 Is an abnormal mass of tissue, the growth

of which exceeds and is uncoordinated

with that of normal tissues and persists in
the same excessive manner after the
cessation of the stimuli which evoked the
change.
Epidemiology;-
1) Geographic and environmental factors.
Environmental factors are related to
type of food, occupational hazards,
sunlight and social habits e.g. cigarette
smoking and alcohol consumption.
2. Age;-
 In general the frequency of cancer

increases with age.

3. Heredity;-
Inherited susceptibility may play a role in

the genesis of several common cancers e.g.

retinoblastoma, and Wilms' tumor
4. Acquired preneoplastic disorders. These
include;
 Hyperplasia and dysplasia
 Chronic atrophic gastritis
 Chronic ulcerative colitis
 Villous adenoma of the colon
 Chronic skin fistula,
 long unhealed wound,
 and cirrhosis of the liver.
 Neoplasm are classified as either
malignant or benign based on their
behavior.
 They are described by terms derived
from the appearance of the neoplasm,
tissue of origin or degree of
differentiation.
 They are capable of invasion (spread of
the neoplasm into adjacent structures) and
metastasis (implantation of neoplasm in
distant sites).
Metastasis is the most defining characteristic
of malignancy, although there are some
malignant tumors such as basal cell
carcinoma of the skin that rarely
metastasize.
 Malignant tumors are usually less
differentiated than benign tumors
 Are marked by anaplasia (poorly
differentiated), and exhibit
pleomorphism, hyperchromatism (dark
staining nuclei), an increase N/C ratio
(nuclear/cytoplasmic ratio), abnormal
mitosis, cellular dispolarty and often
prominent nucleoli.
 Is the malignant tumor of epithelial origin
and can be seen in the following variations
1) squamous cell carcinoma (s.c.c);- originate
from stratified squamous epithelium of e.g.
the skin, mouth, esophagus and vagina. Is
marked by production of keratin. Can also
originate from areas of squamous
metaplasia.
2) Transition cell carcinoma;- arise from
transitional cell epithelium of the urinary
tract.
3) adenocarcinoma;- is the carcinoma of
the glandular epithelium and includes
malignant tumors of the gastrointestinal
mucosa, endometrium and pancreas.
Is often associated with desmoplasia (tumor
induced proliferation of non-neoplastic
fibrous C.T) particularly in adenocarcinoma
of the breast pancreas and prostate.
 Is the malignant tumor of mesenchymal
origin. Is often used with prefix that
denotes the tissue of origin of the tumor
as;-
 osteosarcoma (bone),
 rhabdomyosarcoma (skeletal muscle),
 leiomyosarcoma (smooth muscle),
 and liposarcoma (fatty tissue)
Other tumors not obeying the rule
 Burrkeitt's lymphoma
 Hodgkin's lymphoma
 Wilm's tumor
 Leukemia
 Lymphoma
 Melanoma
 Retinoblastoma .
-Are usually well differentiated, closely
resemble the tissue of origin.
-Do not mestastasize and grow slowly .
-They can be harmful if their growth
compresses adjacent tissues e.g. benign
intracranial tumors can be more lethal than
some malignant skin tumors.
- benign tumors tends to be encapsulated.
-are denoted by suffix –oma as in lipoma,
and fibroma.
-however this suffix also applied to some
malignant neoplasm such as hepatoma,
melanoma, mesothelioma, and
retinoplastoma.
- benign tumors can be seen in the
following variants.
1) Papilloma;- is a benign neoplasm most
often arising from surface epithelium such as
squamous epithelium of the skin , larynx or
tongue.
- papilloma is composed of delicate finger-
like epithelial processes overlying a core of
connective tissue stroma that contains blood
vessels.
- papilloma may develop from transitional
epithelium of the urinary bladder, ureter or
renal pelvis.
2) Adenoma;-
is a benign neoplasm of glandular tissue

that occurs in several variants;-

a) Papillary cystadenoma;-
is characterized by adenomatous papillary

processes that extends into cystic spaces

as in cystadenoma of the ovary.
b) Mucinous cystadenoma
is characterized by cystic spaces lined by

mucus secreting epithelium (columnar).

