Neoplasia

Gemechu MD
 Cell biology

• The reproduction or division of somatic cells involves two

sequential phases

1. mitosis, or nuclear division

2. cyto- kinesis, or cytoplasmic division

• These phases occur in close succession, with cytokinesis

beginning toward the end of mitosis
 Con’t…

• Most of the preparation for division occurs during the

growth phase or interphase.

• The alternation between mitosis and interphase in all

tissues that have cellular turnover is known as the cell
cycle.
 Con’t…

There are four designated phases of the cell cycle

1. The G1 phase, which is the period between the M phase

and the start of DNA synthesis.

2. The S phase (synthesis) in which DNA is synthesized in the

cell nucleus

3. The G2 phase, in which RNA and protein synthesis occurs.

4. The M phase (mitosis) which includes both nuclear and

cytoplasmic division

• Interphase, consisting of the G1, S, and G2 phases, is the

 con’t…

• The difference between slowly and rapidly dividing cells

is the length of time spent in the G1 phase of the cell
cycle.

• Once a cell has progressed out of the G1 phase, it must

complete the S, G2, and M phases
Interphase
The M phase of the cell cycle, mitosis and cytokinesis

1. Prophase

• Each chromosome has two identical halves called

chromatids that lie side by side and are attached together
at a site called a centromere.

• The nuclear membrane disappears in this phase.

Spindle fibres are microtubules

 Con’t….

2. Metaphase

The spindle fibres pull the centromeres until they are

aligned in the middle of the spindle or at the equatorial
plate

3. Anaphase

Begins when the centromeres separate and the genetically

identical chromatids are pulled apart

4. Telophase

A new nuclear membrane is formed around each group of

 Normal cell cycle phases

INHIBITORS: Cip/Kip, INK4/ARF

Tumor (really growth) suppressor genes: p53

 Neoplasia

• Neoplasia literally means “new growth.”

• Neoplasia is ‘a mass of tissue formed as a result of

abnormal, excessive, uncoordinated, autonomous and

purposeless proliferation of cells even after cessation of

stimulus for growth which caused it

 Con‘t….

• Neoplasms therefore enjoy a certain degree of autonomy

and tend to increase in size regardless of their local
environment

• Their autonomy is by no means complete, however, some

neoplasms require endocrine support

• The branch of science dealing with the study of neoplasms or

tumours is called oncology (oncos=tumour, logos=study)

 Con’t…

Tumors are broadly classified based on clinical behaviors

• Benign neoplasim when they are slow-growing and

localised without causing much difficulty to the host, or

• Malignant neoplasim when they proliferate rapidly, spread

throughout the body and may eventually cause death of the

host.
 Con’t…

All tumours, benign as well as malignant, have 2 basic

components:

• Parenchyma: comprised by proliferating tumour cells;

parenchyma determines the nature and evolution of the
tumour.

• Supportive stroma: composed of fibrous connective tissue

and blood vessels; it provides the framework on which the
parenchymal tumour cells grow
Properties of Benign/Malignant Tumor
The histologic features of malignancy:

• Pleomorphism: Variation in nuclear and cytoplasmic

shape between cells.

• Abnormal mitotic figures and increased numbers of

mitotic figures.

• Hyperchromasia, increased basophilia of the nucleus.

• Hypercellularity, with a loss of normal polarity

 Con’t….

• prominent nucleoli, and increased nuclear-to-cytoplasmic

ratios (approaching 1:1 versus normal ratios of 1:4 or 1:6)

• Loss of polarity: disturbed orientation and tendency for

forming anarchic, disorganized masses

• Tumor giant cells with single polyploid nuclei or multiple

nuclei

• Ischemic necrosis due to insufficient vascular supply

 Tumor nomenclature

Benign tumors typically end with the suffix –oma

• Benign mesenchymal tumors include

Lipoma,

Fibroma

Angioma

Osteoma

Leiomyoma
 Con’t…benign

• Benign epithelial tumors also typically uses the -oma suffix

but in addition incorporates elements of histogenesis,
macroscopic appearance, and microscopic architecture

Squamous cell papiloma

Transitional cell papiloma

Liver cell adenoma

 Con’t….

• Adenomas: Epithelial tumors arising in glands or

forming glandular patterns.

• Cystadenomas: Adenomas producing large cystic

masses, common in .

• Papillomas: Epithelial tumors forming gross or

microscopic fingerlike projections.

• Polyp: Tumor projecting macroscopically above the

mucosa (e.g., a colon polyp)
 con’t…nomenclature

Malignant tumors are categorized as the following:

• Carcinomas derived from epithelial cells.

• Sarcomas of mesenchymal cell origin.

Squamous cell carcinoma,

Adenocarcinomas

Rhabdomyosarcoma

Osteosarcoma
 con’t….nomnclature

Some exceptions:

• Hepatoma : malignant neoplasm of liver

• Melanoma : malignant neoplasm of melanocytes

• Mesothelioma : malignant neoplasm of mesothelial

cells

• Seminoma : malignant germ cell neoplasm of testis

Terminology related to microscopic appearance of

neoplasms

• Differentiation: refers to how closely tumor cells

histologically (and functionally) resemble their normal cell
counterparts

- Differentiation is a subjective determination made by the

pathologist
 Con’t…

• Benign lesions are well differentiated.

