Paper I
Question
Define Metastasis, Enumerate the routes of metastasis and explain the mechanisms
Answer
Definition
- Metastasis is the spread of malignant tumour cells from the primary site to a discontinuous, distant site, forming secondary tumour deposits; it is the defining feature that distinguishes malignant from benign neoplasms
Routes of metastasis
1. Direct seeding of body cavities/surfaces
- Occurs when a tumour penetrates into a natural body cavity (peritoneal, pleural, pericardial) and its cells implant/spread along the serosal surface
- Example: ovarian carcinoma spreading throughout the peritoneal cavity (“omental cake”), gastric carcinoma causing Krukenberg tumour of the ovary
2. Lymphatic spread
- The most common route for carcinomas
- Tumour cells invade lymphatic channels and are carried to regional lymph nodes, which trap and may be colonized by the tumour cells (may follow natural drainage patterns, or “skip metastases” can occur)
- Example: breast carcinoma spreading to axillary lymph nodes
3. Haematogenous spread
- The typical route for sarcomas, though also used by carcinomas
- Tumour cells invade venules (thinner walls, easier penetration than arteries) and are carried via the bloodstream
- Organ distribution often follows the pattern of venous drainage — e.g., tumours draining via the portal system commonly metastasize to the liver; tumours draining into the systemic venous system commonly metastasize to the lungs
- Certain tumours show a “seed and soil” tropism to specific distant organs regardless of vascular pathway (e.g., prostate cancer to bone)
Mechanism (metastatic cascade)
- Local invasion (loss of cell adhesion, matrix degradation) → intravasation into vessels → survival in circulation (evading immune surveillance/shear stress, often with platelet aggregation for protection) → adhesion to distant endothelium → extravasation into the new tissue → colonization (proliferation, induction of angiogenesis to sustain growth of the metastatic deposit)