SOFT TISSUE TUMOR

SINDRAWATI FKWM, BLOK 3.3

GENERAL OUTLINE

 PROLIFERATIVE, REACTIVE; NON NEOPLASTIC TUMOR LIKE

LESION
 BENIGN SOFT TISSUE TUMOR
 MALIGNANT SOFT TISSUE TUMOR

 CLASSIFICATION ACCORDING TO WHO

 GRADING & STAGING ACCORDING TO WHO
GENERAL OUTLINE

 Many benign tumors and reactive tumor-like lesions

commonly occur in soft tissue. Malignant soft tissue
tumors (sarcomas) are rare and their diagnosis and
classification form a highly specialist area of pathology.
 TUMOR OF ADIPOSE TISSUE
 FIBROUS TUMOR
 SKELETAL MUSCLE TUMOR
 SMOOTH MUSCLE TUMOR
 TUMOR OF UNCERTAIN ORIGIN
 EPIDEMIOLOGY
 With the exception of skeletal muscle neoplasms, benign soft tissue
tumors outnumber their malignant counterparts, the sarcomas, by
100 fold.
 Sarcomas, however, cause 2% of all cancer mortality, reflecting
their aggressive behavior.
 Most soft tissue tumors arise in the extremities, especially the thigh.
 Of the benign soft tissue tumours 99% are superficial and 95% are
less than 5 cm in diameter
 Approximately 15% arise in children but the incidence increases with
age.
 Half of the vascular tumours occur in patients younger than 20
years.
EPIDEMIOLOGY

 Soft tissue sarcomas may occur anywhere but three

fourths are located in the extremities (most common in
thigh) and 10 percent each in the trunk wall and
retroperitoneum.
 There is a slight male predominance.
 Like almost all other malignancies, soft tissue sarcomas
become more common with increasing age; the
median age is 65 years.
 Of the extremity and trunk wall tumours one third are
superficial with a median diameter of 5 cm and two-
thirds are deep-seated with a median diameter of 9 cm
 Retroperitoneal tumours are often much larger before
they become symptomatic.
 EPIDEMIOLOGY
 The age-related incidences vary;
 embryonal rhabdomyosarcoma occurs almost exclusively in
children,
 synovial sarcoma mostly in young adults
 pleomorphic high grade sarcoma, liposarcoma and
leiomyosarcoma dominate in the elderly
 One tenth of the patients have detectable metastases (most
common In the lungs) at diagnosis of the primary tumour.
 Overall, at least one-third of the patients with soft tissue sarcoma die
because of tumour, most of them because of lung metastases.
Benign
 Most benign soft tissue tumours do not recur locally.
 Those that do recur do so in a non-destructive fashion
and are almost always readily cured by complete local
excision.
 Exceedingly rarely (almost certainly <1/50,000 cases,
and probably much less than that), a morphologically
benign lesion may give rise to distant metastases.
 This is entirely unpredictable on the basis of conventional
histological examination and, to date has been best
documented in cutaneous benign fibrous histiocytoma
Intermediate (locally aggressive)

 Soft tissue tumours in this category often recur locally

and are associated with an infiltrative and locally
destructive growth pattern.
 Lesions in this category do not have any evident
potential to metastasize but typically require wide
excision with a margin of normal tissue in order to ensure
local control.
 The prototypical lesion in this category is desmoid
fibromatosis
Intermediate (rarely metastasizing)
 Soft tissue tumours in this category are often locally
aggressive (see above) but, in addition, show the well-
documented ability to give rise to distant metastases
 in occasional cases. The risk of such metastases appears
to be <2% and is not reliably predictable on the basis of
histomorphology.
 Metastasis in such lesions is usually to lymph node or
lung.
 Prototypical examples in this category include plexiform
fibrohistiocytic tumour and so-called angiomatoid
fibrous histiocytoma
Malignant

