• Neoplasia means new growth, the new growth produced is

called neoplasm or tumor.

• All new growth are not neoplasm (embryogenesis,

regeneration, repair, hyperplasia)

• Branch of science dealing with study of neoplasm is called

oncology
Definition

• a neoplasm is an abnormal mass of tissue, the growth of

which exceeds and is uncoordinated with that of the
surrounding normal tissues and persists in the same
excessive manner after cessation of the stimuli that evoked
the change.
Epidemiology

• Worldwide, it is estimated that about 20% of all deaths are

cancer-related.
According to country

• Developed countries: lung, breast, prostate and colorectal.

”

• Developing countries: liver, cervix, oral cavity, oesophagus.

According to types

• Most (90%) neoplasms arise from epithelium

• The remainder arise from mesenchymal cells
Predisposition to cancer

a. Familial and genetic factors

• Risk of developing cancer in relatives of known cancer

patient is almost three times higher

1. Retinoblastoma: 40% familial and autosomal dominant

2. Familial polyposis coli: autosomal dominant

3. Cancer of breast: female relatives of breast cancer patient

have 2to3 times higher of developing cancer
b. Environmental and cultural factors

1. Cigarette smoking: oral cavity, pharynx, larynx,

oesophagus, lungs, pancreas, urinary bladder

2. Alcohol abuse: oropharynx, larynx, liver, osophagus

3. Cancer of cervix: early age of sexual intercourse, multiple

sexual partner

4. Penile cancer: less in circumcised individual

5. Betel nut : cancer of cheek, tongue

c. Age

1. Generally occurs in older individual

2. Some have 2 peaks like acute leukaemia

d. Gender

3. Most tumors are generally more common in men than in

women except cancer of the breast, gallbladder, thyroid
and hypopharynx.
e. Geographic and racial factors

i. Stomach cancer-Japan » United States

ii. Breast cancer-United States> > Japan
iii. Liver hepatoma -Asia> > United States
iv. Prostate cancer-African American> Caucasian
f. PRE-MALIGNANT AND NON-NEOPLASTIC CONDITIONS
i. Cervical dysplasia
ii. Endometrial hyperplasia

Some benign tumor:

1. Multiple adenoms of large intestine

2. Pleomorphic adenoma
 g. Miscellaneous conditions
• Certain inflammatory (both infectious and non-infectious)
and hyperplastic conditions are prone to development of
cancer.

i) HPV-induced chronic cervicitis.

ii) Cirrhosis of the liver : hepatocellular carcinoma.

iii) H. pylori gastriits developing gastric cancer and lymphoma.

iv) Chronic bronchitis in heavy cigarette smokers may develop

cancer of the bronchus.
Carcinogenic Agents(carcinogen)

• Agent which can induce tumors are called carcinogens

1. Chemical carcinogens

a. Direct-acting chemical carcinogens.

• These are mutagens that cause cancer directly by

modifying DNA

• Alkalating agents: leukemia, lymphoma, other cancers

 B. Indirect-acting chemical carcinogens
(procarcinogens).
• These require metabolic conversion to form active
carcinogens

• Nitrosamines: gastric cancer

• Asbestos: bronchogenic carcinoma
• Arsenic: squamous cell carcinomas of skin and lung.
• Aromatic amines and azo dyes: hepatocellular carcinoma
• Napthylamine: bladder cancer
2. Physical carcinogen

Radiation
a. Ultraviolet radiation
i. UVB sunlight is the most carcinogenic.
ii. Increased risk of skin cancer

b. Ionizing radiation
i. X rays and gamma rays, alpha and beta particles, protons,
neutrons
ii. Atomic bomb: leukemias, thyroid cancer.
iii. Uranium miners: lung cancer
3. Oncogenic viruses

• RNA oncogenic viruses.

1. The human T-cell leukemia virus (HTLV-l) causes adult T-
cell leukemia/lymphoma.

• DNA oncogenic viruses

1. Hepatitis B virus causes hepatocellular carcinoma
2. Epstein-Barr virus (EBV) : Burkitt lymphoma,
Nasopharyngeal carcinoma
3. Human papilloma virus (HPV) causes Benign squamous
papillomas (warts), Cervical cancer
4. Hormonal carcinogens
• Oestrogen: endometrial carcinoma
• Contraceptive hormones: breast cancer
• Anabolic steroid: liver tumor
Carcinogenesis

1. General

• It means induction of tumor

• Carcinogenesis is a multistep process involving a sequence

of initiation (mutation) followed by promotion
(proliferation)
A. Initiation

• Can initiate the process of neoplastic transformation

• Converting target cell into initiated cell

• Steps

a. Metabolic activation
• By cytochrome P45O system (for indirect carcinogen)
b. Reactive electrophiles

• Direct-acting carcinogens are intrinsically electrophilic

• Indirect-acting substances become electron-deficient after

metabolic activation.

