Neoplasia New

7/31/2019 Neoplasia New

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NEOPLASIA


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Neoplasia

- new growth

- It is defined as abnormal mass of tissue,

the growth of which exceeds and isuncoordinated with that of the normal tissue

and persists in the same manner after

cessation of stimuli which evoked the

change


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- Cancer- common term to all malignancies

- All neoplasms utimately depends on the host

for their nutrition and vascular supply.

- Two basic components of Neoplasia :

1. proliferating neoplastic cell-parenchyma

2. supportive stromaconnective tissue andblood vessels.


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Nomenclature

ParenchymaProliferating neoplastic

cells

StromaConnective tissue and

blood vessels


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Classification of Neoplasms

A. Site

B. Biologic Behaviorbenign, borderline,

malignant

C. Cell ( tissue of origin )

D. Embryologic derivation

E. Differentiation potential of cell of origintotipotent cell

F. Etiology


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Tumors are classified to 2broad categories: benign

and malignant.


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Benign vs. Malignant

Slow growing

Encapsulated

Expansile growth No Metastasis

Well Differentiated

Rapidly growing

Non encapsulated

Infiltrative growth Metastasis

Well-Poorly

differentiated


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NOMENCLATURE

Benign Tumors

suffix oma

Malignant Tumors

2 broad categories:

Carcinomas - epithelial cells

sarcomas - mesenchymal tissues

Some tumors with more than one parenchymalcell type: mixed tumors & teratomas

Two non-neoplastic lesions bear the names thatare deceptively similar to tumors: choristomas&hamartomas


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Choristoma: ectopic rest of normal tissue


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Hamartoma: mass of disorganized but mature

specialized cells or tissue native to theparticular site


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Benign Tumors Cell of origin + OMA

Fibroma, chondroma, osteomaAdenoma: derived from glands/ glandular

pattern Tubular adenoma, colon


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Papillomas: architecture finger like

projections


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Polyp: macroscopic projection of mucosalsurface


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CHARACTERISTICS OF

MALIGNANT NEOPLASMS

Malignant tumors:

differentiation and anaplasiadysplasia

Rapid rate of growth

Widespread invasion

metastases


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1. Anaplasia

Lack of differentiation

Hallmark of malignant transformation

Numerous morphologic changes


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Pleomorphism: variation in size and shape


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Abnormal nuclear morphology:hyperchormatic (abundant DNA), increased

N:C ratio (normal 1:4- 1:6)


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Mitoses: increased, bizarre


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Loss of polarity


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Tumor giant cells


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Dysplasia: disordered growth

Loss of uniformity

Loss of architecture

Pleomorphism

Hyperchromasia

Abnormal located mitosis


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Cell (tissue) of Origin:

I. Composed of One Parenchymal Cell type:

A. Epithelial

B. Mesenchymal

II. More than one Neoplastic Cell Typederived

from one germ layer:A. Salivary Gland

B. Breast

C. Renal AnlageIII. More than one Neopalstic Cell Type derived

from more than one germ layer:

Teratoma


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More than one neoplastic cell- MIXEDSalivary gland Pleomorphic adenoma Malignant mixed tumor

of salivary gland origin

Renal Wilms tumor

Teratogenous ( from more than one germ cell layer

Totipotential cells Mature teratoma/

dermoid cyst

Immature teratoma,

teratocarcinoma


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Pre-malignant (pre-cancerous)

Lesions:

A. Hyperplasia

-Endometrial Hyperplasia

-Lobular and Ductal Hyperplasia

-Cirrhosis of the liverB. Dysplasia

C. Metaplasia

-Barrets Esopahgus

D. Inflammatory Lesions-Ulcerative Colitis, Atorphic Gastritis

-Autoimmune(Hashimotos) Thyroiditis

E. Benign neoplasms

- Colonic Adenoma


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Mechanisms and Causes of

Neoplasia- At MOLECULAR LEVEL , neoplasia is

defined as disorder of growth regulatory

genes ( proto-oncogenes and tumor

suppressor genes ).

- Origin of Neoplasia:

1. Monoclonal Origin

2. Field Origin


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MOLECULAR BASIS OF CANCER

Oncogenes and Cancer Oncogenes

Protooncogenes

Protein products of OncogenesActivation of Oncogenes

Point mutations

Chromosomal rearrangements Gene amplifications


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Proto-oncogenes(Cellular Oncogenes )

- code for a variety of of growthfactors, receptors, and signal-relayor transcription factors which act inconcert to control entry into the cellcycle.


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Tumor suppressor Genes (anti-oncogenes)which serve to down-regulate the cellcycle.

note: a net increase in the production ofstimulatory (promoter) factors, a decreasein inhibitory (suppressor) growth factors

may lead to uncontrolled cell growth.