 In addition to the potential for locally destructive growth

and recurrence,
 malignant soft tissue tumours (known as soft tissue
sarcomas) have significant risk of distant metastasis,
ranging in most instances from 20% to almost 100%,
depending upon histological type and grade.
 Some (but not all) histologically low grade sarcomas
have a metastatic risk of only 2-10%, but such lesions
may advance in grade in a local recurrence, and
thereby acquire a higher risk of distant spread (e.g.,
myxofibrosarcoma and leiomyosarcoma).
 GRADING SYSTEM
 In the past, sarcomas were often considered to arise
from the tissue type which they resembled, e.g.
liposarcomas were thought to develop due to
malignant transformation of normal or benign adipose
tissue.
 It is now accepted that most sarcomas do not arise from
benign precursor lesions. Classification is therefore based
upon the concept that tumour cells may differentiate so
that they resemble normal tissues to a lesser or greater
degree.
 Classification of soft tissue tumors
 Clinically, soft tissue tumors range from benign, self-limited lesions
that require minimal treatment to intermediate grade, locally
aggressive tumors with minimal metastatic risk to highly aggressive
malignancies with significant metastatic risk and mortality.
 The term sarcoma is applied somewhat inconsistently such that
some, but not all, locally aggressive tumors fall into this category.
 Tumors with significant metastatic potential are, of course, con-
sidered sarcomas.
 Pathologic classification integrates morphology (e.g., muscle
differentiation), immunohistochemistry and molecular diagnostics
 In addition to accurate diagnosis, grade (degree of differentiation)
and stage (size and depth) are important prognostic indicators.
 Reactive processes and tumour-like lesions
 Some soft tissue masses do not satisfy the usual criteria to be
classified as true benign neoplasms and are considered to be
reactive rather than neoplastic.
 These lesions may arise following a minor injury or in areas exposed
to repetitive trauma, but such a history is not always obtained.
 The line between benign soft tissue tumours and reactive tumour-
like lesions is not always clear and, in recent times, molecular
evidence of clonality has begun to emerge for some of the entities
conventionally considered to be reactive.
 It is of great importance to note that some reactive soft tissue lesions
may be very rapidly growing, causing clinical suspicion of
malignancy.
 Such lesions may also appear alarming histologically, showing
active proliferation with numerous mitotic figures. This possibility must
always be considered before suggesting a diagnosis of soft tissue
sarcoma.
 Reactive processes
 A large number of soft tissue masses fall into this broad group
but the majority are encountered only rarely in clinical
practice.
 The traumatic or amputation neuroma is a reactive mass
which may form following damage to a peripheral nerve
 A ganglion is a fairly common lesion which is probably related
to repeated minor damage around sites of excessive tendon
and joint use, e.g. around the wrists and hands of pianists and
typists
 Giant cell tumour of tendon sheath (also known as nodular
tenosynovitis) also tends to occur around the hands and
wrists
 As the name suggests, the nature of this lesion has been the
subject of considerable debate and there is increasing
evidence that it may be a true benign neoplasm.
 Pseudosarcoma
 Some reactive processes in soft tissue appear extremely alarming,
both clinically and histologically, and may be described as
pseudosarcomas.
 One example is nodular fasciitis. This typically presents as a very
rapidly growing soft tissue swelling, appearing over the course of a
few weeks.
 On close questioning, there may be a history of preceding trauma.
 The mass tends to be situated in the superficial fascia and usually
has ill-defined margins (unlike most benign tumours which tend to
be encapsulated).
 Histologically, this is a proliferation of spindle cells, often with very
numerous mitotic figures.
 There is a high risk of over-diagnosing malignancy in this setting and
great care is required to recognize that this is a reactive process,
rather than a sarcoma.
Ganglia

most commonly affect the hands and wrists, presenting as a firm

and mobile mass in the vicinity of tendons and synovial joints.

This simple intervention often causes the lump to disappear by

dispersing fluid contents, but most lesions recur over time and
surgical excision provides a more definitive solution.