• Both will bind to electron rich portion of other molecules

of cell like DNA, RNA.
c. Target molecules
• It is mainly DNA, producing mutagenesis
• It leads to initiated cell OR gets repaired

d. Initiated cell
• The unrepaired damage produced in the DNA of cell
becomes permanent only if the altered cell undergoes at
least one cycle of proliferation
• This result in transferring the change to next progeny of
cell so that DNA damages becomes permanent and
irreversible
B. Promotors

i. Cause cellular proliferation of mutated (initiated) cells

ii. Proliferation of a mutated cell may lead to accumulation of

additional mutations

Iii .Phenols ,hormones:estrogen

Progression of Carcinogenesis

• Stage when mutated proliferated cell shows phenotypic

features of malignancy.

• These features pertain to morphology, biochemical

composition and molecular features of malignancy.

• Such phenotypic features appear only when the initiated

cell starts to proliferate rapidly and in the process acquires
more and more mutations.
Loss of polarity
• Normally, the nuclei of epithelial cells are oriented along
the basement membrane which is termed as basal polarity

Pleomorphism
• means variation in size and shape of the tumour cells.

Anisonucleosis
• Just like cellular pleomorphism, the nuclei too, show
variation in size and shape in malignant tumour cells
HOST RESPONSE AGAINST TUMOR
(TUMOR IMMUNOLOGY)

• Body’s immune system can recognize tumor cells as ‘non-

self’ and they attempt to destroy them and limit the
spread of cancer.

.
1. TUMOR ANTIGENS
Tumor cells express surface antigens

It is of two types based on their patterns of expression:

1. Tumor-specific antigens
• Present only on tumor cells

2. Tumor-associated antigens
• Present on tumor cells and also on some normal cells.
Main classes of tumor antigens

Products of Mutated Genes

• Mutated proteins represent antigens that have never been
seen by the immune system and thus can be recognized as
non-self

Overexpressed or Abnormally Expressed Cellular Proteins

• Tumor antigens are structurally normal proteins that are
produced at low levels in normal cells and overexpressed
in tumor cells.

Tumor Antigens Produced by Oncogenic Viruses.

ANTI-TUMOUR IMMUNE RESPONSES

• Cytotoxic T lymphocytes
• Natural killer cells
• Macrophages
• Antibodies
Immune regulatory mechanisms
Most cancers grow relentlessly in spite of host immunity.
Antigen masking

The cell surface antigens of tumors may be hidden, or

masked, from the immune system by glycocalyx molecules.

Apoptosis of cytotoxic T cells

EFFECT OF TUMOR ON HOST

A. LOCAL EFFECTS
i) Compression
ii) Mechanical obstruction
• Benign and malignant tumors in the gut may produce
intestinal obstruction.

iii) Tissue destruction

• infiltrate and destroy the vital structures.

iv) Infarction, ulceration, hemorrhage

• Cancers have a greater tendency to undergo infarction,
surface ulceration and hemorrhage than the benign
tumors. Secondary bacterial infection may supervene.
B. SYSTEMIC MANIFESTATIONS

1. CANCER CACHEXIA
• Cancer patient Suffers progressive loss of body fat and
lean body mass accompanied by profound weakness,
anorexia, and anemia, referred to as cachexia (meaning
wasting).

2. FEVER
• Fever of unexplained origin may be presenting feature in
some malignancies such as in Hodgkin’s disease,
adenocarcinoma kidney.
3. TUMOUR LYSIS SYNDROME

• This is a condition caused by extensive destruction of a

large number of rapidly proliferating tumour cells

• It is characterised by hyperuricaemia, hyperkalaemia,

hyperphosphataemia and hypocalcaemia, all of which may
result in acidosis and renal failure.
4. PARANEOPLASTIC SYNDROMES

• Paraneoplastic syndromes (PNS) are a group of

conditions developing in patients with advanced cancer
which are neither explained by direct and distant spread
of the tumour, nor by the usual hormone elaboration by
the tissue of origin of the tumour.
 RATE OF GROWTH

• The tumor cells generally proliferate more rapidly than the

normal cells.

• In general, benign tumors grow slowly and malignant

tumors rapidly.
The rate depends upon 2 main factors:

1. Rate of cell production, growth fraction and rate of cell

loss

2. Degree of differentiation of the tumor.

• Differentiation refers to the extent to which neoplastic

parenchymal cells resemble the corresponding normal
parenchymal cells, both morphologically and functionally;
lack of differentiation is called anaplasia.
1. Rate of cell production, growth fraction and rate of cell
loss
• Depends upon 3 important parameters:

i) Doubling time of tumor cells,

ii) Number of cells remaining in proliferative pool (growth

fraction), and

iii) Rate of loss of tumor cells by cell shedding.

• Malignant tumour cells have increased mitotic rate
(doubling time) and slower death rate

• Malignant tumours grow in size because the cell

production exceeds the cell loss.
2. Degree of differentiation

• Rate of growth of malignant tumour is directly

proportionate to the degree of differentiation.

• Poorly differentiated tumours show aggressive growth

pattern as compared to better differentiated tumours.

