Pathomechanism of metaplasia and dysplasia, examples

1. Metaplasia

• Reversible replacement of one differentiated cell type by another better suited to stress — a form of cellular adaptation.
• Mechanism: reprogramming of stem cells by growth factors, cytokines, ECM signals from chronic persistent injury (not direct conversion of mature cells).
• Reversible if the noxious agent is removed; if persistent → malignant transformation.

Examples

• Squamous metaplasia of bronchus (columnar → squamous): commonest type; smokers; loses cilia/mucus → risk of dysplasia + squamous cell carcinoma.
• Barrett esophagus (squamous → intestinal-type columnar with goblet cells): from GERD/acid reflux → risk of adenocarcinoma of lower 1/3 esophagus.
• Osseous metaplasia in soft tissue.

2. Dysplasia

• Disordered epithelial proliferation with loss of uniformity & architectural orientation — pre-cancerous.
• Often arises in long-standing hyperplasia/metaplasia.
• Features: de-differentiation, cell size/shape variation (pleomorphism), ↑N:C ratio, hyperchromasia, disarray / loss of polarity, ↑mitoses.
• Sequence: Normal → Metaplasia → Dysplasia → Neoplasia (adaptation → mutation accumulation → clonal selection).

Cervical intraepithelial neoplasia (CIN)

• At the squamo-columnar junction; basal (progenitor) cells progressively replace the epithelium:
  • CIN1 = lower 1/3 (LSIL); CIN2 = 2/3; CIN3 = full thickness (HSIL) ≈ carcinoma in situ.
• Breach of basement membrane → invasive carcinoma.

💡 High-yield: Metaplasia = reversible cell-type switch via stem-cell reprogramming (Barrett, smoker’s bronchus). Dysplasia = premalignant atypia (↑N:C, pleomorphism, disarray); high-grade/full-thickness without invasion = carcinoma in situ.