of DFSP percent of subcutaneous MFH displayed an infiltra-
treated with conservative margins the rate of recur- tive growth pattern in contrast to only 24 percent of
rence was 44 percent in contrast to 18 percent for intramuscular cases.107,108 Higher rates of involved
series treated with greater than 2 cm margins. Many margins occurred in cases displaying infiltrative
authors, suggesting a better local control rate with growth, advocating a need for wide surgical mar-
this modality, have advocated the use of Mohs’ gins. Local recurrences occurred exclusively in
surgery in the management of DFSP. The use of cases displaying infiltrative growth. Wide resection,
adjuvant radiation has been suggested to be of ben- with margins over 2 cm, is advocated for cutaneous
efit in selected cases, but this has not been clearly MFH. Adjuvant radiation therapy should be consid-
substantiated.99,100,102,103 Factors influencing out- ered in locally advanced cases.
come are the size of the primary tumor, extent of
resection margins, mitotic index, and the presence of
SURGICAL MANAGEMENT OF
fibrosarcomatous change.
SKIN CANCER
Malignant Fibrous Histiocytoma
Anatomic Considerations
Malignant fibrous histiocytoma (MFH) is the most
common soft tissue sarcoma in adults, but involves The scalp is a unique adaptation of the epithelial
the head and neck region in only 1 to 3 percent of covering of the body. Anatomical variations present
cases.104–106 There is a 3:2 male to female predomi- in the scalp modify both tumor behavior and the
nance, and the majority of cases occur in patients 50 treatment of tumors in this area. The hair-bearing
to 70 years of age. Subcutaneous lesions form only area of the scalp consists of a thick padding of hair
a small proportion of head and neck MFH, with the follicles, sweat glands, fat fibrous tissue and lym-
majority arising from the upper aerodigestive tract phatics that are interspersed with numerous arteries
and deep tissues of the neck. Overall, MFH accounts and veins (Figure 4–1). This thick padding is sup-
for only 0.01 percent of cutaneous malignan- ported by a tough aponeurotic layer that is fused in
cies.104,106 Studies suggest that MFH in the subcutis the anterior region with the frontalis muscle, and in
has a more infiltrative growth pattern and higher the posterior region with the occipital muscle. This
rate of recurrence after surgical treatment. A study inelastic layer rests loosely on the periosteum of the

Figure 4–1. The anatomical layers of the scalp.

82 CANCER OF THE HEAD AND NECK

skull creating a potential subaponeurotic space. Lat- cles and offers facial expression. Thus, the skin of
erally, the temporalis muscle provides an additional the central part of the face is mobile, while there are
barrier between the galea and the periosteum. areas of facial skin along the lateral aspect of the
Three principal arteries provide a rich blood sup- nose, the bridge of the nose, and along the preauric-
ply to each side of the scalp. Two of these, the super- ular region and temple which are relatively immo-
ficial temporal and occipital, are branches of the bile. These unique characteristics of the facial skin
external carotid artery, while the supraorbital artery have significant surgical implications. Similar to the
is a branch of the internal carotid artery. The lym- scalp, the facial skin has a rich blood supply through
phatic network of the scalp is also unique in that the the facial and superficial temporal arteries. How-
scalp has no lymph barriers and contains many ever, unlike the scalp, the facial skin has predictable
medium-caliber channels both subdermally and sub- patterns of lymphatic drainage to preauricular and
cutaneously. The lymphatics drain toward the peri-parotid lymph nodes as well as perivascular
parotid gland, the preauricular area, the upper neck, facial lymph nodes adjacent to the body of the
and the occipital region. mandible, eventually draining into the deep jugular
In contrast to the scalp, facial skin is also unique chain of lymph nodes.
in that it has several distinguishing characteristics on The most common malignant lesions of the skin
various parts of the face with unique anatomic fea- of the face and scalp are basal cell carcinomas, squa-
tures providing different functions. For example, the mous cell carcinomas, and melanomas. Occasionally
skin around the eyelids is extremely thin with almost one may see rare lesions such as a keratoacanthoma,
no subcutaneous fat. In contrast, the skin around the Merkel cell tumor, and sweat gland carcinoma. If the
central part of the face adjacent to the nose and lips extent of the excision is such that a primary closure
is intimately attached to the underlying facial mus- through an elliptical defect is not possible, then one

Figure 4–2. The extent of surgical procedure that would be required for tumors of the scalp depends on the extent and depth of invasion of
the tumor.
 Skin Cancers of the Head and Neck 83

must consider the applicability of split-thickness or to embarking upon excision of a facial skin lesion.
full-thickness skin graft or local, regional or com- Generally, an elliptical incision is best suited for
posite microvascular free flaps. small lesions. Configuration of the facial skin lines
and potential directions for elliptical incisions are
Principles of Treatment shown in Figure 18–4. Remember that the facial
skin lines are at right angles to the muscle fibers of
The extent of surgical resection for scalp tumors the underlying muscles of facial expression (Figure
depends largely upon the depth of infiltration by the 4–3). By asking the patient to grimace, the line of
tumor. Excision through partial thickness of the direction of the long axis for elliptical incision is
scalp can be carried out for superficial tumors while established. These lines are horizontal on the fore-
excision through the entire thickness of the scalp head and around the bridge of the nose and the outer
including the periosteum may be necessary in canthus of the eye. Near the cheek the tension lines
deeply infiltrating tumors. On the other hand, run obliquely or perpendicularly; near the lips they
tumors that are adherent to or involve the underlying run radially from the mouth opening, and on the
cranium must have removal of the outer table of chin they run horizontally on the midline and
skull or a through-and-through resection up to and obliquely perpendicular at the sides. On the sides of
including the dura if necessary. The extent of the the neck, the wrinkles and tension lines run
surgical procedure that would be required for tumors obliquely downward and forward. Horizontal ellipti-
of the scalp depends on the extent and depth of inva- cal excision of a small growth of the lower eyelid or
sion by the tumor as shown in Figure 4–2. the upper eyelid is perfectly suitable, but larger exci-
Small lesions of the skin of the face are excised sions of the lower eyelid performed in this manner
in the direction of the cleavage planes which are at result in ectropion. Meticulous attention should be
right angles to the pull of the facial muscles. A brief paid to approximation of subcutaneous tissues using
review of the skin lines of the face is important prior absorbable interrupted sutures, and the skin should

Figure 4–3. Facial skin lines are at right angles to the muscle fibers of the underlying muscles of facial expression.
84 CANCER OF THE HEAD AND NECK

be closed with fine sutures, which can be removed lymph nodes for intermediate thickness malignant
as early as 4 days postoperatively. Alternatively one melanomas of cutaneous origin.
may elect to use a subcuticular suture, particularly in
the area of the eyelids where the skin is very thin. Selection of Treatment
Application of split- or full-thickness skin graft
is best suited to that part of the face with minimal Surgery and radiotherapy remain the mainstay of
facial motion such as the lateral aspect of the bridge treatment for cutaneous malignancies of the scalp
of the nose or the temple. Similarly, a skin graft can and facial skin. Radiotherapy is particularly of ben-
be used in the parotid region because the facial efit in patients with basal cell carcinomas of the eye-
movement in this area is minimal and cosmetic dis- lids where surgical resection is likely to result in sig-
figurement is minimal. The most suitable donor sites nificant morbidity. Extensive basal cell carcinomas
for obtaining full-thickness skin grafts are from the may be treated by radiotherapy under select circum-
retroauricular or supraclavicular regions. stances with a palliative intent.
Flaps from the immediate neighborhood of the Mohs’ micrographic surgery is an ideal method to
defect are most desirable from both the functional secure histologic clearance of all subdermal and intra-
and esthetic points of view. Primary closure of the dermal extensions of cutaneous cancers. It is of par-
donor site defect can usually be accomplished with ticular value in patients with the morphea form of
ease by proper planning of local skin flaps. When basal cell carcinomas, recurrent basal cell carcinomas
repair of a surgical defect demands more adequate adjacent to vital areas of the face, and extensive recur-
full-thickness reconstruction, local flaps are best rent skin cancers in previously irradiated fields where
suited for this purpose. The blood supply of facial the clinical assessment of the extent of disease is sub-
skin and soft tissues is extremely rich, as the termi- optimal. On the other hand, this technique is not cost-
nal branches of the external carotid artery provide a effective for most patients with small skin cancers,
major source of blood to the facial skin. In addition which can be adequately excised surgically with pri-
to this, there is an extensive subdermal anastomotic mary repair of the surgical defect.
network, which facilitates the use of several random
flaps with relative ease. Some flaps carry an identi- Selected Cases
fiable axial blood supply while others are more ran-
dom. Examples of axial skin flaps are: nasolabial, Case 1. Excision of Scalp Tumor and
glabellar, Mustarde cheek, and temporal forehead; Split-thickness Skin Graft
examples of random flaps are: cervical, rhomboid,
and bilobed. If local flaps are not suitable, then con- The patient shown in Figure 4–4A has a nodular-
sideration should be given to regional or distant pigmented basal cell carcinoma of the scalp measur-
microvascular free flaps for appropriate repair of ing approximately 2.5 × 4.5 cm. This skin tumor is
large surgical defects in the facial region. freely mobile over the underlying periosteum, so the
Metastatic dissemination to regional lymph galea aponeurotica will form the deep margin of the
nodes from primary cutaneous malignancies of the surgical specimen for this tumor.
scalp and face is infrequent. In general, squamous Although most of the lesion is nodular and pro-
carcinomas less than 2 cm in diameter have an tuberant in nature, there is an additional intracuta-
exceedingly low risk of metastatic potential and neous component, which could only be seen after
therefore elective treatment of regional lymph nodes the scalp was shaved. Generally, a margin of at least
is not recommended. Lesions larger than 2 cm have 1 cm around the lesion is desirable. A fairly thick
a proportionately higher risk of regional lymphatic split-thickness skin graft (1/18,000”) is desirable to
dissemination. In general, however, elective resec- avoid ulceration and trauma to the scalp. Thin split-
tion of regional lymphatics does not offer significant thickness skin grafts give a very tight and shiny
therapeutic advantage. Slight improvement in prog- appearance and are prone to ulceration even with
nosis is observed with elective dissection of regional trivial trauma.
 Skin Cancers of the Head and Neck 85

The deep surface of the surgical specimen

showed galea aponeurotica which was grossly unin-
volved by tumor. When the bolster dressing is
removed, trimming of crust and clots at the edges of
the surgical defect is necessary to keep it clean until
full maturation of the grafted area takes place. The
patient should be instructed in avoiding direct
trauma or injury to this area.
A
The postoperative appearance of the patient
approximately 6 months following surgery shows a
100 percent take of the skin graft (Figure 4–4B). The
split-thickness skin graft can be used effectively to
provide immediate coverage for defects in the scalp
when the periosteum can be preserved.

Case 2. Excision of Scalp Tumor with

Advancement Rotation Flap

Surgical excision of tumors in the non-hair-bearing

areas of the scalp requires coverage of the surgical
defect with tissues that resemble the normal tissues
in the area for a satisfactory esthetic appearance. B
Although split-thickness skin graft can be used to Figure 4–4. A, A pigmented basal cell carcinoma of the scalp. B,
cover such surgical defects, its esthetic appearance The defect of surgical excision was reconstructed with a split-thick-
is unacceptable. Advancement rotation scalp flaps ness skin graft and resulted in an acceptable appearance 6 months
postoperatively.
provide a very satisfactory method of closure of
such surgical defects. The defect is covered with the
adjacent scalp while the donor site deformity is vated because of its inelasticity and consequent inabil-
transferred posteriorly in the hair-bearing area of the ity to provide sufficient mobilization and coverage.
scalp which may be either closed primarily or, on The blood supply of this scalp flap is through both the
occasion, covered with a split-thickness skin graft. superficial temporal as well as the occipital artery. The
Alternatively, large defects of the non-hair-bearing flap is advanced anteriorly and rotated inferiorly to
area of the scalp or forehead can be repaired with a cover the surgical defect. Meticulous attention should
radial forearm microvascular free flap. be paid in the outline of the flap by appropriate mea-
When surgical excision of a scalp tumor requires suring of the surgical defect and the rotated scalp flap,
excision of the underlying periosteum, then bare keeping the pivot point in mind. A measurement can
bones of the calvaria are exposed. Scalp flaps or be taken using 4 × 8 inch gauze, holding one end at the
microvascular free flaps are the ideal method of cov- pivot near the external ear and the other extended to
erage of such surgical defects. the apex of the surgical defect inferomedially. Using
The patient shown in Figure 4–5A had a recurrent that length as a radius, the scalp flap is outlined all the
basal cell carcinoma involving the midline frontal area way up to the parieto-occipital region. Thus, if proper
of the scalp. A local excision was performed for measurements are taken, the flap will satisfactorily
biopsy purposes elsewhere prior to presentation. The rotate and cover the surgical defect.
intended extent of surgical excision and the outline of The flap is reflected laterally showing its proximal
the rotation advancement flap are shown in Figure mobilization up to the vascular pedicle near the pinna.
4–5A. Even though the anticipated surgical defect is The flap is now rotated both anteriorly and inferiorly
relatively small, a large area of the scalp has to be ele- to cover the surgical defect (Figure 4–5B and C). The
86 CANCER OF THE HEAD AND NECK

anterior end of the scalp flap should be adequate to Case 3. Excision and Full-thickness
match the lower border of the surgical defect. Skin Graft on the Nose
The postoperative appearance of the patient
approximately 7 months following surgery is shown This patient presented with Hutchinson’s melanotic
in Figure 4–5D. There is excellent coverage of the freckle (lentigo maligna) on the dorsum of the nose.
surgical defect near the hairline without any signifi- The desired extent of excision is marked out with a
cant functional or esthetic deformity. skin marking pen and its dimensions are measured.
Advancement rotation scalp flaps are very satis- The ideal donor site is the skin of the supraclavicu-
factory for most defects of the anterior scalp. How- lar region for a defect of this size.
ever, if these defects are of significant size, then pri- The postoperative appearance of the skin graft in
mary closure of the donor site is not possible and a this patient immediately after surgery is shown in
split-thickness skin graft would be necessary in the Figure 4–6A and 6 months postoperatively in Figure
occipital region. 4–6B. Since sensations on this skin are absent, the

C D
Figure 4–5. A, Incisions outlined for excision of a recurrent basal cell carcinoma of the frontal scalp. B and C, A scalp flap is elevated rotated
and advanced into the surgical defect. D, Postoperative appearance of the patient 7 months following surgery.
 Skin Cancers of the Head and Neck 87

Figure 4–6. A, Immediate postoperative appearance of a full-thick-

ness skin graft on the dorsum of the nose. B, The same patient 6
months later.

patient must avoid trauma to prevent ulceration and

infection. The esthetic result with a full-thickness B
skin graft is excellent on the lateral aspect of the
nose with no specific donor site deformity.

Case 4. Glabellar Flap

This flap is best suited for reconstruction of surgical

defects at either the bridge or the upper half of the
nose. It is an axial flap, which derives its blood sup-
ply mainly from the supratrochlear artery and also
from the dorsal nasal branches. The flap can also be
used for complex defects of the nasal dorsum with a
split-thickness skin graft on its undersurface.
The patient shown here has a basal cell carcinoma
involving the skin of the bridge of the nose (Figure
4–7A). The skin is freely mobile over the underlying C
periosteum. The lesion is excised and flap rotated
Figure 4–7. A, The lesion is a basal cell carcinoma of the skin of
into place for reconstruction (Figure 4–7B). The skin the nose. B, The defect of surgical excision and outline of the glabel-
flap has set well in place with well balanced eye- lar flap. C, The flap is inset and the donor defect is closed primarily.
88 CANCER OF THE HEAD AND NECK

brows on both sides and satisfactory coverage of the nal branches of the facial artery. The width to length
skin and soft-tissue defect at the bridge of the nose. ratio can be as much as 1:5 in select circumstances.
Closure of the donor site leaves an esthetically The nasolabial flap is a highly reliable and very ver-
acceptable midline vertical scar (Figure 4–7C). satile flap. It is generally employed in reconstruction
A modification of this procedure is an island of surgical defects resulting from excision of skin
glabellar flap where the flap is tunneled under an cancers on the side of the nose or the ala of the nose,
intact bridge of skin at the glabella, keeping its as well as for full-thickness reconstruction of
blood supply intact on the vascular pedicle contain- excised nasal ala, philtrum and columella.
ing the supratrochlear artery and vein. However, ele-
vation of an island flap in this fashion is risky and Case 5a. Inferiorly Based Nasolabial Flap
has very limited application.
Since the vascular supply of the nasolabial flap is
Case 5. Nasolabial Flap through the nasolabial artery, it would appear logical
to have the flap based inferiorly. This flap is ideally
The nasolabial flap is an axial flap deriving its blood suited for small defects of the lateral aspect of the
supply from the nasolabial artery, one of the termi- nose in its lower half (Figure 4–8). The elevated dis-

A B

C D

Figure 4–8. A, This superficial lesion of the lateral nose was a basal cell carcinoma. B, The extent of surgical excision and in inferiorly based
nasolabial flap have been marked out. C, Immediate postoperative appearance of the flap set into the surgical defect. The donor defect is
closed primarily. D, Postoperative appearance of the patient 6 months later.
 Skin Cancers of the Head and Neck 89

tal part of the flap is rotated downward and anteri-

orly to fill the surgical defect. However, the length
of a flap used in this way is limited since the skin at
the root of the nose near the medial canthus is rather
tight and little flexibility is available for closure of
the donor site defect.
Edema of the flap and slight duskiness is not
unusual on the first postoperative day. Although the
flap may look dusky or bluish, its vascularity is guar-
anteed; the discoloration is usually due to venous con-
gestion, but the arterial blood supply of the flap is usu-
ally intact. Satisfactory healing of the skin is achieved
in approximately 5 to 7 days. Excessive fat retained on A
the flap will result in a so-called fat flap, which may
require defattening under local anesthesia; but this
procedure is not recommended for at least 6 months to
a year. If sufficient care is taken to match the thickness
of the flap to the thickness of the surgical defect with
appropriate excision of excess fat from the flap at the
time of the closure, one can avoid a fat flap complica-
tion. Postoperative appearance of the patient several
months later shows an excellent cosmetic result with
essentially very little facial deformity at either the
donor site or along the nasolabial skin crease.
B

Case 5b. Superiorly based Nasolabial Flap

Reconstruction for a Complex Defect
of the Alar Region

A patient with a recurrent basal cell carcinoma involv-

ing the skin of the ala and through the alar cartilage
and nasal mucosa into the nasal vestibule is shown in
Figure 4–9A. The lesion had previously been treated
by electrodesiccation and curettage on two occasions.
The plan of surgical excision requires a through-
and-through resection of the ala of the nose includ-
ing the underlying mucosa, and a superiorly based
nasolabial flap is planned for reconstruction of the
surgical defect, providing external and inner lining
(see Figure 4–9A).
The excision is completed showing a through- C
and-through defect. The superiorly based nasolabial Figure 4–9. A, The patient has a basal cell carcinoma of the skin
flap is elevated (Figure 4–9B). The flap is elevated of the nasal ala adherent to the underlying cartilage and mucosa.
The extent of surgical excision is outlined along with a superiorly
lateral to the nasolabial crease with a generous based nasolabial flap. B, A composite resection including the skin,
amount of fat on the undersurface. The tip of the flap cartilage and mucosa resulted in a full-thickness alar defect. C, The
superiorly based nasolabial flap is elevated and set into the defect.
is turned in to provide inner lining and the donor Its tip is turned on to itself to provide inner lining and the donor defect
defect can be easily approximated primarily. is closed primarily.
90 CANCER OF THE HEAD AND NECK

The nasolabial flap used in this way is ideal for

repair of a complex defect of the alar region of the
nose. The flap is folded over itself to replace the free
edge of the ala (Figure 4–9C) and is esthetically
quite acceptable. Cartilage support is usually not
necessary unless the alar defect extends from the tip
of the nose to the region of the nasolabial crease.

Case 6. Rhomboid Flap

This versatile geometric flap was described by Lim-

berg, a mathematician. It can be used in many areas A
of the body and provides a satisfactory closure of
surgical defects, particularly in patients with lax skin.
The patient shown in Figure 4–10A was referred
having undergone excisional biopsy of a malignant
melanoma of the cheek. The scar of previous surgery
was widely encompassed in the surgical incisions
which were planned to provide access for superficial
parotidectomy at the same operation. The rhomboid
flap outline should be made in such a way that the
donor site closure line will match facial skin lines. A
surgical defect of any shape can be converted to a
rhomboid, thus allowing design and elevation of this
flap. Surgical excision of the recurrent cancer is car-
ried out to include the subcutaneous tissue but
B
remains superficial to the muscular layer. In this par-
ticular patient, terminal branches of the facial nerve
remain at risk because of their proximity to the deep
margin of the surgical specimen. These branches
must be preserved by meticulous dissection, unless
tumor invasion is demonstrated. A superficial
parotidectomy was completed in this patient and the
inferiorly based rhomboid flap (Figure 4–10B) was
used to reconstruct the defect with an acceptable
esthetic result approximately 6 months after surgery
(Figure 4–10C).
The rhomboid is a random flap and therefore has
limited application for coverage of larger-size
defects. It is a highly reliable flap, and when prop-
erly planned as to placing the incisions for flap ele- C
vation, the eventual esthetic result is excellent. Figure 4–10. A, The patient had undergone excisional biopsy of a
malignant melanoma of the cheek elsewhere. The scar of previous
excision was widely encompassed in the surgical incisions which
Case 7. Bilobed Flap were planned to provide access for a superficial parotidectomy. B, An
inferiorly based cervical Limberg flap has been elevated and the sur-
gical bed of resection shows the branches of the facial nerve pre-
The bilobed flap is a random flap but is excellent for served. C, Postoperative appearance of the patient approximately 6
coverage of various surgical defects throughout the months following surgery.
 Skin Cancers of the Head and Neck 91

body. The principle of “borrowing from Peter to pay The surgical excision is completed and Figure
Paul” is exemplified in the design and elevation of 4–11B shows the defect, exposing the branches of
this flap. the facial nerve in the upper part of the surgical
The bilobed flap can be used very effectively on field. The bilobed flap is elevated, superficial to the
defects of the anterior cheek. Surgical defects of the facial musculature but keeping all the subcutaneous
skin and soft tissues of the cheek overlying the fat on the flap. The flap is rotated into the defect and
zygoma and the buccinator muscle are very well final skin closure is shown in Figure 4–11C.
suited for reconstruction using a bilobed flap. The The postoperative appearance of the patient
patient shown here has a recurrent malignant approximately 2 months following surgery shows sat-
melanoma involving the skin and subcutaneous tis- isfactory closure of the surgical defect with an accept-
sues of the left zygomatic region. The area of skin at able esthetic result (Figure 4–11D). Bilobed flaps used
risk around the tumor which measures approximately in this fashion provide a very readily available tool
5 cm in diameter is outlined, and the inferiorly based for the closure of sizable skin defects of the cheek.
bilobed flap has been planned (Figure 4–11A). The flap works best in patients who have excess or

A B

C D
Figure 4–11. A, The lesion is a malignant melanoma in the left zygomatic region. A generous area of excision is outlined around the tumor
and the inferiorly based bilobed flap is planned. B, The primary lesion has been excised in continuity with the superficial parotid lobe and the
contents of the upper neck. The branches of the facial nerve have been carefully preserved and are clearly demonstrated in the surgical bed.
The bilobed flap has been elevated and retracted laterally. C, The bilobed flap is rotated into the surgical defect and sutured into place. D,
Approximately 2 months later the flap has healed well and has produced an acceptable cosmetic result.
92 CANCER OF THE HEAD AND NECK

lax skin providing easy rotation of the flap and clo- A patient with a Hutchinson’s melanotic freckle
sure of the donor site deformity, leaving a transverse (lentigo maligna or in situ melanoma) presenting on
scar along the upper skin crease in the neck. the skin of the cheek in the right infraorbital region is
shown in Figure 4–12A. The superior margin of the
Case 8. Mustardé Advancement surgical defect and the Mustardé flap are kept as
Rotation Cheek Flap close to the tarsal margin as possible, depending on
the location of the lesion and the surgical defect. In
Skin defects resulting from surgical excision of this particular patient, the medial border of the defect
lesions involving the skin in the infraorbital region was aligned to the nasolabial skin crease. The extent
and medial part of the cheek are best suited for of surgical resection depends on the surface dimen-
repair using a Mustardé flap. The major blood sup- sion, depth, and histology of the primary tumor.
ply of this skin flap is from the posterior branches of Excision of the tumor is completed, preserving the
the facial artery with the wide pedicle of the flap orbicularis oculi and its nerve supply but carefully
remaining inferiorly. excising a generous margin of underlying fat (Figure

A B

C D

Figure 4–12. A, The area of excision around a superficial pigmented lesion in the right infraorbital region is marked out. B, The defect of sur-
gical excision. C, A Mustarde-type advancement flap has been elevated to reconstruct the defect. D, Postoperative appearance of the patient
3 months later.
 Skin Cancers of the Head and Neck 93

4–12B). Skin incision is completed for elevation of excised skin and soft tissues. The color match is also
the Mustardé flap (Figure 4–12C) and the flap is excellent for coverage of facial surgical defects. The
rotated anteromedially to cover the surgical defect. disadvantages are that the size of the flap is limited
The postoperative appearance of the patient approx- and occasionally it may be hair-bearing. It is impor-
imately 3 months later shows an acceptable esthetic tant to ensure smooth rotation of the pedicle since a
result achieved by this technique (Figure 4–12D). kink in the vascular pedicle of the flap can result in
a disaster with complete loss of flap.
Case 9. Cervical Flap A patient with a recurrent basal cell carcinoma
who had previous curettage and desiccation as well
Skin defects resulting from excision of lesions of the as surgical excision of this lesion performed else-
skin of the chin or the lower part of the face present where is shown in Figure 4–14A. The lesion is
a problem best handled by reconstruction using a indurated and adherent to the underlying zygoma.
cervical flap. The transverse-oriented cervical flap is The plan of surgical excision and repair showing
a random flap, so the length to which it can be ele- the incision at the site of the primary tumor is shown
vated with ease without compromise of blood supply in Figure 4–14A. The surgical defect shows a
is limited. Generally, a width to length ratio of 1:3 is through-and-through three-dimensional excision of
the maximum that a random flap can tolerate.
A patient with a recurrent nodular basal cell carci-
noma involving the skin, soft tissues and the underly-
ing musculature of the chin is shown in Figure 4–13A.
A cervical flap is marked out inferior to the proposed
surgical defect (Figure 4–13B). Surgical excision in
this patient will be carried down to the bone because
of the depth of the tumor infiltration, so the cervical
flap requires inclusion of the underlying subcutaneous
tissue and platysma to provide soft tissue in addition
to skin. The resultant donor defect can be easily
closed primarily if the orientation of the flap takes
advantage of the laxity of the tissues of the neck. A
A satisfactory esthetic result can be accom-
plished in a one-stage procedure for a sizeable
defect of the skin of the chin. Minor revision and de-
fatting of the flap can be undertaken at a later stage
to enhance the esthetic appearance of the patient.

