Neoplasia

Dr. Methaq Mueen

Lec.2
Characteristics of Benign & Malignant
tumors:
Characteristics of differentiation between
benign & malignant tumors are:
1-Differentiation & Anaplasia.
2-Rate of growth.
3-Local invasion.
4- Metastasis.
 Rate of growth
Most benign tumors grow slowly.
Most of malignant tumors (cancers) grow faster
& eventually spread locally & to distant sites
(metastasis) & causing death.
In some exception, some benign tumors grow
more rapidly than some cancers, e.g.
leiomyoma (uterine fibroid), which is benign
smooth muscle tumor influence by estrogen
& so increase in size during pregnancy.
In malignant tumors:
rate of growth is inversely related to level of
differentiation
well differentiated cancer is slowly growing,
while undifferentiated cancer are grow rapidly).
Some of malignant tumors undergo spontaneous
regression, regress the whole primary cancers &
leave only their metastasis e.g.
Choriocarcinoma.

Rapidly growing malignant tumors usually have

central area of necrosis (ischemic) because
inadequate bloods supply to provide the rapid
growth of cancer.
Characteristics of Benign & Malignant
tumors:
Characteristics of differentiation between
benign & malignant tumors are:
1-Differentiation & Anaplasia.
2-Rate of growth.
3-Local invasion.
4- Metastasis.
 Local invasion:

Benign tumors are:

1. Localized at the site of origin,
2. Not invade the surrounding tissue.
3. Not metastasized.
4. Most of benign tumors have surrounding capsule (derived
from the original normal tissue as a result of atrophy of
parenchymal cells & by the pressure of benign tumors.
e.g. leiomyoma of uterus.
Important note:
Not all benign tumors are capsulated
e.g. benign vascular neoplasm of the dermis.
 Malignant tumors are:

1. Rapid progressive growth

2. Infiltration, invasion, & penetration of the
surrounding,.
3. Malignant tumors not develop well defined
Capsule,
4. Always metastasized
Local invasion is the second most reliable feature
(after metastasis) that distinguishes Malignant
from benign tumors.
Invasion (lung small cell carcinoma)
It is this invasiveness that makes surgical resection
of cancers difficult.
is necessary during surgery to remove a margin of
apparently normal tissues (margin of safety)
adjacent to infiltrative cancer.
One of the prime functions of the pathologist is to
indicate, in his report of a surgically excised
malignant tumor, of whether the tumor is totally
removed (free excision margins) or not
incompletely excised (positive excision margins).
In the latter instance recurrence of the tumor is a
strong possibility.
Characteristics of Benign & Malignant
tumors:
Characteristics of differentiation between
benign & malignant tumors are:
1-Differentiation & Anaplasia.
2-Rate of growth.
3-Local invasion.
4- Metastasis.
 Metastasis:
It means development of secondary implants discontinuous
with primary tumor, possibly in remote tissues.
Metastasis is the most important characteristic of malignancy.
Not all cancers have equal ability of development metastasis,
e.g. Basal cell carcinoma (BCC) of skin & most of CNS
malignancies are highly locally invasive but rarely
metastasis.
• While osteosarcoma is usually metastasize to lung at the
time of initial diagnosis
• In general, the more anaplastic & the larger the primary
neoplasm, the more likely is metastatic spread, with some
exception extremely small cancers have been known to
metastasize.
•
Metastasis to liver
 Benign malignant

Rate of growth Slow growth More rapid increase in size

Mitosis Mitotic figures are rare Mitotic figures are

and normal numerous and abnormal

Degree of differentiation Resemblance to tissue of Wide range of

origin (well differentiated) differentiation (WD,
MD,PD or undifferentiated
called anaplasia)

Local invasion Well Circumscribed or Poorly circumscribed and

encapsulated have a Tendency to invade
Lack of invasion surrounding tissues

Distant metastasis Absence of metastases Ability to metastasize to

distant tissues
 Pathways of Metastasis
Seeding within body cavities: These occur when
cancers invade the body cavities (pleura,
peritoneum, pericardium, subarachnoid, and
joint space)
e.g. carcinoma of colon, carcinoma of stomach
invade the peritoneal cavity in female extend
to both ovaries (Krukendurg tumors),
carcinoma of lung or breast invade the pleura,
& malignancy of ovary invade the peritoneum.
small tan tumor nodules seen over the peritoneal
surface of the mesentery
 Lymphatic spread

This is characteristically seen in carcinomas, while

sarcomas are more spread by vascular system.
There are numerous interconnections between lymphatic
& vascular systems, so all forms of cancer may spread
through either or both systems.