c) Fibroadenoma;-
is marked by proliferation of C.T

surrounding neoplastic glandular

epithelium; e.g. fibroadenoma of the breast.
3) Benign tumors of mesenchymal
origin
are most often named by the tissue of

origin; e.g. leiomyoma, rhabdomyoma,

lipoma, fibroma, and chondroma
they include the most common neoplasm

of women, the uterine leiomyoma or fibroid

tumor.
Item of comparison Malignant tumor Benign tumor

metastasis yes no
Differentiation ? Poorly differentiated Well differentiated

Rate of growth rapid slow

encapsulation no yes
Cellular dispolarity yes no

pleomorphism yes no
hyperchromatism yes no
Nuclear\cytoplasmic increased normal
ratio
Local invasion:
Benign tumors Malignant tumors
Grow by expansion Grow by infiltration
Have a capsule No capsule.
No invasion of the capsule Invasion destroys normal
tissue

Surgical enucleation can be Surgical enucleation is

done impossible, but removal with a
safety margin is required.
The metastatic cascade can be divided
into;-
1) Invasion of extracellular matrix
It is an active process that can be
described in 4 steps;-
a) loosing up of the tumor cells.
b) attachment of tumor cells to extracellular
matrix.
c) local degradation of basement
membrane by proteases.
d) migration of tumor cells through degraded
basement membrane.
2) Vascular dissemination and homing of tumor
cells.
After invasion, tumor cells circulate in the

blood then adhere to the vascular endothelium

degrade the basement membrane. Then
migrate through the degraded basement
membrane.
.
Carcinoma tends to metastasize via lymphatic
spread except renal cell carcinoma and
hepatocellular carcinoma which invade the
blood vessels (venous) early.
sarcoma tends to invade blood vessels early.
Target organs
Are most commonly the liver, lungs, brain, bone
marrow, lymph nodes, and adrenal glands.
Sarcoma tends to spread to the lungs & liver,
while carcinoma spread to regional lymph
nodes.
 Is a reversible change, often precedes
malignancy.
 Morphologically manifests by disorderly
maturation and spatial arrangement of
cells
 Shows marked variability in nuclear size
and shape (pleomorphism) and increase,
often, abnormal mitosis.
 Affecting not more than 2/3 (two thirds)
of epithelium thickness. If it affects more
than 2/3, is called carcinoma in situ.
 Is exemplified by dysplasia of squamous
epithelium of the cervix which is often a
precursor of malignancy.
 Is replacement of well differentiated
epithelium by another well differentiated
tissue.
 Examples of metaplasia are;-

1) squamous metaplasia seen in;-

a- ciliated pseudostratified columnar
epithelium of the bronchi due to chronic
irritation by smoking.
b-mucus secreting of the nose, salivary ducts
and gall bladder due to chronic irritation
by e.g. stones or vitamin A deficiency .
c- transitional epithelium of the urinary
bladder due to schistosomaisis.
2) intestinal metaplasia seen in gastric

mucosa due to autoimmune chronic

gastritis.
3) connective tissue metaplasia occurs

between fibrous tissue bone and cartilage.

 Is a non-neoplastic disorganized, tumor-
like overgrowth of cell types that are
regularly found within the affected organ.
 Examples include;-
1. Hemangioma is an irregular accumulation
of blood vessels
2. Other types of hamartoma are;
melanocytic hamartoma, skeletal
(cartilage) hamartoma, juvenile polyps
and Peutz-jeghers polyps.
 Teratoma is a neoplasm derived from all
three germ cell layers, which may contain
structures such as skin, bone, cartilage,
teeth, and intestinal epithelium. It may
be either malignant or benign and usually
arises in the ovaries or testes.
 Choristoma. This is a small non -
neoplastic area of normal tissue
misplaced within another organ, such as
pancreatic tissue within the wall of the
stomach.
 Mixed tumors:
 Derived from one germ cell layer, that
differentiates into more than one cell type
 The best example is mixed salivary tumors,
that contain epithelial structures, myxoid
tissue and cartilage.
 Is an increase in the size of an organ or
tissue due to an increase in the number
of the cells .
 An example is glandular proliferation in
the breast during pregnancy.
 Another example is RBC hyperplasia in
high altidude.
 In some instances hyperplasia occurs
with hypertrophy as in uterine
enlargement during pregnancy.
1) Loss of contact inhibition.
2) Loss of adhesion i.e. grow separately rather
than clusters due to abnormal cytoskeleton.
3) Loss of anchorage dependence grow.
4) Expression of surface proteases which
facilitate invasion
5) chromosomal aneuploidy i.e. increase
number of chromosomes (not multiple of 23).
6) Expression of tumor specific antigens (TSA).
7) Originate from a single cell (monoclonal).
 Cell proliferation can be readily resolved
into the following steps;-
1. Binding of growth factor to its receptor
2. Activation of growth factor receptor.
3. Signal transduction across the cytosole to
the nucleus via second messenger.
4. Induction and activation of transcription
factors.
5. Entry and progression of the cell into the
cell cycle
1. Cell division is inhibited by pRb and
other tumor suppressor genes (TS
genes)
2. Cell division is stimulated by CDK (cyclin
dependent kinases).
3. Cell division is inhibited by CDK inhibitors
such as P16 , P53, P21.
4. GTPase inhibit signal transduction.
5. Growth factors and their receptor have
short half-life.
6. When cell division is stopped, any insult
in DNA is repaired by mismatch and
nucleotide excision repair.
7. If the DNA repair fails, the cell is directed
by the product of P53 gene to undergo
apoptosis. Apoptosis is a physiological
process that can be inhibited by Bcl-2
product.
In summary;-
•cell division and growth is stimulated by