Case 10. Island Pedicle Flap

Island pedicle flaps with their vascular pedicles can

be isolated in various locations in the head and neck
area. One of the most versatile and easily available
island pedicle flaps is based on the anterior branch
of the superficial temporal artery and vein which
provides blood supply to the forehead. This flap is
elevated from the lateral aspect of the forehead. B
Its advantages include fairly regular and identifi-
Figure 4–13. A, The patient has a basal cell carcinoma on the left
able artery and vein, a long vascular pedicle, and chin. B, An area of excision has been outlined around the tumor
thick forehead skin to provide for replacement of along with the proposed cervical flap for reconstruction of the defect.
94 CANCER OF THE HEAD AND NECK

the recurrent basal cell carcinoma (Figure 4–14B). temporal artery and vein (see Figure 4–14Band C).
All margins of resection are checked at this point to The flap is elevated, rotated and sutured into place
ensure adequacy of excision. and the donor defect is covered with a split-thick-
The island pedicle flap is now isolated with a cir- ness skin graft.
cular disk of skin from the forehead on the vascular The postoperative appearance of the patient
pedicle from the anterior branch of the superficial approximately 2 months after surgery is shown in

A B

C D

Figure 4–14. A, The surgical excision is outlined around the scar of previous surgery and a corresponding island of skin is marked on the
lateral forehead based on the anterior branch of the superficial temporal artery. B and C, After excision of the primary lesion, the flap is ele-
vated on its vascular pedicle, rotated cauded to fill the surgical defect, and the donor site is skin grafted. D, The postoperative appearance of
the patient 2 months after surgery.
 Skin Cancers of the Head and Neck 95

Figure 4–14D. Although excellent coverage of the

surgical defect is obtained, the esthetic result is not as
pleasing as one would like to see, due largely to loss
of underlying zygoma and masseter muscle, causing
lack of soft-tissue support. This in turn causes lack of
fullness and a sunken appearance of the cheek.
Island pedicle flaps are excellent for coverage of
certain surgical defects resulting from loss of skin and
soft tissues in the region of the nose or the side of the
cheek. However, extreme caution and skill must be
exercised in anticipation of the size of both the surgi-
cal defect and the elevated skin flap. Meticulous atten-
A
tion should be paid to extremely careful and skillful
dissection and gentle handling of the vascular pedicle,
as injury to the vascular pedicle would mean loss of
the flap. Those branches of the vessels that are not nec-
essary for the vascularity of the flap are sacrificed, but
short stumps of these vessels must be left attached to
the main vascular pedicle so that the lumen of the
feeding artery and draining vein is not compromised.
Similarly, extreme care must be exercised during
transport of the flap and its rotation to avoid any kink-
ing or torsion. The island flap generally manifests
venous congestion in the first 48 hours, but as long as
capillary filling is present the flap will survive.

Case 11. Excision and Repair of a Large Defect

of Facial Skin with Myocutaneous Free Flap

Larger defects of the facial skin are best repaired B

using a free tissue transfer where unlimited quanti-
ties of skin and soft tissue are available to repair the
surgical defect. The disadvantage of free tissue
transfer is that the color match often is not satisfac-
tory and occasionally the tissue may be too bulky.
The patient shown in Figure 4–15A has a locally
advanced, fungating squamous cell carcinoma of the
preauricular region requiring wide excision, superfi-
cial parotidectomy and a neck dissection. A gener-
ous portion of the skin in the preauricular region was
excised to encompass a three-dimensional resection
in continuity with an ipsilateral comprehensive neck
dissection (Figure 4–15B). The surgical defect thus C
created was repaired with a myocutaneous rectus
Figure 4–15. A, Locally advanced squamous cell carcinoma of the
abdominis flap. Postoperative appearance of the right preauricular skin showing extent of surgical excision outlined. B,
patient shows a satisfactory reconstruction of this The surgical specimen shows the extent of excision of the primary
tumor en bloc with the contents of the right neck. C, The defect was
large surgical defect, although the color match is not reconstructed using a myocutaneous rectus abdominis flap—seen
ideal (Figure 4–15C). here 1 month after surgery.
96 CANCER OF THE HEAD AND NECK

Case 12. Wedge Excision of the External Ear satisfactorily. Surgical defects resulting from exci-
sion of one-third of the vertical height of the pinna
Malignant tumors of the skin of the external ear are suitable for primary closure by approximating
often invade the underlying cartilage or perforate the edges of the surgical defect. The height of the
through to present on both sides of the external ear. pinna is reduced, but the esthetic result is acceptable.
These lesions require a through-and-through exci- The preoperative appearance of the anterior sur-
sion of a portion of the pinna to remove the tumor
face of the pinna of a patient with a recurrent basal
cell carcinoma involving the underlying cartilage
mainly presenting on the posterior aspect is shown
in Figure 4–16A. The lesion involves the helix and
the underlying cartilage.
A plan of surgical excision is outlined by an inci-
sion drawn to resect a wedge of the ear with the apex
of the wedge in the retroauricular skin crease (see
Figure 4–16A). A similar incision is marked out on
the anterior aspect of the pinna so that the apex of the
surgical defect meets at approximately the same
A point both anteriorly and posteriorly. Excision is
made with a scalpel in a through-and-through fash-
ion along the pre-drawn skin incision. A wedge of the
pinna is excised, including the skin of the anterior
aspect, the cartilage beneath as well as the skin of the
posterior aspect until the two skin incisions meet at
the apex of the wedge. An extra margin of the carti-
lage is removed to facilitate skin closure. The skin
edges usually retract over the cartilage immediately
following excision of the tumor (Figure 4–16B).
Wedge excision of the pinna is a very acceptable
and satisfactory operative procedure for lesions
B requiring through-and-through excision of any parts
of the external ear. Primary closure is possible for
defects not exceeding one-third of the vertical height
of the pinna (Figure 4–16C). Larger defects are not
suitable for primary closure.

CONCLUSION

Cancers of the skin are the most common human

malignancies. Skin cancers include a myriad of
tumors, which vary widely in their clinical behavior.
The epidemiology, evaluation and treatment of many
C of the skin cancers is changing, as highlighted in
malignant melanoma, where increasing incidence,
Figure 4–16. A, The patient has a recurrent basal cell carcinoma
of the pinna involving the underlying cartilage and presenting mainly application of screening techniques, use of molecu-
on the posterior aspect. A wedge-shaped area of excision has been lar markers and advent of novel treatments are
marked out. B, The full-thickness surgical defect showing retraction
of the skin edges over the cartilage. C, The surgical defect is closed
changing the clinical course of the disease. An
primarily in layers. understanding of the biology of each pathologic sub-
 Skin Cancers of the Head and Neck 97

type is required to plan and deliver successful treat- double-blind controlled study. Br J Dermatol 1987;
116(4):549–52.
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16. Kurwa HA, Yong-Gee SA, Seed PT, et al. A randomized
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17. Kurwa HA, Barlow RJ. The role of photodynamic therapy in
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19. Chun K, Vazquez M, Sanchez JL. Nevus sebaceus: clinical
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Clin Oncol 1995;13(11):2776–83. Surg Oncol 2000;7(9):696–704.
86. Kerin MJ, Gillen P, Monson JR, et al. Results of a prospec- 103. Barnes L, Coleman JA Jr, Johnson JT. Dermatofibrosarcoma
tive randomized trial using DTIC and interferon as adju- protuberans of the head and neck. Arch Otolaryngol
vant therapy for stage I malignant melanoma. Eur J Surg 1984;110(6):398–404.
Oncol 1995;21(5):548–50. 104. Singh B, Shaha A, Har-El G. Malignant fibrous histiocytoma
87. Guida M, Abbate I, Casamassima A, et al. Long-term subcu- of the head and neck. J Craniomaxillofac Surg 1993;
taneous recombinant interleukin-2 as maintenance ther- 21(6):262–5.
apy: biological effects and clinical implications. Cancer 105. Singh B, Santos V, Guffin TN Jr, et al. Giant cell variant of
Biother 1995;10(3):195–203. malignant fibrous histiocytoma of the head and neck. J
88. Wallack MK, Sivanandham M, Balch CM, et al. A phase III Laryngol Otol 1991;105(12):1079–81.
randomized, double-blind multi-institutional trial of vac- 106. Camacho FM, Moreno JC, Murga M, et al. Malignant fibrous
cinia melanoma oncolysate-active specific immunother- histiocytoma of the scalp. Multidisciplinary treatment. J
apy for patients with stage II melanoma. Cancer Eur Acad Dermatol Venereol 1999;13(3):175–82.
1995;75(1):34–42. 107. Fanburg-Smith JC, Miettinen M. Angiomatoid “malignant”
89. Meisenberg BR, Ross M, Vredenburgh JJ, et al. Randomized fibrous histiocytoma: a clinicopathologic study of 158
trial of high-dose chemotherapy with autologous bone cases and further exploration of the myoid phenotype.
marrow support as adjuvant therapy for high-risk, multi- Hum Pathol 1999;30(11):1336–43.
node-positive malignant melanoma. J Natl Cancer Inst 108. Fanburg-Smith JC, Spiro IJ, Katapuram SV, et al. Infiltrative
1993;85(13):1080–5. subcutaneous malignant fibrous histiocytoma: a compar-
90. Lejeune FJ. Phase III adjuvant studies in operable malignant ative study with deep malignant fibrous histiocytoma and
melanoma [review]. Anticancer Res 1987;7(4B):701–5. an observation of biologic behavior. Ann Diagn Pathol
1999;3(1):1–10.
 5
Oral Cavity Cancer
JAY O. BOYLE, MD
ELLIOT W. STRONG, MD, FACS

Oral cavity cancer is the sixth leading cause of cancer Chronic carcinogen exposure causes mucosal
worldwide. In the United States alone, there are over cells to acquire genetic abnormalities. When these
21,500 oral carcinomas diagnosed each year, and genetics abnormalities result in the activation of
6,000 Americans die of oral cancer each year.1 The proto-oncogenes and the inactivation of tumor-sup-
incidence of oral carcinoma varies throughout the pressive genes, the cells may be afforded a growth
world, with estimates exceeding 40 in 100,000 in advantage. Dysregulated proliferation due to aber-
parts of France, Southeast Asia, Hungary and Singa- rant cell cycle control leads to clonal populations of
pore.2 Thus oral cancer is a major cause of morbidity premalignant, genetically abnormal mucosal cells.
worldwide. Ninety percent of oral malignancies are These populations of cells have a high tendency to
squamous cell carcinomas and therefore are the prin- accumulate additional genetic abnormalities due to
cipal topic of this chapter. However, the treatment of genomic instability. Genomic instability is the result
some other oral malignancies, like sarcoma and of rapid cell cycling with decreased genomic sur-
minor salivary gland carcinoma, is also primarily sur- veillance, decreased capacity to repair genetic
gical excision, and the surgical principles are applica- defects and ineffective signalling of apoptosis or
ble to the treatment of these other tumors as well. programmed cell death. In these cell populations the
The etiology of oral cancer is exposure to car- rate of accumulation of acquired genetic abnormali-
cinogens in tobacco and the tumor-promoting effects ties increases logarithmically with time.8
of alcohol. Ninety percent of the risk of oral cancer Eventually these abnormal cells acquire the
in the United States is directly attributable to smok- malignant phenotype in which they lose normal dif-
ing.3 Tobacco smoke and alcohol are synergistic in ferentiation, invade the basement membrane,
their carcinogenic effects in the oral cavity. The rel- become locally destructive, and metastasize region-
ative risk of oral cancer for heavy smokers is 7 times ally or distantly. These cells evade immune surveil-
that of nonsmokers. The risk for heavy drinkers is 6 lance of the body, produce angiogenic factors allow-
times that of nondrinkers. The risk for patients abus- ing ingrowth of blood vessels, and become clinical
ing both alcohol and tobacco is 38 times that of carcinomas.
those who abstain from both.4 Chewing tobacco and
betel quid also increase the risk of oral cancer.5 ANATOMY
Chronic carcinogen exposure creates a field effect
and the entire mucosa of the upper aerodigestive The critical functions normally accomplished by oral
tract is at risk for malignancy in smokers and tissues include articulation of speech, facial expres-
drinkers.6 After successful treatment of oral cancer, sion and cosmesis, respiration, mastication, degluti-
the risk of a second primary cancer is 3.7 percent per tion, and taste. Ablative surgery for oral cancer
year and increases to 24 percent at ten years.7 Ces- removes the malignant tumor en bloc with a margin
sation of alcohol and tobacco exposure reduces the of normal tissue, and the integrity of functionally
risk of second aerodigestive carcinoma. important structures is not violated unnecessarily.

100
 Oral Cavity Cancer 101

The oral cavity is bounded anteriorly by the skin upper lip possesses two peaks forming a “cupid’s
and the vermilion border of the upper and lower lips. bow” where the filtrum ascends to the columella of
The oral cavity extends posteriorly to the circumval- the nasal septum.
late papillae of the tongue, the junction of the hard The orbicularis oris muscle receives motor inner-
and soft palates, and the anterior faucial arch. The vation from the marginal and buccal branches of the
tonsil, soft palate and posterior one-third of the facial nerve and performs a sphincteral function to
tongue are oropharyngeal structures and are not con- maintain oral competence and to facilitate articula-
sidered in our discussion of the oral cavity. Laterally tion of speech. This muscle has many attachments
the oral cavity is bounded by the buccal mucosa. from other muscles of facial expression that elevate
The oral cavity is divided into the following sub- and depress the lips. Of clinical importance is the
sites: the lip, anterior two-thirds of the tongue, floor innervation of the depressor anguli oris muscle by
of mouth, gingiva, retromolar trigone, buccal the marginal mandibular branch of the facial nerve.
mucosa, and hard palate (Figure 5–1). Figure 5–2 Sensation of the lower lip is provided by the men-
demonstrates the distribution of oral tumors by sub- tal nerve, the terminal segment of the alveolar branch
site. Tumors of different subsites demonstrate dis- of the mandibular division of the trigeminal nerve.
tinct clinical behavior. The nerve exits the mental foramen of the mandible
The lip is a common site of skin cancer. The lay- near the root of the canine tooth. Paresthesia of the
ers of the lip, from external to internal, include the chin suggests extensive mandible invasion and infe-
epidermis, dermis, subcutaneous tissue, the orbicu- rior alveolar nerve involvement by oral carcinoma.
laris oris and attached musculature, the oral submu- The anterior two-thirds of the tongue is called the
cosa and the oral mucosa. The oral submucosa con- oral or mobile tongue and is bounded posteriorly by
tains minor salivary glands, copious lymphatic the V-shaped line of the circumvallate papillae. Pos-
vessels, blood vessels and sensory nerves. The lip is terior to this line is the base of tongue, which is part
supplied by the labial arteries and veins, which are of the oropharynx. The oral tongue has ventral and
branches of the facial vessels. The generous lym- dorsal surfaces. The mucosa of the tongue is simple
phatics of the lower lip cross and drain bilaterally to stratified squamous epithelium with interspersed
level I nodes of the submental and submandibular papillae or taste buds of four morphologies: fili-
triangles. Pre- or post-facial nodes lie anterior and form, foliate, fungiform, and circumvallate.
posterior to the facial vessels in the superior aspect The tongue is comprised of intrinsic and extrinsic
of the submandibular triangle and are potential sites muscles. The intrinsic muscles are arranged in vertical
of metastasis of lip cancers. Lymphatic channels of and horizontal fascicles that allow the mobile tongue
the upper lip respect the midline and drain to sub- to change shape and consistency. There are three pairs
mandibular, periparotid, or preauricular nodes. The of extrinsic muscles that provide mobility of the
tongue: genioglossus, hyoglossus, and styloglossus.
Protrusion of the tongue is primarily accomplished by
the action of the genioglossus muscle which originates
from the mandibular tubercles on the lingual surface
of the arch of the mandible, and inserts diffusely into
the substance of the intrinsic musculature on each side
of the tongue. The motor supply to the intrinsic and
extrinsic tongue muscles is the hypoglossal nerve (CN
XII), which exits the skull through its own hypoglos-
sal canal and courses laterally and anteriorly between
the external and internal carotid arteries, immediately
inferior to the occipital artery.
The sensation of the tongue is supplied by the lin-
Figure 5–1. Diagram of the oral cavity and subsites. gual nerve, a branch of the mandibular division of the
102 CANCER OF THE HEAD AND NECK

Figure 5–2. Distribution of oral cancers by subsite. A selected series of cases presenting
to the head and neck service of Memorial Sloan-Kettering Cancer Center, New York.

trigeminal nerve (CN V3). The lingual nerve also face is innervated by alveolar branches of the second
transports parasympathetic fibers from the chorda and third divisions of the 5th cranial (trigeminal)
tympani branch of the facial nerve to the sub- nerve.
mandibular ganglion. The blood supply to the tongue The retromolar trigone is that portion of adherent
is derived from the paired lingual arteries. keratinized mucosa covering the ascending ramus of
The lymphatic drainage of the tongue begins in a the mandible from the third mandibular molar to the
rich submucosal plexus, which may drain bilaterally maxillary tubercle. It represents the area between
when lesions approach the midline, the tip, or espe- the buccal mucosa laterally and the anterior tonsillar
cially the base of the tongue. Tumors of the lateral pillar medially and posteriorly. Tumors of this small
mid-tongue drain predictably to the ipsilateral lymph region spread readily to the adjacent mandibular
nodes. The first echelon nodes for lesions of the tip bone, alveolar foramen, masticator space, oropha-
include the submental nodes. The lateral and ventral ryngeal tonsil, floor of mouth and base of tongue.
tongue lesions metastasize to submandibular or The hard palate lies within the horseshoe shape
jugulodigastric nodes while the base of tongue of the maxillary alveolar process. Keratinized adher-
drains to the jugulodigastric and deep jugular nodes. ent mucosa covers the palatal bone, which is divided
Lesions of the anterior tongue may metastasize into the primary and secondary bony palate. The pri-
directly to the low jugular lymph nodes (level IV) of mary palate consists of the palatal processes of the
the neck. maxillary bones and represents the premaxilla ante-
The buccal mucosa lines the lateral oral cavity rior to the incisive foramen. The secondary palate is
and blends with the gingiva superiorly and inferiorly made up of the horizontal processes of the L-shaped
and with the retromolar trigone posteriorly. The palatine bones. On the posterior hard palate, near the
mucosa is pierced by the Stensen’s duct of the maxillary second or third molar, are found the
parotid gland at the papilla adjacent to the second greater and lesser palatine foramina which transmit
maxillary molar tooth. their respective vessels and nerves which are the ter-
The gingiva consists of thick keratinized mucosa minal branches of the sphenopalatine vessels
with deep rete pegs and submucosal adherence to (branches of the internal maxillary artery) and
the periosteum. The mucosa covers the alveolar nerves (branches of V2). Anteriorly, the midline inci-
processes of the mandible and the maxilla. sive foramen near the incisors transmits the terminal
The mandible possesses lingual and buccal cor- branches of the nasociliary nerve and vessels to sup-
tices which envelop cancellous bone, dental sockets, ply the primary palate region. Lymphatic drainage of
and the mandibular canal transmitting the mandibu- the palate includes the deep jugular chain as well as
lar vessels and nerves (branch of CN V3). The the retropharyngeal nodes. Anterior lesions may
mandibular surface is innervated by branches of the metastasize to pre-vascular facial lymph nodes of
lingual and mental nerves while the maxillary sur- the submandibular region.
 Oral Cavity Cancer 103

The floor of the mouth is a soft thin layer of U- A complete examination of the head and neck is
shaped mucosa overlying the insertion of the mylohy- performed to assess the precise location and extent
oid muscle laterally, the hyoglossus muscle medially, of the primary tumor, identify regionally metastatic
and the insertion of the genioglossus muscle anteri- disease and to rule out multiple primary malignan-
orly. It covers the sublingual salivary glands, sub- cies. Grossly, the earliest cancers may present as
mandibular (Wharton’s) duct, and the lingual nerve. nonulcerous white or red patches. More advanced
The blood supply is from the lingual vessels. Its lym- oral squamous cell carcinomas (SCC) present as
phatic plexus is copious and drains bilaterally in the mucosal lesions, although occasionally an SCC may
midline. The lymphatic drainage patterns include the present as predominantly submucosal with little or
submental and bilateral submandibular nodes, as well no mucosal involvement. Firm submucosal lesions
as the ipsilateral jugulodigastric nodes posteriorly. are often minor salivary gland neoplasms. SCC may
be ulcerative and invasive, fungating and exophytic
DIAGNOSIS or both (Figure 5–3). They may arise within prema-
lignant lesions such as leukoplakia or erythroplakia.
The diagnostic evaluation of a patient with oral car- The following characteristics of the lesion should be
cinoma consists of the history and the physical documented: appearance and character, location,
examination, histopathologic tissue diagnosis, and size in centimeters, texture to palpation, mobility,
imaging—when indicated. proximity to surrounding structures—especially
The clinical history begins with the present ill- bone, and the estimated palpable thickness (superfi-
ness and includes the duration and location of symp- cial vs. deeply infiltrating).
toms such as non-healing ulcer, mass in the oral cav-
ity or neck, pain, bleeding, and any symptoms of
cranial nerve deficits. A thorough exploration of the
patient’s past medical and surgical history, and the
review of systems yield operative risk data. A thor-
ough history of etiologic risk factors for squamous
carcinomas not only reflects the patient’s relative
risk of malignancy but also suggests factors that
affect the patient’s overall health, fitness for surgery
and emotional state. Current and distant abuse of
tobacco and alcohol are critical factors and may be
underreported by the patient. In many parts of the A
world the use of oral chews (“pan,” betel nuts, etc.)
is the chief etiologic factor.9 These may contain
tobacco, slaked lime and other irritants and may be
retained in the oral cavity nearly constantly. An
occupational exposure to heavy metals such as
nickel,10 and previous radiation exposure to head
and neck are other important risk factors of head and
neck cancer that are elicited in the history.
The social history impacts strongly on the
patient’s ability to comply with and tolerate treat-
ment and rehabilitation programs, and these issues
are resolved during the treatment planning phase. B
The family history reflects any familial tendencies
Figure 5–3. A, An exophytic lesion involving the right lateral bor-
toward malignant disease and completes the histori- der of the tongue. B, An endophytic lesion of the right lateral border
cal data. of the tongue.
104 CANCER OF THE HEAD AND NECK

Trismus suggests ominous pterygoid and masti- of the extent of the disease by history and physical
cator space involvement. The condition of the denti- examination and imaging, or the presence of symp-
tion should be noted as tumors may, as the first sign, toms referable to the trachea, larynx, hypopharynx
displace or loosen teeth. The distance from the and esophagus that need endoscopic assessment. It
tumor to the mandible and the mobility of the lesion is not cost-effective screening to perform panen-
in relation to the mandible are critical elements in doscopy on all patients with head and neck can-
determining the management of perimandibular cer.11–13 Symptoms suggesting lesions of the trachea,
cancers. A complete examination of the cranial larynx, hypopharynx, or esophagus include: dyspha-
nerves is performed, emphasizing sensation over the gia, odynophagia, pain, hoarseness, hemoptysis or
chin for mandibular nerve deficit, tongue mobility stridor. A careful history and meticulous head and
for hypoglossal nerve deficit, facial nerve function, neck exam is necessary to identify these lesions.
palatal elevation and gag reflex, and function of the Evaluation of the deep extent of oral cancer often
accessory nerve. A mirror or a flexible or rigid tele- requires the use of imaging modalities. Imaging stud-
scope is needed to document vocal cord mobility ies, however, will not adequately identify the superfi-
and to ensure that no lesions exist in the oropharynx, cial mucosal extent of disease, which must be estab-
nasopharynx, endolarynx, and visible hypopharynx. lished by visualization, palpation and biopsy. Plain
Small lesions of the hypopharynx may only be visi- radiographs such as panorex, dental films or a sub-
ble by direct examination under anesthesia with the mental occlusal film may demonstrate gross bone
rigid laryngoscopes. involvement but do not show early cortical invasion.
The neck should be thoroughly palpated for Computed tomography (CT) is the most common
metastatic disease in the nodal groups at risk, and for modality employed to assess the extent of oral can-
other abnormalities of the great vessels and the thy- cers (Figure 5–4). Advantages of CT include good
roid gland which might impact treatment. Masses of soft-tissue discrimination and vessel identification
the neck should be measured in centimeters, charac- and excellent definition of bone soft-tissue inter-
terized for site (level), mobility, consistency, skin faces. CT scans are readily available and affordable.
involvement, and proximity to vital structures. Nor- Cortical destruction and tumor in the alveolar canal
mal neck structures commonly mistaken for metasta- and the bone marrow can be seen on CT. Special
tic masses include: the transverse process of C2 in the coronal reconstructions of dedicated mandible CT
jugulodigastric region of thin patients, the scalene
muscles, a tortuous carotid artery, a carotid aneurysm,
a prominent carotid bulb, a cervical rib, and ptotic
submandibular glands.
A complete general physical examination should
be performed emphasizing the cardiovascular and
pulmonary systems, which are commonly abnormal
in this oral cancer population. The systemic effects of
malnutrition or excessive alcohol intake should also
be noted.
The history and physical examination with or
without adjunctive imaging and histopathologic tis-
sue diagnosis are sufficient to plan and execute sur-
gical treatment for many patients with oral cancer.
However, some patients will benefit from examina-
tion under anesthesia including direct palpation with
or without biopsy, laryngoscopy, esophagoscopy,
and bronchoscopy. The indications for examination Figure 5–4. CT scan demonstrating an invasive carcinoma in the
under anesthesia include an inadequate assessment right half of the tongue with involvement of lymph nodes at level II.
 Oral Cavity Cancer 105

scans (Dentascan) is particularly helpful in imaging irreparably while sparing the normal tissue. Either
the mandible. CT scans of the oral cavity should be modality is effective in controlling early oral carci-
combined with neck CT to assess for suspicious sub- nomas, but the use of both modalities in combina-
clinical metastatic nodes. Axial and coronal views tion is necessary to control locally advanced disease.
with bone and soft-tissue windows with contrast The role of chemotherapy alone in localized disease
from the orbital floor to the base of the tongue as is palliative. Currently, distantly metastatic disease
well as axial views of the neck are obtained. Disad- is incurable but can often be effectively palliated
vantages of CT scanning include radiation exposure, with chemotherapy and radiation.
possible contrast dye sensitivity, dental amalgam Treatment choices are best made after consider-
interference, difficult positioning for coronal views, ing tumor factors, patient factors and resources fac-
and no direct sagittal views. tors. Tumor factors include subsite, T stage, N
Compared to CT scanning, magnetic resonance stage, histologic characteristics, endophytic vs. exo-
imaging (MRI) offers enhanced soft-tissue discrimi- phytic morphology, and proximity to bone. Patient
nation, excellent skull base and CNS assessment, factors include the patient’s age, co-morbidities, con-
sagittal views, and no radiation exposure (Figure venience, rehabilitation potential, and the patient’s
5–5). Disadvantages are that the examination takes wishes. Resource factors include the availability of a
longer, is more expensive, is poorly tolerated by well-trained surgeon or radiotherapist with a dedi-
some, and the black signal of bone makes cortical cated interest in head and neck cancer, availability
bone abnormalities difficult to see. An experimental of advanced hardware for the planning and delivery
imaging modality with promise is positron emission of radiation, and the availability of funds to pay for
tomographic scanning. Positron emission tomogra- the treatment.
phy (PET) is a nuclear medicine study that demon- The mainstay of treatment of early oral cancer is
strates the difference in metabolism of radiolabeled surgery. External beam radiation therapy alone can be
glucose molecules between normal and malignant effective for some early superficial lesions of the
tissues. The clinical usage of this modality is cur- tongue or floor of mouth but sequelae of xerostomia
rently not well-defined, but will likely aid in the
diagnosis of recurrent and metastatic lesions.14
The appropriate metastatic evaluation of the patient
with oral carcinoma is chest radiographs and serum
liver function tests. The routine use of CT scanning of
the chest, abdomen, and brain, or radionuclide bone
scanning to evaluate oral cancer patients is not cost-
effective and should be discouraged.
When all of the data from the history, physical
examination, biopsy, imaging, and metastatic work-
up are available, the tumor is staged according to the
AJCC staging system (Table 5–1).

