Transcript 17 oncology 1 growth disturbances

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 131–201
TUMOURS

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.
2.
3.
differential diagnosis
precursors
both 1. and 2.
pseudotumours
precanceroses
(preblastomatoses)
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 Viruses
DNA
 HPV
 SV 40 – polyoma
 Adenoviruses
 Herpesviruses
Epstein– Barr
 Hepatitis
B
RNA
 Rous sarcoma
 Leukemia
 HIV
Cell Cycle Regulators
– control of cellular proliferation
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
 polypeptide
Cell Cycle Regulators – growth factors
Polypeptide growth
stimulators
PDGF, TGF α
(protooncogenes)
 EGF,
cytokins
– IL-1,
– TNF
angiogenesis
Polypeptide growth
inhibitors
 T(ransforming)GF
 interferon
α
 prostaglandin
E-2
β
Cell Cycle Regulation Disorders
– uncontroled cellular proliferation
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
 polypeptide
Molecular Biological and Morphological
Tumour Progression
Normal cell
Loss of
growth
control
Loss of
apoptosis
control
dysplasia
adenoma
Loss of Senescence
control
genomic instability
infiltrating
activation proteases
carcinoma
Metastasising tumour cell
Molecular biological
Morphological
Tumour Progression
Host - Neoplasm Interactions

immune
surveillance




immune
response
spontaneous regression


local preassure
cachexia
anaemia
immunodepression
products of
neoplastic cells
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
