INTRODUCTION TO NEOPLASIA

 DEFINITION

An abnormal tissue mass whose

growth exceeds and is uncoordinated
with that of adjacent normal tissue
and persists after cessation of the
stimuli that provoked it.
 CLASSIFICATION

Classification according to their tissue of origin :-

1) epithelial (neoplasia of lining tissues),
2) mesenchymal (neoplasia of connective
tissue derivatives),
3) germ cell (neoplasia of undifferentiated stem
cells ,sperm,
 Benign Neoplasm
 A neoplasm that grows without
invading adjacent tissue or spreading
to distant sites. It is usually fairly
well-circumscribed due to the lack of
invasion of surrounding tissues
Malignant Neoplasm
 A neoplasm that invades the
surrounding normal tissue and
usually spreads to distant sites given
sufficient time.
 Nomenclature
 Neoplasms have two components
1. Parenchyma= neoplastic cells
 decides behavior & Pathologic consequences

1. Stroma= Supportive ( connective tissue &

Vessels)
 Determines Growth & Evolution

 Soft & fleshy neoplasm Scant stroma

 Neoplasia- Nomenclature
Benign
Mesenchymal Epithelial
 Easy =Cell origin + oma  Not easy

 Chondro + Oma = • Adenoma  benign epithelial tumor

Chondroma derived from or present with glandular
pattern
{Cartilage} • Papilloma  finger-like or warty
 Fibro + Oma = Fibroma
projections from the epithelial
{Fibroblast} surfaces (MC - skin)
 Lipo + Oma = Lipoma • Polyp  fist-like projection from
mucosal epithelial surfaces( MC -
{Fat/ lipocyte /
colon)
adipocyte}
• Cystadenomas: forms large cystic
mass (ovaries)
• Papillary cystadenoma: papillary
patterns that protrude into the cystic
spaces (ovaries)
 Neoplasia- Nomenclature
Malignant
Mesenchymal
Epithelial
 Sarcoma  carcinoma (any germ layer)
 Greek = “fleshy” ( little  Adenocarcinoma glandular growth
stroma) pattern
 Chondro + sarcoma =  Squamous cell carcinoma squamous

Chondrosarcoma cell differentiation

 specify organ of origin Renal cell
{Cartilage}
 Fibro + sarcoma = adenocarcinoma, Bronchogenic
 Undifferentiated/ poorly differentiated
Fibrosarcoma
Can’t determine tissue of origin
{Fibroblast}  Mixed tumors Pleomorphic adenoma
 Lipo + sarcoma =
 Divergent differentiation of a single
Liposarcoma
germ line of parenchymal cells
{Fat/ lipocyte / (salivary gland)
adipocyte}  Teratoma  From Totipotential cells
 Rhabdomyo +sarcoma =
(gonads), > one germ layer { Dermoid
Rhabdomyosarcoma cyst  ovary}
{striated muscle}
Malignant neoplasias with benign
suffixes
Lymphoma
Mesothelioma
Myeloma
Astrocytoma
Glioma
 Benign -Epithelial

B
A
 Benign

Mesenchymal Epithelial
Leiomyoma Adenoma = thyroid
 Pleomorphic adenoma - Salivary gland

cartilage

Epithelial components
Teratoma
 Dysplasia
 Atypical proliferation of cells
characterized by nuclear
enlargement and failure of
maturation and differentiation, short
of malignancy.
Anaplasia
 Loss of differentiation
 (Carcinoma in situ (cis
 Full-thickness dysplasia extending from
the basement membrane to the surface
of the epithelium. Applicable only to
epithelial neoplasms. If the entire lesion
is no more advanced than CIS, then the
risk of metastasis is zero. This is because
there are no blood vessels or lymphatics
within the epithelium above the
basement membrane.
 Carcinoma

Carcinoma in-situ
Squamous cell carcinoma
 Differentiation

The tissue type represented by the

.tumor
Well-differentiated tumors resemble
identifiable tissue types, while poorly
differentiated tumors may only be
identifiable by the expression of cell
markers or by extremely focal and
subtle histologic and/or cytologic
findings.
 Metastasis
 Spread of tumor to distant sites by
lymphatic, hematogenous routes, or
seeding of body cavities.

Local Invasion
 Growth into the surrounding tissue
by direct expansion.
 DIFFERENCES
Features Benign Malignant
Boundaries Encapsulated Irregular
Surrounding Often Usually invaded
tissues compressed
Size Usually small Often large
Growth Slow & Rapid & infiltrating
expanding
Capsule Present Absent
Degeneration Rare Common
Recurrence Not common Common
Fixity Absent Present
 DIFFERENCES
Features Benign Malignant
Pattern Usually Poor
resemble resemblence
Basal polarity Retained Lost
Pleomorphism Not present Often present
N/C ratio Normal Increased
Anisonucleosis Absent Present

Hyperchromati Absent Present

sm
Mitosis Typical mitosis Atypical &
 DIFFERENCES
Features Benign Malignant
Tumour giant Without nuclear With nuclear
cells atypia atypia
Cytoplasm Normal Decreased or lost
constituents
Function Well maintained Lost or abnormal