Most lesions appear to arise from the sheath of synovium which

invests the tendons, although some can be shown to connect with
an adjacent synovial joint.
Histologically,
there is usually a cystic space
C with a fibrous wall W and no
discernable lining.
Foci of myxoid change M are
present in the surrounding
connective tissue.
Sometimes, the cystic spaces
may be lined by histiocytic
cells resembling synovial lining
cells.
 Giant cell tumour of tendon sheath
(nodular tenosynovitis)
 This is a common lesion which typically occurs around the
fingers.
 It is usually a firm nodule with a lobulated surface.
 Histologically, there is a proliferation of bland polygonal cells
with eosinophilic cytoplasm, as well as a scattering of
multinucleate, osteoclast-like giant cells. Some lesions show
areas of haemosiderin deposition within macrophages, and
collections of foamy macrophages containing lipid may also
be prominent.
 TUMOR LIKE LESION IN JOINT
pigmented villonodular synovitis.
 This disorder usually affects the synovium of the knee
joint and typically presents with swelling, joint pain and
reduced joint mobility.
 Although the histological features are extremely similar,
this process diffusely affects the joint and frequently
recurs following treatment.
SARCOMA; pathogenesis
 The approach to diagnosis is rather similar to that used in
haematolymphoid pathology and typically requires careful
correlation of the clinical and radiological findings with the
histological appearance and pattern of immunohistochemical
staining.
 Molecular studies may also be of value because many soft tissue
tumours have characteristic non-random chromosomal
rearrangements.
 The majority of sarcomas are sporadic and have no known
predisposing cause.
 A small minority of soft tissue neoplasms are associated with
germline mutations in tumor suppressor genes (neurofibromatosis 1,
Gardner syndrome, Li-Fraumeni syndrome, Osler-Weber Rendu
syndrome).
Pathogenesis of sarcoma

 A few tumors can be linked to known environmental

exposures such as radiation, burns or toxins.
 Unlike tumors such as colonic carcinoma that usually
arises from easily recognized precursor lesions, the origin
of sarcomas is unknown.
 The best guess is that the tumors arise from pluripotent
mesenchymal stem cells, which acquire somatic “driver”
mutations in oncogenes and tumor suppressor genes.
 Despite heterogeneous mechanisms of tumorigenesis
among sarcomas, some generalizations can be made
based on their karyotypic complexity
TUMOR OF ADIPOSE TISSUE
very common tumour most frequently during middle adulthood,
usually occurs within the subcutaneous fatty tissue of the trunk or limbs.
Macroscopy: soft, fairly well-defined lesions which are usually painless.
Microscopy
well-defined edge (encapsulated)
The lesion is composed of sheets of uniform adipocytes.
These cells have a very small nucleus which is displaced to the
periphery of the cell by a large globule of lipid
In some patients, multiple tender lesions occur and,
histologically, these differ from usual lipomas in that they contain
multiple small blood vessels, some of which contain fibrin
thrombi. These lesions are called angiolipomas
EPIDEMIOLOGY
 There is a relation between the type of tumour,
symptoms, location and patient’s age and gender.
 Lipomas are painless, rare in hand, lower leg and foot
and very uncommon in children
 Multiple (angio)lipomas are sometimes painful and most
common in young men,
 Angiomyolipoma are often painful and common in
lower leg of middle-aged women,
 Infrequently, lipomas are large, intramuscular, and
poorly circumscribed.
 LIPOSARCOMA
 one of the most common sarcomas of adulthood.
 occurs mainly in people in their 50s to 60s in the deep soft tissues of
the proximal extremities and in the retroperitoneum.
 Amplification of 12q13-q15 and t(12;16) are characteristic of well-
differentiated and myxoid liposarcomas, respectively. One of the
key genes in the amplified region of chromosome 12q is MDM2,
which encodes a potent inhibitor of p53.
 Pleomorphic liposarcomas contain complex karyotypes without
reproducible genetic abnormalities.
 All types of liposarcoma recur locally and often repeatedly unless
adequately excised.
 The well-differentiated variant is relatively indolent, the
myxoid/round cell type is intermediate in its malignant behavior,
while the pleomorphic variant usually is aggressive and frequently
metastasizes.
LIPOSARCOMA; MORPHOLOGY