products of a group of genes known

collectively as cellular proto-oncogenes,
which become (c-onc) when activated.
•The c-onc may be a growth factor, its

receptor, second messenger, or transcription

factor.
•Cell division is inhibited by products of a

group of genes known collectively as tumor

suppressor genes e.g. P53, P16, DCC, Rb.
•Cell growth is under control of the process of

apoptosis which is further under control of a

group of gene products e.g. P53, Bcl-2.
 The transformation of normal to
neoplastic cell is caused by both
endogenous and exogenous factors
including;-
1. Chemical, physical & biological(e.g.
viruses) agents (known collectively as
environmental factors).
2. activation of cancer promoting genes,
3. inhibition of cancer suppressor genes
4. and inhibition of apoptosis genes.
 The mechanism by which cellular proto-
oncogenes become tumorigenic include
the following;-
1. promoter insertion (insertional mutation)
2. point mutation
3. chromosomal translocation e.g. 9;22
translocation in chronic myeloid
leukemia.
4. Gene amplification.
Inactivation of cancer suppressor gene
This is most often by deletion e.g. deletion

by Rb gene in retinoblastoma.
Inhibition of apoptosis
Mutation in P53 is found in many tumors.

Derangement of DNA repair gene

The best example is the defective excision
repair gene in xeroderma pigmentosum
which lead to development of malignant
tumors of the skin.
Environmental factors
1.viral carcinogenesis

2.chemical carcinogenesis

3.radiation
 Virus can cause cancer by;-
1. Insertion of their promoters near proto-
oncogene and activating them. This type
of viruses are known as slow transforming
viruses.
2. Insertion of their V-onc in host genome.
This type of viruses are known as acute or
rapidly transforming viruses. They are
characterized by processing V-onc which
acquired from host genome during their
replication.
Examples of viral-associated cancer are;-
a) cervical carcinoma is associated with
HPV
b) hepatocellular carcinoma is associated
with HBV.
c) nasopharyngeal carcinoma is associated
with Epstein Barr Virus (EBV).
What is the difference between v-onc and c-
onc
1. Ultra violet radiation
U/V radiation in form of sunlight, is clearly

related to skin cancer as S.C.C, basal cell

carcinoma and melanoma.
2. Ionizing radiation
In lethal dose, they cause death (used for

treatment of cancer).
In less lethal dose, they cause irreversible

change leading to cancer e.g.

1. leukemia in radiologist.
2. Thyroid and thymus cancer in those
receiving neck radiation therapy.
3. Osteosarcoma in radium workers.
 Radiation cause point mutation and
chromosomal translocation.
 There are 2 types of chemical carcinogens;-
1. Promoters;- they are ineffective on their
own, but enhance the action of initiators.
 Examples are hormones, phorbol esters and

phenols.
2. Initiators;- are tumorgenic on their own by
DNA mutation. They are 2 types;-
a) Direct reacting carcinogens i.e. they are
active in the form in which they are
administered.
b) Indirect reacting carcinogenesis require
metabolic conversion from procarcinogenes
to active ultimate carcinogens. Example is
β-naphthline.
Examples of chemical associated with

tumors;-
 aflatoxin associated with hepatocellular
carcinoma.
 Arsenic associated with squamous cell
carcinoma and basal cell carcinoma.
 Asbestosis associated with mesothelioma.