Growth rate Slow Rapid

Local Compreses the Infiltrates &
invasion surrounding invades the
.tissue tissues
 Malignant tumors

Feature Sarcoma Carcinoma

Arise from mesenchymal tissue Arise from epithelial tissue
Origin
Usually larger since harder to Usually smaller since easier
Mass size detect them in deep tissue. to detect on surface

Takes longer to diagnose Takes shorter period of

Time of time to diagnose from
diagnosis onset
Goes directly to vascular Goes through lymphatics
Route of system/ Blood vessels (i.e. first – longer route to
Metastasis blood) vascular system
Worse prognosis Good/worse
Prognosis
 Malignant tumors

Mesenchymal Epithelial
Sarcoma Adenocarcinom
a
 Hamartoma
 May be mistaken for a true tumour
 Focal , circumscribed overgrowth.
 Improper proportions of tissue.
 No continuous overgrowth.
 Tumour - like malformation.
 Tissues of which is composed are
present in that area.
 Choristoma
 Similar to hamartoma.
 Tissues of which is composed are not
normally present in that area.
 Eg :-adrenal gland tissue in urinary
bladder.
MOLECULAR
BASIS
OF
NEOPLASM
Carcinogenesis
Induction of tumor is carcinogenesis &
agents which can induce tumor are
carcinogens.
Carcinogens can be:-
1. Chemical carcinogens.

2. Physical carcinogens.

3. Hormonal carcinogens.

4. Biologic carcinogens.
Chemical carcinogens:
These can be:-
 Direct acting-which require no
prior activation.
 Indirect acting- which require
prior activation.
 Physical carcinogens:-
It includes
1.Radiation

2. Non radiation carcinogens.

For e.g. ultraviolet rays,

ionizing rays, chronic
irritation etc.
Hormonal carcinogens:-
Certain hormones e.g. oral
contraceptives and anabolic steroids
increase the risk of developing benign
and malignant tumors. Hormone
sensitive tissues are breast,
endometrium, myometrium, thyroid,
liver and prostate.
Biologic carcinogens:-
It includes
1.Viral carcinogens, e.g. HPV,
EBV, HBV etc.
2.Parasitic carcinogens, e.g.
schistosomiasis.
3.Bacterial carcinogens, e.g.
Helicobacter pylori.
Rate of growth

The growth rate of tumors

correlates with their level of
differentiation, and thus malignant
tumors grow more rapidly than do
the benign lesions, though
examples of benign tumors with a
higher growth rate also exist.
 The rate of growth of benign as well
as malignant tumors is therefore not
constant over time.
Various factors govern the rate of
growth of tumors, e.g.:
 Hormone dependence

 Adequacy of blood supply

 Unknown influences.
For e.g.:
Leiomyomas of uterus are benign
smooth muscle tumors. These may
show no significant increase in size or
may even undergo atrophy post
menopause, but, may enter a rapid
growth phase during pregnancy, under
the influence of circulating steroid
hormones , particularly estrogen.
Clinical picture of leiomyoma
uterus
 An abrupt increase in size
and disseminating behaviour
of malignant neoplasm is
believed to be the result of
emergence of aggressive
subclone of transformed cells.
 Modes of spread

Neoplasia can spread by:-

1. Local invasion

2. Metastasis.
Local invasion:-

Almost all benign tumors

* grow as cohesive expansile
masses.
* remaining localized to site of
origin.
* do not have capacity to infiltrate,
invade or metastasize to
distant sites.
 As these expand and grow slowly,
they develop a rim of compressed
connective tissue called the fibrous
capsule.
 Separates tumor from host tissue.
 Derived from native tissue.

 Makes neoplasm discrete, readily

palpable & easily movable mass that can
be surgically enucleated.
Benign tumor of vertebral column.
There are exceptions for
e.g. hemangioma, which
is a neoplasm of tangled
blood vessels n are often
unencapsulated & may
appear to permeate the
site of origin.
 While benign tumors are non
invasive, the growth of cancers is
accompanied by progressive
infiltration, invasion & destruction of
surrounding tissues. Sometimes the
slowly expanding malignant tumors
may develop an apparent capsule.
Histology of this capsule shows tiny
crab like feet penetrating the margins
and infiltrating adjacent tissues.
 Thus, malignant tumors are invasive, and
recognize no anatomical boundaries,
making surgical resection difficult.
Therefore, it is necessary to remove a
considerable margin of apparently normal
tissue around infiltrative neoplasm.
 Invasiveness is one of the
reliable factors differentiating
benign and malignant tumors.
Preinvasive stage of tumors in
which they do not invade the
basement membrane is termed
as carcinoma in situ.
:-Metastasis
Metastasis are
tumor implants
discontinuous
with the primary
tumor.
Metastasis in progress
 Metastasis alone mark s a
tumor as malignant.
Almost all cancers metastasize .
Exceptions are few for e.g.
1. Glioma, malignant neoplasm of
glial cells of CNS.
2. Basal cell
carcinoma,
locally invasive
neoplasm also
known as rodent
ulcer but does
not metastasize
 In general, the more aggressive, the
more rapidly growing & the larger
the primary neoplasm is the greater
are the chances of metastasis.
Approximately 30% of newly
diagnosed patients of solid tumors
present with metastasis.
Presence of metastasis reduces the
cure rate.
 Pathways of
spread

Dissemination of tumor
cells occurs by:-
 Lymphatic spread.