TREATMENT GOALS AND ALTERNATIVES;

FACTORS AFFECTING CHOICE
OF TREATMENT

The surgeon’s goal is complete removal of all

cells of the primary tumor and any cancer cells in
regional lymph nodes, while preserving the integrity
Figure 5–5. A T2N0 squamous carcinoma of the left lateral border
of uninvolved structures. Similarly, the radiothera- of the tongue seen infiltrating the superficial musculature of the
pist endeavors to damage the abnormal cells tongue on an MRI scan.
106 CANCER OF THE HEAD AND NECK

and mandible irradiation, and long duration and tion include decreased cost, decreased time of treat-
expense of treatment make radiation a poor choice. ment, the generation of a surgical specimen for exam-
Also, bone involvement by oral cancer limits the ination of potential prognostic features and, in some
effectiveness of external beam radiation, so lesions of instances, an opportunity to sample the regional clin-
the gingiva and hard palate are best treated with ically negative nodes for occult disease. Advantages
surgery due to the close proximity of bone and the of radiation therapy for early lesions are preservation
high incidence of bone invasion. Advantages of of tissue and no need for general anesthetic.
surgery for T1 and T2 oral cancer compared to radia- Advanced T3 and T4 lesions are best treated with
a combination of surgery and radiation therapy.
Table 5–I. UICC/AJCC STAGING SYSTEM FOR ORAL CANCER
Improvement in locoregional control of advanced
Primary Tumor
oral cancer is attributable to the addition of postop-
(T) erative radiation.15,16
TX Primary tumor cannot be assessed Brachytherapy can sometimes be employed for
T0 No evidence of primary tumor
Tis Carcinoma in situ oral cancers (especially tumors of the tongue) utiliz-
T1 Tumor 2 cm or less in greatest dimension ing after-loading catheters.17 However, resection of
T2 Tumor more than 2 cm but not more than 4 cm in greatest
dimension
small lesions is usually simpler and less morbid, and
T3 Tumor more than 4 cm in greatest dimension surgery followed by radiation is more appropriate for
T4 Tumor (lip) invades adjacent structures (eg, through cortical
treating the large volume T3 or T4 lesion. Close
bone, tongue, skin of neck) Tumor (oral cavity) invades
adjacent structures (eg, through cortical bone, into deep proximity of the tumor to the mandible, complex sur-
[extrinsic] muscle of tongue, maxillary sinus, skin) face anatomy, and uncertainty of the tumor margins
Regional Lymph Nodes are tumor factors that also limit use of brachytherapy
(N)
NX Regional lymph nodes cannot be assessed for oral cavity cancers. Tumors of the oral cavity are
N0 No regional lymph node metastasis poorly responsive to traditional organ sparing
N1 Metastasis in a single ipsilateral lymph node, 3 cm or less
in greatest dimension
approaches combining either sequential or concomi-
N2 Metastasis in a single ipsilateral lymph node, more than tant chemotherapy and radiation therapy. The control
3 cm but not more than 6 cm in greatest dimension; or in
rates for oral cavity cancers using these regimens are
multiple ipsilateral lymph nodes, none more than 6 cm in
greatest dimension; or in bilateral or contralateral lymph the lowest of all head and neck sites.18 Chemotherapy
nodes, none more than 6 cm in greatest dimension alone for oral cavity cancers is palliative. While some
N2a Metastasis in single ipsilateral lymph node more than
3 cm but not more than 6 cm in greatest dimension complete clinical responses can be obtained, they are
N2b Metastasis in multiple ipsilateral lymph nodes, none not durable. Preoperative chemotherapy for oral can-
more than 6 cm in greatest dimension
N2c Metastasis in bilateral or contralateral lymph nodes,
cers is usually not helpful because adequate resection
none more than 6 cm in greatest dimension margins do not shrink with the clinical response of
N3 Metastasis in a lymph node more than 6 cm in the tumor. Studies show that microscopic tumor foci
greatest dimension
exist where previous gross tumor has been shrunken
Distant Metastasis
(M) by chemotherapy treatment. It is therefore not ordi-
MX Presence of distant metastasis cannot be assessed narily possible to reduce the extent of surgical resec-
M0 No distant metastasis
M1 Distant metastasis tion and the morbidity of oral cancer surgery by
Stage Grouping tumor shrinkage with preoperative chemotherapy.19
Stage 0 Tis N0 M0 It is important that all head and neck cancer
Stage I T1 N0 M0
Stage II T2 N0 M0
patients and their cases be discussed in a multi-
Stage III T3 N0 M0 modality treatment conference setting to insure
T1 N1 M0
appropriate management.
T2 N1 M0
T3 N1 M0
Stage IV T4 N0 MO
T4 N1 M0 SURGICAL TREATMENT
Any T N2 M0
Any T N3 M0 Most patients with oral cancer are in their fifth to
Any T Any N M1
seventh decades of life with a history of tobacco and
 Oral Cavity Cancer 107

alcohol abuse, and therefore warrant preoperative hemorrhage, (3) the presence of any bolster or other
clearance by the patient’s medical doctor, a cardiol- aspiratable dressing material, (4) pre-existing pul-
ogist, and/or an anesthesiologist prior to surgery. All monary disease or obstructive sleep apnea, or the
patients require preoperative chest radiographs, simultaneous operation or compromise of the nasal
EKG, CBC and blood chemistry evaluation. airway, and (5) the need for frequent endotracheal
A significant portion of oral cancer patients will suctioning or ventilation support.
present in the malnourished state due to odynopha- The anesthetist should be instructed to avoid par-
gia or alcoholism. The malnourished patient will not alyzing agents if nerve stimulators are to be used to
withstand aggressive surgical and postoperative help identify motor nerves. Also, fluid overload
radiation treatment without complications. For this should be avoided in oral cancer cases. Patients
reason, preoperative nutritional support should be undergoing head and neck surgeries have a
considered for patients with weight loss greater than decreased need for intraoperative fluid replacement,
10 percent of body weight and those with low serum compared to patients undergoing abdominal surg-
albumin. The benefits of 2 or 3 weeks of enteral eries of similar duration. This is due to less third
feeding supplementation, to place the patient in a spacing of fluid and less insensate losses of fluid in
positive nitrogen balance, outweigh the risk of treat- head and neck cases compared to abdominal cases.
ment delay in these patients. Nasogastric tube place-
ment is the most common route of enteral supple- Management of Leukoplakia
mentation. However, if patients require significant
cancer resection, complex reconstruction, postoper- During the carcinogenic process, some abnormal
ative radiation therapy and extended swallowing clonal populations of mucosal cells form clinical
rehabilitation, the temporary placement of a gastros- premalignant lesions. These are manifested as
tomy tube is safe and well-tolerated. The benefits of leukoplakia or erythroplakia. Leukoplakias are com-
consistent nutrition and hydration during treatment mon lesions in smokers and patients with a previous
and rehabilitation cannot be overemphasized.20 history of head and neck cancer. These are also
In patients with oral cancer undergoing general noted in patients without heavy carcinogenic expo-
anesthesia, the management of the airway is the sure. In general, dysplastic leukoplakia should be
responsibility of both the surgeon and the anesthesi- treated while lesions harboring only hyperplasia and
ologist. Preoperative communication and preparation hyperkeratosis may be observed. Clinical character-
are critical. Patients may be difficult to orally intubate istics of lesions suggesting the presence of dysplasia
due to trismus, hemorrhage, or tumor bulk, and the include large size, tongue or floor of the mouth loca-
presence of the oral endotracheal tube may interfere tion, red color, friability, and the patient’s prior his-
with the resection. The appropriate solution is nasal tory of oral cancer or dysplasia. It should be empha-
intubation with or without flexible fiberoptic naso- sized that any lesion which is red or red-speckled
pharyngoscopic guidance. Another option for airway (erythroplakia) is of the highest risk for dyplasia or
management is preoperative tracheostomy under local carcinoma and should be biopsied.
anesthetic. In the event of an airway emergency the Treatment of dysplastic leukoplakia is generally
surgeon must be prepared to secure a surgical airway surgical. While the vitamin A analogue isotretinoin
via cricothyroidotomy or an emergent tracheostomy. (13 cis-retinoic acid or Accutane™) has been shown
This must be performed within minutes of desatura- to be effective in the treatment of dysplastic oral
tion to prevent anoxic brain injury or cardiac arrest. leukoplakia, most lesions will recur after therapy has
Similarly, postoperative airway management is been stopped and many patients do not tolerate the
critical to safe surgery of the oral cavity. Indications mucocutaneous toxicity of isotretinoin treatment. 21,22
for tracheostomy after oral cancer surgery include: Small dysplastic leukoplakia lesions may be eas-
(1) the anticipation of significant postoperative ily excised in the office under local anesthesia with
edema of the pharynx, floor of the mouth or the base millimeter margins. All excised leukoplakia should
of the tongue, (2) a significant risk of postoperative be submitted for histopathologic assessment. Laser
108 CANCER OF THE HEAD AND NECK

excision of oral leukoplakias can also be accom- Tongue cancer may spread along the mucosal
plished with good hemostasis and little tissue reac- surface to involve the floor of the mouth and the
tion.23 Other treatment options for leukoplakia mandible, or the oropharynx, or it may spread by
include destruction by electrodesiccation, and deep invasion between muscle fascicles which offer
cryotherapy with liquid nitrogen. Local recurrence little resistance to tumor spread (Figure 5–7). It is
is common and occurs in up to one-third of cases.24

SURGERY FOR ORAL CANCER

The lip is the most common site for oral cancer. It is

usually considered separately from cancers of other
oral subsites as it behaves more like skin cancer. It
occurs in sun-exposed surfaces and more commonly
on the lower lip than upper lip. It is usually diag-
nosed early due to bleeding and a visible ulcer.
Large lesions may rarely invade the mandible or the
mental nerve and foramen.
T1 and T2 lesions are usually cured by wedge
resection of the lip with primary closure, (Figure B
5–6) although primary radiation therapy is also
highly effective. Large T3 or T4 lesions require
resection of involved tissues, bilateral upper neck
dissections, complex reconstruction, and postopera-
tive radiation therapy.
Depending on the size of the mouth and the pres-
ence of dentition, up to 50 percent of the lower lip
can be resected and closed primarily in three layers
with care to close the orbicularis oris muscle
securely. Re-approximation of the vermilion line is
important cosmetically. If greater than 40 to 50 per-
cent of the lip is to be resected an Abbe or Estlander
lip switch reconstruction borrows lip tissue from the B
normal upper lip. Karapandzic advancement flaps
can also be useful for large lip reconstructions.25
Free flap reconstruction is sometimes necessary but
always inferior cosmetically and functionally due to
the lack of orbicularis oris function and difficulty
with commissure reconstruction.26
The anterior two-thirds of the tongue is the most
common site of primary lesions accounting for 40
percent of oral cancers. Most malignancies occur on
the lateral borders and ventral surface but are occa-
sionally confined to the tip or the dorsum. Even
small lesions of the oral tongue are visible and usu-
ally symptomatic, so oral tongue lesions tend to pre- C
sent in earlier stages: 37 percent stage I, 34 percent Figure 5–-6. A to C, Wedge resection of lower lip carcinoma with
stage II, 21 percent stage III, and 8 percent stage IV.27 primary closure in layers.
 Oral Cavity Cancer 109

Peroral resection is the most common approach

for T1 and T2 lesions of the oral tongue (Figure
5–8). A partial glossectomy is easily performed
using electrocautery to maximize hemostasis. A 1 to
1.5 cm margin of normal tongue tissue is maintained
in all dimensions, and both visual assessment and
palpation of the tongue guide the resection. Intraop-
erative margin specimens for frozen section are
taken with a scalpel to minimize cautery artifact.
Resection can be performed with a carbon dioxide
laser. Whenever feasible, the resection is planned in
a transverse wedge fashion. Intraoperative frozen
sections of the margins are mandatory. The defect of
a partial glossectomy is closed in the horizontal
direction causing a foreshortening of the tongue.
The appearance and function after horizontal clo-
sure are excellent. This is preferable to a longitudi-
nal closure, which results in a thin pointed tongue.
Figure 5–7. The anatomical routes of spread of oral tongue cancer. The size and the extent of the tumor will determine
the orientation of the resection.
easy to underestimate the deep extension of tongue For many T2 and T3 oral tongue tumors, and for
tumors and great care should be exercised to take any sized tumor in the posterior portion of the
more than 1 cm cuff of normal tongue musculature tongue or floor of mouth, the mandibulotomy
as the margin of surgical resection. The midline approach provides the exposure required to perform
raphe of the tongue does not provide any substantial an oncologically sound resection. The low morbidity
resistance to tumor spread for lesions approaching of paramedian mandibulotomy is always preferred
or crossing the midline. to the poor visualization and inadequate assessment

A B C
Figure 5–8. A to C, Peroral wedge excision and primary closure of a T1 cancer of the tongue with horizontal closure.
110 CANCER OF THE HEAD AND NECK

of the deep and posterior margins that result from mucosa and mylohyoid muscles are divided posteri-
inappropriate peroral excision.28,29 In addition, the orly up to the anterior tonsillar pillar, and one cen-
majority of these patients benefit from staging elec- timeter from the medial aspect of the mandible.28
tive supraomohyoid neck dissection, which provides Appropriate tumor resection is performed through the
the neck exposure needed for the mandibulotomy exposure thus provided (Figure 5–10).
approach (Figure 5–9). The reconstruction requires the floor of mouth
This procedure begins with elective supraomohy- incision to be closed in layers, and the bone re-
oid or modified radical neck dissection, in which the approximated with the preformed plates and screws
skin and muscle flaps of the neck are raised exposing (Figure 5–11). The lip is closed meticulously in three
the lower border of the mandible. The floor of the layers with attention to the orbicularis oris muscle
mouth is exposed via the submandibular triangle. and the exact apposition of the vermilion border. The
Next the lower lip splitting incision is performed. The best reconstructive options for partial and hemiglos-
vermilion border is marked to ensure accurate sectomy are primary horizontal closure if the defect
realignment, and the lip is split sharply in the midline is not too large, or free flap reconstruction. Other
and connected with the anterior extent of the neck options include closure by secondary intention, split-
incision. The periosteum of the mandible is left undis- thickness skin grafting and pedicled flaps. After large
turbed while the soft tissues of the lip and cheek are resections of the oral tongue, patients require speech
elevated to identify and preserve the mental nerve. and swallowing therapy for functional recovery.
The gingival mucosa and periosteum are incised at Every effort should be made to achieve negative
the mandibulotomy site anterior to the mental fora- margins with the initial resection. Intraoperative pos-
men and lateral to the insertion of the digastric mus- itive frozen-section margins in tongue surgery signif-
cle. The cut is planned either between the lateral icantly reduce local control and survival, even when
incisor and the canine tooth, or directly through the additional resection and ultimately negative frozen
root of a lateral incisor tooth that is extracted. Cuts and permanent sections are obtained.30 When intra-
between tooth roots may damage both roots and both operative positive frozen sections occur it reflects a
teeth may be lost subsequently. Prior to performing tumor biology that is more invasive and aggressive
the bone cut, the 4-hole reconstructive plates for the than is estimated by the surgeon and thus warrants
lateral and inferior margin of the mandible are consideration of postoperative radiation therapy.
molded and the screw holes drilled to ensure accurate Final histopathology report of margins may show
realignment. The cut is performed at right angles to foci of premalignant change, carcinoma in situ
the alveolar ridge and angled 45 degrees anteriorly (CIS), close surgical margins (less than 5 mm) or the
below the tooth roots for better stabilization. Taking presence of microscopic foci of invasive cancer. The
care to avoid the lingual nerve, the floor of mouth presence of any of these findings at the surgical mar-

Figure 5–9. The mandibulotomy approach to tumors of the posterior oral cavity.
 Oral Cavity Cancer 111

Figure 5–10. The mandibulotomy approach to tumors of the posterior oral cavity. Biplane fixation of
the mandible is necessary.

gin increases the risk of local recurrence twofold, vival and control of disease in the neck. In a study of
and significantly increases the mortality from oral early staged cancers of the tongue and floor of the
cancers. Any of these histologic findings suggest a mouth, the 5-year survival of patients with thin
role for postoperative radiation therapy.31,32 lesions was greater than 95 percent, while survival of
Early tongue cancers demonstrate occult spread to patients with thick lesions was less than 80 percent,
the cervical lymph nodes in 20 to 30 percent of cases. regardless of T stage (Table 5–2).34 An appreciation of
The frequency of metastasis is related to the T stage tumor depth can aid in the decision to perform elec-
and depth of invasion of tongue cancers. Increasing T tive neck dissection. Except for oral cancers less than
stage correlates with increasing incidence of metasta- 2 mm thick, all early staged oral cancer patients
tic disease. A depth of invasion by tongue cancer of should receive elective supraomohyoid neck dissec-
greater than 5 mm is associated with an increased tion (SOHND). On the other hand, elective radiother-
incidence of occult metastasis.33 Tumor depth greater apy to the neck should be employed if radiation ther-
than 2 mm is correlated with significantly lower sur- apy is the treatment selected for the primary tumor.
Survival after treatment for tongue cancers has
improved over the last 15 years, due to the use of
combined modality treatment for advanced disease,
and the aggressive treatment of the neck in early
stage disease. Franceschi reported 5-year survival of
82 percent for patients treated between 1978 and
1987 with stage I and II disease and 49 percent for

Table 5–2. THICKNESS OF ORAL CANCER PREDICTS

SURVIVAL AND TREATMENT FAILURE
Tumor 5-year Disease Treatment
Thickness Specific Survival (%) Failure (%)

< 2mm 97 2
2–8mm 83
45
>8mm 65

Data from Spiro RH, et al. Predictive value of tumor thickness in squamous
Figure 5–11. The mandibular osteotomy is fixed using miniplates cacinoma confined to the tongue and floor of the mouth. Am J Surg
which provide accurate dental occlusion, and stability. 1986,152:345–50.
112 CANCER OF THE HEAD AND NECK

stage III and IV disease. These are improvements does not pass through the mandibular periosteum
over the survival rates in their experience from the nor through the substance of the mandible.
period 1967 to 1978 (Figure 5–12).27 An additional advantage to routine mandibular
The floor of the mouth is the second most com- resection in decades past was improved access and
mon subsite accounting for 20 percent of oral can- visualization of oral cancers. However, the morbidity
cers. Due to its dependent location, carcinogens may and reconstructive challenges of segmental
pool in the floor of mouth leading to high rates of mandibulectomy led surgeons to reconsider the indi-
cancer. Because of the small size of this area, floor of cations for this procedure, and to explore the possibil-
the mouth lesions often extend to involve the tongue ity of partial-thickness mandibular resections. In these
and the mandibular gingiva. The size distribution of procedures only the alveolar ridge and/or the lingual
floor of mouth cancers at the time of diagnosis is 30 plate of the mandible is resected (marginal
percent T1, 37 percent T2, 19 percent T3, and 14 per- mandibulectomy), and the inferior alveolar artery and
cent T4.28 Forty-one percent of patients present with nerve and the continuity of the mandibular arch are
regional neck metastasis, and micrometastases are spared. In order to justify the oncologic soundness of
identified histologically in 17 percent of elective marginal mandibulectomy, studies were undertaken to
neck dissection specimens. Of all treatment failures, understand the routes of invasion and spread of cancer
21 percent recur locally, 37 percent recur in the neck in the mandible. The results allow a rational approach
and 29 percent at both sites. Staging elective suprao- to management of the mandible in oral cancer.
mohyoid neck dissection is appropriate for all but McGregor and colleagues have reported that the
very superficial T1 lesions of the floor of the mouth, primary route of SCC invasion of the edentulous
and bilateral staging neck dissection is indicated for mandible is through cortical deficiencies of the
midline lesions. Finally, survival for floor of mouth occlusal surface of the bone.38 The route of spread in
lesions is 88 percent, 80 percent, 66 percent, and 32 the dentate nonirradiated mandible is via the tooth
percent for disease of stages I to IV respectively.35 sockets, and the presence of teeth is a relative barrier
Because of the frequent involvement of the to tumor infiltration. Also, the dentate mandible has
mandible by floor of the mouth tumors, management a greater height from the floor of the mouth than
of the mandible is an important aspect of planning does the edentulous mandible due to the resorption
resections of the floor of the mouth. The key clinical of the alveolar ridge after tooth loss. Therefore,
question is: does the mandible require resection, and if tumors of the floor of the mouth must advance far-
so how much—the periosteum, a marginal mandibular ther up the gingival mucosa to reach the occlusal
resection or a segmental resection? Management of
the mandible depends on the lesion’s proximity to the
mandible, whether the mandible is dentate or edentu-
lous, the degree of atrophy of the alveolar ridge,
whether the mandible has been irradiated, and whether
there is mandibular invasion.
Historically, a segmental mandibular resection
was often performed not only for bone involvement
by cancer, but also to accomplish a monobloc resec-
tion of the primary carcinoma with cervical lymph
nodes. It was incorrectly presumed that lymphatics
from the oral cavity passed through the periosteum
of the mandible to the neck and that in-transit metas-
tasis could be resected with the mandible. The ele-
gant histologic work of Marchetta and col- Figure 5–12. Graph demonstrating improved survival in tongue can-
cer from the years 1967 through 1978 to the years 1978 through 1987.
leagues36,37 has conclusively demonstrated that the Data from Franceschi et al. Improved survival in the treatment of squa-
lymphatic drainage of the tongue and floor of mouth mous carcinoma of the oral tongue. Am J Surg 1993;166:360–5.
 Oral Cavity Cancer 113

Figure 5–13. The routes of spread of oral cancer to the mandible in the dentate and eden-
tulous mandible.

surface of the dentate mandible than the edentulous oral carcinoma. Because the dentate mandible is rel-
mandible (see Figure 5–13). atively resistant to cancer infiltration by adjacent
Cancer invasion of the irradiated mandible lesions, marginal resection of the alveolar ridge
occurs not only through the occlusal surface but also and/or the lingual plate, sparing the alveolar artery, is
directly through cortical bone of other surfaces.39 sometimes acceptable treatment for disease in prox-
This suggests the loss of barrier function of the imity to the bone. First, the proximity of the tumor is
periosteum after irradiation. assessed by observation, palpation, and by CT scan if
In both radiated and nonirradiated mandibles, the the lesion is fixed to the bone. If the tumor is greater
spread of squamous carcinoma within the cancel- than 1 cm away from the bone, then no mandible
lous bone is generally directed inferiorly toward the resection is needed. If the tumor is less than 1 cm
inferior alveolar nerve canal. Brown and colleagues from the mandible, then a marginal resection of the
reported that the early phase of mandibular invasion mandible will ensure 1 cm margins. If the tumor
is erosive and that this phase progresses to an infil- involves the gingival mucosa and the periosteum
trative phase as the depth of invasion increases.40 In without clinical or radiologic evidence of cortical or
the histologic studies by McGregor and McDonald, cancellous bone involvement, then a marginal resec-
tumor spread proximally and distally within the can- tion of the mandible is satisfactory, because any sub-
cellous bone of the mandible was observed to be no clinical bone involvement is likely to be localized to
farther than 5 mm beyond the region of overlying the alveolar process. If the tumor is fixed to the
soft-tissue involvement, suggesting that a 5 to 10 occlusal surface with clinical or radiologic evidence
mm bony margin, beyond the extent of the soft-tis- of cortical or cancellous bone involvement, then a
sue tumor, is oncologically sound.40 On the other segmental resection is performed because, once the
hand, invasion of the alveolar canal by oral cancer occlusal cortex is breached, there is no barrier to the
allows extensive perineural spread. By this route, vertical spread of tumor through cancellous bone to
disease can travel distally or proximally to the skull the alveolar canal. Totsuka and colleagues published
base, but does not tend to seed the bone along the studies showing that marginal mandibular resection
course of the nerve or form skip lesions. Invasion of was safe for some tumors with minimal gross bone
the ramus via the body of the bone occurs readily, invasion if there was a histologically “expansive”
especially in the irradiated mandible.41 rather than “infiltrative” pattern of invasion. How-
With these principles in mind, one can develop a ever, this pattern of invasion was not readily pre-
rational approach to management of the mandible in dictable based on radiographic findings.42,43
114 CANCER OF THE HEAD AND NECK

When extensive involvement of the cancellous to reroute the duct to the posterior edge of the resec-
bone is noted, the alveolar nerve must be assessed by tion if the submandibular gland is not resected in the
frozen section, and further resection along the neck dissection. Caution is taken to identify and pre-
course of the nerve to the inferior alveolar foramen, serve the uninvolved branches of the lingual nerve as
the mental foramen, or the skull base is considered. anesthesia of the tip of the tongue will result from
Contraindications to marginal resection of the their sacrifice. Small defects may be closed primar-
mandible include gross involvement of the cortical or ily but many can be allowed to granulate and heal by
cancellous bone of the mandible, inability to pre- secondary intention. A split-thickness skin graft is an
serve the inferior alveolar artery, significant resorp- excellent reconstruction for small defects in the floor
tion of the mandible—suggesting very thin and of mouth that expose the mylohyoid muscle.
weak residual bone, a previously irradiated mand- Excision of small lesions of the floor of the
ible, and cancer abutting the mandible on more than mouth may require local resection with en bloc mar-
two surfaces. ginal resection of the mandible (Figure 5–14).44 This
Small T1 lesions that are 1 cm from the mandible may be accomplished via a peroral approach. The
are amenable to wide local excision via the peroral mucosal and soft-tissue excision is left attached to
approach. This is easier in the edentulous patient due the mandible, the extraction of teeth at sites of alve-
to better visualization. The mucosal margin is at least olar cuts is performed, and the bone cuts are per-
one centimeter. The deep margin is just below the formed with the sagittal saw and ultra-thin blades.
sublingual salivary gland for superficial lesions. Smooth cuts rather than right-angle cuts are favored
Wharton’s duct may be ligated, but the authors prefer to evenly distribute forces of mastication and pre-

Figure 5–14. Resection of floor of the mouth cancer with marginal mandibulectomy.
 Oral Cavity Cancer 115

Figure 5–15. Segmental resection of the mandible through a lower cheek flap approach for a large
floor of the mouth carcinoma with gross mandibular bone involvement.

vent subsequent fractures. When the dentate section is always indicated in surgical treatment of
mandible is encroached upon by tumor at the lingual large floor of the mouth tumors and this provides good
plate only, a vertical partial mandibular resection inferior exposure for the resection of the mandible.
can be accomplished using the tooth roots as the ver- Tooth extractions and gingival mucosal incisions are
tical plane of resection. The related teeth are then performed. Mandibular reconstruction plates
extracted and the right-angle saw blade is used to may be pre-bent and screw holes drilled. With the soft-
resect only the lingual plate, exercising caution to tissue portion of the tumor well defined and protected,
preserve the alveolar artery. Elective or therapeutic the bone cuts are performed with the sagittal saw and
neck dissection improves the exposure of the lower the specimen removed en bloc, often with the neck
mandible. The specimen is delivered en bloc. The specimen attached as well.44 A frozen-section assess-
resulting defects of the floor of the mouth and the ment of the alveolar nerve is prudent. Reconstruction
mandible can be left to granulate, however mucosal of lateral mandibular defects with reconstruction
advancement flaps or a split-thickness skin graft can plates or free bone grafts requires excellent soft-tissue
often close these defects well.45,46 coverage with myocutaneous flaps although the fail-
Most T3 and T4 floor of mouth cancers require ure rate is 50 percent. Exposure of reconstruction
extended local resections including partial glossec- plates used for anterior arch reconstruction
tomy or a segmental mandibular resection, which is approaches 100 percent. The free tissue transfer of
performed through a lower lip splitting incision and a fibula with attached muscle and skin is the state of the
lower cheek flap exposure (Figure 5–15). The mental art reconstruction for large composite resections,
nerve is sacrificed. An elective or therapeutic neck dis- especially when the anterior arch is involved.
116 CANCER OF THE HEAD AND NECK