Liposarcomas are histologically divided into three morphologic

subtypes:
 Well-differentiated liposarcoma contains adipocytes with scattered
atypical spindle cells
 Myxoid liposarcoma contains abundant basophilic extracellular
matrix, arborizing capillaries and primitive cells at various stages of
adipocyte differentiation reminiscent of fetal fat
 Pleomorphic liposarcoma consists of sheets of anaplastic cells,
bizarre nuclei and variable amounts of immature adipocytes
(lipoblasts).
NODULAR FASCIITIS
 a self-limited fibroblastic and myofibroblastic proliferation that
typically occurs in young adults in the upper extremity.
 A history of trauma is present in approximately 25% of cases and the
tumors grow rapidly over a period of several weeks or months,
typically no larger than 5 cm.
 Whereas nodular fasciitis was historically considered a reactive
inflammatory lesion, identification of t(17;22) that produces a MYH9-
USP6 fusion gene indicates that it is a clonal, but self-limited,
proliferation. It appears that the proliferating cells lack some key
hallmark of cancer, perhaps the ability to avoid senescence.
Intriguingly, ABC (discussed earlier), another tumor that sits in a gray
zone between reactive and neoplastic proliferations, also contains
USP6 fusion genes. Nodular fasciitis typically spontaneously regresses
and if excised, it rarely recurs.
NODULAR FASCIITIS, MORPHOLOGY
 Nodular fasciitis arises in the deep dermis, subcutis, or muscle.
 Grossly the lesion is less than 5 cm, circumscribed, or slightly
infiltrative.
 The lesion is richly cellular and contains plump, immature-appearing
fibroblasts and myofibroblasts arranged randomly or in short
fascicles reminiscent of tissue culture fibroblasts
 A gradient of maturation (zonation) from cellular, loose, and myxoid
to organized and fibrous is typical.
 The cells vary in size and shape (spindle to stellate) and have
conspicuous nucleoli; mitotic figures are abundant.
 Lymphocytes and extravasated red blood cells are common but
neutrophils are unusual.
FIBROMATOSIS; Superficial fibromatosis

 An infiltrative fibroblastic proliferation that can cause local

deformity but has an innocuous clinical course.
 All forms of superficial fibromatosis affect males more frequently
than females.
 They are characterized by nodular or poorly defined broad
fascicles of fibroblasts in long, sweeping fascicles, surrounded by
abundant dense collagen.
 Several clinical subtypes have been identified
 FIBROMATOSIS; Superficial fibromatosis
 Palmar (Dupuytren contracture): Irregular or nodular thickening
of the palmar fascia either unilaterally or bilaterally (50%). Over a
span of years, attachment to the overlying skin causes puckering
and dimpling. At the same time a slowly progressive flexion
contracture develops that mainly affects the fourth and fifth
fingers of the hand.
 Plantar: Common in young patients, unilateral and without
contractures.
 Penile (Peyronie disease): Palpable induration or mass on the
dorsolateral aspect of the penis. Eventually, it may cause
abnormal curvature of the shaft, constriction of the urethra, or
both.
 In about 20% to 25% of cases, the palmar and plantar fibromatoses
stabilize and do not progress, in some instances resolving
spontaneously. Some recur after excision, particularly the plantar
variant.
 Deep Fibromatosis (Desmoid Tumors)

 large, infiltrative masses that frequently recur but do not

metastasize.
 They are most frequent in the teens to 30s, predominantly in
women.
 Abdominal fibromatosis generally arises in the musculoaponeurotic
structures of the anterior abdominal wall but tumors can arise in the
limb girdles or the mesentery.
 Deep fibromatoses contain mutations in the APC or β-catenin
genes, both of which lead to increased Wnt signaling.
 The majority of tumors are sporadic, but individuals with familial
adenomatous polyposis (Gardner syndrome) who have germline
APC mutations are predisposed to deep fibromatosis.
Deep Fibromatosis (Desmoid Tumors)

 In addition to possibly being disfiguring or disabling, deep-seated

fibromatosis is occasionally painful.
 Because of the extensively infiltrative nature, complete excision is
often difficult.
 Recent efforts have concentrated on medical therapy with
cyclooxygenase 2 inhibitors, tyrosine kinase inhibitors, or hormonal
blockade (tamoxifen).
FIBROMATOSIS; morphology

