General Pathology Basic Principles

of Cellular and Organ Pathology

Oncology - I

Jaroslava Dušková

Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague

General Oncology - 1 Disorders of the cell proliferation and

growth (hypertrophy, hyperplasia,

metaplasia) Neoplasms – disorders of cell

proliferation and differentiation Molecular biology of neoplasia -

oncogenesis Host - neoplasm interactions

Tumour

swelling of any kind

NEOPLASIA

NEOPLASIA

Def.: persistent abnormal relatively autonomous

proliferation of cells

NEOPLASIA – history I.

Ramayana – 2000 B.C. therapy with knife chemotherapy arsenical

compounds

NEOPLASIA – history II.

Galen – AD 131–201TUMOURS

according to nature

pregnancy exceeding nature

inflammatory, reparative, callus against nature

true neoplasms

Growth Disturbances &

Their Relation to Neoplasms

Nonneoplastic Growth Disturbances – I

MALFORMATIONS complete or partial lack of

development (aplasia, hypoplasia) asymmetry oversize hamartoma choristoma ectopic tissue

-+

Hamartia – Hamartoma

Def.:

A mass of disorganized tissue indigenous to the particular site.

Choristia - Choristoma

Def.:

A mass of ectopic tissue (cells) with a limmited growth potency

Nonneoplastic Growth Disturbances – II

repair hypertrophy / atrophy -

(incl.pseudohypertrophy) hyperplasia metaplasia dysplasia anaplasia – undifferentiation

Nonneoplastic Growth Disturbances – II

repair hypertrophy / atrophy -

(incl.pseudohypertrophy) hyperplasia metaplasia dysplasia anaplasia – undifferentiation

Nonneoplastic Growth Disturbances – II

repair hypertrophy / atrophy hyperplasia metaplasia dysplasia anaplasia – undifferentiation

Nonneoplastic Growth Disturbances – II

repair hypertrophy / atrophy hyperplasia metaplasia dysplasia anaplasia – undifferentiation

Nonneoplastic Growth Disturbances – II

repair hypertrophy / atrophy hyperplasia metaplasia dysplasia anaplasia – undifferentiation

Growth Disturbances to

Neoplasms Relation

1. differential diagnosis pseudotumours

2. precursorsprecanceroses (preblastomatoses)

3. both 1. and 2.

NEOPLASIA

Def.: persistent abnormal relatively autonomous

proliferation of cells

Neoplasia (Tumour)

DNA disease Stepwise accumulation

of genetic abnormalities Escape of immunological

clearing systems

Neoplasia - causes

External Irradiation chemical

cancerogens oncogenic viruses

Internal immunosupression

(inborn, acquired)

chronic irritation (inflammation)

Oncogenic VirusesDNA HPV SV 40 – polyoma Adenoviruses Herpesviruses

Epstein– Barr

Hepatitis B

RNA Rous sarcoma Leukemia HIV

Cell Cycle Regulators– control of cellular proliferation

polypeptide growth factors EGF, PDGF , FGF, TGFα, β (protooncogenes)

ligand receptor binding activation via conformation alteration (kinase) signal transduction – second messengers (tyrosine

kinases) activation of transcription factors DNA synthesis initiation cyclins and cyclin dependent kinases cdk cdk associated inhibitors cki

Cell Cycle Regulators – growth factors

Polypeptide growth stimulators

EGF, PDGF, TGF α (protooncogenes)

cytokins – IL-1,

– TNF angiogenesis

Polypeptide growth inhibitors

T(ransforming)GF β

interferon α

prostaglandin E-2

Cell Cycle Regulation Disorders– uncontroled cellular proliferation

polypeptide growth factors (e.g. EGF, PDGF , FGF,…)

acting as oncogenes via overexpression ligand receptor amplification signal transducing proteins (e.g. ras oncoproteins) -

activation othe mitogenic signaling pathway nuclear DNA synthesis regulators (myc, jun, fos) mitochondrial oncogenes (bcl-2) – prevention of

apoptosis

Molecular Biological and Morphological Tumour Progression

Normal cell

Loss of growth control

Loss of apoptosis

control

Loss of Senescence control

Metastasising tumour cell

dysplasia

adenoma

infiltrating

carcinoma

Molecular biological MorphologicalTumour Progression

genomic instability activation proteases

Host - Neoplasm Interactions

immune surveillance

immune response

spontaneous regression

local preassure cachexia anaemia immunodepression products of

neoplastic cells

NEOPLASIA – functionNEOPLASTIC CELL PRODUCTS: immunoglobulin osteiod keratin mucus melanin hormones

NEOPLASIA – functionNEOPLASTIC CELL PRODUCTS: immunoglobulin osteiod keratin mucus melanin HORMONES

ENDOCRINE NEOPLASIAHormone Production and Function

may or may not be present unregulated – may be excessive benign tumours more likely to be active size of tumour not related to the

degree of function metastases may cause hyperfunction