An alternative surgical approach to T3 and T4 and survival were: size greater than 3 cm, bone
floor of the mouth lesions that do not require seg- involvement, and positive surgical margins. As dis-
mental mandibular resection is the transcervical cussed above, marginal mandibular resection is
pull-through procedure.47 The primary tumor speci- appropriate for periosteal involvement and segmen-
men is delivered into the neck with or without mar- tal resection indicated when the cortical bone is
ginal mandibular resection. Bilateral upper neck dis- involved with cancer.
sections are usually performed. If necessary a Peroral wide local resection with marginal
marginal or lingual plate resection of the mandible is mandibular resection can be performed for smaller
accomplished. The remaining soft-tissue attach- lesions, while segmental resection requires lip split-
ments to the mandible, including the mylohyoid ting incision and lower cheek flap elevation as
muscles, are divided and the oral contents delivered described previously.
inferiorly into the neck. This provides good visual- Tumors of the retromolar trigone occur with a
ization of the tumor for the remainder of the soft-tis- disproportionately high frequency considering the
sue resection. It is critical that the oral tissues are small surface area (Figure 5–16). Fifteen percent of
properly re-suspended and that the remaining extrin- oral cancers occur in the retromolar trigone. This
sic tongue musculature is appropriately attached to site is difficult to assess clinically because of its pos-
the mandible for postoperative swallowing function. terior location, mucosal irregularity, small area, and
Maxillary and mandibular gingival lesions are visual interference by the dentition. Trismus, if pre-
often reported in the literature together as gingival sent, may also inhibit the examination, and is indica-
lesions. Surgically, lesions of the mandibular gingiva tive of pterygoid involvement. Retromolar lesions
and retromolar trigone are similar and will be dis- are relatively difficult to treat because they spread
cussed together. Lesions of the maxillary gingiva are early to deep structures such as the ascending ramus
surgically similar to those of the hard palate and so of the mandible, pterygoid muscles, the masticator
these two subsites will subsequently be addressed. space, and the skull base. Another avenue of local
Three-quarters of gingival lesions involve the spread is the foramen of the inferior alveolar nerve
mandibular alveolus and one-quarter involve the into the ramus of the mandible. Tumor may also
maxillary alveolus. A report of 283 mandibular alve- spread proximally along the perineurium or within
olar lesions from Memorial Sloan-Kettering Cancer the nerve to the trigeminal ganglion and the CNS.
Center showed the distribution of these primary Surgical access to this region is challenging. Bone
tumors to be 30 percent T1, 48 percent T2, 17 percent resection is nearly always indicated, and recurrence
T3 and 11 percent T4.48 Only 5 percent were resected is difficult to diagnose.
without bone, 32 percent were amenable to marginal
resection and 63 percent required segmental bone
resection. Local recurrence was 25 percent when the
mandible was initially involved with tumor. Occult
neck metastasis was found in only 6 of 107 elective
radical neck dissections, indicating a low incidence
of occult neck disease compared to tumors of other
subsites of the oral cavity. Staging elective suprao-
mohyoid neck dissection is indicated for T2 or larger
lesions in conjunction with segmental mandibular
resection. Five-year survival for all alveolar cancers
was 77 percent stage I, 70 percent stage II, 42 percent
stage III, and 24 percent stage IV.
Overholt49 reviewed the M.D. Anderson Hospital
experience of 155 mandibular alveolar lesions and
determined that parameters affecting local control Figure 5–16. An exophytic lesion in the retromolar trigone.
 Oral Cavity Cancer 117

lary alveolus or partial maxillectomy may be neces-

sary if they are involved with cancer.
Soft-tissue reconstruction with primary closure,
or healing by secondary intention over the retromo-
lar trigone is occasionally satisfactory. Posteriorly-
based buccal mucosal random-pattern rotational
flaps, soft palate, tongue, and masseter muscle flaps
are all described for this area. The need for thin tis-
sue here suggests an advantage for skin grafting and
radial forearm free flap reconstructions. If the ramus
is sacrificed, a bulkier pectoralis pedicled flap may
cover reconstructive hardware but tends to pull infe-
riorly with time. The excellent bone stock of the
fibular free flap is detracted from by its association
with bulky muscle, and variable survival of the over-
lying skin paddle. It is infrequent today that a lateral
mandibular defect is left unreconstructed, but this
Figure 5–17. Bone cuts for marginal and conservative segmental defect is tolerated well by many patients and it
resections of the mandibular ramus and body.
allows easier assessment of the region for recur-
rence. Defects that are small, posterior and occur in
The peroral approach to the retromolar region is the edentulous patient are tolerated well.
rarely satisfactory due to the posterior location of the Carcinomas of the hard palate (Figure 5–18) and
trigone and the necessity for bone resection since the upper alveolus are relatively uncommon, accounting
periosteum or bone is usually involved with cancer. for 10 percent of oral cancers,50 except in areas of
Often a segmental resection of the ascending ramus Southeast Asia where reverse smoking is prac-
of the mandible and part of the pharynx is necessary. ticed.51 In the United States, carcinoma of the hard
Mandibular rim resection of the molar alveolus and palate is only half as common as carcinoma of the
the ascending ramus of the mandible is acceptable soft palate52,53 and carcinoma of the maxillary alve-
for small lesions without gross bony involvement. olar ridge is only one-third as common as carcinoma
Marginal mandibular resection of the ascending of the mandibular alveolar ridge.48 These areas are
ramus through the open mouth is not satisfactory. lined with adherent keratinized mucosa, which pro-
If bone is grossly involved by clinical or imaging
evaluation, then segmental resection of the ramus
and/or body is required. If superficial involvement
of the molar alveolus or ascending ramus is identi-
fied, then conservative segmental mandibular resec-
tion sparing the condyle and a posterior strut of
ascending ramus is satisfactory bone resection.41
Cuts are performed through the mandibular notch
and the coronoid process (Figure 5–17). The alveo-
lar foramen and nerve are included in the resection.
Intraoperatively, a frozen-section margin on this
nerve is important. Assessment of the superior
extent of the disease, including the coronoid process
of the mandible, the temporalis muscle, maxillary
tubercle, masticator space, and pterygomaxillary
space is necessary. Marginal resection of the maxil- Figure 5–18. Squamous cell carcinoma of the hard palate.
118 CANCER OF THE HEAD AND NECK

vides protection from the trauma of mastication, and

may provide relative protection of the basal nuclei
from the effects of carcinogens.
Histologically, carcinomas of the upper alveolar
ridge are nearly all squamous cell carcinomas, but
up to one-third of hard palate cancers are of minor
salivary gland origin.54 In contrast to squamous cell
carcinomas, palatal minor salivary gland tumors are
often submucosal masses rather than ulcerative or
fungating mucosal lesions. Kaposi’s sarcoma can be
seen on the hard palate of patients with acquired
immunodeficiency syndrome. Malignant melanoma
of the oral cavity, while rare, occurs most frequently
on the palate.
Lesions of the maxillary alveolar ridge are symp-
tomatic, thus allowing early diagnosis. Eighty-two
percent of maxillary alveolar ridge carcinomas are
T1 or T2 at the time of diagnosis, and 86 percent are
N0.48 Palatal carcinomas tend to be larger when Figure 5–19. Bone cuts for subtotal maxillectomy preserving the
diagnosed but only 13 percent have regional metas- inferior orbital rim and floor of the orbit.
tases when diagnosed.49 The presence of regional
metastases to the neck or locally advanced disease
decreases 5-year survival from approximately 70
percent to approximately 30 percent.53
Surgery is the treatment of choice for cancer of
the maxillary alveolus and the hard palate, and it is
frequently necessary to resect periosteum and bone
in order to ensure an adequate margin. The mucosa
and the underlying periosteum are fused in this
region forming a mucoperiosteum. Invasive carcino-
mas of this area frequently involve the periosteum or
the underlying bone, thus reducing the effectiveness
of primary radiation therapy for these lesions. How-
ever, postoperative radiation therapy for aggressive
minor salivary gland malignancies or advanced
squamous carcinoma is recommended.54,55
T1 and T2 lesions may be amenable to peroral
wide local excision with resection of the involved
mucoperiosteum and usually the underlying bone.
Mucosal incisions are performed with electro-
cautery, allowing a 1 cm margin of normal tissue.
Teeth are extracted at the osteotomy sites, and bony
cuts are performed with an oscillating saw. Many
small defects granulate well and close by secondary
intention. Primary closure is usually not possible
due to the immobility of the surrounding adherent Figure 5–20. The Weber-Ferguson incision and its subciliary and
mucosa. A posteriorly-based buccal mucosa flap brow extensions for maxillectomy.
 Oral Cavity Cancer 119

with random blood supply is effective in closing lat- the antrum is not involved, and posterior to the ptery-
eral palatal and alveolar defects. A flap of the palatal goid plates if the posterior wall and the pterygomax-
mucoperiosteum, based on the greater palatine illary space are involved with cancer. The cut is made
artery in the posterior aspect of the hard palate, can using a curved osteotome and the heavy curved Mayo
be rotated to cover a small defect, and the donor site scissors under palpation guidance with cognizance of
left to granulate or be skin grafted. If the nasal and the proximity of the internal carotid artery in the deep
antral mucosa are intact after the resection, the oral aspect of the parapharyngeal space, and the apex of
defect can be closed with a local flap with a low risk the orbit superomedially. Hemostasis is obtained, the
of oronasal fistula formation. lacrimal sac is tacked open with chromic suture
T3 or T4 cancers with invasion of the maxillary and/or the lacrimal duct cannulated with silastic tub-
antrum or nasal cavity often require partial or subto- ing, and the cavity is skin grafted. The graft is sup-
tal maxillectomy. Advanced lesions invade the nasal ported by packing with xeroform gauze, which is sup-
cavity, maxillary sinus, the pterygomaxillary space, ported by a preformed dental obturator that is wired
pterygoid plates and skull base. T3 and T4 cancers to the remaining maxillary teeth or the alveolar bone.
requiring subtotal maxillectomy (preservation of the Only rarely is total maxillectomy (including the
infraorbital rim and floor of the orbit ) (Figure 5–19) orbital rim and floor) or radical maxillectomy
need exposure via an extended Weber-Ferguson inci- (including orbital exenteration) necessary for oral
sion and an upper cheek flap for maximum exposure cavity cancers.
(Figure 5–20), or exposure via the midface degloving
approach. A midface degloving approach provides REHABILITATION
excellent exposure for anterior lesions involving the
lower maxilla and nasal cavity bilaterally without any The rehabilitation of function after oral surgery is a
external incisions, but superior exposure is limited critical element in effective oral cancer surgery. After
above the orbital rim.56,57 After the exposure is major oral resections the patients need rehabilitation
obtained, the soft-tissue cuts and dental extractions of speech, swallowing, dentition and mastication as
are performed as needed. Alveolar cuts should be well as cosmesis. This process is best accomplished
made through the sockets of extracted teeth and not in a multidisciplinary environment which include the
between them. This allows good bony support for the head and neck surgeons, plastic surgeons, speech and
remaining teeth that will bear considerable forces language therapists, nurses, dentists, prosthodontists
from dental rehabilitation. The following cuts are per- and oral and maxillofacial surgeons.
formed using the oscillating saw: (1) from the lateral Perhaps the most important element of rehabili-
maxillary wall to the infraorbital rim preserving the tation is optimizing the patient’s resection and
latter, (2) from the infraorbital rim to the nasal cavity reconstruction at the time of surgery. While the
through the lacrimal fossa, (3) from the nasal cavity oncologic soundness of the tumor resection must not
through the alveolar ridge, and (4) through the hard be compromised for functional reasons, neither
palate (see Figure 5–19). The remaining cuts are the should excessive resection of uninvolved soft tissue,
lateral nasal wall cut, which joins the lacrimal cut to nerve or bone be performed. Whenever oncologi-
the nasopharynx using a thin osteotome and Mayo cally possible, preservation of the hypoglossal, lin-
scissors, and finally the posterior cut. The posterior gual and mental nerves should be attempted. Gentle
cut is performed only after all other aspects of the handling of tissues, hemostasis, and obliteration of
maxilla are freed. This is because significant bleeding dead space are general principles of surgery which
can occur from the pterygoid venous plexus and the should be adhered to. This, in combination with anti-
internal maxillary artery after this cut is performed. septic preparation of the oral cavity preoperatively
The expedient removal of the specimen and prompt and the use of perioperative antibiotics, may reduce
packing of the maxillectomy defect are necessary to inflammation and improve healing and reduce scar
adequately control bleeding. The final cut is made tissue formation, which will tend to maximize post-
anterior to the pterygoid plates if the posterior wall of operative function.
120 CANCER OF THE HEAD AND NECK

Reconstruction of oral defects after ablative tication requires intact sensation of the dentition,
surgery is critical for oral rehabilitation. Perhaps the gingiva, tongue and buccal mucosa, and intact motor
most important advance in head and neck surgery in function of the hypoglossal nerve for tongue muscu-
the last 15 years has been the safe and effective use lature, the facial nerve for oral competence and the
of free tissue transfer for reconstruction. Free tissue third division of the trigeminal nerve for buccinator
transfer techniques now allow the excellent recon- function. This combination of sensory and motor
struction of the mandible, skin, and mucosa of the functions allows the food to be kept in the plane of
oral cavity. Bone flaps from the fibula, iliac crest the molars without biting the soft tissues.
and scapula are available to the reconstructive sur- Continuity of the mandibular arch provides great
geon. Soft tissue from the radial forearm, lateral advantage for mastication. However, a patient with a
arm, trapezius, rectus abdominis and other sites pro- segmental defect of the body of the mandible can
vide vascularized, nonirradiated soft tissue for frequently masticate some foods satisfactorily.
reconstructive purposes. It is clear that the appropri- Occasionally a guide plane prosthesis is helpful to
ate use of these reconstructive tissues has dramati- maximize occlusion of the teeth in a patient with a
cally improved the functional outcome of oral can- lateral mandible defect. These guide plane prosthe-
cer patients. They should be employed whenever ses help overcome the deviation of the mandible to
necessary. Adequate reconstruction of the mandibu- the resected side from the unopposed action of the
lar arch, and soft tissues of the tongue and floor of intact contralateral pterygoids. An unreconstructed
mouth will significantly increase the likelihood of defect of the anterior mandible is uncommon today.
acceptable speech and swallowing after major oral This defect will prohibit mastication of solids and
cavity cancer surgery. patients will tolerate no more than a puréed diet. The
Rehabilitation of swallowing after oral cavity combination of poor mastication, swallowing,
surgery is important. Swallowing can be divided into speech and articulation, cosmetic defect and oral
the preparation phase, the oral phase and the pharyn- incompetence makes the anterior mandibular arch
geal phase. Oral cavity surgery impacts most on the defect something to be avoided in almost every cir-
preparatory phase and the oral phase. The preparatory cumstance. The oral preparatory phase of swallow-
phase of swallowing begins with lubrication of the ing can also be inhibited by trismus, which is com-
food bolus by saliva. This is impaired when pre- or mon after surgery and/or irradiation of the posterior
postoperative radiation therapy is employed. Signifi- oral cavity and oropharynx.
cant xerostomia results in the majority of irradiated The oral phase of swallowing consists of prepa-
patients. The xerostomia significantly limits the types ration of the food bolus followed by presentation to
and consistencies of food that can be swallowed. Most the oropharynx, where the swallowing reflex is initi-
patients with oral cavity radiation require frequent ated during the oropharyngeal phase. The oral phase
sips of water to maintain moisture and liquid to wash is volitional. Preparation of the bolus is accom-
down the food at mealtimes. One experimental strat- plished by the tongue, cheek, teeth and palate. After
egy to try to limit xerostomia is to use a salivary gland mastication and lubrication, the bolus is then pro-
protectant such as Salagen (pilocarpine pelled to the oropharynx by elevation of the tongue
hydrochlonde) during radiation. The benefit of Sala- against the hard palate. When the bolus is sensed in
gen™ is not yet proven and it is contraindicated in the the oropharynx the reflexive portion of the oropha-
presence of coronary artery disease. Amifostine is ryngeal phase of swallowing is initiated. Tongue ele-
approved for the prevention of radiation-induced vation can be restricted due to either loss of tissue
xerostomia. It is not widely used. A number of prepa- volume or motor function after surgery. Patients
rations are marketed for xerostomia but are not supe- with near total glossectomy can be sometimes well
rior to water for the majority of patients. rehabilitated with a palatal drop prosthesis, which
Mastication is critical to an effective preparatory lowers the level of the hard palate so that the resid-
phase of swallowing. Certainly the quality and quan- ual tongue tissue can articulate with it to propel the
tity of the teeth are important for mastication. Mas- bolus posteriorly (Figure 5–21).
 Oral Cavity Cancer 121

staged process and the ingrowth of healthy bone into

and around the implants results in a very secure
foundation for oral prostheses.58 Osseointegrative
implants can be placed in fibula free flap recon-
structions of the mandible after the healing and
removal of the fibula fixation hardware (Figure
5–24). Osseointegrative implants should be avoided
in the atrophic edentulous mandible especially after

A
B
Figure 5–21. A, Patient with poor tongue mobility with a palatal
drop prosthesis in place. B, Palatal drop prosthesis.

The oral prosthodontist plays a critical role in the

rehabilitation of swallowing after oral cancer treat-
ment. The proper number and quality of teeth and
their alignment can be restored by maxillary and/or
gingival dentures. After resection of the maxilla or
hard palate, a dental obturator to cover the oro-antral
and oronasal fistulae is necessary for swallowing
B
without nasal regurgitation (Figure 5–22). Patients
with large maxillary defects can attain excellent
functional results with an obturator. For defects of
the soft palate, dysphagia due to nasal regurgitation,
hyponasal speech and difficulty with articulation of
speech sounds, an obturator with a nasopharyngeal
bulb is effective in minimizing nasal regurgitation
and improving hyponasal speech. The bulb is prop-
erly positioned in the nasopharynx articulating with
the posterior pharyngeal wall at the prominence of
the body of C2, allowing the remainder of the soft
palate to seal off the nasopharynx during swallowing
(Figure 5–23).
Osseointegrated implants are an important C
advance in oral rehabilitation. If adequate bone Figure 5–22. A, Maxillectomy defect with split-thickness skin graft.
stock exists, titanium posts can be placed in a multi- B, Prosthesis in place. C, Prosthesis.
122 CANCER OF THE HEAD AND NECK

radiation. Osseointegration can also be utilized They can often recommend exercises for the artic-
effectively for external fixation of cosmetic prosthe- ulation of speech and can help both the patient and
ses after extended surgery for oral cavity cancer, prosthodontist to optimize prostheses and to rec-
which includes soft tissues of the face. It is impor- ommend alternative methods of phoneme forma-
tant for the patient’s rehabilitation that they have an tion.59 Patients with significant resections of the
acceptable cosmetic appearance in public. lips, maxilla, tongue and palate will often benefit
Many patients benefit from evaluation and ther- from speech therapy.
apy by certified speech and swallowing therapists. Speech and swallowing therapists can also help
improve swallowing in patients who have undergone
oral surgery.60 A modified barium swallow under flu-
oroscopic observation by a radiologist and a speech
therapist may be helpful diagnostically.61 From this
study, abnormalities of mastication, bolus preparation
and bolus presentation of the oropharynx can be
observed and studied frequently from this data.
Strategies for improved function can be devised and
taught to the patient and exercises implemented.
Accompanying abnormalities of the pharyngeal
phase of swallowing can also be diagnosed. Based on
A

C B

Figure 5–23 A, Soft palate defect after surgical resection and free Figure 5–24. A, Panorex of osseointegrated implants in the ante-
flap reconstruction of the lateral pharyngeal wall. B, Prosthesis in rior and right lateral aspects of a fibula free flap reconstruction of the
place. C, The nasopharyngeal bulb prosthesis. mandible. B, The prosthesis in place.
 Oral Cavity Cancer 123

the clinical findings and the modified barium swal- working together. Each can contribute significantly
low, therapists can also suggest optimal consistencies, toward the rehabilitation of speech, swallowing and
and temperatures of food that can be best managed. appearance of the oral cancer patient.
Consultation with a trained nutritionist with expe-
rience in treating head and neck cancer patients is SEQUELAE, COMPLICATIONS AND
essential to provide patients with information and THEIR MANAGEMENT
suggestions regarding optimal foods to maintain a
balanced nutrition within the patient’s consistency Complications can be minimized by appropriate pre-
restrictions. Patients with impaired oral function risk operative evaluation including medical cardiology
nutritional deficiency unless an appropriately varied and anesthesia consultation as indicated. Since the
diet is maintained. Many patients benefit from pre- majority of oral cancer patients are elderly, many will
pared commercial supplements, which are formulated have significant co-morbidities which need assess-
specifically as a balanced diet. Some patients may ment, diagnosis or intervention prior to, or after,
subsist on liquid dietary supplements alone, while the surgery. A preoperative medical evaluation is recom-
majority benefit from regular foods as tolerated with mended for all patients over the age of 60 regardless
additional dietary supplements as needed. Nearly any of their health status. Routine preoperative testing
everyday food can be puréed with liquid in a blender should screen for previously undiagnosed major
and drunk. Patients should be weighed frequently in organ diseases and should consist of at least a preop-
the postoperative period to monitor for weight loss. erative chest radiograph, serum tests of renal and
Supplemental tube feeding may be necessary while hepatic function and electrocardiography. Patients in
the patient is relearning swallowing. negative nitrogen balance due to poor nutrition
Members of the rehabilitation team must educate would be considered for a nasogastric feeding tube
the oral cancer patient regarding oral hygiene. Teeth placement and several weeks of nutritional therapy
brushing and fluoride treatments should be done at prior to surgery. Properly selected patients should
least twice daily. The patient should perform these have a low incidence of major complications.62
fluoride treatments at home regularly using molded The most common complications after oral
dental trays. Patients with post-radiation xerostomia surgery are wound related. The excellent blood sup-
require frequent sips of water, and may benefit from ply to the oral cavity helps to ensure good healing of
sialagogues such as lozenges or chewing gum; how- soft tissues and to resolve infection. Careful surgical
ever it is critical that these be sugar free as the risk of technique can help to minimize complications. It is
caries is dramatically increased after radiation treat- important to handle tissues atraumatically, avoid
ment. All patients with impaired oral function should excessive char from electrocautery, observe careful
be instructed to cleanse the oral cavity after eating. hemostasis, obliterate any dead spaces and to mini-
This may involve simple rinsing with water or saline mize bacteria colony counts by gentle antiseptic pre-
solution or irrigation with a hanging bag and warm operative preparation and copious irrigation with
saline solution. Reconstruction flaps with skin lining saline with or without antibiotics. Careful techniques
the oral cavity may require frequent brushing to of closure will help to minimize postoperative wound
eliminate accumulated skin debris and sometimes complications. Closure under tension should be
trimming of the hair growing on the skin flaps is nec- avoided, especially of an irradiated tissue. Separate
essary for patient comfort and to decrease the adher- suture layers of muscle and mucosa should be per-
ence of food. Reconstructive flaps that have been formed. Oral wounds closed by primary intention
irradiated no longer grow hair. Mouth washes, which will heal best. Many oral lesions will granulate well
contain alcohol, should be avoided as they dry the over several days to several weeks. Skin grafts can be
tissues and cause burning and discomfort. Normal helpful but are frequently lost when placed over
saline or saline with bicarbonate of soda is preferred. mobile surfaces or directly over cortical bone. Any
Successful oral rehabilitation after oral cancer exposed bone or cartilage in the oral cavity will lead
surgery requires a dedicated team of specialists to granulation tissue formation and delay of healing.
124 CANCER OF THE HEAD AND NECK

Obviously carious or infected teeth should be appropriate patient selection, preoperative evalua-
removed at the time of surgery. Twenty-four hours of tion, meticulous technique and appropriate postop-
IV antibiotics, initiated at least 1 hour prior to erative care.
surgery, may help to reduce the wound infection rate.
Other intraoperative measures to decrease com- OUTCOMES AND FUNCTION
plications include consideration of procedure dura-
tion to minimize the time of general anesthesia. Judi- Outcomes in oral cavity surgery may be divided into
cious intraoperative use of crystalloid will prevent survival and functional outcomes. Five-year survival
postoperative complications of fluid overload. Insen- rates for early (T1 and T2) oral cancers are reported
sate fluid loss in oral cavity surgery is significantly to be in the 70 to 90 percent range. In all head and
less than in abdominal surgery, which results in a neck sites, the presence of metastatic nodes to the
lower requirement of intravenous fluid for oral cavity neck decreases the survival by 50 percent. Five-year
surgery patients than for abdominal surgery patients. survival for patients with stage IV disease, espe-
Postoperative management impacts significantly cially with bulky or bilateral lower neck metastases,
on complications of oral surgery. Aggressive oral is less then 20 percent.27
irrigation should begin on the first day of the surgery. In resectable stage III and stage IV tumors with N0
It should be accomplished with normal saline or nor- or N1 disease, 5-year survival has been increased to
mal saline and bicarbonate of soda solution in hang- the 50 to 60 percent range by the aggressive addition
ing irrigation bags or via compressed air-sprayer. of postoperative radiation therapy.15,16 With improved
Major systemic complications are uncommon in local control rates a higher percentage of deaths are
oral cavity surgery. Cardiopulmonary complications due to distant disease and second primary carcinomas
occur due to pre-existing co-morbidities, the physi- rather than from uncontrolled locoregional disease.
ologic stress of surgery and fluid overload. Respira- Factors that predict survival of oral cancer
tory complications such as pneumonia can be mini- patients are low T stage, low N stage, low overall
mized by appropriate early mobilization and the use stage, and the absence of significant co-morbidities.
of sequential compression devices, and careful While the study of the molecular genetics of oral
observation for aspiration of liquids. Due to early cancer is rapidly evolving, there are currently no
mobilization, oral cavity cancer patients rarely suf- molecular markers which have been shown to pre-
fer from deep venous thrombosis (DVT) or pul- dict survival in head and neck cancer patients in
monary embolism, however, immobilized patients large prospectively gathered series. It is however
should be placed on appropriate DVT prophylaxis, likely that in the next several years valid molecular
such as subcutaneous heparin or sequential com- markers will be developed which can predict tumor
pression devices.63 behavior, response to surgical and non-surgical
The majority of wound complications will heal treatment and patient survival rates.
with aggressive cleansing and infection control. Functional outcomes for surgery for early oral
Management of co-morbidities, such as diabetes cancers is excellent. It is rare for patients to suffer
mellitus, malnutrition and hypothyroidism, in order significant loss of speech and swallowing function
to maximize wound healing is critical. Poor healing after surgical resection for T1 or T2 lesions. Even
or a persistent oral cutaneous fistula may result from large T2 lesions of the tongue rehabilitate extremely
the presence of a foreign body such as hardware, well due to the plasticity of the tongue as well as its
non-absorbable suture or sequestered bone. Persis- good blood supply, copious sensory innervation and
tent or recurrent tumor must be ruled out by biopsy the presence of intact musculature. Over 6 to 12
in any non-healing wound after oral cancer surgery. months, the patients invariably find dramatic
The frequency, complexity and duration of wound improvement in articulation of speech sounds, mas-
complications are greater in the irradiated patient. tication and swallowing. Aggressive and appropriate
In summary, the incidence of major complica- rehabilitation with speech and swallowing therapy
tions in oral cancer surgery can be minimized by and prosthodontics is critical to these results.
 Oral Cavity Cancer 125

With increasing volumes of resected tissue, func- able procedure? Otolaryngol Head Neck Surg 1989;101:
426–8.
tional outcomes diminish. Tissues impacting most
14. Hanasono MM, Kunda LD, Segall GM, et al. Uses and limita-
on function include tongue muscle, hypoglossal tions of FDG positron emission tomography in patients with
nerve, lingual nerve, anterior mandibular arch, and head and neck cancer. Laryngoscope 1999;109:880–5.
soft palate. When extensive or multiple resections of 15. Vikram B, Strong EW, Shah JP, Spiro R. Failure at the pri-
mary site following multimodality treatment in advanced
the above structures are undertaken for advanced head and neck cancer. Head Neck Surg 1984;6:720–3.
disease, patient function may be poor even with the 16. Vikram B, Strong EW, Shah JP, Spiro R. Failure in the neck
most advanced reconstructive and rehabilitative following multimodality treatment for advanced head and
techniques. Despite improvements in postoperative neck cancer. Head Neck Surg 1984;6:724–9.
17. Rudoltz MS, Perkins RS, Luthmann RW, et al. High-dose-rate
function attributed to free flap reconstruction, the brachytherapy for primary carcinomas of the oral cavity
degree of coordination of motor and sensory func- and oropharynx. Laryngoscope 1999;109:1967–73.
tion necessary for good oral function cannot be 18. Wolf GT, Forastiere A, Ang K, et al. Workshop report: organ
preservation strategies in advanced head and neck can-
attained with the current technology. These patients
cer—current status and future directions. Head Neck
are gastrostomy tube-dependent and speak poorly. 1999;21:689–93.
Xerostomia from oral radiation therapy and trismus 19. Schuller DE, Metch B, Stein DW, et al. Preoperative
from surgery or radiation are also factors that can chemotherapy in advanced resectable head and neck can-
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dramatically compromise function. Laryngoscope 1988;98:1205–11.
20. Williams EF III, Meguid MM. Nutritional concepts and con-
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 6
Tumors of the Oropharynx
SNEHAL G. PATEL, MD, FRCS
JATIN P. SHAH, MD, FACS

It has been estimated that there will be about 8,400 proper2 as tumors of the arch tend to be less virulent
new cases and 2,100 deaths from pharyngeal cancer in than those arising at other subsites. For the purpose
the United States during 2001.1 The majority of tumors of tumor classification, however, 4 main anatomical
of this region are squamous cell carcinomas that are subdivisions are described (Table 6–1).
related to chronic abuse of tobacco and alcohol. The The anterior wall of the oropharynx is formed by
critical location of this part of the pharynx at the cross- the base or posterior third of the tongue bounded
roads between the respiratory and digestive tracts anteriorly by the v-shaped line of circumvallate
means that tumors involving the oropharynx are prone papillae. Numerous lymphatic aggregates give the
to alter swallowing, speech and breathing. Treatment base of the tongue its characteristic nodularity, a
planning for these tumors must therefore be guided normal feature that may cause great difficulty in the
not only by disease-free survival statistics but also by diagnosis of early lesions of this region. Lymphatics
the functional outcome of each therapeutic approach. from the tongue base course downward toward the
hyoid bone where they pierce the pharyngeal wall to
ANATOMY drain into the upper deep cervical chain or level II
nodes. The jugulodigastric lymph node, the largest
The oropharynx extends from the level of the hard of these nodes, is frequently the first to be involved
palate above to the hyoid bone below (Figure 6–1). by metastatic tumor followed by those at levels III
On a practical basis, this region may be divided into and IV. Disruption of normal lymphatic channels by
the palatine arch consisting of the soft palate, uvula the presence of a tumor or surgery to the neck may
and the anterior faucial pillar, and the oropharynx result in aberrant patterns of spread to levels I and V,

Anterior Posterior
View View

Figure 6-1. The anatomical boundaries of the oropharynx.