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Cancer-Suppressor Genes Protein Products of Tumor Suppressor Genes

Gene amplifications

p53 BRCA-1 and BRCA-2APC gene

NF-1 gene

cell surface receptors

WT-1

Genes That Regulate Apoptosis bcl-2

Genes That Regulate DNA Repair hMSH2 and hMLH1

Molecular Basis of MultistepCarcinogenesis gatekeeper genes- APC, NF-1, and Rb

caretaker genes- DNA repair genes


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Selected oncogenes, their mode of activation, andassociated human tumors

Category Protooncogenes Mechanism Associated Tumor

Growth Factors

PDGF- chain sis overexpression AstrocytomaGrowth Factor Receptors

EGF-receptor family erb-B1 overexpression Squamous cell CA of thelungs

Proteins involved in Signal Transduction pathwayGTP-binding ras Point mutations CA ofLung, colon,

pancreas; many leukemiasNuclear Regulatory proteins

Transcriptional activators myc Translocation Burkitt lymphoma

Cell Cycle Regulators

Cyclins cyclin D Translocation Mantle cell lymphoma


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Activationis the functional concept

whereby the normal action of growth

regulation is diverted into oncogenesis.

Mechanisms of Occurrence :

1. Mutation

2. Translocation

3. Insertion


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KARYOTYPIC CHANGES INTUMOR CELLS

Three types of nonrandom chromosomalabnormalities have been described:

(1) translocation

(2) deletions

(3) amplification


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Neoplasia Associated with ConstantGenetic Abnormality:

a. Philadelphia Chromosome- CML

b. Retinoblastoma-Rb gene

c. Wilms Tumor-WT-1

d. Familial Polyposis Coli-APC


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BIOLOGY OF TUMOR GROWTH

Kinetics of Tumor Cell Growth

variables influence tumor cell growth:

doubling time of tumor cells growth fraction

cell production and loss

Tumor Angiogenesis 2 most important tumor angiogenic factors are:

vascular endothelial growth factor (VEGF)

basic fibroblast growth factor (bFGF).


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BIOLOGY OF TUMOR GROWTH

Tumor Progression and Heterogeneity Mechanisms of Invasion and Metastasis

Invasion of Extracellular Matrix Detachment of tumor cells

attachment to matrix components

degradation of extracellular matrix

Migration of tumor cells Vascular Dissemination and Homing of Tumor Cells


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CARCINOGENIC SITES

Chemical Carcinogenesis Initiation

Promotion

Molecular Targets of Chemical Carcinogens DNA

Carcinogenic Chemicals alkylating agents, aromatic hydrocarbons, azo dyes etc


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CARCINOGENIC SITES

Radiation Carcinogenesis UV rays and ionizing radiations

Viral and Microbiological

Carcinogenesis DNA Viruses

(1) HPV, Epstein-Barr virus (EBV) and Hepatitis B virus(HBV)

RNA Oncogenic Viruses (HTLV-1)


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HOST DEFENSE AGAINST


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HOST DEFENSE AGAINSTTUMORS

Immunosurveillance Increased frequency of cancers in patients with

congenital or acquired immunodeficiency

increased susceptibility to EBV infections and EBV-

associated lymphoma in boys with X-linkedimmunodeficiency

Tumors may escape immunosurveillance

selective outgrowths of antigen-negative variants

loss or reduced expression of histocompatibility

antigens

tumor-induced immunosuppression

failure of sensitization

apoptosis of cytotoxic T cells

CLINICAL FEATURES OF


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CLINICAL FEATURES OFTUMORS

Local and Hormonal Effects related to location

hormone production

Cancer Cachexia

Paraneoplastic Syndromes endocrinopathies

Hypercalcemia Acanthosis nigricans

clubbing of fingers and hypertrophic osteoarthopy

thromboembolic diatheses

Paraneoplastic syndromes


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Paraneoplastic syndromes


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Approach to Cancer Diagnosis:

I. Clinical Suspicion

II. Screening Tests

III. Tumor Markers

IV .Definitive Diagnosis

- tissue biopsy ( most accurate )

1.Ordinary H and E stain2. Immunohistochemistry

3. Electron Microscopy

LABORATORY DIAGNOSTICS OF


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LABORATORY DIAGNOSTICS OFCANCER

Histologic and Cytologic Methods Fine-Needle Aspiration

Cytologic (Papinacolaou Smears) Immunohistochemistry

DNA Probe Analysis

Flow Cytometry Tumor Markers

GRADING AND STAGING OF


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GRADING AND STAGING OFTUMORS

Grading grades I to IV with increasing anaplasia

imperfect because (1) the differentiated parts of the same tumor may

display different degrees of differentiation

(2) the grade of tumor may change as the tumorgrows

Staging anatomic extent of the tumor

TNM


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Information Provided by Pathologic Diagnosis:

1. Type of Neoplasm - name of the neoplasm

2. Biologic Behavior- benign or malignant

3. Histologic Gradedegree of differentiation

4. Degree of Invasion- depth

5. Staging - size of the mass/depth ofinvolvement

- involvement of nodes

- +/- metastasis


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Treatment of Neoplasms:

A. Benignsurgical removal

B. Malignant

- surgery ( radical, wide excision,palliative surgery )

- Lymph node removal

- Palliative :

a. Chemotherapy

b. Radiotherapy

c. Immunotherapy


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What Are The Final Complications Of Malignancy(Causes Of Death)

PNEUMONIA

CACHEXIA

RENAL FAILURE

BLEEDING SEVERE ANEMIA, THROBOCYTOPEINA

INFECTIONS

HYPERCOAGULABILITY

DIC PAIN MORE OF DEVASTATING SYMPTOM THAN A

COMPLICATIONHAS TO BE CONTROLED

MULTIPLE ORGAN FAILURE


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