Updated: 12/15/2019

Principles of Neoplasia

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Overview
  • Acquired abilities of neoplastic tissue 
    • apoptotic evasion
    • self-sustained monoclonal growth
      • all cells in a neoplasm are derived from a single progenitor cell
        • can be measured by the presence of single G6PD isoform or Ig heavy and light chain
    • resistance to anti-growth signals
    • angiogenesis
      • must supply nutrients to rapidly growing neoplasm
    • limitless replicative potential
    • invasion
    • metastasis
      • key difference between benign and malignant neoplasms
        • benign remain localized
  • Systemic effects of neoplasia
    • cachexia
      • muscle wasting leading to increased autophagic vacuole formation 
Steps of neoplastic progression 
  • Normal
    • histological characteristics
      • basal to apical differentiation
      • small nucleus:cytoplasm (N:C) ratio
      • intercellular adhesion
  • Hyperplasia
    • histological characteristics
      • increased cell number
      • otherwise normal histology
    • reversible
  • Dysplasia 
    • histological characteristics
      • increased cell number
      • loss of cellular orientation
      • increased cell size
    • reversible
  • Carcinoma in situ (preinvasive) 
    • histological characteristics
      • increased N:C ratio
      • nuclear changes (chromatin clumping)
      • basement membrane remains intact
    • non-reversible
  • Invasive carcinoma 
    • histological characteristics
      • a neoplasm that has breached the basement membrane but is still localized to tissue of origin
    • requirements
      • reduced intercellular adhesions (↓ cadherin
      • increased attachment to ECM proteins (↑ laminin and integrin receptors)
      • upregulated matrix metalloproteinases to pass through basement membrane
    • non-reversible
  • Metastasis
Other Types of Cellular Growth Alterations
  • Metaplasia
    • histological characteristics
      • replacement of 1 adult cell type by another
        • e.g., Barrett's esophagus
          • stratified squamous replaced by simple columnar
    • often a response by a tissue to a change in tissue environment
      • e.g., irritation by smoke, gastric acid, etc.
    • reversible
  • Anaplasia
    • histological characteristics
      • dramatic change in tissue morphology with no resemblance to original tissue
      • most often a malignant neoplasm
    • irreversible
  • Desmoplasia
    • histological characteristics
      • fibrous response to neoplastic growth
    • irreversible

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