 Fibromatoses are gray-white, firm, poorly demarcated masses

varying from 1 to 15 cm in greatest diameter.
 They are rubbery and tough, and have marked infiltration of
surrounding muscle, nerve and fat.
 Cytologically bland fibroblasts arranged in broad sweeping
fascicles amid dense collagen are the characteristic histologic
pattern
 The histology resembles scar.
SKELETAL MUSCLE TUMOR; almost always malignant
 Rhabdomyosarcoma is a malignant mesenchymal tumor with skeletal
muscle differentiation.
 Three subtypes are recognized: alveolar (20%), embryonal (60%) and
pleomorphic (20%).
 Rhabdomyosarcoma (alveolar and embryonal) is the most common soft
tissue sarcoma of childhood and adolescence, usually appearing before
age 20.
 Pleomorphic rhabdomyosarcoma is seen predominantly in adults.
 The pediatric forms often arise in the sinuses, head and neck and
genitourinary tract, locations that do not normally contain much skeletal
muscle, underscoring the notion that sarcomas do not arise from mature,
terminally differentiated muscle cells.
 Rhabdomyosarcomas are aggressive neoplasms that are usually treated
with surgery and chemotherapy, with or without radiation therapy.
 Rhabdomyosarcoma
 The embryonal and pleomorphic subtypes are genetically
heterogeneous.
 Alveolar rhabdomyosarcoma frequently contains fusions of the
FOXO1 gene to either the PAX3 or the PAX7 gene, rearrangements
marked by the presence of (2;13) or(1;13) translocations,
respectively.
 PAX3 is a transcription factor that initiates skeletal muscle
differentiation, and it appears that the chimeric PAX3-FOXO1 fusion
protein interferes with the gene expression program that drives
differentiation, a mechanism similar to many of the transcription
factor fusion proteins that are found in various forms of acute
leukemia.
 The histologic type and location of the tumor influence survival. The
botryoid variant of embryonal rhabdomyosarcoma has the best
prognosis, while the pleomorphic subtype is often fatal.
Rhabdomyosarcoma; morphology
 Embryonal rhabdomyosarcoma presents as soft gray infiltrative
mass. The tumor cells mimic skeletal muscle at various stages of
embryogenesis and consist of sheets of both primitive round and
spindled cells in a myxoid stroma
 Rhabdomyoblasts with visible cross-striations may be present.
 Sarcoma botryoides, described in ; is a variant of embryonal
rhabdomyosarcoma that develops in the walls of hollow, mucosal-
lined structures, such as the nasopharynx, common bile duct,
bladder, and vagina.
 Where the tumors abut the mucosa of an organ, they form a
submucosal zone of hypercellularity called the cambium layer.
 Rhabdomyosarcoma; morphology
 Alveolar rhabdomyosarcoma
 traversed by a network of fibrous septae that divide the cells into
clusters or aggregates, creating a crude resemblance to
pulmonary alveoli.
 Those in the center of the aggregates are discohesive, while
those at the periphery adhere to the septae.
 The tumor cells are uniform round, with little cytoplasm—cross
striations are not a common feature.
 Pleomorphic rhabdomyosarcoma
 characterized by numerous large, sometimes multinucleated,
bizarre eosinophilic tumor cells and can resemble other
pleomorphic sarcomas histologically.
 Immunohistochemistry (e.g., myogenin) is usually necessary to
confirm rhabdomyoblastic differentiation.
SMOOTH MUSCLE TUMOR; Leiomyoma,

 a benign tumor of smooth muscle, often arises in the

uterus; in fact, uterine leiomyomas are the most
common neoplasm in women
 They develop in 77% of women and, depending on their
number, size, and location, may cause a variety of
symptoms including infertility.
 Leiomyomas may also arise from the erector pili muscles
(pilar leiomyomas) found in the skin, nipples, scrotum,
and labia and rarely in the deep soft tissues and the
muscularis of the gut.
 Pilar leiomyomas may be multiple and painful.
 SMOOTH MUSCLE TUMOR; Leiomyoma
 The phenotype of multiple cutaneous leiomyomas may be
transmitted as an autosomal dominant trait that is also associated
with uterine leiomyomas and renal cell carcinoma—hereditary
leiomyomatosis and renal cell cancer syndrome.
 This disorder is associated with a germline loss-of-function mutation
in the fumarate hydratase gene located on chromosome 1q42.3.
 Fumarate hydratase is an enzyme that participates in the Krebs
cycle, and this association thus constitutes another intriguing
example of the link between metabolic abnormalities and certain
forms of neoplasia.
Leiomyoma
 Soft tissue leiomyomas are usually 1 to 2 cm and are
composed of fascicles of densely eosinophilic spindle
cells that tend to intersect each other at right angles.
 The tumor cells have blunt-ended, elongated nuclei and
show minimal atypia and few mitotic figures.
 Solitary lesions are easily cured. However, multiple
tumors may be so numerous that complete surgical
removal is impractical.
 Leiomyosarcoma
 Leiomyosarcoma accounts for 10% to 20% of soft tissue
sarcomas.
 They occur in adults and afflict women more frequently
than men.
 Most develop in the deep soft tissues of the extremities
and retroperitoneum.
 A particularly deadly form arises from the great vessels,
especially the inferior vena cava.
 Leiomyosarcoma

 Leiomyosarcomas have complex genotypes that stem

from underlying defects that lead to profound genomic
instability.
 Treatment depends on tumor size, location, and grade.
 Superficial or cutaneous leiomyosarcomas are usually
small and have a good prognosis, whereas those of the
retroperitoneum are large, cannot be entirely excised,
and cause death by both local extension and
metastatic spread, especially to the lungs.
Leiomyosarcoma; morphology

 Leiomyosarcomas present as painless firm masses.