127
128 CANCER OF THE HEAD AND NECK

Table 6–1. ANATOMICAL SUBDIVISIONS parapharyngeal space with its base at the temporal
OF THE OROPHARYNX bone and its apex at the greater cornu of the hyoid
Anterior wall (glossoepiglottic area) bone. This potential space contains several important
Tongue posterior to the circumvallate papillae (base of tongue)
Vallecula excluding the lingual surface of the epiglottis
neurovascular structures such as the carotid artery, the
Lateral wall internal jugular vein, the sympathetic chain, and cra-
Tonsil nial nerves IX through XII (Figure 6–2). Involvement
Tonsillar fossa and faucial pillars
Glossotonsillar sulcus of this space not only results in cranial nerve deficits
Posterior wall and trismus, but also provides tumors access to the
Superior wall
Inferior surface of the soft palate
base of skull superiorly or the neck inferiorly.
Uvula The tonsil is the largest aggregation of lymphoid
tissue in Waldeyer’s ring and is characterized by deep
crypts in which squamous carcinomas may arise
or to the contralateral side of the neck. Crossover without causing obvious surface ulceration. The ton-
patterns of lymphatic drainage have been demon- sils have a rich lymphatic network that drains directly
strated and tumors involving or growing close to the through the pharyngeal wall into the upper deep cer-
midline exhibit bilateral nodal involvement in vical (jugulodigastric) nodes. Lymph node metastasis
approximately one-third of patients. is less frequent from primary tumors of the tonsillar
The lateral wall of the oropharynx includes the pillars compared to tumors of the tonsillar fossa.
tonsil, the tonsillar fossae, the faucial pillars and more Lesions of the posterior tonsillar pillar are more
posteriorly, the lateral pharyngeal wall that blends likely to metastasize to the spinal accessory and
into the posterior wall. Immediately lateral to the lat- upper posterior triangle nodes. Metastatic squamous
eral pharyngeal wall lies the inverted cone-shaped carcinoma deposits involving nodes from an asymp-

Figure 6-2. Cross-section of the oropharynx demonstrating its relationship to the parapharyngeal space.
 Tumors of the Oropharynx 129

tomatic, small tonsillar primary have a tendency to or referred pain to the ear that is mediated through
undergo cystic degeneration. Fine needle aspiration the glossopharyngeal and vagus nerves. Over two-
of the cystic mass may draw fluid that is often acel- thirds of patients present with a neck lump. As the
lular or non-diagnostic, prompting local excision of tumor grows and infiltrates locally, it may cause
the mass with a mistaken diagnosis of branchial cyst. progressive impairment of tongue movement which
Lymphatics from the upper part of the lateral wall affects speech and swallowing, and necrosis and
drain to the retropharyngeal nodes, of which the only secondary infection may result in foul breath or
constant one is the node of Rouvière situated close to even hemorrhage.
the skull base between the internal carotid artery and All patients must undergo a complete and thor-
the lateral wall of the pharynx. ough clinical examination of the upper aerodigestive
The posterior pharyngeal wall extends from the tract and the neck, including fiberoptic nasolaryn-
level of the hard palate and Passavant’s ridge superi- goscopy. Most aspects of the pharynx and larynx can
orly to the level of the hyoid bone inferiorly where it be readily assessed in the office with a flexible
becomes continuous with the hypopharynx. In con- endoscope under topical anesthetic, but areas such
trast to other areas of the oropharynx, the mucosa is as the pharyngoglossoepiglottic folds and the poste-
smooth and contains only occasional small aggre- rior surface of the soft palate may be difficult. The
gates of lymphoid tissue. The primary echelons of visual extent of the tumor is often misleading, and
drainage from posterior pharyngeal wall tumors are accurate assessment must include bimanual palpa-
the retropharyngeal nodes and the nodes at levels II tion of the tumor. Particular note must be taken of
and III. The risk of lymph node metastasis ranges the inferior limit and circumferential extent of the
from 25 percent for T1 lesions to over 75 percent for tumor, its superior extent towards the nasopharynx,
T4 tumors.3 and mobility of structures at or below the level of the
The roof of the oropharynx is formed by the hyoid. Advanced tumors that cause trismus may be
curved arch of the inferior surface of the soft palate better assessed under a general anesthetic. Morpho-
and the uvula in the midline. Tumors of the soft logically, a squamous cell carcinoma may present
palate drain lymph to the upper jugulodigastric and either as an exophytic (Figure 6–3) or ulcerative
the retropharyngeal nodes. About a third of patients (Figure 6–4) lesion. Tumors of the minor salivary
present with clinically positive neck nodes and glands may present as smooth, lobulated swellings
involvement of the tonsillar fossa increases this risk. without surface ulceration (Figure 6–5), and malig-
Occult nodal metastases occur in 16 percent of nant lymphomas typically cause nodular enlarge-
patients, and about 15 percent of patients who have ments in the tonsil or tongue base.
a midline primary lesion will have bilateral or con- Direct involvement of the XIIth nerve with the
tralateral neck metastases.4 tumor, or infiltration from a metastatic neck node
results in paralysis that is manifested by wasting of
CLINICAL PRESENTATION the ipsilateral tongue with deviation to that side on
AND DIAGNOSIS protrusion. Involvement of the glossopharyngeal and
vagus nerves near the skull base must be suspected
Small tumors at certain sites, such as the crypts of when there is impaired movement of the soft palate
the tonsils, the glossotonsillar sulci and the tongue and ipsilateral vocal cord paralysis respectively. Sim-
base rarely produce symptoms and are not always ilarly, involvement of the inferior alveolar nerve
easy to detect. When present, the initial symptoms (impaired sensation over the anterior chin which is the
of oropharyngeal cancer are often vague and non- sensory distribution of the mental nerve) and the lin-
specific, leading to a delay in diagnosis. Conse- gual nerve in the infratemporal fossa (altered sensa-
quently, the overwhelming majority of patients pre- tions over the lateral part of the tongue) are ominous
sent with locally advanced tumors. signs that indicate locoregionally advanced disease.
Presenting symptoms may include sore throat, Fine-needle aspiration cytology (FNAC) of any
foreign-body sensation in the throat, altered voice suspicious node in the neck at the initial consultation
130 CANCER OF THE HEAD AND NECK

be complemented by appropriate imaging studies in

these cases to rule out an obvious mucosal primary
lesion before an open biopsy of a suspicious neck
node is attempted.
Apart from the obvious advantages of CT and MRI
in detection of subclinical nodal disease, imaging can
also provide other information that may be vital to
treatment planning. The controversy about the superi-
ority of one imaging modality over the other seems
unwarranted because both CT and MRI have their spe-
cific advantages, and may be used to complement
each other based on the specific information required
for making accurate treatment decisions. As a general
rule, MRI enables superior distinction of tumor from
Figure 6-3. An exophytic lesion of the base of the tongue.
muscle and other soft tissue while CT is better at
imaging cortical bone. Gadolinium-enhanced MRI
generally allows the clinician to establish tissue has also been shown to reliably demonstrate invasion
diagnosis in patients in whom the primary tumor is along nerves. Both CT and MRI are effective in eval-
not readily visible. Occasionally, aspiration of cystic uating neck metastases, but accurate prediction of
fluid from a necrotic metastatic node may give a invasion of structures such as the carotid sheath and
false-negative result. The false-negative rate can be prevertebral fascia is usually not possible until direct
reduced somewhat by completely removing cyst assessment at surgery. Imaging may identify retropha-
fluid and repeating FNA of any residual solid mass. ryngeal nodes that are ordinarily out of bounds to pal-
A complete and detailed head and neck exam must pation. Imaging is also especially valuable in assessing
the neck in obese patients or those with a thick neck.
Assessment of the post-radiotherapy or postsurgical
neck is unreliable because differentiation between

Figure 6-4. An infiltrating, ulcerative lesion of the base of the Figure 6-5. An endoscopic view of a minor salivary gland tumor of
tongue. the base of the tongue.
 Tumors of the Oropharynx 131

tumor, edema, inflammation and fibrosis is difficult. Squamous Cell Carcinoma

18
FDG-PET scanning5 may be the most sensitive tech-
nique currently available for these situations. The role In common with squamous cancers at other upper
of imaging in the detection of early mandibular inva- aerodigestive sites, chronic abuse of tobacco is the
sion remains questionable, and a meticulous evalua- most important etiologic factor, and alcohol abuse
tion under anesthetic has been shown to be more reli- may potentiate its carcinogenic effect synergisti-
able in assessing bony involvement.6 A preoperative cally. Other factors such as genetic, environmental
Panorex (orthopantomogram) may be necessary to and dietary influences also play a part, and may
assess the state of the dentition prior to instituting explain some of the geographic variations in inci-
radiotherapy. Radiologic imaging, however, is essen- dence. The disease is more common in men than in
tial to treatment planning if a mandibulotomy or any women (2.5:1) and is most frequently seen between
form of mandibular resection is planned. Dynamic the sixth and seventh decades of life. Premalignant
contrast imaging using videofluoroscopy provides lesions such as leukoplakia and erythroplakia do not
vital information on the functional aspects of degluti- seem to have the same significance in predisposition
tion and protection of the airway, both pre- and post- for oropharyngeal cancer as they do for squamous
operatively. It is also a useful aid for prescribing carcinoma of the oral cavity.
speech and swallowing exercises. A plain radiograph The most common sites for carcinoma in the
oropharynx are the base of the tongue and the tonsil,
of the chest helps screen for metastatic carcinoma,
while tumors of the soft palate and posterior wall are
synchronous bronchial primary and coexisting acute
less common (Figure 6–6). Most squamous cancers
or chronic pulmonary disease. Further investigation
initially expand along the mucosal surface and even-
with chest CT scan, pulmonary function tests or bron-
tually invade the deeper structures, spreading along
choscopy is generally merited based only on the
fascial planes and neurovascular structures. The base
patient’s symptoms or an abnormal chest film.
of the tongue is an exception because tumors tend to
A detailed examination and biopsy under general
invade its musculature early, resulting in decreased
anesthetic may be the only accurate method of
mobility or fixation of the tongue and nodal metas-
assessing the extent of tumors such as those of the
tasis. The anterior surface of the soft palate is
tongue base that may be in a submucosal location. It
affected more frequently than its posterior surface
may be prudent to use this opportunity to carry out
and delineation of the lesion from leukoplakia and
dental extractions in patients with poor dentition
keratinization may be difficult in heavy smokers.
who will require radiation therapy in order to mini-
Tumors of the pharyngeal wall are commonly asso-
mize delay in treatment. The information collected
ciated with extensive submucosal spread and so-
by clinical, endoscopic and radiologic examination
called skip lesions.
is then collated and used to assign a TNM stage to
each individual tumor.
Pharyngeal

Pathology Wall

Tumors of the oropharynx may arise from any of its

Soft Palate
constituent tissues, but the vast majority of epithelial
tumors are squamous cell carcinomas. As there is a Base of Tongue
higher concentration of lymphoid tissue in this
region, the incidence of lymphomas is considerably
higher compared to other sites in the upper aerodi- Tonsil

gestive tract. The minor salivary glands of the soft

palate, uvula and base of tongue can be the site of
salivary gland tumors. Other rarer entities include soft
tissue sarcomas and metastases from distant sites. Figure 6-6. Site distribution of tumors of the oropharynx.
132 CANCER OF THE HEAD AND NECK

The majority of patients present with locoregion- Table 6–2. NODAL METASTASES
ally-advanced tumors (Figure 6–7). Between 30 and IN OROPHARYNGEAL CARCINOMA
80 percent of patients develop nodal metastases at Site Node Positive (%) Bilateral Nodes (%)
some stage of their disease (Table 6–2) and various Base of tongue 78 34
characteristics of the primary tumor may be respon- Tonsil 76 21
Soft palate 44 19
sible.7 Tumors arising in areas of rich lymphatics Anterior faucial pillar 45 7
such as the tongue base and tonsillar fossae have a Posterior wall 37 —
high risk of metastatic nodal disease at presentation
compared with those in other areas such as the soft
palate and anterior faucial pillar.8 Levels II, III and Patients with oropharyngeal tumors, especially pos-
IV are at greatest risk of metastasis. Involvement of terior pharyngeal wall tumors10 are at high risk to
levels I and V is rare (1.4% each) in the clinically N0 develop second and subsequent primary tumors.
neck but the risk is higher (12.6% for level I and Lymphoepithelioma or undifferentiated carci-
9.7% for level V) in the clinically positive neck. noma of nasopharyngeal type (UCNT) is a variant of
Level V involvement occurs only in presence of squamous cell carcinoma that is characterized by an
metastasis at other levels and isolated skip metasta- increased propensity to metastasize and by its
sis to level I is also extremely rare (0.4%).9 Although extreme radiosensitivity. While the squamous com-
the risk of nodal involvement is generally propor- ponent of the tumor may be extremely undifferenti-
tional to the size of the primary tumor, early-stage ated, a non-neoplastic lymphocytic infiltrate often
oropharyngeal tumors, especially those of the tonsil permeates widely throughout the tumor. Nodal
and tongue base, can give rise to massive nodal dis- metastases consist of squamous cells similar to
ease. The grade of the primary lesion does not seem those of the primary tumor and usually lack the reac-
to influence the risk of nodal metastases. Risk fac- tive lymphoid component of the primary tumor.
tors for bilateral nodal metastases include tumors of Lymphoma, especially the non-Hodgkin’s type,
the base of tongue or soft palate, tumors approach- accounts for about 8 percent of oropharyngeal
ing or involving the midline, and alteration of the tumors.11 The tonsil and base of tongue are the
cervical lymphatics either by tumor or treatment most frequently involved sites and B-cell lym-
(previous surgery, or irradiation or both). phoma is the most common type. Although the
Distant metastases, most often to the lungs, lesion arises in the submucosa, it can ulcerate the
bones and liver, occur in up to 20 percent of patients mucosa and present like a squamous cancer. An
with oropharyngeal tumors. The majority of these adequate biopsy specimen must be submitted to
patients have active locoregional disease, primary or avoid confusion with lymphoid hyperplasia. If a
recurrent, at the time of detection of metastases. lymphoma is suspected, the clinician must have the
foresight to consult the pathologist and submit
fresh tissue for special studies which may include
immunohistochemical stains, flow cytometry, and
molecular genetic techniques.
Salivary gland tumors arise from the minor
salivary glands of the soft palate and tongue base,
and account for about 5 percent of oropharyngeal
tumors.12 The majority of these tumors are malig-
nant and adenoid cystic carcinoma is the most com-
mon histologic variant. As with other sites in the
head and neck, the tumor has a tendency to spread
along nerve sheaths in the perineural lymphatics and
metastasizes late to lymph nodes, lung and bone.
Figure 6-7. Stage distribution of oropharyngeal tumors. Although the short-term prognosis for these tumors
 Tumors of the Oropharynx 133

is excellent, eventually about 60 to 80 percent of between the surgeon, radiation oncologist and med-
patients die from or with metastatic disease. ical oncologist. Specialist medical consultations and
appropriate investigations must be ordered for
TREATMENT GOALS AND patients suffering from diabetes, or cardiovascular,
TREATMENT ALTERNATIVES pulmonary or other medical problems. The process
of rehabilitation must begin before treatment is insti-
tuted, and successful rehabilitation depends on
General Principles
involvement of all the individuals who will be
Treatment of tumors of the oropharynx has the responsible for postoperative care of the patient, eg,
potential to cause significant functional deficit, the maxillofacial prosthodontist, nursing staff,
and the optimal treatment plan must strike a bal- speech therapists, nutritionists, physical therapists
ance between minimum functional derangement and social workers.
and long-term disease-free survival. Surgery or
radiation therapy, alone or in combination, are cur- Factors Affecting Choice of Treatment
rently accepted as standard treatment for oropha-
ryngeal cancer. Other modalities such as chemo- Although a variety of interrelated factors must be
therapy must be considered experimental and are considered as guidelines when choosing the appro-
generally reserved for patients with advanced or priate treatment, on a practical basis, the treatment
recurrent disease that is not amenable to conven- must be tailored to the individual patient.
tional therapy
Locoregional control and survival for patients Tumor Factors
with early tumors (T1-2) is equivalent with surgery
or radiation therapy. The decision to choose one Small, superficial lesions in accessible sites such as
form of therapy over the other must weigh the the soft palate or tonsil are easily treated by peroral
expectation of disease control against the perceived surgical excision with minimal functional deficit.
functional outcome of treatment. In selected On the other hand, patients with advanced tumors of
instances when a small primary tumor presents with the base of the tongue who require total glossectomy
advanced nodal disease, a so-called bimodality with or without laryngectomy may benefit from
approach using neck dissection followed by radia- nonsurgical treatment, reserving surgery for salvage.
tion to the primary site and neck may provide the Lesions with well-defined borders can be accurately
best functional results without compromising resected, but if the margins are diffuse or the lesion
locoregional control. Advanced lesions (stages III exists within “unstable” mucosa, radiation therapy is
and IV) are best treated using combined therapy usually the better option. Lymphoepitheliomas and
with radical surgery followed by postoperative radi- lymphomas are exquisitely sensitive to radiation
ation. Choosing optimal treatment for T3 to T4 while other tumors such as those of minor salivary
tumors of the base of the tongue is more difficult gland origin are not. Endophytic, deeply ulcerative
because radical surgery generally involves loss of a lesions are best treated with surgery and postopera-
significant part of the tongue and possibly the lar- tive radiation therapy, as these tumors respond
ynx. Due consideration must therefore be given to poorly to primary radiation and the results of surgi-
the option of organ preservation, using a combina- cal salvage are dismal.13
tion of chemotherapy and radiation, when laryngec-
tomy is required for surgical excision of the tumor. Patient Factors
Curative treatment may not be feasible for patients
with very advanced or disseminated disease, and Performance status and comorbidity are important
palliative therapy may be the only option. factors that affect outcome of treatment. Although
Optimal management of the patient’s disease aggressive therapy may be technically feasible, poor
hinges on close multidisciplinary cooperation performance status or significant comorbidity may
134 CANCER OF THE HEAD AND NECK

preclude safe delivery of treatment. The patient’s viduals who have had previous radiation therapy or
preference, ability and willingness to cope with the surgery. The following is a general description of the
treatment and its functional consequences may also commonly used approaches to tumors of the
influence the decision. The presence of advanced oropharynx, but obviously the one used for a partic-
dental and alveolar disease has the potential to delay ular patient will depend as much on the factors
and complicate radiation therapy. Surgical excision described as the surgeon’s individual preference.
may be the preferred option in such patients even if Transoral excision may be appropriate for very
the tumor would ordinarily be amenable to radiation select, small, superficial cancers with well-defined
therapy. Logistic problems and social factors must margins located in the anterior portion of the
also be considered and the input of the social worker oropharynx. Early tumors of the tonsils, faucial
and the family may be invaluable. arches and the soft palate may be safely resected
using either diathermy or transoral endoscopic laser,
Functional Outcome and Long-term Sequelae and a discontinuous neck dissection may be com-
bined if indicated.14 The resultant mucosal defect
The functional deficit that is expected to result from may be closed primarily, skin-grafted or left to
a proposed treatment is a useful parameter to help epithelialize. All other tumors that require resection
make the choice when one or more options are of bone, or those that are located more posteriorly,
known to produce equivalent locoregional control. mandate more extensive access.
For instance, both surgical excision and primary Anterior (supra- or transhyoid) pharyngo-
radiotherapy can be expected to control early lesions tomy has been used to approach selected small
equally well. Surgery for an easily resectable tumor lesions of the tongue base, posterior pharyngeal wall
results in minimal functional deficit and may be pre- and for low-grade salivary gland tumors.15 The
ferred over radiation therapy that invariably has irre- oropharynx is accessed by either transecting or
versible effects such as xerostomia and loss of taste. excising the hyoid bone (transhyoid approach) or
In addition, long-term sequelae of radiation such as displacing it inferiorly (suprahyoid approach) (Fig-
the risk of second tumors must be considered, espe- ure 6–8). After resection of the tumor inferiorly from
cially in younger patients. Conversely, when surgical the neck, the resultant defect is closed primarily. The
excision requires sacrifice of structures such as the main drawbacks of the procedure are that the vallec-
tongue or larynx, due consideration must be given to ula is entered blindly and access is very limited.
organ-sparing nonsurgical approaches. A lateral pharyngotomy approach may be used
for small lesions of the posterior and posterolateral
Surgical Treatment pharyngeal walls. The oropharynx is entered
through the mucosa of the superior aspect of the
Successful outcome after surgery should provide the pyriform sinus after carefully retracting the superior
patient with durable locoregional control of the dis- laryngeal nerve. Exposure, however, is limited supe-
ease and minimal functional deficit. This depends riorly by the lower border of the mandible, and this
on meticulous planning with accurate mapping of approach is applicable in only selected instances.
both surface and deep extent of the tumor. The The anterior midline labiomandibuloglosso-
anatomic extent of the surgical defect must be antic- tomy approach (Figure 6–9) may be used to resect
ipated in all dimensions, and the need for recon- locally limited lesions of the base of the tongue.
structive effort considered prior to surgery. Through a midline lip-splitting incision, a median
The approach chosen must afford good exposure, mandibulotomy is carried out and the tongue is
both for accurate and complete resection of the bisected anteriorly in its relatively avascular midline
lesion but also for reconstruction of the defect. Inci- to access the region of the base. After resection of
sions must be planned to provide optimal access the tumor, the surgical defect is closed primarily and
while minimizing cosmetic defects. Appropriate the bisected halves of the anterior tongue are sutured
modifications may be required when treating indi- back in layers, usually resulting in excellent postop-
 Tumors of the Oropharynx 135

Figure 6-8. Suprahyoid pharyngotomy.

erative function. The operation is, however, not tion of the anatomy of the region and results in fewer
advisable if excision of the tumor is likely to result functional deficits postoperatively as compared to
in a substantial soft-tissue defect with a tongue rem- the other two types of osteotomy.
nant of doubtful viability. For a paramedian mandibulotomy, the lower lip is
The mandibulotomy approach with paralin- split in the midline and the incision carried over into
gual extension, the so-called mandibular swing pro- the ipsilateral gingivolabial sulcus to just beyond the
vides the best exposure for resection of most tumors canine tooth. Bilateral flaps are raised for a short
of the oropharynx.16 The site of the mandibular distance, dissecting in the plane above the perios-
osteotomy directly influences the exposure obtained teum and taking care to limit dissection to the point
at surgery and the functional results of the proce- where the mental nerve exits the mental foramen.
dure. Table 6–3 describes the salient features of the We prefer to use an angled osteotomy (Figure 6–10)
3 types of mandibulotomy that have been in com- that creates a single notch and provides good stabil-
mon use. We prefer to use the paramedian mandibu- ity with very little risk of fracture. An oscillating
lotomy when extensive access is required to the power saw with the thinnest available blades is
oropharynx. This operation causes minimal disrup- essential for accurate bony cuts and to prevent

Figure 6-9. Anterior midline labiomandibuloglossotomy.

