Principles of Neoplasia

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