PA23.8 | Colorectal Carcinoma — Summary & Reflection

REFLECT

Consider the patient from our opening scenario — the 68-year-old woman with iron-deficiency anaemia and positive FOBT.

1. If colonoscopy reveals a 3 cm caecal carcinoma that is confined to the submucosa with no lymph node involvement, what is the Dukes stage? What 5-year survival would you quote to her family?

1. Her son's sigmoid lesion turns out to be a Dukes C tumour (T3, N1, M0). Post-operatively his CEA drops to normal. Three months later it rises again. What is your interpretation and what would you do next?

1. If we had screened both of them with an annual FOBT from age 50, at what stage in the adenoma-carcinoma sequence might these tumours have been detected, and how would that have altered the outcome?

This is the essence of why pathology drives clinical decision-making — understanding the biology predicts the behaviour.

KEY TAKEAWAYS

Colorectal Carcinoma — Core Summary

Risk factors: Age >60, low-fibre/high-fat/red-meat diet, obesity, UC (highest IBD risk), previous adenomas, positive family history.

Precursor lesions: Adenomatous polyps — tubular (lowest risk) → tubulovillous → villous (highest risk, sessile, rectal). Risk increases with size >2 cm, high-grade dysplasia, multiplicity.

Adenoma-carcinoma sequence: 10–15 years; APC mutation initiates → KRAS → SMAD4 → TP53 (CIN pathway). Provides the rationale for colonoscopic surveillance and screening.

Polyposis syndromes: FAP = APC germline mutation, thousands of polyps, inevitable CRC by 40; Lynch/HNPCC = MMR germline mutation, MSI, right-sided, mucinous, also endometrial/ovarian.

Molecular pathways: CIN (APC/β-catenin, MSS, 85%, left-sided) vs MSI (MMR loss, 15%, right-sided, better prognosis, responds to immunotherapy).

Gross morphology: Right-sided → polypoid/fungating → anaemia. Left-sided → annular napkin-ring → obstruction.

Microscopy: Adenocarcinoma (gland-forming, dirty necrosis, graded G1–G3); mucinous (>50% mucin, MSI-H); signet-ring (worst prognosis).

Spread: Local → lymphatic → haematogenous (portal vein → liver first) → transcoelomic.

Staging: Dukes A (>90%) → B (65–75%) → C (30–40%) → D (<5%). TNM equivalents: I, IIA-C, IIIA-C, IV.

CEA: NOT for diagnosis or screening. Use post-operatively to monitor recurrence.

Screening: Annual FOBT/FIT → colonoscopy if positive. Colonoscopy every 10 years (average risk). Interrupts adenoma-carcinoma sequence.