136 CANCER OF THE HEAD AND NECK

Table 6–3. SALIENT FEATURES OF THE 3 TYPES OF MANDIBULAR OSTEOTOMY

Lateral Median Paramedian

Site of osteotomy Through the body/angle of mandible In the midline Between lateral incisor and canine
Exposure Limited Good Good
Dental extraction May be necessary One central incisor Not required
Inferior alveolar nerve Must be transected Can be spared Can be spared
and vessels
Division of genial Not required Inevitable Not required-only the mylohyoid
muscles needs division
Mechanical stability Poor due to unequal pull of muscles Good Good
on the two mandibular segments
Fixation of osteotomy May require intermaxillary fixation which Miniplates or stainless Miniplates or stainless steel wire
interferes with maintenance of steel wire
postoperative oral hygiene
Postoperative radiation Osteotomy lies within the lateral portal— Lies outside the lateral Lies outside the lateral portal—safe
therapy increased risk of complications portal—safe

excessive bone loss. The vertical limb of the the field, and once they are transected the mandible
osteotomy is carried down to a level just beyond the can be swung out laterally to expose the oropharynx
dental apices between the lateral incisor and canine (Figure 6–11).
teeth, and the cut is then angled medially. This is After resection of the tumor and reconstruction
possible without extracting the teeth or exposing or of the defect, the mandibulotomy can be fixed using
damaging their roots because of their diverging con- either stainless steel wires or miniplates with com-
figuration (see Figure 6–10). After the osteotomy is parable stability.17 Pre-localizing the fixation drill
complete, the mucosa and muscles of the floor of the holes on the intact mandible, before the osteotomy
mouth are incised posteriorly right up to the anterior cuts are actually made, and fixation in more than
pillar of the soft palate. The floor-of-mouth incision one plane are probably more important to accurate
must be placed more toward the tongue than the dental occlusion and stability than the actual mode
alveolus so that there is an adequate mucosal cuff of fixation itself. If miniplates are preferred, 2 plates
attached to the alveolus. This step is vitally impor- are used across the osteotomy, one on the anterior
tant to accurate watertight closure of the incision. surface and the other is contoured to fit the inferior
The lingual nerve and the styloglossus muscle cross edge of the mandible (Figure 6–12). Slight discrep-
ancies in dental occlusion tend to correct themselves
spontaneously as the fracture site matures and
moulds to the stresses of chewing postoperatively.
The lip and neck incisions are then closed in layers
over suction drains as usual.
The base of the tongue may be difficult to assess
for the extent of a tumor due to its normal nodular-
ity—careful palpation is vital to ensure adequate
margins as excision proceeds. Advanced tumors of
the tongue are associated with diffuse infiltration,
and surgical margins have been reported positive by
some authors in as many as one-quarter of the
cases.18 Frozen-section evaluation of the margins
and the base of excision can therefore only minimize
Figure 6-10. A paramedian osteotomy can be safely sited
between the lateral incisor and the canine teeth to avoid damage or
the chances of incomplete resection. Partial glossec-
exposure of the dental roots. tomy may be oncologically adequate for limited
 Tumors of the Oropharynx 137

Figure 6-11. Incision of the floor of the mouth allows the mandible to be swung out laterally to gain
access to the tumor in the oropharynx.

tumors of the base of the tongue, and postoperative tissue such as a split-thickness skin graft or a free
functional outcome depends upon the orientation of radial forearm flap. For more advanced tumors,
the resection, the volume of tongue resected, the resectability depends on ascertaining that the under-
method of repair, as well as the mobility, sensitivity
and the shape of the tongue remnant. Substantial
defects of the tongue must therefore be adequately
and appropriately reconstructed (Figure 6–13).
Access to posterior pharyngeal wall lesions may
require transhyoid or lateral pharyngotomy, median
labiomandibular glossotomy or paramedian mandibu-
lotomy. Early lesions rarely involve the prevertebral
fascia and the intervening avascular retropharyngeal
space usually provides a good plane of cleavage dur-
ing surgical dissection. Superficial lesions that
involve only part of the pharyngeal circumference
can be excised safely while preserving the larynx.19 Figure 6-12. The two halves of the mandible are secured in place
Reconstruction of the defect requires thin, pliable using miniplates at the end of the procedure.
138 CANCER OF THE HEAD AND NECK

struction of segmental mandibular defects combined

with osseointegrated dental implants is necessary
for restoration of useful masticatory function.
Early lesions at some sites such as the soft palate
and the posterior pharyngeal wall are at low risk for
nodal metastases, and the clinically negative neck in
these patients may be safely observed. In all other
patients, elective treatment of the N0 neck must be
considered. In general, if the primary tumor is
treated with radiation therapy, the neck is included
Figure 6-13. Free radial flap reconstruction of the surgical defect
in the fields, and if surgical treatment is chosen for
after partial resection of the soft palate, and tonsil.
the primary, a selective neck dissection is carried
out. The uninvolved neck in well-lateralized lesions
lying prevertebral fascia is not involved, a question of the tonsil and tongue may be treated unilaterally,
that is most often resolved only at surgical explo- but both sides need treatment in lesions approaching
ration. Locally advanced pharyngeal wall tumors or involving the midline. Dissection of levels II, III
that involve a substantial portion of the circumfer- and IV generally encompasses the majority of nodes
ence usually require a total laryngopharyngectomy at risk in the clinically N0 neck. Grossly suspicious
with restoration of pharyngeal continuity using free nodes should be subjected to frozen-section analysis
jejunal transfer or other reconstructive options. and the dissection extended to include the remaining
As described above, the mandibulotomy approach levels as appropriate. Clinically involved nodes
provides excellent access to all sites within the require a comprehensive neck dissection including
oropharynx, and there can be no excuse for resecting
the uninvolved mandible solely to gain access to the
tumor. Tonsillar or lateral pharyngeal wall tumors
that abut against the periosteum of the mandible
need marginal resection of the ascending ramus of
the mandible (Figure 6–14). More advanced tumors
are resected by combining soft-tissue resection en
bloc with mandibulectomy, the so-called commando
operation (Figure 6–15). Appropriate bony recon-

Figure 6-14. Marginal resection of the ascending ramus of the Figure 6-15. Composite resection of an advanced base of tongue
mandible. tumor including the mandible: the "commando" operation.
 Tumors of the Oropharynx 139

all 5 nodal levels, and a modified radical neck dis- ferential defects are best restored using microvascu-
section preserving the spinal accessory nerve is the lar jejunal transfer or gastric pull-up. Restoration of
procedure of choice. Bilaterally involved nodes are mandibular continuity after segmental resection
treated with simultaneous or staged bilateral neck using free-tissue transfer with secondary osseointe-
dissection. Postoperative radiation therapy is given grated dental implants has the potential for resulting
for the usual indications, based on adverse features in excellent cosmesis and function, and this complex
of either the primary or the neck nodes. issue has been discussed in other chapters.
Locally advanced oropharyngeal tumors can Ancillary procedures such as cricopharyngeal
cause considerable difficulty during endotracheal myotomy, laryngeal suspension and palatal augmen-
intubation, mainly by obstructing visualization of tation may help improve functional results after
the larynx, but also because invasion of the ptery- major glossectomy. Patients who have had major
goid muscles may result in trismus. Although oropharyngeal resection and reconstruction, and
fiberoptic endoscope-guided endotracheal intuba- those scheduled for postoperative radiation therapy
tion is an option, it may be safer to perform a pre- generally require prolonged nutritional support, and
liminary tracheostomy under local anaesthetic. a percutaneous endoscopic gastrostomy must be
Patients who have had significant surgical resection considered at the time of the operation.
and reconstruction require a temporary tra-
cheostomy to protect the airway in the postoperative NONSURGICAL TREATMENT
period. A cuffed, low-pressure high-volume tra-
cheostomy tube minimizes aspiration in the early Treatment of early tumors of the oropharynx using
postoperative period. Apart from the ability to toler- radiation therapy has been reported to be equally
ate plugging of the tube, factors such as the efficacy effective as surgical excision20 with the advantage of
of deglutition, the extent of aspiration and the per- “superior function.” Even for tumors of the base of
formance status of the patient generally determine the tongue21 where the functional results have been
when postoperative decannulation of the tra-
cheostomy can be safely undertaken.
Deeply invasive tumors only need to breach the
hyoepiglottic ligament to gain access to the pre-
epiglottic space (Figure 6–16) from where they can
spread to involve the framework of the larynx. Com-
plete excision of such lesions requires either partial
supraglottic or total laryngectomy in addition to
excision of the base of the tongue.
For practical purposes, major soft-tissue defects
of the oropharynx can be divided into those that
require thin, pliable flaps for resurfacing and those
that need bulkier myocutaneous flaps to provide vol-
ume. The posterior pharyngeal wall is an example of
the former, and is best resurfaced using either a split
skin graft or a free radial forearm flap. On the other
hand, substantial defects of areas including the base
of the tongue and tonsillar region need reconstruc-
tion with bulkier myocutaneous flaps such as the
pectoralis major or the latissimus dorsi pedicled
flaps or a composite free flap. Pedicled myocuta-
neous flaps are generally used to reconstruct partial Figure 6-16. Invasion of the preepiglottic space from a tumor of
circumference defects of the pharynx while circum- the base of the tongue.
140 CANCER OF THE HEAD AND NECK

assessed, this “advantage” of radiation over surgery opposed portals. Depending on the risk of occult
is largely assumed due to selection bias of favorable nodal metastases, the entire neck may need to be
lesions. There is no prospective randomized trial for irradiated even if there is no clinical evidence of
cancer of the base of the tongue comparing the two metastases. For patients presenting with clinically
modalities with respect to tumor control and func- palpable nodal disease, bilateral neck treatment is
tional assessment. In general, superficial and exo- recommended based on the relatively high risk of
phytic lesions are best treated by radiotherapy, and contralateral nodal metastases. Except for very
deeply infiltrating lesions are best treated by surgery radiosensitive tumors such as undifferentiated carci-
followed with postoperative radiotherapy. Surgical noma, especially of the nasopharyngeal type,
treatment of small lesions at most other sites, with planned neck dissection, either before or after radio-
the probable exception of the soft palate, produces therapy to the primary tumor is advisable for the
very little functional deficit, in contrast to radiation majority of patients with significant neck disease.
therapy that almost invariably causes irreversible Postoperative radiotherapy is indicated for large
xerostomia and loss of taste, with the potential risk or infiltrating primary tumors, high-risk features of
of dental decay and radionecrosis. the primary tumor such as lymphatic or vascular
For more advanced tumors, initial treatment with invasion, close or positive surgical margins, multiple
nonsurgical “organ-sparing” approaches have nodal involvement or extracapsular spread from
recently come into vogue and concurrent chemora- nodal metastasis. A dose of 60 Gy is generally deliv-
diation therapy seems to hold promise. ered to the primary site and involved nodal areas, and
areas of residual disease are boosted to higher doses
Radiation Therapy of up to 70 Gy using either electron beam therapy or
brachytherapy catheters. The opposite uninvolved
Conventional techniques have delivered radiation side of the neck in patients with unilateral nodal dis-
using external beam therapy, brachytherapy or a com- ease is electively irradiated to a dose of 50 Gy based
bination of both. More recent advances include altered on the high risk of contralateral metastases.
fractionation schedules, radiation combined with
chemotherapy or other sensitizers, and the use of accu- Role of Chemotherapy and
rately targeted beams with three-dimensional treat- Organ-preserving Approaches
ment planning or intensity-modulated radiotherapy.
Important considerations in the delivery of radiation Although numerous randomized trials have failed to
therapy include determination of adequate treatment demonstrate any survival benefit for neoadjuvant or
volume (initial portals), reduction of portals at the sequential chemotherapy schedules, the major spin-
appropriate doses (shrinking fields), design of neck off of the neoadjuvant approach was the observation
portals, boosting the site of the primary tumor, and that function of important structures such as the lar-
hyperfractionation. Radiation portals are designed to ynx and tongue could be preserved without compro-
include adequate margins around the primary tumor as mising local control or survival.26 More recently, the
well as the neck nodes, especially the retropharyngeal radiosensitizing effects of chemotherapy have been
nodes which may be involved in as many as 50 percent exploited in designing concurrent chemoradiation
of patients with stage III and IV tumors.22 Tumors in protocols, and 3-year local control rates of 64 per-
sites such as the tongue base in selected patients can cent were achieved at the Memorial Sloan-Kettering
be effectively boosted using interstitial brachyther- Cancer Center (MSKCC) for a subset of patients
apy.23 Treatment using more than one daily fraction, or with oropharyngeal tumors treated with concomitant
hyperfractionation,24 and the use of the radiation sen- chemoradiation and delayed accelerated fractiona-
sitizer nimorazole25 have been reported to have an tion.27 For the surgeon, there are several considera-
advantage over conventional regimes. tions in operating on patients who have persistent or
Except for well-lateralized lesions of the tonsil, residual disease after nonsurgical treatment. Apart
most other tumors require the use of parallel from the technical difficulties and risks associated
 Tumors of the Oropharynx 141

with surgery in previously treated patients, assess- plications associated with poor oral hygiene, naso-
ment of the margins of the tumor may be extremely gastric feeding tubes, tracheostomy tubes, deep vein
difficult and unreliable, especially in tumors of the thrombosis, and decubitus ulcers.
base of the tongue. Although well-planned nonsurgi- Mucositis during radiation therapy can be severe
cal therapy has the potential to preserve function, it enough to affect swallowing and nutritional intake,
must also be emphasized that these approaches requiring institution of tube feeding to prevent signif-
require special multidisciplinary expertise and expe- icant weight loss. In some patients, this may prolong
rience, and their current use should generally be the course of radiation or even force it to be aban-
restricted to specialized head and neck units or to a doned with adverse prognostic effect. Decreased
clinical trial setting. mucus secretion combined with an increase in vis-
cosity cause symptoms such as dry mouth and a
SEQUELAE, COMPLICATIONS AND sticky throat, depending on the fields of radiation.
THEIR MANAGEMENT Xerostomia and loss of taste sensation are however
not as severe as those after radiation for oral cavity
Although modern anesthetic and surgical technique tumors because uninvolved oral mucosa and one
has greatly increased the safety of surgery for parotid can be safely shielded. Desquamation of the
oropharyngeal tumors, careful planning and meticu- skin of the neck may cause painful ulceration and
lous technique are vital to successful outcome. The may delay completion of therapy. The incidence of
most common complications of surgery arise due to soft-tissue complications such as fibrosis and
difficulties associated with inadequate exposure and radionecrosis has decreased significantly with mod-
the failure to anticipate the need for reconstruction. ern radiotherapy techniques, but may still have a dev-
Incisions must be planned to take previous surgery astating impact on the patient’s quality of life. In
and/or radiation into consideration. It is important to addition, persistent or new ulceration at the site of the
resist the temptation to close a borderline surgical primary tumor may make it impossible to rule out
defect primarily as any tension or tightness almost residual tumor or recurrence. Osteoradionecrosis of
always results in a breakdown of the suture line with the mandible is a particularly difficult problem to
all its attendant complications such as fistula, infec- treat, but its development can be largely prevented by
tion and major vessel erosion. Poor surgical tech- a few simple precautions. Almost all bone necrosis
nique and inappropriate reconstruction are also likely occurs around diseased teeth within the radiation
to result in narrowing of the lumen and/or outlet of fields, and it is vital that dental and alveolar disease
the neo-pharynx causing difficulties in swallowing. be adequately treated before radiation is commenced.
In addition, inadequate clearance and pooling of Brachytherapy using interstitial implants runs the
saliva predisposes to aspiration and pulmonary com- risk of producing major hemorrhage that may require
plications. Conservative measures to improve the sit- surgical control. Complications such as soft tissue
uation (such as dilation) are generally inappropriate and bone necrosis are more common after implants,
and almost always ineffective, and corrective recon- but appropriate treatment selection combined with
structive surgery can be extremely difficult. Aspira- good nursing care can minimize the risk. Combining
tion of saliva, especially during the early postopera- chemotherapy with radiation to treat locally
tive period, is a common but generally transient advanced tumors can result in severe toxicity and a
consequence of surgery. Most patients overcome higher-than-usual rate of treatment-related mortality.
these initial problems with appropriate rehabilitative
therapy, and long-term aspiration is usually a result REHABILITATION AND QUALITY OF LIFE
of poor surgical planning and inadequate or inappro-
priate reconstruction. Complications such as postop- Although appropriate reconstructive measures can
erative bleeding and hematoma, wound breakdown, minimize the effect on function, rehabilitation is
and chyle fistulae can follow neck dissection. Expert often a prolonged and painstaking process that
postoperative nursing care should minimize the com- requires a great deal of patience. Successful reha-
142 CANCER OF THE HEAD AND NECK

bilitation depends on close multidisciplinary coop- Table 6–4. 2-YEAR ACTUARIAL LOCAL CONTROL RATES
eration between the surgeon, the speech therapist, FOR EXTERNAL BEAM RADIOTHERAPY
the prosthodontist, the dietitian, the nursing staff OF CARCINOMA OF THE BASE OF TONGUE

and the physiotherapist. Cessation of high-risk No. of

Author Patients T1 (%) T2 (%) T3 (%) T4 (%)
activity such as smoking and alcohol abuse must be
emphasized. Jaulerry37 166 96 57 45 23
Fein38 107 90 92 76 40
Quality of life and functional issues are now rec- Henk49 33 – 78 72 –
ognized as important outcome measures of treat-
ment but data on these is largely retrospective and
Surgery is equally effective in controlling early
subjective. There is however, objective proof that
lesions of the base of the tongue. Although a retro-
even nonsurgical treatments that are delivered with
spective report has shown that radiation therapy pro-
the purpose of organ preservation can cause func-
vides a better post-treatment performance status than
tional problems. Problems are especially associated
surgery for both early as well as advanced tumors,21
with eating dysfunction28 and pain control, but the
there are no prospective randomized comparisons of
quality of vocal function may also suffer.29 Quality-
the oncologic and functional results in the literature
of-life measures need to be undertaken prospec-
of surgery versus radiation alone or combined treat-
tively, preferably using pretreatment function as a
ment. Table 6–6 lists the survival rates and functional
baseline, and carrying out long-term longitudinal
results after surgical treatment of base-of-tongue
assessments using devices that are simple to use and
tumors as reported in recent literature. The stage-
which take cultural differences into account. It is
wise survival rates after treatment for cancer of the
also vital that quality-of-life assessments are
base of the tongue are shown in Table 6–7.
reported in conjunction with survival statistics to
allow meaningful interpretation. Carcinoma of the Tonsil
Long-term follow-up of these patients is essen-
tial for monitoring locoregional recurrence, distant Table 6–8 lists the local control rates after radical
metastases and second primary tumors. Periodic radiation therapy for tonsillar carcinoma. Local
clinical examination must be combined with the recurrence rates are, however, unacceptable for more
judicious use of imaging and biopsy under anes- advanced disease that has spread to involve the base
thetic in suspicious cases. of the tongue (47%) or the lateral pharyngeal wall
(33%).30 Although surgical resection is not com-
OUTCOMES AND RESULTS monly used for early tumors of the tonsil, excellent
OF TREATMENT control rates have been reported for such a policy.31
Surgery combined with postoperative radiation is
As discussed above, outcome measures must include generally recommended for locally advanced lesions
evaluation of function as well as control of tumor and but there are advocates of radical irradiation, reserv-
survival statistics. Unfortunately, most series have ing surgery for salvage.32 Some authors33 have
reported only limited information that is based on ret- shown a survival benefit for combination therapy in
rospective assessment. The following is a compilation the treatment of advanced tonsillar carcinoma while
of results of treatment for tumors involving each of others34 could not demonstrate any advantage in
the individual subsites within the oropharynx.
Table 6–5. RESULTS OF COMBINED EXTERNAL BEAM
Carcinoma of the Base of the Tongue AND BRACHYTHERAPY FOR CARCINOMA
OF THE BASE OF TONGUE
The results of primary irradiation in recently No. of 2-Year 5-Year
reported series of base-of-tongue carcinomas treated Author Patients Local Control (%) Survival (%)
by external beam radiotherapy alone are listed in Harrison23 36 87.5 87.5
Table 6–4 and those for external beam with Crook39 48 75 50
Puthawala40 70 83 33
brachytherapy are listed in Table 6–5.
 Tumors of the Oropharynx 143

Table 6–6. SURVIVAL AND FUNCTIONAL RESULTS AFTER SURGICAL TREATMENT OF BASE OF TONGUE TUMORS
Concomitant /
Total Mandibular Impaired “Useful” Severe Interval
No. of Survival Glossectomy Resection Swallowing Speech Aspiration Laryngectomy
Author Patients (%) (%) (%) (%) (%) (%) (%)

Weber18 n=27 51 at 2 years 27 — 56 92 11 0/8

Ruhl41 n=54 41 at 5 years 54 — — — — —
Razack42 n=45 20 at 5 years 45 49 69 84 37 40 / 13
Gehanno43 n=80 65 at 1 year 80 — 49 39 — —
Kraus44 n=100 65 at 5 years — 14 — — — 20

treating stage III and IV disease using a combined rules for tumor staging: oropharyngeal tumors are
modality approach. Table 6–9 lists the stage-wise classified by size while hypopharyngeal tumors are
survival of patients treated for tonsillar carcinoma. classified according to the number of sites involved.
Combined with their relative rarity, this makes retro-
Carcinoma of the Posterior Pharyngeal Wall spective comparisons of treatment modalities unreli-
able and difficult.
The staging of posterior pharyngeal wall tumors is Radiation therapy alone has limited effectiveness
often difficult because most lesions transgress 2 sep- in treatment mainly because of the technical diffi-
arate anatomical regions that have their own distinct culty in delivering adequate doses to tissue in close
proximity to the spinal cord, but also because these
Table 6–7. STAGE-WISE SURVIVAL RATES IN PATIENTS tumors are not very radiosensitive.
TREATED FOR CARCINOMA OF THE BASE OF THE TONGUE Surgical treatment of these tumors is prone to a
Follow-up Stage I Stage II Stage III Stage IV high incidence of local failure which ranges between
Author (yrs) (%) (%) (%) (%) 30 and 40 percent.3,10 Local recurrence increases
Thawley45 5 50 44 45 28 from 16 percent for stage I to 63 percent for stage IV,
Weber18 5 100 72 50 30
and only about 40 percent of patients are success-
Barrs46 3 68 55 55 11
Kraus44 5 77 77 64 59 fully salvaged. Table 6–10 shows a list of studies that
Foote47 5 60 48 76 20–35* have reported the results of treatment of posterior
* Tumors were staged based on the American Joint Committee on Cancer, pharyngeal wall tumors.
1988 recommendations.

Carcinoma of the Soft Palate

Table 6-8. LOCAL CONTROL RATES AFTER RADICAL
Primary irradiation controls early lesions effectively
RADIOTHERAPY FOR CARCINOMA OF
but local control rates for T3 and T4 tumors are 45
THE TONSILLAR FOSSA
and 25 percent respectively, and the results of sal-
No. of
Author Patients T1 (%) T2 (%) T3 (%) T4 (%) vage surgery in these patients are poor.35 Overall 5-
year survival rates range from 80 to 90 percent for
Bataini48 465 90 84 64 47
Fein38 200 87 79 71 44 stage I and II tumors and 30 to 60 percent for stage
Henk49 52 100 58 76 – III and IV lesions36 (Table 6–11).

Table 6–9. RESULTS OF TREATMENT OF TONSILLAR CARCINOMA

Author No. of Patients Follow-up (yrs) Stage I (%) Stage II (%) Stage III (%) Stage IV (%)

Perez50 218 3 76 40 42 25
Spiro34 117 3 89 83 58 49
Dasmahapatra33 174 5 83 72 23 15
Amornmarn51 185 5 100 73 52 21
Mizono52 171 5 92 77 56 29
Givens53 104 5 93 57 27 17
144 CANCER OF THE HEAD AND NECK

Table 6–10. RESULTS OF TREATMENT OF POSTERIOR in patients with oral and oropharyngeal squamous carci-
PHARYNGEAL WALL CARCINOMA noma. Clin Otolaryngol 1997;22:239–45.
7. Shah JP. Patterns of cervical lymph node metastasis from
No. of Follow-up Survival squamous carcinomas of the upper aerodigestive tract.
Author Patients Treatment* (yrs) (%) Am J Surg 1990;160:405–9.
Wang54 36 R 3 25 8. Lindberg RD. Distribution of cervical lymph node metastases
Pene55 131 S, R 5 3 from squamous cell carcinoma of the upper respiratory
Marks56 51 R±C 3 14 and digestive tracts. Cancer 1972;29:1446–50.
Schwaab57 24 C+R 3 60 9. Candela FC, Kothari K, Shah JP. Patterns of cervical node
5 25 metastases from squamous carcinoma of the oropharynx
Jaulerry58 98 R 3 30 and hypopharynx. Head Neck 1990;12:197–203.
5 14 10. Spiro RH, Kelly J, Vega AL, et al. Squamous carcinoma of the
Spiro10 78 S±R 2 49 posterior pharyngeal wall. Am J Surg 1990;160:420–3.
5 32 11. Stell PM, Nash JRG. Tumours of the oropharynx. In: Kerr A,
editor. Scott-Brown’s otolaryngology. 5th ed., London:
*R = radiation, S = surgery, C = chemotherapy
Butterworth; 1987.
12. Spiro RH, Koss LG, Hajdu SI, Strong EW. Tumours of minor
salivary gland origin: a clinicopathologic study of 492
Table 6–11. RESULTS OF TREATMENT FOR cases. Cancer 1973;31:117–29.
CARCINOMA OF THE SOFT PALATE 13. Rodriguez J, Point D, Brunin F, et al. Surgery of the orophar-
No. of Follow-up Survival
ynx after radiotherapy. Bull Cancer Radiother 1996;83:
Author Patients Treatment* (yrs) (%) 24–30.
14. Eckel HE, Volling P, Pototschnig C, et al. Transoral laser
Esche59 43 I±R 3 81 resection with staged discontinuous neck dissection for
5 64 oral cavity and oropharynx squamous cell carcinoma.
Keus60 146 R 3 59 Laryngoscope 1995;105:53–60.
5 53 15. Zeitels SM, Vaughan CW. Suprahyoid pharyngotomy for
Leemans61 52 S, R, C, L 5 77 oropharynx cancer including the tongue base. Arch Oto-
Medini62 24 R 3 81 laryngol Head Neck Surg 1991;117:757–60.
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16. Spiro RH, Gerold FP, Shah JP, et al. Mandibulotomy approach
apy, L = laser resection. to oropharyngeal tumours. Am J Surg 1985;150:466–9.
17. Shah JP, Kumarawamy SV, Kulkarni V. Comparative evalua-
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1997;107:1316–21. 62. Medini E, Medini A, Gapany M, Levitt SH. External beam
42. Razack MS, Sako K, Bakamjian VY, Shedd DP. Total glos- radiation therapy for squamous cell carcinoma of the soft
sectomy. Am J Surg 1983;146:509–11. palate. Int J Radiat Oncol Biol Phys 1997;38:507–11.
 7
Cancer of the Nasopharynx
SUZANNE L. WOLDEN, MD

Nasopharyngeal carcinoma is rare in the United floor is formed by the superior surface of the soft
States, with an annual incidence of 0.6 per 100,000 palate and is in communication with the oropharynx
people. The incidence in Southern China is 50 times at the level of the uvula. The posterior wall of the
higher than in the United States.1 Native people of nasopharynx lies anterior to the first 2 cervical ver-
North Africa, the Middle East, Alaska, and Malaysia tebrae, pre-vertebral and buccopharyngeal fascia,
have an intermediate risk. The peak incidence for superior pharyngeal constrictor muscles and the
this cancer occurs in the fourth to fifth decade of life pharyngeal aponeurosis. The roof is formed by the
but it may occur in children and in the elderly. The basisphenoid and basioccipital bones of the skull
male to female ratio is 2 to 3:1. base. The lateral walls lie medial to the maxillopha-
The etiology of nasopharynx cancer is thought to ryngeal space, pterygoid plates, and parapharyngeal
be multifactorial with genetic, viral, dietary, and space. The eustachian tube orifices enter the
environmental influences. A genetic predisposition nasopharynx in the lateral walls and each is sur-
has not been explicitly demonstrated but data from rounded by a cartilaginous protuberance called the
China show common human leukocyte antigen torus tubarius. A recess behind the torus tubarius,
(HLA) patterns among some patients with the dis- Rosenmüller’s fossa, is the most common location
ease.2 The Epstein-Barr virus (EBV) has been for cancers to arise.
closely associated with cancer of the nasopharynx. Cancers of the nasopharynx have multiple routes
Molecular studies have shown evidence of EBV for local spread. Tumors commonly extend into the
infection of malignant epithelial cells within a nasal cavity, oropharynx, parapharyngeal space and
majority of tumor specimens.3 Clinical correlation skull base. The sphenoid sinus is more commonly
confirms that many patients have elevated antibody invaded than the ethmoid or maxillary sinuses. The
titers to EBV that subsequently decrease with effec- orbit, cervical vertebrae and pterygoid structures
tive treatment of the cancer. A diet high in salted may be involved in advanced disease. Invasion of the
fish, especially during childhood, has been impli- clivus occurs frequently. Tumors may extend
cated as a risk factor among Southern Chinese.4 through the foramen lacerum, ovale, or spinosum to
Salted fish contains a known carcinogen, dimethyl- the cavernous sinus, potentially involving cranial
nitrosamine. Cigarette smoking also appears to be a nerves (CN) II to VI. Less commonly, tumors may
weak risk factor.5 invade the cranium through the carotid canal, jugu-
lar foramen, or hypoglossal canal.
ANATOMY Branches of the external carotid artery provide
blood supply to the nasopharynx while venous
The nasopharynx is a hollow passageway, lined by drainage is through the pharyngeal plexus, to the
mucosa, that serves to connect the nasal cavity to the internal jugular vein. Nerve supply is provided by
oropharynx (Figure 7–1). It is bounded anteriorly by branches of cranial nerves V2, IX, and X, as well as
the posterior nasal choanae and nasal septum. The sympathetic nerves. The nasopharynx has a rich