 Hematogenous spread.

 Direct seeding of body

cavity/surfaces.
 Direct transplantation of
tumor cells, for e.g. by
surgical instruments, may
occur theoretically, but is
considered an artificial mode
of dissemination .
Lymphatic spread:-
It is the most common pathway for
initial dissemination of carcinomas.
Regional lymph nodes serve as an
effective barrier to further
dissemination of tumor cells, at least
for sometime. The cells may be
destroyed by tumor specific immune
response.
 This drainage of tumor
cell debris or tumor
antigens or both may
induce reactive
changes in the nodes.
The enlargement of nodes may be
caused by:-
1. Spread and growth of cancer cells

2. Reactive hyperplasia

Thus, nodal enlargement in

proximity to a cancer , does not
necessarily mean dissemination of
primary lesion
 The pattern
of lymph
node
involvement
follows the
natural routes
of drainage.
For e.g.
carcinomas of
lung arising in
major
respiratory
passage
metastasize to
prehilar
tracheobronchial
and mediastinal
lymph nodes.
 Skip metastasis is also sometimes seen i.e.
bypassing of a lymph node. This occurs due
to:-
1.Venous lymphatic anastomoses in the area.

2.Inflammation obliterated channels.

3.Radiation obliterated channels.

.Diagrammatic representation of lymphatic metastasis
 Hematogenous
spread:-
It is typical of
sarcomas but may also
be seen in carcinomas.
It can spread by two
ways:-

1.Arterial
spread.
2.Venous spread.
Arterial spread:-
Arteries have thicker walls than veins, and
thus are less readily penetrated.
Arterial spread may however occur when
tumor cells pass through the pulmonary
capillary beds, arteriovenous shunts or
when pulmonary metastasis themselves
gives rise to additional tumor emboli.
Venous spread:-
The cells follow the venous drainage.
Liver &lungs are most commonly involved
secondarily in such hematogenous
dissemination.
All portal areas drainage flows to the
liver, and all caval areas drainage flows to
the lungs.
Certain cancers have the
propensity for invasion of
veins. For e.g. renal cell
carcinoma invades branches
of renal vein & renal vein
itself grows in snake like
fashion to IVC & may reach
right heart.
.Hematogenous spread
Direct seeding of body
cavities & surfaces:-
Seeding occurs whenever a
neoplasm penetrates into
natural OPEN FIELDS.
Mostly it is the peritoneal
cavity but any cavity may be
involved.
 Direct seeding of body cavity
is common in carcinomas
arising in the ovaries, where
the peritoneal surface gets
coated with a heavy layer of
cancerous glaze.
 METASTATIC CASCADE
 Invasionof ECM
& vascular
dissemination.
 Homing of
tumor cells.
 INVASION OF ECM
 Detachment of tumor cells from each
other.
 Local degradation of the basement
membrane & interstitial connective
tissue.
 Changes in attachment of tumor cells
to ECM proteins.
 Migration of tumor cells.
 Detachment of tumor
cells from each other

 Loosening of tumor
cells due to loss of
function of
E-cadherins &
beta catenin.
Local degradation of the basement
membrane & interstitial
connective tissue

 Tumor cells secrete

proteolytic enzymes
or induce stromal
cells to eloborate
proteases (MMPs,
cathepsin D,
urokinase
plasminogen
activator).
 Changes in attachment of
tumor cells to ECM proteins

 Tumor cells are

resistant to
apoptosis.
 Matrix itself is
modified in ways
that promote
invasion &
metastasis.
 Migration of tumor cells
 Tumor cells are propelled
through the degraded
basement membrane &
zones of matrix proteolysis.
 Such movement is
potentiated by: tumor cell-
derived cytokines (AMF) &
stromal cells derived
paracrine effectors.
VASCULAR DISSEMINATION
& HOMING OF TUMOR
CELLS
 In the bloodstream, some tumor cells form
emboli by aggregating & adhering to
circulating leukocytes, particularly platelets.
 Extravasation of free tumor cells or tumor
emboli involves adhesion to the vascular
endothelium, followed by egress through the
basement membrane into the organ
parenchyma by mechanisms similar to those
involved in invasion.
 The site of extravasation & organ distribution
of metastasis generally can be predicted by
the location of the 1o tumor & its vascular or
lymphatic drainage.
 After extravasation, tumor cells are dependent
on a receptive stroma for growth. Thus,
tumors may fail to metastasize to certain
target tissues because they present a non-
permissive growth environment.