General Pathology

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General Pathology

• Basic Principles of Cellular and Organ Pathology
• Oncology - I

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

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Tumour

• swelling of any kind
• NEOPLASIA

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NEOPLASIA

• Def.
• persistent
• abnormal
• relatively autonomous
  proliferation of cells

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NEOPLASIA history I.

• Ramayana 2000 B.C.
• therapy with knife
• chemotherapy arsenical compounds

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NEOPLASIA history II.

• Galen AD 131201
• TUMOURS
• according to nature
• pregnancy
• exceeding nature
• inflammatory, reparative, callus
• against nature
• true neoplasms

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Growth Disturbances Their Relation to
Neoplasms
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Nonneoplastic Growth Disturbances I

• MALFORMATIONS
• complete or partial lack of
  development (aplasia, hypoplasia)
• asymmetry
• oversize
• hamartoma
• choristoma
• ectopic tissue

-

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Hamartia Hamartoma

• Def.
• A mass of disorganized tissue indigenous to the
  particular site.

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Choristia - Choristoma

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

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Nonneoplastic Growth Disturbances II

• repair
• hypertrophy / atrophy -
  (incl.pseudohypertrophy)
• hyperplasia
• metaplasia
• dysplasia
• anaplasia undifferentiation

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Nonneoplastic Growth Disturbances II

• repair
• hypertrophy / atrophy -
  (incl.pseudohypertrophy)
• hyperplasia
• metaplasia
• dysplasia
• anaplasia undifferentiation

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Nonneoplastic Growth Disturbances II

• repair
• hypertrophy / atrophy
• hyperplasia
• metaplasia
• dysplasia
• anaplasia undifferentiation

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Nonneoplastic Growth Disturbances II

• repair
• hypertrophy / atrophy
• hyperplasia
• metaplasia
• dysplasia
• anaplasia undifferentiation

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Nonneoplastic Growth Disturbances II

• repair
• hypertrophy / atrophy
• hyperplasia
• metaplasia
• dysplasia
• anaplasia undifferentiation

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Growth Disturbances to Neoplasms Relation

• differential diagnosis pseudotumours
• precursors precanceroses
  (preblastomatoses)
• both 1. and 2.

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NEOPLASIA

• Def.
• persistent
• abnormal
• relatively autonomous
  proliferation of cells

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Neoplasia (Tumour)

• DNA disease
• Stepwise accumulation
• of genetic abnormalities
• Escape of immunological clearing systems

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Neoplasia - causes

• External
• Irradiation
• chemical cancerogens
• oncogenic viruses

• Internal
• immunosupression (inborn, acquired)
• chronic irritation (inflammation)

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Oncogenic Viruses

• DNA
• HPV
• SV 40 polyoma
• Adenoviruses
• Herpesviruses
• Epstein Barr
• Hepatitis B

• RNA
• Rous sarcoma
• Leukemia
• HIV

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Cell Cycle Regulators control of cellular
proliferation

• polypeptide growth factors EGF, PDGF , FGF, TGFa,
  ß (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

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Cell Cycle Regulators growth factors

• Polypeptide growth stimulators
• EGF, PDGF, TGF a (protooncogenes)
• cytokins
• IL-1,
• TNF angiogenesis

• Polypeptide growth inhibitors
• T(ransforming)GF ß
• interferon a
• prostaglandin E-2

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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

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Molecular Biological and Morphological
Tumour Progression
Normal cell

• dysplasia
• adenoma
• infiltrating
• carcinoma

Loss of growth control
Loss of apoptosis control
Loss of Senescence control
genomic instability
activation proteases
Metastasising tumour cell
Molecular biological
Morphological Tumour Progression
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Host - Neoplasm Interactions

• immune surveillance
• immune response
• spontaneous regression

• local preassure
• cachexia
• anaemia
• immunodepression
• products of neoplastic cells

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NEOPLASIA function

• NEOPLASTIC CELL PRODUCTS
• immunoglobulin
• osteiod
• keratin
• mucus
• melanin
• hormones

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NEOPLASIA function

• NEOPLASTIC CELL PRODUCTS
• immunoglobulin
• osteiod
• keratin
• mucus
• melanin
• HORMONES

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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