The pattern of involvement of lymph node depends

principally on the site of the primary neoplasm &
lymphatic pathways of this site e.g. lung carcinoma
metastasize first to the regional bronchial lymph nodes,
then to the hilar lymph nodes
Cancer cells arranged themselves inside the lymphatics either
as Emboli (commnest), or as continuous
growth(permeation).

In some cases, the cancer cells seem to traverse the

lymphatic channels within the immediately proximate
nodes to be trapped in subsequent lymph nodes, this is
called (Skip lesions),e.g. cancer of stomach, cancer of
prostate involve the cervical lymph nodes.
It should be remembered, that lymph nodes enlargement
with cancers, not always means cancerous nodal
involvement, it may be due to necrotic debris of the cancer
& tumor antigens, which may induce nodal enlargement in
form of lymphadenitis, & sinus histiocytosis .
Differentiation between the two is only possible through
microscopic examination of sections from the excised nodes.
A "sentinel lymph node" is defined as the first
lymph node in a regional lymphatic area that
receives lymph flow from a primary tumor
,therefore, this node is a representative of the
regional lymph nodes status.
It can be delineated by injection of blue dyes or
radiolabelled material.
Biopsy of sentinel lymph nodes allows
determination of the extent of spread of
tumor, and can be used to plan treatment
a biopsy of sentinel node is often used In breast cancer,
determining the involvement of axillary lymph nodes is very
important for assessing the future course of the disease and
for selecting suitable therapeutic strategies.
Usually, lymphatic spread of breast cancers is assessed by
performing a full removal of axillary lymph nodes.
But this procedure is associated with considerable surgical
morbidity like lymphedema of the arm
If the sentinel lymph node is negative(free from metastatic
carcinoma deposit )so there will not performing axillary
clearance because involvement of the other nodes is less
likely.
Assessment of sentinel node has also been used for detecting
lymphatic spread of melanomas, colon cancers, and other
tumors.
Metastatic adenocarcinoma
Metastatic papillary thyroid carcinoma
 Hematogenous spread
is the most feared consequence of a cancer; it is the favored
pathway for sarcomas.
Arteries are penetrated less readily than veins; because of the
wall thickness is more in arteries.
Source of these malignant cells is from emboli within the
lymphatics.
The liver & lungs are the most frequently involved secondary
sites in such hematogenous spread (all portal area drainage
flows to the liver, & all caval blood flows to the lungs).
Cancers arising near the vertebral column often embolize
through the paravertebral venous plexus to set into vertebrae
(e.g. carcinoma of thyroid & prostate).
Intraepithelial cancer spread:
This form of spread may occur where cancer develop in gland or
its duct e.g. carcinoma of breast spread to the areolar skin
(Paget’s disease of breast).
Epidemiology of cancer
Incidence of cancer: incidence varies with geography, age, race and genetic
background.
In male 30% Carcinoma of prostate
14% Carcinoma of Lung
11% Carcinoma of colon & rectum

In female 31% breast carcinoma

12% carcinoma of lung
12% carcinoma of colon
6% uterine carcinoma

Cancer death:
In male 31% carcinoma of lung
11% carcinoma of prostate

In female: 25% carcinoma of lung

15% carcinoma of breast
 Etiology of cancer:
Although both genetic and environmental factors contribute,
environmental influences are the dominant risk
factors for most cancers
Many factors may play a role in etiology of cancer:

I. Geographical & environmental factors:

These factors form about 65% of all cancer etiology,
while genetic factor form about 26%- 42% of cancer etiology.
There is geographical difference in the death from specific forms of cancer,
e.g. death from carcinoma of breast is about 4- 5 times higher in U.S.A than
Japan.
e.g. death from carcinoma of stomach in man & women is about 7 times
higher in Japan than in U.S.A.

