NEOPLASIA

Neoplasia means "new growth." A neoplasm, as

defined by Willis, 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 the cessation of the stimuli which evoked the
change.".

NOMENCLATURE
A neoplasm is often referred to as a tumor, and the study of
tumors is called oncology (from oncos, "tumor," and logos,
"study of").

Types:
Benign tumor
Malignant tumor

All tumors, benign and malignant, have two basic components:

(1) Parenchyma, made up of transformed or neoplastic cells.
(2) Stroma, host-derived, non-neoplastic supporting tissue

Parenchyma of the neoplasm largely determines its biologic

behavior, and it is this component from which the tumor derives
its name

 Benign Tumors: In general, benign tumors are

designated by attaching the suffix -oma to the cell
type from which the tumor arises.
Examples:
Fibrous tissue tumor is a Fibroma
Cartilaginous tumor is a chondroma.

Malignant Tumors:
1.Mesenchymal tissue or its derivatives are called
sarcomas.eg Fibrosarcoma
2.Epithelial tissue origin are called carcinomas. Eg.
Adenocarcinomas

BENIGN TUMORS

MALIGNANT TUMOR

Degree of differentiation
Benign tumors resemble the
tissue of origin and are well
differentiated;

Degree of differentiation,
malignant tumors are poorly or
completely undifferentiated
(anaplastic).

Rate of growth Benign tumors

are slow growing,.

Rate of growth, malignant

tumors generally grow faster

Local invasiveness Benign

tumors are well circumscribed
and have a capsule;

Distant spread Benign tumors

remain localized to the site of
origin,

Local invasiveness, malignant

tumors are poorly circumscribed
and invade the surrounding
normal tissues.

Distant spread. malignant

tumors are locally invasive and
they metastasize to distant sites

Tumor Characteristics
Reference: Kristine Krafts, M.D.

Neoplasia Outline
Tumor nomenclature
Tumor characteristics

Differentiation and anaplasia

Rate of growth
Local invasion
Metastasis

Differentiation and Anaplasia

Differentiation = how much the tumor cells resemble their
cells of origin
well-differentiated closely resembles
moderately-differentiated sort of resembles
poorly-differentiated doesnt resemble

Benign tumors are usually well-differentiated

Malignant tumors can show any level of differentiation

Differentiation and Anaplasia

Anaplasia = a state of complete undifferentiation
" It implies dedifferentiation, or loss of the structural and
functional differentiation of normal cells

Misnomer! Cells dont de-differentiate.

Just means cells are very poorly-differentiated
Almost always indicates malignancy

Differentiation and Anaplasia

Anaplastic cells show:
Pleomorphism (marked variation in size and shape)
Hyperchromatic, large nuclei
Bizarre nuclear shapes, distinct nucleoli
Lots of mitoses, and atypical mitoses
Architectural anarchy

Abnormal mitoses

Rate of Growth
Generalizations
Malignant tumors grow faster than benign ones.
Poorly-differentiated tumors grow faster than welldifferentiated ones.

Growth is dependent on:

Blood supply
Hormonal factors
Emergence of aggressive sub-clones

Neoplasia Outline
Tumor nomenclature
Tumor characteristics
Differentiation and
anaplasia
Rate of growth
Local invasion

Local Invasion
Benign tumors
Stay where they are.
Cant invade or metastasize.
Usually encapsulated.

Malignant tumors
Infiltrate, invade, destroy surrounding tissue.
Then metastasize to other parts of body.
Not encapsulated.

Malignant tumor invading

Neoplasia Outline
Tumor nomenclature
Tumor characteristics

Differentiation and anaplasia

Rate of growth
Local invasion
Metastasis

Metastasis
Metastasis = development of
secondary tumor implants in distant
tissues

Metastasis depends on:

Type of tumor
Size of tumor
Degree of differentiation of tumor

Carcinoma in situ

Invasive carcinoma

Invasive carcinoma

Metastasizing carcinoma

Liver with multiple

Three ways tumors metastasize

Seeding
Lymphatic spread
Hematogenous spread

Metastasis
Three ways tumors metastasize

Seeding
Tumor invades body cavity
Bits break off and implant on peritoneal
surfaces
Ovarian cancer

Metastasis
Three ways tumors metastasize
Seeding
Lymphatic spread
Tumor spreads to local lymph nodes
Moves through thoracic duct
Empties into subclavian vein

