NEOPLASIA

Course Faculty: Shahana Sharmin

 Definition of Neoplasia
“A neoplasm is an abnormal mass of tissue,
the growth of which exceeds and is
uncoordinated with that of the normal
tissues and persists in the same excessive
manner after cessation of the stimuli
which evoked the change” - Willis
 Genetic changes
 Autonomous
 Clonal
 Definition of Neoplasia
 Neoplasia is new growth. The new growth
that is produced is also called neoplasm
or tumor.
 A neoplasm:
 is an abnormal growth of mass of tissue
 due to excessive cell proliferation that
has escaped normal limitations and
regulation
 and persist in the same excessive manner
even after cessation of the stimuli.
 Benign Tumor
A tumor is said to be
benign when its
microscopic and gross
characteristics are
considered relatively
innocent, implying that it
will remain localized
 It cannot spread to other
sites, and it is generally
amenable to local surgical
removal; the patient
generally survives.
 Benign Tumor
 It should be noted, however, that benign
tumors can produce more than localized
lumps, and sometimes they are responsible
for serious disease.
 Malignant Tumor

 Malignant tumors
are collectively
referred to as
cancers, derived
from the Latin word
for crab, because
they adhere to any
part that they seize
on in an obstinate
manner, similar to a
crab.
 Malignant Tumor
 Malignant, as applied to a neoplasm, implies that the lesion can
invade and destroy adjacent structures and spread to distant
sites (metastasize) to cause death.
 Not all cancers pursue so deadly a course. Some are discovered
early and are treated successfully, but the designation
malignant always raises a red flag.
 Benign vs Malignant Features
Feature Benign Malignant

Rate of growth Progressive but Variable. Mitoses

slow. Mitoses few more frequent
and normal and may be
abnormal
Differentiation Well differentiated Some degree of
anaplasia
Local invasion Cohesive growth. Poorly cohesive
Capsule & BM not and infiltrative.
breached
Metastasis Absent May occur
 Common Features of tumor
All tumors, benign and malignant,
have two basic components:
(1) Clonal neoplastic cells that
constitute their parenchyma.
(2) Reactive stroma made up of
connective tissue, blood vessels,
and variable numbers of
macrophages and lymphocytes
Differentiation

 Differentiationis the process in which

the neoplastic parenchymal
cells(immature) resemble the
corresponding normal parenchymal
cells (mature), both morphologically
and functionally.
 Anylack of differentiation is called
anaplasia.
 Differentiation
 Well differentiated neoplasm
Resembles mature cells of tissue of
origin
 Poorly diffentiated neoplasm
Composed of primitive cells with
little diffrerentiation
 Undifferentiated or “anaplastic”
tumor
 Differentiation
 Correlationwith
biologic behavior
Benign tumors
are well
differentiated
Poorly
differentiated
malignant
tumors usually
have worse
prognosis
 “ANAPLASIA”
 As we know
Dysplasia means
potential PRE-cancer
whereas Anaplasia
means cancer.
 Anaplasia is the loss
of the mature or
specialized features
of a cell or tissue, as
in malignant
tumours.
 “ANAPLASIA”
 Abnormal nuclear morphology
 Hyperchromasia (it refers to the dark staining
nuclei which is usually due to increased DNA
content. In this example of small cell carcinoma
of the lung, all of the tumor cells exhibit darkly
stained nuclei. Also note that the cells have very
little cytoplasm.)
 High nuclear cytoplasmic ratio
 Chromatin clumping
 Prominent nucleoli
Dysplasia
 Literally means abnormal growth
 Malignant transformation is a multistep process
 In dysplasia some but not all of the features of
malignancy are present

 Dysplasia may develop into malignancy

 Uterine cervix
 Colon polyps
 Graded as low-grade or high-grade
 Tumor Growth Rate
 Doubling time of tumor cells
 Lengthens as tumor grows
 30 doublings (109 cells) = 1 g (months to years)
 10 more doublings (1 kg) = lethal burden (“)
 Fraction of tumor cells in replicative pool
 May be only 20% even in rapidly growing tumors
 Tumor stem cells
 Rate at which tumor cells are shed or lost
 Apoptosis

 Maturation

 Implications for therapy

Predisposing Factors for Cancer
 Age
 Most cancers occur in persons ≥ 55 years
 Childhood cancers
Leukemias& CNS neoplasms
Bone tumors
 Genetic predispostion
 Familial cancer syndromes
Early age at onset
Two or more primary relatives with the cancer
Multiple or bilateral tumors
 Polymorphisms that metabolize
procarcinogens,
 e.g., nitrites
Predisposing Factors for Cancer
 Nonhereditary predisposing
conditions:

1. Chronic inflammation

2. Precancerous conditions
a. Chronic ulcerative colitis
b. Atrophic gastritis of pernicious
anemia
c. Leukoplakia of mucous membranes
 ONCOGENES
 Are MUTATIONS of NORMAL genes (PROTO-
oncogenes)
 Growth Factors
 Growth Factor Receptors
 Signal Transduction Proteins (RAS)
 Nuclear Regulatory Proteins
 Cell Cycle Regulators