• Malignant neoplasms can range from well differentiated

to completely undifferentiated
 Con’t……

• Anaplasia (lack of differentiation)

• Dysplasia (loss of cellular uniformity and

architectural orientation)

• Carcinoma in situ (Full-thickness dysplasia of the

epithelium)
EPIDEMIOLOGY of cancer
 Mortality due to neoplasms varies slightly from the

incidence

• Carcinomas of the lung, prostate and colonic neoplasim

accounting for the most frequent cause of cancer deaths
in males

• Carcinoma of lung, breast and colonic neolasim account

for most frequent cause of cancer deaths in females
 The causes and sequence of carcinogenesis.

• Oncogenes: are genes that can transform a normal cell

into a cancerous cell when inherited or activated by
oncogenic viruses

• proto-oncogene are that regulate growth and

development by encoding for growth factors and growth
factor receptors
 Con’t….

• Tumor suppressor gene these genes produce proteins

that normally oppose the action of an oncogene or
inhibit cell divisions

• Apoptosis genes : The most common mutations

causing resistance to apoptosis occur in the p53 gene
 Con’t…

• DNA repair genes: These genes encode proteins that repair

damaged DNA, and loss of caretaker genes leads to
increased mutation rates

• Other than germ cells: telomeres are at the ends of each

chromosome and block unlimited cell division, some
cancer cells activate telomerase to restore and maintain
telomeres so cells can divide over and over again
The relationship between epigenetics and genetics.
• Approximately 95% of malignancies arise sporadically (i.e.
, do not have an apparent inherited familial basis)

• Epigenetic changes collaborate with genetic changes

with environmental-lifestyle factors to cause the
development of cancer.
The three major areas of epigenetics are:

1. Methylation (the addition of a methyl group [CH3 ] to a

cytosine ring), an aberrant methylation that can lead to
silencing of tumor-suppressor genes;

2. Histone modifications (histone acetylation, alterations in

chromatin)

3. MicroRNAs (miRNAs), small RNA molecules that can

target gene expression post-transcriptionally
 Predisposing Factors
1. FAMILIAL AND GENETIC FACTORS

• Risk of developing cancer in relatives of a known cancer

patient is almost three times higher

• Familial cancers occur at a relatively early age, appear

at multiple sites and occur in 2 or more close relatives.

• The overall estimates suggest that genetic cancers

comprise not greater than 5% of all cancers
Some of the common examples FAMILIAL AND GENETIC FACTORS

• Retinoblastoma.

• Familial polyposis col

• Multiple endocrine neoplasia (MEN)

• Neurofibromatosis or von Recklinghausen’s disease.

• BRCA-1 and BRCA-2. Mutations cause Cancer of the

breast
 Con’t….

2. RACIAL AND GEOGRAPHIC FACTORS

3. ENVIRONMENTAL AND CULTURAL FACTORS

• Cigarette smoking

• Alcohol abuse

4. Ionizing radiation (IR)

4. Viruses associated with neoplasms

• Human T-cell leukemia virus type 1 (HTLV-1) Associated

with Adult T-cell leukemia/lymphoma

• Human papillomavirus (HPV) Associated with Squamous

cell carcinoma of the cervix, oral pharyngeal cancers.

• Epstein-Barr virus (EBV) associated with Burkitt

lymphoma

• Hepatitis B virus (HBV) associated with Hepatocellular

carcinoma.

• Human herpesvirus 8 (HHV-8): Primary effusion

lymphoma
 • Clinical manifestations of cancer

Pain

• pain will affect individuals who are terminally ill with

cancer.

• Cancer-associated pain arises from multiple sources.

direct pressure, obstruction, stretching of visceral
surfaces, tissue destruction, infection, and inflammation
 Con’t…

• Fatigue is the most frequently reported symptom of

cancer and cancer treatment.

• Cachexia is a wasting, emaciation manifesting symptoms

of anorexia.
•
Anemia is also commonly associated with malignancy
 Tumor cell markers
• Tumor cell markers are substances that are produced by
cancer cells and found on tumor plasma membranes or in
the blood, spinal fluid, or urine.

• They include hormones, enzymes, genes, antigens, and

antibodies
 Con’t….

• It helps us

1. To identify individuals at high risk for cancer,

2. To diagnose the specific type of tumor in an individual

with clinical manifestations of cancer

3. To observe the clinical course of cancer

 Paraneoplastic Syndrome.

• A group of conditions developing in patients with

advanced cancer which are neither explained by direct
and distant spread of the tumour

• They appear in 10% to 15% of patients with cancer, and

their clinical recognition is important for several reasons
 Pathways of Spread

• Lymphatic spread transports tumor cells to regional

nodes and ultimately throughout the body.

• Hematogenous spread is typical of sarcomas but also is

the favored route for certain carcinomas. (e.g., renal)

 Con’t…

Seeding of body cavities and surfaces occurs by

dispersion into peritoneal, pleural, pericardial,
subarachnoid, or joint spaces.

lung and liver are the most common sites of

hematogenous metastases.

veins are more frequently invaded than arteries, and

metastasis
 Grading and staging of cancer
• Grading is based primarily on the degree of
differentiation (how well the tumor resembles its
normal counterpart), and occasionally, architectural
features or number of mitoses.)

• Generaly higher-grade tumors (more poorly

differentiated) are more aggressive than lower-grade
tumors
If cancer exists, it is critical to know the extent of
its spread, or its stage

A four-stage system is used:

• Stage I Cancer confined to the site of origin

• Stage II cancer that is locally invasive

• Stage III cancer that has spread to regional structures

such as lymph nodes

• Stage IV spread to distant sites eg. Lung, liver

 Con’t…

• Stage of cancer alters the choice of therapy

• In general, the lower the stage, the more amenable the

cancer is to treatment.

• More aggressive therapy is delivered to more invasive

disease
Thank you
Any questions???????