Metastasis
Three ways tumors metastasize
Seeding
Lymphatic spread
Hematogenous spread
Veins are easier to invade than arteries
Liver and lungs are most common metastatic destinations

 Cancer pathogenesis

Overview
Basic underlying cause of cancer:
Four kinds of normal genes are damaged:
Genes that promote growth (proto-oncogenes)
Genes that inhibit growth (tumor-suppressor
genes)
Genes that regulate apoptosis
Genes involved in DNA repair

Cancers develop in multiple steps

Genes
Cancer genes cause bad things
in cells:

Autonomous growth
Insensitivity to growth-inhibitory signals
Evasion of apoptosis
Limitless replication
Sustained angiogenesis
Invasion and metastasis

1. Autonomous Growth
Definitions
Proto-oncogene: a normal gene whose
product promotes cell growth.

Oncogene: mutated proto-oncogene!

Causes cell to grow autonomously!

Oncoprotein: the product of an oncogene.

Autonomous Growth
In cancer cells
Growth factors may be made by cell itself!
Receptors may be over expressed or always on
Signal-transducing proteins may always be on
Nuclear transcription factors may always be expressed
Cyclins may be overactive

Cell divides on its own!!!

Autonomous Growth
Example: RAS gene

RAS is a signal transduction protein

Mutated RAS is always on
therefore, always transducing signals
therefore, cell is always dividing.

2. Insensitivity to Growth-Inhibitory
Signals

Tumor-suppressor genes: normal genes

whose products act as brakes on the
cell cycle.

Mutation cause loss of these brakes!

Insensitivity to Growth-Inhibitory
Signals

3. Evasion of Apoptosis
Many proteins involved in apoptosis:

Fas (the death receptor)

Executioner caspases (cut DNA)
BCL2 protein family
p53 (the guardian)

If genes for these proteins are mutated, the

cell becomes immortal!

4. Limitless Replication
Normal human cells: only 60-70 doublings
Telomeres keep getting shorter
leading to cell cycle arrest
Stem cells and cancer cells use telomerase to
maintain telomere length and keep replicating!

Molecular pathogenesis of cancer

p53 Gene: Guardian of the Genome

5. Sustained Angiogenesis
Definitions
Tumor cells need blood too!
Cant grow >1-2 cm without new vessels
Tumor cells eventually learn how to stimulate
angiogenesis
Lots of cytokines involved
Tumor vessels are abnormal!

6. Invasion and Metastasis

To invade, tumor cells must:

Loosen contacts between cells
Degrade extracellular matrix
Migrate away from original site

Some tumors lodge in nearest capillary

bed
Some tumors show tropism

clonal growth
metastatic
subclone

intravasation

tumor cell
embolus

extravasation

Tumor cells now within

Carcinogenic Agents

Chemicals
Radiation
Viruses

Carcinogenic Agents
Chemicals

Direct-acting agents
Carcinogenic as-is
Most are chemotherapy drugs
Cause secondary malignancies

Carcinogenic Agents
Chemicals
Direct-acting agents
Indirect-acting agents
Require conversion to become carcinogenic
Examples:
Hydrocarbons (in tobacco)
Aflatoxin B (from Aspergillus-infected grains, nuts)
Nitrites (food preservative)

Carcinogenic Agents
Chemicals
Direct-acting agents
Indirect-acting agents
Mechanism
Highly reactive groups bind to DNA
Important targets: RAS and p53

Carcinogenic Agents
Radiation
Ionizing radiation
Causes chromosome breakage, translocations
Examples:
Unprotected miners: lung cancer
Atomic bomb survivors: leukemia, other cancers
Therapeutic head/neck radiation: thyroid cancer

Carcinogenic Agents
Radiation

Ionizing radiation
UV light
Causes formation of pyrimidine dimers
Examples: Melanoma

Laboratory Diagnosis of Cancer

Morphologic Methods

Frozen-section diagnosis
Fine-needle aspiration
Cytologic smears
Immunocytochemistry

Biochemical assays

Molecular Diagnosis

PCR & FISH (flouresence in situ hybridization) are used for the detection of

Melignancy by distinction between monoclonal

(neoplastic) and polyclonal (reactive) proliferations .
Prognosis and behavior: detect amplification of
oncogenes such as HER-2/NEU and N-MYC
Detection of minimal residual disease: detection of
minimal residual disease after treatment.
Diagnosis of hereditary predisposition to cancer

THANKS FOR PATIENCE AND HAVE A

GOOD DAY