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 .

: persistent abnormal relatively autonomous proliferation of cells .NEOPLASIA Def.

NEOPLASIA – history I. Ramayana – 2000 B.C.  therapy with knife  chemotherapy arsenical compounds .

NEOPLASIA – history II. callus  against nature true neoplasms . Galen – AD 131–201 TUMOURS  according to nature pregnancy  exceeding nature inflammatory. reparative.

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.

Choristoma Def.Choristia .: 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 .

pseudohypertrophy)  hyperplasia  metaplasia  dysplasia  anaplasia – undifferentiation .Nonneoplastic Growth Disturbances – II  repair  hypertrophy / atrophy - (incl.

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 .

differential diagnosis pseudotumours 2. and 2. Growth Disturbances to Neoplasms Relation 1. . precursors precanceroses (preblastomatoses) 3. both 1.

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 Internal  Irradiation  immunosupression  chemical (inborn. acquired)  chronic irritation cancerogens (inflammation)  oncogenic viruses .

Oncogenic Viruses DNA RNA  HPV  Rous sarcoma  SV 40 – polyoma  Leukemia  Adenoviruses  HIV  Herpesviruses Epstein– Barr  Hepatitis B .

PDGF . FGF. Cell Cycle Regulators – control of cellular proliferation  polypeptide growth factors EGF. 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 .

TGF α  T(ransforming)GF β (protooncogenes)  interferon α cytokins  prostaglandin E-2 – IL-1.Cell Cycle Regulators – growth factors Polypeptide growth Polypeptide growth stimulators inhibitors  EGF. – TNF angiogenesis . PDGF.

g.Cell Cycle Regulation Disorders – uncontroled cellular proliferation  polypeptide growth factors (e. fos)  mitochondrial oncogenes (bcl-2) – prevention of apoptosis .…) acting as oncogenes via overexpression  ligand receptor amplification  signal transducing proteins (e. EGF. ras oncoproteins) - activation othe mitogenic signaling pathway  nuclear DNA synthesis regulators (myc.g. PDGF . FGF. jun.

Molecular Biological and Morphological Tumour Progression Normal cell Loss of Loss of dysplasia growth apoptosis control control adenoma Loss of Senescence control genomic instability activation proteases infiltrating carcinoma Metastasising tumour cell Molecular biological Morphological Tumour Progression .

Neoplasm Interactions  immune  local preassure surveillance  cachexia  anaemia  immune  immunodepression response  products of neoplastic cells spontaneous regression . Host .

NEOPLASIA – function NEOPLASTIC CELL PRODUCTS:  immunoglobulin  osteiod  keratin  mucus  melanin  hormones .

NEOPLASIA – function NEOPLASTIC CELL PRODUCTS:  immunoglobulin  osteiod  keratin  mucus  melanin  HORMONES .

ENDOCRINE NEOPLASIA Hormone 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 .