146
 Cancer of the Nasopharynx 147

Figure 7–1. Mid-sagittal section of the nasopharynx and surrounding structures. Inset
demonstrating the relationship of the nasopharynx to foramina of the skull base.

lymphatic network with multiple pathways for Jacod’s syndrome (CN II to VI) and Villaret’s syn-
drainage. The first echelon lymph nodes are in the drome (CN IX to XII and sympathetic nerves). The
parapharyngeal and retropharyngeal space. The former may result from intracranial extension to the
highest paired lymph nodes in this chain are named cavernous sinus and the latter may occur when
the nodes of Rouvière. Drainage to the jugular chain nerves are invaded in the retropharyngeal space.
may occur by way of the parapharyngeal lymph Symptoms of advanced tumors may also include
nodes or by direct channels. A separate direct path- trismus, dysphagia, and proptosis. Distant metastatic
way leads to lymph nodes of the spinal accessory disease is detected in 3 percent of patients at diag-
chain, in the posterior triangle. Further drainage may nosis but may occur in up to 50 percent of patients
occur to the contralateral neck and down the cervi- during the course of the disease.7–9 The most com-
cal chains to the supraclavicular lymph nodes. mon sites of hematogenous spread are the lungs,
bones and liver.
Diagnosis The diagnosis of nasopharynx cancer is made by
biopsy, preferably of the primary tumor. A variety of
Presenting symptoms may include a neck mass, neoplasms may arise within the nasopharynx,
epistaxis, nasal obstruction, a change in voice qual- including lymphomas and sarcomas. This chapter is
ity, pain, otalgia, decreased hearing, or cranial neu- restricted to epithelial carcinomas, categorized by
ropathies. Approximately 85 percent of patients have the World Health Organization (WHO) into 3 histo-
cervical adenopathy and 50 percent have bilateral logic types. Type I is described as keratinizing squa-
neck involvement.6 Serous otitis media may occur mous cell carcinoma and Type II is non-keratinizing.
due to eustachian tube obstruction. Cranial nerve VI Type III, undifferentiated carcinoma, is the most
is most frequently affected but multiple cranial common subtype.10 The term lymphoepithelioma is
nerves may be involved. Common combined neuro- often used to describe epithelial carcinomas with a
logic findings are described as petrosphenoid or rich infiltrate of benign lymphocytes.
148 CANCER OF THE HEAD AND NECK

A complete work-up includes a history and phys- system. The AJCC/UICC system typically used in
ical examination, including visualization of the the United States and the western world is outlined
nasopharynx by endoscopy or mirror examination. in Table 7–1.13
Magnetic resonance imaging (MRI) and/or comput-
erized tomography (CT) of the skull base, nasophar- Treatment Goals and
ynx and neck is necessary to determine the extent of Treatment Alternatives—The Role
disease (Figure 7–2). Every patient should have a of Multidisciplinary Treatment
chest radiograph, complete blood count, urinalysis,
biochemical profile, including liver and kidney func- Cure is the goal of treatment for most patients with-
tion tests, and serum IgA titers to the EBV viral cap- out distant metastases. Prognosis depends upon dis-
sid antigen. Prior to treatment with radiotherapy, ease stage, histology, and biological factors such as
patients require a dental evaluation. Bone scan and degree of angiogenesis.9,14–16 Palliation of symptoms
CT scan of the lungs or liver should be done if there is a secondary goal for patients with curable disease
is reason to suspect metastases because of symptoms and a primary goal for patients with distant metasta-
or results of standard tests. Positron emission tomog- tic disease. Palliative approaches range from sup-
raphy (PET) scan is a new imaging modality that portive care to chemotherapy, radiation therapy and,
may prove to be useful in some clinical situations.11 rarely, surgical intervention.
Numerous staging systems for nasopharynx can- The optimal management of nasopharynx cancer
cer have been used throughout the world. The Ho requires multidisciplinary collaboration. A head and
system has been used for decades in China and has neck surgeon often makes the diagnosis and per-
been prognostically validated.12 The American Joint forms the necessary biopsies. The patient should be
Committee on Cancer/Union Internationale Contre referred to a radiation oncologist as soon as the diag-
Cancer (AJCC/UICC) staging classification was nosis is established, as radiotherapy is the foundation
modified in 1997 to incorporate features of the Ho of curative treatment. A medical oncologist should

Figure 7–2. Magnetic resonance images (MRI) of an advanced

nasopharyngeal cancer. A, Axial T2-weighted image with fat sup-
pression demonstrating a large, left-sided nasopharynx tumor with
parapharyngeal extension and skull base invasion. B, Sagittal T1-
A weighted image of the same tumor.
 Cancer of the Nasopharynx 149

Table 7–1. 1997 AJCC/UICC NASOPHARYNGEAL However, the standard of care for patients with
CANCER STAGE CLASSIFICATION advanced locoregional disease has recently changed
T Stage Primary Tumor Extent in the United States. Despite a number of negative
T1 Confined to the nasopharynx trials of neoadjuvant and post-radiation chemother-
T2 Extends to oropharynx or nasal cavity apy,17–19 a large Head and Neck Intergroup Trial
2a Without parapharyngeal extension
2b With parapharyngeal extension
(#0099) was conducted in the United States to study
T3 Invades bones or paranasal sinuses the effect of concurrent and adjuvant chemotherapy
T4 Involvement of cranial nerves, intracranial con-
with radiotherapy.20 Patients with 1992 AJCC
tents, infratemporal fossa, hypopharynx or orbit
Stage III and IV (but M0) disease were randomized
N Stage Lymph Node Disease to receive 70 Gy radiation therapy alone, or the same
N0 No lymph node metastases radiotherapy with 3 cycles of concurrent cisplatin
N1 Unilateral lymph node(s) ≤ 6 cm
chemotherapy followed by 3 cycles of cisplatin and
N2 Bilateral lymph nodes ≤ 6 cm
N3 Metastases in lymph nodes 5-fluorouracil. Patients in the combined modality
3a Greater than 6 cm arm enjoyed a significant improvement in 3-year
3b With extension to the supraclavicular fossa
progression-free survival (69% vs. 24%, p< 0.001)
M Stage Distant Metastases
and overall survival (76% vs. 46%, p < 0.001) over
M0 Absent patients treated with radiotherapy alone.
M1 Present
Patients with stage II cancers according to the
Stage Group T Stage N Stage M Stage 1997 AJCC criteria were previously classified as
I T1 N0 M0 stage III in the 1992 system and would have been
IIA T2a N0 M0 eligible for the Intergroup trial. For this reason, it is
IIB T2b N0 M0
T1–T2b N1 M0
recommended that patients with 1997 AJCC stage II
III T3 N0–1 M0 to IVB disease receive combined modality therapy.
T1–T3 N2 M0 Based on current data, patients with stage I tumors
IVA T4 N0–2 M0
IVB T1–4 N3 M0 should be managed with radiotherapy alone and
IVC T1–4 N0–3 M1 those with stage IVC disease should be treated with
Data from: L. Sobin and C. Wittekind, editors, UICC, TNM classification of chemotherapy, adding radiation for palliation of
malignant tumors. 5th ed. New York: Wiley-Liss; 1997. local symptoms.
also be consulted because the role of chemotherapy
is increasing in the treatment of this disease. Other Surgical Treatment
important members of the multidisciplinary team
The role of surgery in nasopharynx cancer is limited.
include the radiologist, pathologist, and dentist. Spe-
Surgical biopsy is necessary to establish the diagno-
cialized nurses, dieticians, occupational therapists
sis. Neck dissection is indicated only if there is evi-
and counselors may also provide useful services.
dence of residual disease in cervical lymph nodes fol-
Factors Affecting Choice of Treatment
lowing treatment with radiotherapy with or without
chemotherapy. Nasopharyngectomy is a challenging
Because of anatomical constraints and the radiosen- procedure that may be performed by highly special-
sitivity of carcinoma of the nasopharynx, primary ized surgeons in selected patients with limited resid-
surgical resection is not indicated. Radiation therapy ual or recurrent disease within the nasopharynx.21
is the principal treatment modality for curative ther-
apy and may also be used to palliate local symp- Nonsurgical Treatment
toms. Chemotherapy has been studied as an adjuvant
to primary radiotherapy and serves as systemic treat- Effective radiotherapy requires careful simulation and
ment for patients with disseminated disease. treatment planning. The patient generally lies supine
The basic treatment of nasopharynx cancer has while the head is immobilized with the neck extended
consisted of radiation therapy alone for many years. using a headrest and customized mask. A tongue
150 CANCER OF THE HEAD AND NECK

blade is inserted to depress the tongue away from the define the planning target volume. It is important to
palate, and palpable lymph nodes are outlined with adequately treat the skull base and anterior as well as
wires. The most common field arrangement consists posterior cervical lymph nodes.
of opposed lateral fields to encompass the primary Radiation therapy is most often delivered with a
tumor and upper neck (Figure 7–3). A third, anterior linear accelerator in fractions of 1.8 to 2 Gy per day.
field is matched below the lateral fields to treat the Various accelerated fractionation regimens have also
lower cervical and supraclavicular lymph nodes. The been used.22,23 A shrinking field technique is used to
larynx is generally shielded and care must be taken to give a range of doses to various regions. For
avoid overlapping fields on the spinal cord. The treat- instance, the optic nerves and spinal cord should be
ment design must be individualized for each patient, blocked from photon irradiation after a dose of 40 to
depending upon disease distribution and stage. CT or 45 Gy. The posterior neck may then be treated to the
MRI scans should be used to define the gross tumor appropriate total dose with electron beams. Elec-
volume and this should be expanded by 1 to 2 cm to tively treated nodal regions should receive doses of

Figure 7–3. Initial lateral simulation film for a patient

with a stage T3 nasopharyngeal cancer invading the
skull base. The cavernous sinuses, posterior ethmoid
sinuses and skull base are included in the treatment
field. The eyes and oral cavity are shielded. A palpa-
ble lymph node is marked with a wire. The field should
be reduced during the course of therapy to prevent
overdosing critical structures such as the optic
nerves, optic chiasm, brain stem, and spinal cord.
Treatment fields must be customized for each patient
based on the extent of disease.
 Cancer of the Nasopharynx 151

45 to 54 Gy. The portals may then be reduced to treat A variety of techniques exist for delivering
the primary tumor and gross adenopathy to total higher doses of radiation to the nasopharynx while
doses in the range of 65 to 75 Gy. minimizing the dose to critical structures such as the
The appropriate radiation dose for an individual brainstem, optic nerves, mandible, temporal lobes,
patient is derived by balancing the likelihood of and inner ears. Intracavitary brachytherapy is a tra-
achieving local control with the risks of radiation ditional technique whereby radiation sources are
toxicity. Large tumors may require higher doses than placed within the nasopharynx (Figure 7–4).28,29
small tumors. In general, several retrospective stud- Alternative external beam techniques have also been
ies have shown improved local control using cumu- used and this approach has been aided by the devel-
lative doses of > 70 Gy.24–26 Yan and colleagues con- opment of CT scan planning.30 Newer technologies
ducted a study randomizing patients with residual for boosting this region include stereotactic radio-
disease after a dose of 70 Gy to receive a boost to surgery and intensity modulated radiotherapy
90 Gy or no additional treatment.27 Local failure was (IMRT) as demonstrated in Figure 7–5.31,32
significantly lower for patients receiving the boost Nasopharynx cancer responds to a wide variety
but there was an increase in radiation toxicity. of chemotherapy agents. The most commonly used

Figure 7–4. Verification film for a patient receiving

an intracavitary brachytherapy boost for a stage T1
nasopharyngeal cancer. Radioactive sources are
placed in catheters within the nasopharynx. In this
case, the applicator has a thin metal shield inferiorly
to allow relative sparing of the soft palate. The dose
distribution is represented by the colored lines: red =
29 Gy, blue = 10 Gy, and brown = 5 Gy.
152 CANCER OF THE HEAD AND NECK

Figure 7–5. Axial and sagittal views of an intensity modulated radiotherapy (IMRT) plan for a stage T3 nasophar-
ynx cancer. Seven beam angles are used in this case. Isodose curves are labeled by color. The target volume con-
sists of the gross tumor plus a margin and is covered by the 100 percent dose level. The brain stem receives less
than 50 percent of the prescribed dose.

regimen for patients with advanced disease in the weight loss, and fatigue.14 In cases where patients
United States includes cisplatin and 5-fluorouracil, cannot maintain a reasonable oral intake, a feeding
based on the Head and Neck Intergroup study.20 tube may be placed to ensure that they receive ade-
Patients should have measurement of creatinine quate nutrition. Cisplatin chemotherapy may also
clearance, an electrocardiogram, and an audiogram cause nausea and suppression of blood counts. The
to ensure that they are appropriate candidates before addition of adjuvant 5-fluorouracil may prolong
starting this chemotherapy. Cisplatin 100 mg/m2 is mucositis. The mucosa of the nasopharynx becomes
generally given on days 1, 22, and 43 during radio- dry following treatment, causing formation of
therapy, with appropriate hydration and supportive synechiae and crusted mucus. This can interfere
care. Following chemoradiotherapy, patients receive with physical examination but may be minimized by
3 cycles of cisplatin 80 mg/m2 and 5-fluorouracil instructing patients to perform regular nasal irriga-
1000 mg/m2/day (96-hour infusion) every 4 weeks. tions and to use humidifiers.
Local recurrence after primary radiotherapy may Most of the acute effects of radiotherapy resolve
be managed with re-irradiation or nasopharyngec- within 1 to 2 months. However, the majority of
tomy in selected cases.33,34 A discussion of these patients will have some degree of permanent xeros-
techniques is beyond the scope of this chapter. tomia, dental problems, skin hyperpigmentation, and
Regional nodal recurrence in the neck may be man- soft-tissue fibrosis.35 Efforts to reduce long-term
aged with a neck dissection. Most patients with xerostomia include the use of radioprotectors such as
locoregional recurrence and those with distant amifostine or salivary stimulants such as pilo-
metastases should be offered systemic chemotherapy. carpine.36,37 Meticulous dental care and daily fluo-
ride therapy are effective in minimizing the risk of
Sequelae, Complications, and serious dental complications. Approximately one-
their Management third of patients will eventually develop hypothy-
roidism. This is usually subclinical and detected by
The acute side effects of radiotherapy are significant annual screening with thyroid function tests. Thyroid
and are increased when concurrent chemotherapy is hormone replacement should be prescribed in this
given. Nearly all patients will experience a radiation setting. Chronic serous otitis media occurs in approx-
skin reaction, mucositis, xerostomia, altered taste, imately 15 percent of patients and may be managed
 Cancer of the Nasopharynx 153

with placement of myringotomy tubes. Radiation ously described study published by Al-Sarraf and
effects, along with cisplatin ototoxicity, could cause colleagues, combined modality therapy resulted in a
permanent hearing loss. Therefore, patients should 3-year actuarial progression-free survival of 69 per-
be monitored with follow-up audiograms.9 cent and overall survival of 78 percent. Long-term
More serious complications of radiotherapy follow-up of patients receiving chemoradiotherapy
include severe trismus and osteoradionecrosis (5 to will be necessary to confirm the survival advantage
10% of patients).35 Options for management of these and to assess complication rates.
problems are limited but include stretching exercises The majority of patients (52%) experiencing a
for the former, and antibiotics as well as hyperbaric failure will do so in the first year after therapy.
oxygen for the latter. Extensive necrosis with bone
sequestration will require surgical intervention.
Table 7–2. LOCAL CONTROL OF NASOPHARYNX
Pituitary dysfunction is rarely reported but may CANCER BY STAGE WITH RADIOTHERAPY*
occur in younger patients, necessitating hormonal Stage (% Controlled)
therapy. Fortunately, devastating neurologic compli- No. of
cations of radiotherapy occur in less than 1 percent Author Patients T1 T2 T3 T4

of patients in this country.14,15 These include carotid Hoppe14 82 87 94 68 44

Perez26 143 85 75 67 40
artery stenosis, brain necrosis, blindness, cranial Lee40 4128 80 81 75–82 59–78
neuropathies and spinal myelitis. Neurologic com- Sanguineti41 378 87 75 63 55
plications are generally irreversible but may be pre- Wang42 259 72 66 49
Vikram24 107 74 100 63
vented with careful radiation treatment planning.
Radiation-induced second malignancies are rare but * Based on staging prior to 1997 AJCC revisions.

may include salivary gland neoplasms, skin cancers,

sarcomas, meningiomas and thyroid cancers. Table 7–3. REGIONAL CONTROL OF NASOPHARYNX
CANCER BY STAGE WITH RADIOTHERAPY*
Rehabilitation and Quality of Life Stage (% Controlled)
No. of
Author Patients N0 N1 N2 N3
Scientific studies of quality of life following treat-
ment for nasopharynx cancer are lacking. The afore- Hoppe14 82 96 92 87 89
Mesic15 238 100 90 88 82
mentioned acute and long-term toxicities of treat- Perez26 143 82 86 72
ment, as well as direct effects of the cancer are Wang42 259 62 63 67
certainly expected to impact quality of life. The spe- * Based on staging prior to 1997 AJCC revisions.
cific interventions mentioned for each of the side
effects help with rehabilitation. In addition, some
patients may require physical therapy or nutritional Table 7–4. ACTUARIAL FIVE-YEAR SURVIVAL FOR
counseling to restore an optimal level of function. PATIENTS TREATED WITH RADIOTHERAPY ALONE FOR
NASOPHARYNX CANCER, ACCORDING TO T AND N STAGE*
Patients may also benefit from short or long-term
psychological counseling after enduring difficult Stage (% Surviving)
No. of
therapy for this life-threatening illness. Author Patients T1 T2 T3 T4
14†
Hoppe 82 76 68 55 0
Outcomes Wang42‡ 259 65 58 42

N0 N1 N2 N3
Data regarding local and regional control as well as 14†
Hoppe 82 78 70 42 39
survival comes from retrospective series using radi- Wang42‡ 259 63 63 56
ation alone (Tables 7–2, 7–3 and 7–4). Overall out- Chu9** 80 42 27 52 27
comes in the United States have been substantially * Based on staging prior to 1997 AJCC revisions.
†
improved by the addition of chemotherapy (exclud- ‡
Disease-free survival.
Disease-specific survival.
ing stage I cancers) to radiotherapy. In the previ- ** Overall survival.
154 CANCER OF THE HEAD AND NECK

Within 5 years, 90 percent of relapses are apparent 16. Fu KK. Prognostic factors of carcinoma of the nasopharynx.
Int J Radiat Oncol Biol Phys 1980;6:523–6.
but occasional recurrences more than 10 years from
17. Chan AT, Teo PM, Leung TW, et al. A prospective random-
treatment are reported.38 The prognosis following ized study of chemotherapy adjunctive to definitive radio-
disease recurrence is better for patients with no dis- therapy in advanced nasopharyngeal carcinoma [see com-
tant metastases, limited disease extent, and an inter- ments]. Int J Radiat Oncol Biol Phys 1995;33:569–77.
18. Chua DT, Sham JS, Choy D, et al. Preliminary report of the
val of at least 2 years since primary therapy.39 Asian-Oceanian Clinical Oncology Association random-
ized trial comparing cisplatin and epirubicin followed by
radiotherapy versus radiotherapy alone in the treatment of
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 8
The Larynx:
Advanced Stage Disease
JOHN F. CAREW, MD

Of the 295,000 cases of cancer of the head and neck Additionally, the optimal treatment plan which com-
accrued by the National Cancer Data Base over a 10- bines chemotherapy and radiation therapy with
year period, larynx was the most common site regards to timing (sequential vs. concomitant), radi-
accounting for more than 20 percent of all head and ation fractionation, chemotherapeutic agents and
neck cancers.1 Squamous cell carcinoma which arises adjuvants remains undefined. In this section, the
from the mucosa lining the larynx accounted for over diagnosis, treatment and outcome of patients with
90 percent of all cancers in this site.2 In one of the advanced cancer of the larynx will be presented.
larger studies of patients with larynx cancer, 40 per-
cent of patients presented with advanced stage disease ANATOMY
(stage III or IV).2 Despite the use of aggressive mul-
timodality treatment in patients with advanced stage While the basic anatomy of the larynx already has
cancer of the larynx, overall survival for these patients been described in the section on early larynx cancer,
ranges from 42 to 77 percent.2–14 As mentioned in the this section will highlight the critical points relevant
section on early stage disease, other neoplasms such to treating patients with advanced cancers of the lar-
as lymphomas, minor salivary gland tumors, mucosal ynx. The majority of larynx cancers are found in the
melanomas and sarcomas may affect this site, glottic region (56%) followed by the supraglottic
although large series evaluating these specific region (41%), while tumors of the subglottic region
pathologies at this site are lacking in the literature. are relatively infrequent (1 to 2%) (Figure 8–1).2,15 It
Unless otherwise specified, squamous cell carcino- is important to realize that tumors in these different
mas of the larynx will be the subject of this chapter. regions of the larynx have different clinical behav-
The larynx performs several unique and vital iors. Supraglottic tumors, for example, have a much
functions related to phonation, breathing and swal- higher rate of occult and bilateral metastasis than
lowing, and the treatment of patients with neoplasms glottic primaries.10,16 The regional lymph nodes of
of this organ requires consideration of these critical the neck in patients with advanced stage supraglot-
functions. Specifically, the impact of therapeutic tic tumors and clinically negative necks must there-
options on both the extent as well as the quality of fore be addressed in treatment planning.
life needs to be taken into account. As this section The connective tissue barriers which lie between
focuses on advanced cancer of the larynx, most the mucosa and cartilaginous skeleton of the larynx,
treatment options involve multimodality therapy in namely the conus elasticus and quadrangular mem-
the form of either chemotherapy and radiation ther- brane, are critical to the understanding of patterns of
apy or surgery and radiation therapy. The critical spread and clinical behavior of advanced cancers of
decision, which continues to evolve, is selecting the the larynx (Figure 8–2). These membranes provide a
appropriate treatment for each individual patient. barrier to the spread of cancer but are often breached

156
 The Larynx:Advanced Stage Disease 157

Supraglottic involving this area can then spread into the soft tis-
41% sues of the neck via the foramen in the thyrohyoid
membrane or inferiorly via the paraglottic space. In
some patients, however, a connective tissue barrier
separates the preepiglottic and paraglottic space.19
The paraglottic space is the compartment which
Glottic
56% is bounded by the thyroid lamina laterally, the
conus elasticus medially-inferiorly and the quad-
rangular membrane and preepiglottic space medi-
Subglottic
3% ally-superiorly. Loose connective tissue and adi-
pose tissue lying between thyroid lamina and the
connective tissue membranes of the larynx occupy
Figure 8–1. Site distribution of larynx cancers. this space. This area is most commonly involved by
advanced glottic tumors. Once this compartment is
by advanced tumors (Figure 8–3).17 Once a tumor entered, tumors can spread relatively freely in a
has broken through these boundaries, it can spread superior and inferior direction, as well as outside
into the soft tissues of the neck as well as vertically the confines of the larynx via the cricothyroid
within the larynx. membrane or the preepiglottic space. Involvement
Two regions that are deep to the quadrangular of this space frequently results in decreased vocal
membrane and conus elasticus are the preepiglottic fold movement.
and paraglottic space. Advanced tumors often enter Cancers of the larynx can be classified as
these spaces when they transgress these connective advanced (stage III or IV) either by virtue of an
tissue barriers within the larynx and thus enter a advanced primary tumor or by the presence of
compartment where further spread is less hindered. regional lymph node metastasis. When regional
The preepiglottic space is bounded by the thyrohy- lymph node metastases are present they are
oid membrane anteriorly, the valleculae superiorly, described by their location, number and size. The
the epiglottis posteriorly and the hyoid inferiorly. location of the lymph nodes is described by levels in
This space is commonly involved by local spread of the neck as illustrated in the chapter on neck metas-
supraglottic tumors. Once this space is involved, a tasis. Levels II, III and IV are at highest risk for
supraglottic tumor is staged as a T3.18 Tumors lymph node metastasis from cancers in the larynx.

A B
Figure 8–2. A, Sagittal section of larynx demonstrating the preepiglottic and B, coronal section of larynx
demonstrating the paraglottic space.
158 CANCER OF THE HEAD AND NECK

Diagnosis usually requires radiographic imaging to ascertain

the depth of the tumor involvement, preepiglottic
Patients with advanced glottic cancers will present space extension, paraglottic extension, cartilage
with symptoms similar to patients with early glottic involvement and extra-laryngeal spread. High-reso-
cancers. As listed earlier these include hoarseness or lution CT scans with thin cuts through the larynx
a change in the quality of voice, odynophagia, hali- usually give adequate information regarding these
tosis or otalgia. Not suprisingly the more ominous aspects (Figure 8–5).21 Additionally, in patients with
symptoms, such as hemoptysis, dysphagia, airway necks which are difficult to assess clinically, radi-
compromise and neck mass are more common in ographic evaluation may add information in estab-
advanced stage disease. Additionally, the supraglottic lishing the regional lymph node status.
and subglottic lesions tend to be less symptomatic The staging of patients with advanced cancers of
and their insidious growth results in a high percent of the larynx is outlined in Table 8–1.18 As with other
patients presenting with advanced stage disease. sites in the head and neck, the complex anatomy in
As mentioned earlier, adequate examination of this region makes accurate staging challenging. At
the larynx by use of the laryngeal mirror or a rigid times, the location of the lesion appears to carry
telescope or fiberoptic flexible nasopharyngoscope more weight than the tumor burden. For example, a
is essential to staging and treatment planning (Fig- relatively small tumor on the posterior aspect of the
ure 8–4).20 Critical in this evaluation is assessment larynx which involves the post-cricoid area will be
of the epicenter of the tumor, vocal fold mobility, stage T3, while a bulky tumor replacing the
extra-laryngeal involvement and regional lymph aryepiglottic fold, epiglottis and spilling down the
nodes in the neck. Although early tumors are often medial wall of the pyriform sinus will be staged a T2
adequately assessed by history and physical exam as long as the vocal cord remains mobile. While sur-
alone, appropriate evaluation of advanced lesions vival has been related to both T stage and N stage, it

Figure 8–3. Whole organ sections showing tumor involving the

preepiglottic and paraglottic space.
A
 The Larynx:Advanced Stage Disease 159

is most profoundly affected by the nodal status of the 3N1) together into stage III.18 This may arbitrarily
patient.2,10,11 It has long been known that regional group 2 subsets of patients together who have vastly
lymph node involvement in head and neck cancer different prognoses. Both the stage as well as the
patients decreases survival by approximately 50 per- nodal status must thus be considered when interpret-
cent.10,11 The present staging system of the American ing results from the treatment of larynx cancer.
Joint Committee for Cancer (AJCC) groups both Just as there are ominous symptoms in patients
patients with locally advanced tumors (T3N0) and with advanced cancer of the larynx, there are also
patients with regional lymph node metastasis (T1- several physical findings that are harbingers of clin-

A B

Figure 8–4. Endoscopic view and assessment of a laryngeal can-

cer using the A-0°; B-30°; C-70°; D-120° telescopes.