 Retroperitoneal tumors may be large and bulky and
cause abdominal symptoms. They consist of eosinophilic
spindle cells with blunt-ended, hyperchromatic nuclei
arranged in interweaving fascicles.
 Ultrastructurally, the tumor cells contain bundles of thin
filaments with dense bodies and pinocytic vesicles, and
individual cells are surrounded by basal lamina.
 Immunohistochemically, they stain with antibodies to
smooth muscle actin and desmin.
 TUMOR OF UNCERTAIN ORIGIN
SYNOVIAL CELL SARCOMA

described cases arose in the soft tissues near the knee joint
and a morphologic relationship to synovium was
postulated.
this name is a misnomer, as these tumors can present in
locations (chest wall, head and neck) that lack synovium
and their morphologic features are inconsistent with an
origin from synoviocytes.
Synovial sarcomas account for approximately 10% of all
soft tissue sarcomas and rank as the fourth most common
sarcoma.
Most occur in people in their 20s to 40s.
SYNOVIAL CELL SARCOMA

Patients usually present with a deep-seated mass that has

been present for several years.
Synovial sarcomas are treated aggressively with limb-
sparing surgery and frequently chemotherapy.
The 5-year survival varies from 25% to 62%, related to stage
and patient age.
Common sites of metastases are the lung and occasionally
the regional lymph nodes.
Synovial sarcomas; morphology

 Synovial sarcomas are morphologically monophasic or

biphasic.
 Monophasic synovial sarcoma consists of uniform spindle
cells with scant cytoplasm and dense chromatin
growing in short, tightly packed fascicles.
 Many tumors historically classified as fibrosarcoma likely
would be classified as synovial sarcoma today.
 The tumors may calcify.
 Synovial sarcomas; morphology

 The biphasic type contains, in addition to the spindle cell

component above, gland-like structures composed of
cuboidal to columnar epithelioid cells
 Immunohistochemistry is helpful in identifying these
tumors, since the tumor cells, especially in the biphasic
type, are positive for epithelial markers (e.g., keratins),
differentiating them from most other sarcomas.
Undifferentiated pleomorphic sarcoma
 malignant mesenchymal tumors with high-grade, pleomorphic cells
that cannot be classified into another category by a combination
of histomorphology, immunophenotype, ultrastructure or molecular
genetics.
 Despite advances in molecular characterization of sarcomas, UPS
represents the largest category of adult sarcomas.
 Most arise in the deep soft tissues of the extremity, especially the
thigh of middle aged or older adults.
 The diagnosis of malignant fibrous histiocytoma (MFH), sometimes
used interchangeably with UPS, has fallen out of usage because
(1)the category included both undifferentiated tumors and others that
were reclassified with immunohistochemistry or molecular methods
(2)no consensus exists for the morphologic definition of fibrohistiocytic.
Undifferentiated pleomorphic sarcoma

 Not surprisingly, reproducible genetic changes are not

typical of UPS.
 Most tumors are aneuploid with multiple structural and
numerical chromosomal changes.
 UPS are aggressive malignancies that are treated with
surgery and adjuvant chemotherapy and/or radiation.
 The prognosis is generally poor, with metastases arising in
30% to 50% of cases.
Undifferentiated pleomorphic sarcoma
morphology

 UPS are usually large, grey-white fleshy masses and can grow quite
large (10 to 20 cm) depending on the anatomic compartment.
 Necrosis and hemorrhage are common.
 They consist of sheets of large, anaplastic spindled to polygonal
cells with hyperchromatic irregular, sometimes bizarre nuclei
 Mitotic figures, including atypical non-symmetric forms, are
abundant as is coagulative necrosis.
 By definition, tumor cells lack differentiation along recognized
lineages.