 Oncogenes code for ➔ Oncoproteins

 Signal transduction is a generic term which refers
to any process by which a cell converts one kind
of signal or stimulus into another.
Oncogenes and Tumor suppressor
genes
 Oncogenes:  Anti-oncogenes:
 An oncogene is a gene  A tumor suppressor gene,
that has the potential
to cause cancer. In or anti-oncogene, is
tumor cells, these a gene that regulates a cell
genes are often during cell division and
mutated, or expressed replication. If the cell
at high levels grows uncontrollably, it will
 Myc result in cancer. e.g.-
 RAS  p53
 EGFR
 prb
 PIK3CA
MYC
 Encodes for transcription factors
 The protein encoded by this gene is a
multifunctional, nuclear phosphoprotein
that plays a role in cell cycle progression,
apoptosis and cellular transformation
 Myc (cMyc) codes for a protein that binds
to the DNA of other genes. When Myc is
mutated, or overexpressed, the protein
doesn't bind correctly, and often
causes cancer.
Difference between P53 and RAS

p53 RAS
 Activates DNA  H, N, K, etc.,
repair proteins varieties
 Single most
 Sentinel of G1/S
common
transition abnormality of
 Initiates apoptosis dominant oncogenes
in human tumors
 Mutated in more
than 50% of all  Present in about
human cancers 1/3 of all human
cancers
LAB DIAGNOSIS

BIOPSY
CYTOLOGY: (exfoliative)
CYTOLOGY: (FNA, Fine Needle
Aspirate)
Tumor Progression
➢ Tumor progression refers to the phenomenon
whereby tumors become progressively more
aggressive and acquire greater malignant potential.
➢ Progression is related to sequential appearance
within the tumor cells that differs from the aspects
of invasiveness, rate of growth ability to form
metastases and several other attributes.
➢ Thus a clinically detectable tumor although
monoclonal, is usually made up of phenotypically
and genetically heterogeneous cells.
Heterogenecity
➢ Heterogeneity is believed to result
from genetic instability of tumor cells,
which are subject to a high rate of
random mutation, possibly because
the loss of p53, DNA repair genes or
both.
➢ Tumor cell heterogenecity and
progression begin well before clinical
detection of tumors and continue
thereafter.
Tumor Invasion

 Tumor invasion is an active

process in which invasion often
occurs along tissue planes
offering less resistance to tumor
growth such as surrounding
extracellular matrix, peri-neural
space and vascular lamina.
Carcinogen
➢ A large number of agent cause genetic
damage and induce neoplastic
transformation of the cells. These are
called carcinogen.
➢ Several radioactive substances are
considered carcinogens, but their
carcinogenic activity is attributed to the
radiation, for example gamma rays and
alpha particles, which they emit.
➢ Common examples of non-radioactive
carcinogens are inhaled asbestos,
certain dioxins, and tobacco smoke.
Steps of Chemical Carcinogen
Initiation:
➢ Inititation cause mutation (DNA damage).
Initiators are carcinogenic agent that is an
appropiate dose induce initiation. Multiple
divided doses have the same effect.
➢ Initiation is rapid & irreversible process and has
memory initiation alone can not form tumor.
Both direct acting & indirect acting chemical
carcinogens act as initiators.
➢ All direct acting and ultimate carcinogens are
electrophiles (have electron deficient atom)
that can react with nucleophilic (electron rich)
sites of the cell, particularly DNA.
 Steps of Chemical Carcinogen
➢ Promotion
➢ Promoter can not induce tumors by
themselves. They are not mutagenic (ie.
Has no effect ). They can induce tumors
only in initiated cells.
➢ Promoters lead to proliferation and clonal
expansion of initiated (mutated cells).
Hormones and certain drugs are places as
promoters. It is reversible.
➢ Below a dose (threshold level) or when
widely spaced promoter have no effect.
Ultimate Carcinogen

➢ Ultimate carcinogens are indirect acting

compounds or procarcinogens which
require metabolic conversion is vivo to
initiate carcinogenesis.
➢ All ultimate carcinogens have one property
in common: they are highly reactive
electrophiles (have electrons- deficient
atoms) that can react with nucleophilic
sites in the cells.
Difference between initiation
and promotion
Initiation Promotion
1. Initiation results from 1. Promotion can induce
exposure of cells to an tumors in initiated cells but
appropriate dose of a they are non tumorigenic by
carcinogen agent; an themselves
initiated cell is in some
manner altered, rendering it
likely to give rise to a tumor.
2. Initiation causes 2. Promotion does not cause
permanent DNA damage permanent DNA damage

3. Initiation is rapid and has 3. Promotion is not rapid and

memory has no memory

4. Initiation is irreversible 4. Promotion is reversible

Difference between carcinoma and sarcoma
Title Carcinoma Sarcoma

Definition 1. Malignant tumors of epithelial Malignant tumors of

cells mesenchymal tissues

Most common 2. Most common over the age of 50 2. Most comon in 1st and
age years 2nd decades but can
occur at all ages.

Tumor 3. A common malignant tumor A much less common

tumor

Rate of 4. Often slow growing Usually very rapidly

growth growing.

Radio 5. Many carcinomas are highly radio More radio resistant

sensitivity sensitive
THANK YOU
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