C
160 CANCER OF THE HEAD AND NECK

Figure 8–5. A, Axial CT of advanced laryngeal primary tumor

demonstrating paraglottic involvement and cartilage destruction but
without extension into the soft tissues of the neck. B, Axial CT of
advanced laryngeal primary tumor demonstrating cartilage destruc-
tion and extension into the soft tissues of the neck. B

ically aggressive behavior. Extensive spread into the goals in treatment are directed at increasing both the
soft tissues of the neck, involvement of the overlying rate of laryngeal preservation and survival.
skin, regional lymph node metastases which are
fixed or limited in vertical mobility, and bulky dis- Factors Affecting Choice of Treatment
ease low in the neck all suggest a poor prognosis.
Factors affecting choice of treatment can be divided
Treatment Goals and Treatment into patient factors and tumor factors. As demon-
Alternatives–The Role strated in multiple clinical trials, survival is statisti-
of Multidisciplinary Treatment cally equivalent in selected patients with advanced
cancer of the larynx who are treated with either
In the last 2 decades, 5-year survival of patients with chemotherapy and radiation therapy or surgery and
laryngeal cancer has not changed dramatically.22 radiation therapy.3,6,7,9,23–25 Given this, patients who
Maximizing survival, therefore, continues to be the wish to utilize a treatment paradigm that may pre-
ultimate goal in treating patients with advanced serve their larynx, such as chemotherapy and radia-
stage larynx cancer. Recently, however, due to the tion therapy, should be given this nonsurgical option.
lack of improvement in survival, significant efforts Alternatively, there is a cohort of patients who are of
have been made to improve the quality of life in the mindset that they would rather have all cancer
these patients. Paramount to this is preservation of a removed and would prefer surgery and radiation ther-
functional larynx. Toward this goal, treatment apy, understanding that their ability to communicate
options have been formulated with the hopes of will be significantly affected. Finally, any patient
increasing laryngeal preservation without sacrific- who is considering chemotherapy and radiation ther-
ing survival. Multimodality treatment paradigms, in apy as a treatment option must be reliable and must
the form of chemotherapy, radiotherapy and surgical enroll a multidisciplinary team experienced in treat-
salvage, has emerged as a viable treatment option ing patients with advanced cancer of the larynx.
allowing anatomical preservation of the larynx with- Many tumor factors also contribute to the deci-
out decreasing survival.3 Now that a method of sion process in determining the optimal treatment
laryngeal preservation has been established, future for each patient. If a tumor or lymph node metasta-
 The Larynx:Advanced Stage Disease 161

sis shows ominous clinical signs suggesting unre- tion therapy, one could consider a comprehensive
sectability, then certainly a surgical option should neck dissection followed by radiation therapy to the
not be contemplated and consideration given to primary site and the neck. Alternatively, if the pri-
chemotherapy and radiation therapy.26,27 A clinical mary lesion is best treated by a surgical approach,
situation which is interesting but infrequent arises one could consider a partial laryngectomy and neck
when a patient presents with an early stage primary dissection with the addition of adjuvant radiation
lesion and clinically apparent regional lymph node therapy as indicated based on pathologic findings.
metastasis. In this situation several treatment options Of the most important factors in deciding the
exist. If the primary lesion is best treated by radia- optimal treatment are the characteristics of the pri-
mary tumor. Tumors which are endophytic, show
extensive cartilage invasion, involve the soft tissues
Table 8-1. AJCC STAGING OF CARCINOMA OF THE LARYNX of the neck, or involve the airway to such an extent
Supraglottis that a tracheostomy is required, often demonstrate
T1: Tumor limited to one subsite of the supraglottis with normal aggressive clinical behavior and respond poorly to
vocal cord mobility treatment. Whether these patients fare better in a
T2: Tumor invades mucosa of more than one adjacent subsite
of the supraglottis or glottis or region outside the supraglot- surgical treatment arm as opposed to a nonsurgical
tis (eg, mucosa of the base of tongue, valleculae, medial plan has yet to be substantiated in a randomized
wall of pyriform sinus) without fixation of the larynx
T3: Tumor limited to the larynx with vocal cord fixation and/or
prospective trial. The ideal treatment in these
invades any of the following: postcricoid area, preepiglottic patients, therefore, remains controversial. In such
tissues patients, aggressive early surgical intervention will
T4: Tumor invades through the thyroid cartilage, and/or extends
into the soft tissues of the neck, thyroid and/or esophagus improve the chances for locoregional control and
Glottis thus improve the quality of life that would otherwise
be significantly deteriorated with persistent or recur-
T1: Tumor limited to the vocal cord(s) (may involve anterior or
posterior commissure) with normal vocal cord mobility rent disease. Early aggressive surgical intervention
T1A: Tumor limited to one vocal cord may not improve survival or risk of distant metasta-
T1B: Tumor involves both vocal cords
T2: Tumor extends to the supraglottis and/or subglottis, and/or
sis, but would certainly offer avoidance of airway
with impaired vocal cord mobility obstruction, asphyxiation or intractable pain.
T3: Tumor limited to the larynx with vocal cord fixation
T4: Tumor invades through the thyroid cartilage and/or extends
to other tissues beyond the larynx (eg, trachea, soft tissues Surgical Treatment
of the neck, including thyroid, pharynx)

Subglottis In the majority of patients with advanced primary

T1: Tumor limited to the subglottis tumors of the larynx, the surgical treatment consists
T2: Tumor extends to the vocal cord(s) with normal or impaired of a total laryngectomy. It should be remembered,
mobility
T3: Tumor limited to the larynx with vocal cord fixation
however, that partial laryngectomy and conserva-
T4: Tumor invades through the cricoid or thyroid cartilage tional surgical procedures which preserve the func-
and/or extends to other tissues beyond the larynx (eg, tra- tion of the larynx may be options in selected
chea, soft tissues of the neck, including thyroid, esophagus)
patients. As discussed in the section on early larynx
Neck
cancer, vertical partial, supraglottic partial and
N0: No regional lymph node metastasis supracricoid partial laryngectomies can be per-
N1: Ipsilateral lymph node metastasis ≤ 3 cm
N2: Lymph node metastasis in a single ipsilateral lymph node
formed in carefully selected patients. In patients
> 3 cm and ≤ 6 cm, or in multiple lymph nodes none more with advanced lesions, however, the more extensive
than 6 cm (including bilateral nodal metastasis) partial laryngectomies are utilized more frequently
N2A: Lymph node metastasis in single ipsilateral lymph
node > 3 cm and ≤ 6 cm and even more selectively. These procedures,
N2B: Lymph node metastasis in multiple ipsilateral lymph although categorized in broad terms such as near-
nodes all ≤ 6 cm
N2C: Lymph node metastasis in bilateral or contralateral total laryngectomy or supracricoid partial laryngec-
lymph nodes all ≤ 6 cm tomy with cricohyoidopexy, are usually individually
N3: Lymph node metastasis > 6 cm
designed to adequately encompass each patient’s
162 CANCER OF THE HEAD AND NECK

particular tumor while sparing as much functional should be planned in the clinically negative neck.
tissue as oncologically feasible (Figure 8–6).28–31 For a glottic lesion, the ipsilateral levels II to IV
Appropriate management of the neck is critical should be cleared, while for a supraglottic lesion,
to maximizing survival in patients with advanced bilateral levels II to IV are at risk and should be dis-
cancer of the larynx. The treatment of the neck sected. If there is clinically apparent lymph node
depends in part on the treatment of the primary. If metastasis in the neck and the primary is to be
the primary is to be treated by surgical means, then treated by surgery, then a comprehensive neck dis-
an elective dissection of the lymph nodes at risk section (levels I to V) should be performed.

B
Figure 8–6. Schematic diagram of two well-described voice-preserving, extended laryngeal pro-
cedures: A, supracricoid laryngectomy with cricohyoidoepiglottopexy and B, supracricoid laryngec-
tomy with cricohyoidopexy (dotted lines represent line of surgical excision).
 The Larynx:Advanced Stage Disease 163

Alternatively, if a patient with a clinically negative Sequelae, Complications and

neck is to be treated by chemotherapy and radiation their Management
therapy to the primary lesion, the neck at risk should
also be treated electively by radiation therapy. A Surgery and Radiotherapy
somewhat more controversial situation exists if there The complications associated with total laryngec-
is a clinically positive neck and the primary is to be tomy can be divided into acute and chronic. The
treated by chemotherapy and radiation therapy. The acute complications include those related to surgery
options that exist include performing a comprehen- and general anesthesia. These include bleeding,
sive neck dissection prior to chemotherapy/radiation infection, pneumonia and fistula. The most trouble-
therapy, performing a planned comprehensive or some of these is the pharyngocutaneous fistula. The
selective neck dissection after chemotherapy/ fistula rate following total laryngectomy remains
radiation therapy or assessing response following relatively high, ranging from 8 to 22 percent.33–35
chemotherapy/radiation therapy and performing Appropriate treatment of a pharyngocutaneous fis-
appropriate neck dissection based on response. At tula requires early recognition and then wide open-
this time, data is lacking to substantiate an advantage ing of the wound with appropriate wound care. The
in any of these approaches and all are acceptable. patient should stop all oral intake and an alternative
route of alimentation should be established. If sig-
Nonsurgical Treatment nificant carotid exposure is seen, then consideration
should be given to coverage with a regional flap to
The appreciation of the psychosocial consequences afford carotid protection, especially in the setting of
of total laryngectomy has been the impetus for the previous radiation therapy. Often the fistula will
development of treatment options which could pre- close spontaneously with aggressive wound care. In
serve the larynx of patients with advanced stage lar- those cases where it does not, local, regional and
ynx cancer. In the early 1990s, a prospective, ran- even free flaps may be used to obtain closure.
domized trial of patients treated at Veterans Affairs The most common chronic complication of total
Hospitals with stage III and stage IV squamous cell laryngectomy is stricture formation with dysphagia. It
carcinoma of the larynx, comparing conventional is crucial to rule out recurrent tumor whenever a
treatment of surgery and postoperative radiotherapy, patient develops new dysphagia or worsening dys-
with induction chemotherapy followed by radiother- phagia. This is usually best evaluated by endoscopy
apy was performed.3 In this study, patients in the with direct visualization of the mucosa of the
chemotherapy-radiation therapy (chemo/RT) arm neopharynx. Preoperative esophagrams are often
who did not display at least a 50 percent response to helpful in defining the location and extent of stricture.
induction chemotherapy, or who showed persistent If a stricture is seen, it can usually be dilated, although
or recurrent disease following radiation, were sal- repeated treatments are often required. Ultimately, if
vaged with surgery. This landmark study demon- a stricture is unresponsive to these conservative mea-
strated survivals which were not statistically differ- sures, consideration can be given to free tissue trans-
ent between treatment arms (68%), and allowed 64 fer to reconstruct an adequate neopharynx.
percent of patients within chemo/RT arms to pre- The early sequelae of radiation therapy relate pri-
serve their larynx.3 With the results of the Veterans marily to the acute tissue reactions with characteris-
Affairs Larynx Cancer Study Group (VALCSG) tic skin changes and mucositis. These are managed
trial, the combination of induction chemotherapy symptomatically with oral hygiene and topical med-
and radiation therapy has emerged as a treatment ications. The late sequelae of radiation therapy
option which allows preservation of the larynx in include skin changes, xerostomia and, very rarely,
nearly two-thirds of patients. Since this trial, many chondroradionecrosis of the laryngeal skeleton.
other studies have been performed to confirm Xerostomia is treated symptomatically with oral
chemo/RT as an effective treatment for patients with hygiene and humidification. In severe cases where
advanced larynx cancer.6,7,9,23–25,32 chondroradionecrosis profoundly impairs swallow-
164 CANCER OF THE HEAD AND NECK

ing and breathing, a total laryngectomy may need to sisted of total laryngectomy with the resultant delete-
be performed to restore the ability to swallow. rious effects on deglutition, phonation and the cre-
ation of a permanent tracheostoma. The psychosocial
Chemotherapy and Radiotherapy consequences of total laryngectomy have been well
studied.14,37–39 Not suprisingly, quality of life mea-
Treatment protocols using chemo/RT to preserve surements and psychosocial indicators are signifi-
organ function have successfully demonstrated their cantly affected by total laryngectomy. Although tech-
ability to anatomically preserve the larynx without niques for voice rehabilitation have improved, studies
compromising survival. One aspect of these proto- have shown that the psychosocial effects of laryn-
cols that is often underappreciated is the functional gectomy are as much related to loss of voice as they
capacity of the retained organs. Few investigators
are to other factors such as the necessity of a perma-
have clearly documented the functional sequelae of
nent tracheostoma.14,38,39 When the patients treated in
chemotherapy and radiation therapy. Recently,
the Veterans Affairs Laryngeal Cancer Study Group
Lazarus retrospectively studied patients being
were evaluated, an improved long-term quality of life
treated with chemotherapy and radiation therapy and
was seen in the cohort who were randomized to
found that 40 percent had swallowing difficulties.36
chemotherapy and radiation therapy compared to
Clinical evidence of disorders in the pharyngeal
those treated by surgery and radiation therapy.37
phase of swallowing has been demonstrated in
Interestingly, this difference was primarily related to
patients who have undergone chemotherapy and
freedom from pain, better emotional well-being and
radiation therapy for tumors of the upper aerodiges-
lower levels of depression rather than the preserva-
tive tract. Specifically, reduced laryngeal closure,
tion of the ability to speak.
reduced laryngeal elevation and reduced posterior
Nevertheless, several methods are available to
tongue base movement relative to age-matched con-
rehabilitate the ability of a patient to communicate
trols has been documented.36 Certainly, patients who
following total laryngectomy. Many patients are able
successfully undergo chemo/RT treatments to pre-
to acquire esophageal speech, in which air is swal-
serve their larynx have a much improved quality of
lowed and then used to create a voice. Approxi-
life relative to patients requiring total laryngec-
mately 2 decades ago a significant advance in the
tomy.37 Nevertheless, it should be realized that
rehabilitation of patients with laryngectomies took
anatomic preservation does not always result in
place when the tracheoesophageal puncture was
functional preservation. Very rarely, total laryngec-
developed.40 This is a relatively minor procedure
tomy is performed in order to restore the ability to
where a fistula is created between the trachea and
swallow when a larynx is incompetent and nonfunc-
esophagus (Figure 8–7). A prosthesis with a one-
tional but clinically free of cancer.
way valve is placed into this fistula, which allows
In addition to functional sequelae, chemotherapy
the creation of a lung powered voice. In the moti-
(specifically when given in combination with radia-
vated patient, this voice can be quite good.
tion therapy) has some definite toxicities. Toxicity
from induction chemotherapy has prevented 7 to 18
percent of patients from receiving a full course of Outcomes and Results of Treatment
chemotherapy.3,4,6,8 Even mortality, as a result of
Historically, surgery in the form of total laryngectomy
chemotherapy and radiation-related toxicity, has
followed by adjuvant postoperative radiation therapy
been reported to range from 0.6 to 6 percent.3,5–9,25
has been the standard treatment for most patients with
advanced stage cancer of the larynx.10–12,41,42 Addi-
Rehabilitation and Quality of Life
tionally, selected patients with advanced stage larynx
In the past, conventional treatment of advanced stage cancer have been treated with definitive radiation
laryngeal cancer consisted of surgery and postopera- therapy alone.13,42,43 The results of these treatments
tive external beam radiation. Surgical resection of the are summarized in Table 8–2 with 5-year survival
majority of advanced stage laryngeal lesions con- ranging from 54 to 91 percent.10–13,41–43
 The Larynx:Advanced Stage Disease 165

Figure 8–7. Schematic diagram of tracheoesophageal puncture (TEP).

More recently, chemotherapy/radiation therapy ynx preservation rates ranging from 64 to 79 per-
has evolved as an effective treatment for advanced cent, locoregional failure rates ranging from 20 to
stage cancer of the larynx. A summary of results 33 percent and distant failure rates ranging from 8 to
from the various studies evaluating chemo/RT in the 21 percent.3–9,25 It should be noted, however, that
treatment of patients with advanced stage laryngeal only one of these studies was limited only to patients
cancer, with the goal of larynx preservation, are with laryngeal primaries,3 while the remainder of
listed in chronologic order in Table 8–3.3–9,25 In all the studies included patients with hypopharynx,
but one study, more than 90 percent of patients eval- oropharynx, oral cavity and even paranasal sinuses
uated had stage III or IV disease. Most studies as sites of primary tumors.4–9,25 The majority of
included only those patients who would have these studies that included non-laryngeal sites did so
required a total laryngectomy if treated by conven- because surgical treatment of the primary would
tional means with surgery and postoperative radio- have required total laryngectomy. The data presented
therapy. Treatment results for patients treated with
chemo/RT in these studies are fairly consistent with
2-year survival ranging from 50 to 77 percent, lar- Table 8–3. RESULTS OF TREATMENT OF ADVANCED
CARCINOMA OF THE LARYNX UTILIZING
CHEMOTHERAPY AND RADIATION THERAPY

Table 8–2. RESULTS OF CONVENTIONAL TREATMENT 2 yr.

Type of Stage Survival
OF ADVANCED CARCINOMA OF THE LARYNX
Author Year No. Therapy III/IV (%) (%)
5 yr
Type of Stage Survival Jacobs4 1987 30 C/RT 100 52*
Author Year No. Therapy III/IV (%) (%) Demard5 1990 50 C/RT 64 74*
(Response
12
Kirchner 1977 308 S/RT 100 54–56* rate)
Harwood13 1979 353 RT 54 70 Veterans Affairs 1991 166 C/RT 100 68
Harwood43 1983 410 RT 66 57 Larynx Group3 166 S/RT 100 68*
Yuen41 1984 192 S 100 77 Pfister6 1991 13 C/RT 98 77*
50 S/RT 100 91 Karp7 1991 14 C/RT 92 50*
Mendenhall42 1992 100 RT 100 74 Urba8 1994 8 C/RT 93 75*
65 S±RT 100 63 Clayman9 1995 26 C/RT 96 68*
Nguyen11 1996 116 S/RT 100 68 (includes data 52 S/RT 96 81*
Myers10 1996 65 S±RT 100 62† from Shirinian)25

Survival rates refer to disease-free survival when available, otherwise they Survival rates refer to disease-free survival when available, otherwise they
refer to overall survival. refer to overall survival.
* study included both laryngeal and non-laryngeal sites. * Study included both laryngeal and non-laryngeal sites. C = chemotheapy;
S = Surgery; RT = Radiation therapy; † 2-year survival. S = surgery; RT = radiation therapy.
166 CANCER OF THE HEAD AND NECK

in this table refers, whenever possible, to the subset of regrowth after the commencement of cytotoxic
of patients with laryngeal primaries, although this treatment, regardless of whether it is chemotherapy
information was not always available. or radiation therapy.46,47 A longer treatment time will
In several of these aforementioned studies, single therefore result in high rates of failure.48
modality therapy in the form of definitive radiother- In order to minimize these problems, investigators
apy was utilized and yielded disease-specific sur- have evaluated accelerated radiotherapy regimens and
vivals similar to those seen with the combination of concomitant chemo/RT protocols. In the past, accel-
induction chemotherapy and radiation ther- erated (twice a day) courses of radiation therapy have
apy.3–9,13,25,42,43 Although the selected cohort of improved 3-year local control of advanced laryngeal
patients who received radiation therapy alone had tumors (T3-4) from 26 to 59 percent (p < 0.0001).48,49
less stage IV and node-positive patients, the contri- These gains in local control are not accomplished
bution of chemotherapy to these larynx preservation without cost with regards to treatment related mor-
protocols remains undetermined. While previous bidity. In this study, although the larynx was anatom-
randomized prospective trials have not included a ically preserved, its function was profoundly impaired
radiation therapy-only arm, an ongoing prospective in a subset of patients, and significant long-term treat-
randomized trial has included a radiation therapy- ment related morbidity was seen in one-quarter of
only arm, to address this question. This phase III trial patients. Additionally, all patients in this series under-
has 3 treatment arms including: (1) radiotherapy going salvage surgery after radiotherapy experienced
alone, (2) sequential chemotherapy and radiotherapy major wound complications.50 Ultimately a benefit in
and (3) concomitant chemotherapy and radiotherapy. local or regional control or survival was not seen,
Data from this study will help to further define the although the power of this study was limited.
optimal treatment for patients with advanced larynx Another method of shortening treatment time,
cancer. Additionally, 2 studies have recently been decreasing the effects of accelerated tumor cell
published which compared radiotherapy alone to repopulation and improving results involves the use
concurrent chemotherapy (cisplatin/5-fluorouracil) of concomitant chemotherapy and radiation therapy.
and radiotherapy in patients with locoregionally- Prior studies using concomitant chemotherapy and
advanced squamous cell carcinoma of the head and radiation in advanced stage head and neck cancer
neck.44,45 In these studies, between 36 and 56 percent have shown promising results with regard to locore-
of patients had either laryngeal or hypopharyngeal gional control, organ preservation and survival.51,52
primaries. In both studies, a statistically significant Prospective randomized trials assessing the benefit
increase in 3-year relapse-free survival was seen in of concomitant chemotherapy and radiation therapy
the concurrent chemo/RT arm as compared to the as it applies to advanced stage laryngeal cancer,
RT-alone arm (p < 0.00444 and p < 0.0345). however, are limited. As mentioned earlier, a ran-
The debate also continues regarding the optimal domized prospective trial comparing sequential to
fractionation of radiation therapy, chemotherapeutic concomitant chemotherapy and radiation therapy is
agents, and optimal timing of chemotherapy and currently underway.
radiation therapy (sequential vs. concomitant). Pro- Additionally, randomized prospective studies
tocols with accelerated fractionation of radiotherapy comparing sequential chemotherapy and radiation
and plans using concomitant chemotherapy and therapy to concomitant chemo/RT in patients with
radiotherapy have been investigated. It has been pos- unresectable tumors of the head and neck have been
tulated that part of the cause of increased locore- reported.27,53 While an improvement in locoregional
gional failures seen with chemo/RT protocols result control was seen in the concomitant arm in the larger
from an accelerated tumor cell repopulation during study,53 neither study showed a difference in overall
the prolonged course of treatment.46,47 Clinical and survival.27,53 At this time, neither accelerated fraction
experimental evidence suggest that tumor cell popu- radiation therapy nor concomitant chemo/RT have
lations, after a lag period of several weeks, will conclusively demonstrated a benefit in treating
decrease their doubling time and increase their rate advanced stage laryngeal cancer relative to induc-
 The Larynx:Advanced Stage Disease 167

tion chemotherapy followed by conventional frac- substitute for surgery in the treatment of advanced
resectable head and neck cancer. A report from the North-
tion radiation therapy. For this reason, along with the
ern California Oncology Group. Cancer 1987;60(6):
potential for treatment related morbidity, it remains 1178–83.
investigational at this time. 5. Demard F, Chauvel P, Santini J, et al. Response to
Finally, novel treatment strategies continue to chemotherapy as justification for modification of the
therapeutic strategy for pharyngolaryngeal carcinomas.
evolve which intend to further improve the survival Head Neck 1990;12(3):225–31.
and functional outcome in patients with advanced 6. Pfister DG, Strong E, Harrison L, et al. Larynx preservation
cancer of the larynx. One such unique strategy uti- with combined chemotherapy and radiation therapy in
advanced but resectable head and neck cancer. J Clin
lizes the high-dose intra-arterial cisplatin with a sys- Oncol 1991;9(5):850–9.
temic neutralizing agent along with conventional 7. Karp DD, Vaughan CW, Carter R, et al. Larynx preservation
radiation therapy.54 In this study, where the majority using induction chemotherapy plus radiation therapy as
of patients had stage IV disease (86%) and clinically an alternative to laryngectomy in advanced head and neck
cancer. A long-term follow-up report. Am J Clin Oncol
involved regional lymph nodes (79%), a major 1991;14(4):273–9.
response rate was seen in 95 percent of patients. Nine 8. Urba SG, Forastiere AA, Wolf GT, et al. Intensive induction
of 10 patients retained their larynx and 2-year dis- chemotherapy and radiation for organ preservation in
patients with advanced resectable head and neck carci-
ease-specific survival was 76 percent. It should be noma. J Clin Oncol 1994;12(5):946–53.
noted that 3 of the 42 patients experienced central 9. Clayman GL, Weber RS, Guillamondegui O, et al. Laryngeal
nervous system complications as a result of catheri- preservation for advanced laryngeal and hypopharyngeal
cancers. Arch Otolaryngol Head Neck Surg 1995;121(2):
tization of the carotid system. Nevertheless, this 219–23.
remains a promising option and a novel approach in 10. Myers EN, Alvi A. Management of carcinoma of the supra-
the treatment of advanced laryngeal cancer. glottic larynx: evolution, current concepts, and future
trends. Laryngoscope 1996;106(5 Pt 1):559–67.
11. Nguyen TD, Malissard L, Theobald S, et al. Advanced carci-
CONCLUSION noma of the larynx: results of surgery and radiotherapy
without induction chemotherapy (1980–1985): a multi-
The treatment of patients with advanced cancers of variate analysis. Int J Radiat Oncol Biol Phys 1996;36(5):
the larynx has changed dramatically over the last 2 1013–8.
12. Kirchner JA, Owen JR. Five hundred cancers of the larynx
decades. While anatomic preservation of the larynx and pyriform sinus. Results of treatment by radiation and
can now be achieved in a large fraction of patients, surgery. Laryngoscope 1977;87(8):1288–303.
overall survival remains unchanged. The continued 13. Harwood AR, Hawkins NV, Beale FA, et al. Management of
advanced glottic cancer. A 10-year review of the Toronto
optimization of multimodality treatment paradigms experience. Int J Radiat Oncol Biol Phys 1979;5(6):
along with the incorporation of biological markers, 899–904.
novel treatment approaches, novel chemotherapeutic 14. Harwood AR, Rawlinson E. The quality of life of patients fol-
lowing treatment for laryngeal cancer. Int J Radiat Oncol
agents and innovative biologic and gene transfer
Biol Phys 1983;9(3):335–8.
techniques will hopefully further increase our ability 15. Dahm JD, Sessions DG, Paniello RC, Harvey J. Primary sub-
to improve survival in these patients. glottic cancer. Laryngoscope 1998;108(5):741–6.
16. Levendag P, Sessions R, Vikram B, et al. The problem of neck
relapse in early stage supraglottic larynx cancer. Cancer
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 9
The Larynx: Early Stage Disease
WILLIAM M. LYDIATT, MD, FACS
DANIEL D. LYDIATT, DDS, MD, FACS

The American Cancer Society estimated that in the has decreased in several countries, including the
United States there would be 10,600 cases of laryn- United States, and is thought to be due to an
geal carcinoma diagnosed in 1999, and 4,200 increased incidence in women. Age at diagnosis
deaths.1 This accounts for 0.9 percent of cancers ranges from the second to tenth decade, with the sev-
from all sites and 0.8 percent of all cancer deaths. enth the most common. Over 90 percent of all laryn-
Laryngeal carcinoma makes up 1 to 2 percent of can- geal cancers are squamous cell carcinoma, which
cers worldwide, and the incidence is increasing (Fig- will be the primary focus of this chapter. Other his-
ure 9–1). Spain has one of the highest rates in the tologic types include lymphoma, spindle-cell carci-
world with Basque and Navarra regions reaching a noma, neuroendocrine carcinoma, minor salivary
rate of 20 cases per 100,000 persons. There is also a gland carcinomas, mucosal melanoma, and various
very high incidence in France, Italy, and Poland.2 sarcomas. Metastatic lesions and direct extension of
Men are affected 4 times more frequently than thyroi