All these geographical differences are due to environmental rather than

genetic causes.
These environmental factors can present in workplace
(occupational factors), in the food,………etc
Examples on occupation factors &associated cancer are:
Arsenic……………Carcinoma of lung, carcinoma of skin.
Asbestose………………..Carcinoma of lung, mesothelioma.
Benzene…………………Leukemia, lymphoma.
Cadmium…………………carcinoma of prostate.
Chromium…………………carcinoma of lung.
Nickle……………………..tumors of Nose, lung
Vinyl chloride……………..liver malignancy
Other environmental factors that have role in
development of cancer:
1. Alcohol consumption. increases the risk of carcinoma of the
oropharynx, larynx, esophagus and, by the development of
alcoholic cirrhosis, hepatocellular carcinoma.
2. smoking: associated with 90 % of lung cancer,
cancer of the mouth, pharynx, larynx, esophagus, pancreas, and
bladder
3-Infectious agents., human papillomavirus (HPV), associated
with cervical carcinomas and head and neck cancers
4- diet: e.g high fatty diet with low fiber contents increase colon
cancer
5-reproductive history: Lifelong cumulative exposure to
estrogen stimulation, particularly if unopposed by progesterone,
increases the risk of cancers of the breast and endometrium.
Age:
Frequency of cancer increase with Age (most death of cancer
between 55- 75 years), this is could be due to accumulation of
somatic mutations & change in immunity with increase age.
Cancer cause 10% of all death among children (below 15 years)
the types of cancers that predominate in children
are different from those seen in adults; this is because
paediatric cancers are more likely to be caused by inherited mutations
(particularly in tumor suppressor genes and not due to exposure to
environmental carcinogens (e.g., cigarette smoking), so carcinoma
(the most common tumor in adults) are very rare in children.
Major lethal Cancer in children is:
leukemia, CNS tumors, lymphoma , neuroblastoma , Wilms tumor &
soft tissue sarcoma like rhabdomyosarcoma.
 Hereditary factor:
Hereditary forms of cancers can be divided into
1. Inherited cancer syndromes:
These syndromes characterized by:
There is inheritance of a single mutant gene ( increase the risk of cancer).
Mode of inheritance is Autosomal dominant.

e.g. Familial retionoblastoma,

Multiple endocrine Neoplasia,
Neurofibromatosis type I, & type II.

2.Familial cancer:
Virtually all sporadic cancer can be occur in familial pattern:
e.g. Carcinoma of colon, carcinoma of breast, CNS tumors.
 Characteristics of Familial cancer:

1. Early Age of onset.

2. Tumors arising in two or more close relatives of
patient.
3. Multiple or bilateral cancer.
4. Mode of transmission is not clear.

Autosomal recessive syndromes of defective DNA repair.

A small group of autosomal recessive disorders is
collectively characterized by DNA instability.
e.g. xeroderma pigmentosa
 Acquired Predisposing Conditions
Acquired conditions that predispose to cancer
can be divided into:
1-chronic inflammatory disorders
2-precursor lesions
3-immunodeficiency states
 chronic inflammatory disorders

cancer risk is increased in individuals affected by

a wide variety of chronic inflammatory diseases, both
infectious and noninfectious
Pathogenesis:
1-chronic Inflammation ….tissue injury …compensatory
proliferation of cells that serves to repair the damage.
In some cases, chronic inflammation may increase the
pool of tissue stem cells, which may be particularly
susceptible to transformation.
2-activated immune cells produce reactive oxygen
species that may damage DNA
table
Precursors lesion:Acquired pre neoplastic
disorders
Localized morphologic changes that identify a field of epithelium
that is at increased risk for malignant transformation.
1. Hyperplasia, Metaplasia & dysplasia:
Like carcinoma of lung, develop in dysplastic bronchial tissue of habitual
smoker.
endometrial hyperplasia, which is caused by sustained estrogenic
stimulation of the endometrium.
Barrett esophagus(metaplasia..dysplasia…esophageal adenocarcinoma).
3. Chronic atrophic gastritis can predispose to carcinoma of stomach.
4. Chronic ulcerative colitis, predispose to carcinoma of colon.
5. Leukoplakia of oral cavity, vulva and penis (squamous cell
carcinoma).
6. Villous adenoma of colon, increase risk of carcinoma of colon.
Does the benign tumour transform to
malignant?
Some of benign tumors at high risk to become
malignant tumors, like:
1- villous adenoma of colon, when enlarge can
undergo malignant transformation in 50% of
cases if left untreated.
2-Familial adenomatous polyposis of the colon
Some of benign tumours rarely transform to
malignant: Uterine leiomyoma and pleomorphic
adenoma of salivary gland
Other benign tumor like lipoma Not transform
to malignant .

Most of benign have negligible risk of

malignant transformation possible explanation
is that benign tumors at high risk for malignant
transformation possess the cancer enabling
property of genomic instability , whereas other
benign tumors do not.
Genomic instability influencing cancer.
 Immunodeficiency and cancer
Patients who are immunodeficient, particularly
those with deficits in T-cell immunity, are at
increased risk for cancer, especially types caused
by oncogenic viruses, because these individuals
have a higher than normal incidence
of chronic infection with viruses.
These virus-associated tumors include
lymphomas, certain carcinomas, and some
sarcomas