• The regulation of tumour growth is under the control of

growth factors secreted by the tumour cells

• i) Epidermal growth factor (EGF)

• ii) Fibroblast growth factor (FGF)

Nomenclature of neoplasia
• There are general rules fore nomenclature
with few exceptions
• from where does tumor arises, parenchymal
or mesenchymal origin
• clinical behavior benign or malignant
 Naming of benign tumors:
• by adding the suffix –oma to the name of the
tissue from which the tumor arises.
• For example benign tumors of
• Fibrous tissues : fibroma
• Cartilages : Chondroma
• Glands: adenomas
• Bone: Osteoma
 Naming of malignant tumors:

• All malignant tumors are called cancer

• Epithelial tissues are named carcinoma

• Mesenchymal tissues are named sarcoma

• Combination of sarcoma and carcinoma are

encountered called carcinosarcoma
Exception of the rule of nomenclature
• These tumors are malignant , inspite of that,
they ended with the suffix –oma like

• Seminoma: malignant tumor of spermatocyte

• Lymphoma: malignant tumor of lymphoid
tissue
• Melanoma : malignant tumor of melanocytes
(3) Special nomenclature
① Blastoma: tumors rigging in immature tissue or
nervous tissue, most of them are malignant
e.g. medulloblastoma retinoblastoma,
nephroblastoma
③ Some malignant tumors, but called disease.
e. g. leukemias, paget’s disease

④ Some malignant tumors nominated by

scientists’ name
e. g. Hodgkin’s disease, Ewing’s tumor

⑤ Mixed tumors:
e. g. mixed tumor of salivary gland
⑥ Teratomas: tumors containing mature or
immature cells or tissues representative of more
than one germ layer and sometimes all the three
layers.
Tissue of Origin Benign Malignant
COMPOSED OF ONE PARENCHYMAL CELL TYPE
Tumors of Mesenchymal Origin
Connective tissue and Fibroma Fibrosarcoma
derivatives Lipoma Liposarcoma
Chondroma Chondrosarcoma
Osteoma Osteogenic sarcoma
Endothelial and Related Tissues
Blood vessels Hemangioma Angiosarcoma
Lymph vessels Lymphangioma Lymphangiosarcoma
Synovium Synovial sarcoma
Mesothelium Mesothelioma
Brain coverings Meningioma Invasive meningioma
Blood Cells and Related Cells
Hematopoietic cells   Leukemias
Lymphoid tissue Lymphomas
Muscle
Smooth Leiomyoma Leiomyosarcoma
Striated Rhabdomyoma Rhabdomyosarcoma
Tumors of Epithelial Origin
Stratified squamous Squamous cell papilloma Squamous cell carcinoma
Basal cells of skin or adnexa Basal cell carcinoma
Epithelial lining of glands or Adenoma Adenocarcinoma
ducts
Papilloma Papillary carcinomas
Cystadenoma Cystadenocarcinoma
Respiratory passages Bronchial adenoma Bronchogenic carcinoma
Renal epithelium Renal tubular adenoma Renal cell carcinoma
Liver cells Liver cell adenoma Hepatocellular carcinoma
Urinary tract epithelium Transitional-cell papilloma Transitional-cell carcinoma
(transitional)

Placental epithelium Hydatidiform mole Choriocarcinoma

Testicular epithelium (germ   Seminoma
cells)
Embryonal carcinoma
Tumors of Melanocytes Nevus Malignant melanoma
Metastasis

• Is defined as spread of tumor by invasion in such a way that

discontinuous secondary tumor mass are formed at the site of
lodgment
a. Initial routes of metastasis

i. Lymphatic spread is the most common route of spread

for epithelial carcinomas

ii. Wall of lymphatic are readily invaded by cancer cell and

may form a continuous growth in the lyamphatic channel
called lyamphatic permeation, or may detach to form
tumor emboli so as to be carried along the lymph to the
next draining lymph node.
ii. Hematogenous spread
• Metastasis through blood vessels.
• Most sarcomas
• But carcinoma those of lungs, breast, thyroid, kidney,
prostate
• Common site for blood borne metastasis
• Liver, lungs, kidney, brain, bones

Other routes of metastasis

1. Transcoelomic spread

• Carcinoma stomach to peritoneum

• Pleura and pericardium in carcinoma bronchus and breast
ii. Spread along epithelium lined surface

iii. Spread through cerebralspinal fluid

iv. Implantation

• Transplantation via mechanical manipulation (e.g., surgical

incision, needle tracts) may occur but is relatively rare
Malignant tumors Benign tumors Origin of tissues Type of tissues

Fibrosarcoma fibroma fibrous Mesenchymal tissues

Liposarcoma lipoma Fatty tissues

Chondrosarcoma chondroma cartilage

Osteosarcoma osteoma bone

Rhabdomyosarcoma rhabdomayoma Skeletal muscle

Liemyosarcoma leiomyoma Smooth muscles

Squamus cell carcinoma Squamus cell papiloma Squamous epithelium Parenchymal tissues

Basal cell carcinoma Basal cell layer

Adenocarcinoma adenoma Glands

Transitional cell carcinoma Transitional cell adenoma Transitional

epithelium
Haemangiosarcoma haengioma B blood vessels

lymphangiosarco lymphangioma Lymphatic vessels