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Classify colorectal polyps. Describe the adenoma-carcinoma sequence and the morphology of colorectal carcinoma.

Pathology · 2nd Professional — Para-Clinical

Colorectal Polyps

A polyp is any mass projecting into the lumen of the bowel. Polyps may be non-neoplastic or neoplastic (adenomas).

Type	Nature	Malignant potential
Hyperplastic	The commonest; small, left-sided, serrated crypts	None
Inflammatory / pseudopolyp	Regenerating mucosa in inflammatory bowel disease	None
Hamartomatous — juvenile	Children; rectum; sporadic solitary polyps	None if solitary; juvenile polyposis carries risk
PEUTZ–jeghers	Autosomal dominant (STK11); hamartomas with an arborising smooth muscle core; mucocutaneous pigmentation of lips and buccal mucosa	Increased risk of gastrointestinal and extraintestinal cancers
Adenoma — tubular	Pedunculated; about 75%	Low
Adenoma — tubulovillous	Mixed	Intermediate
Adenoma — villous	Sessile, large, frond-like; may secrete protein and potassium causing hypoproteinaemia and hypokalaemia	High — up to 40%
Sessile serrated lesion	Right colon; serrated architecture	Significant — the serrated pathway

Risk of malignancy in an adenoma rises with size (over 4 cm), villous architecture and degree of dysplasia — the three features to state
Familial adenomatous polyposis — autosomal dominant APC mutation; hundreds to thousands of adenomas from adolescence; carcinoma is inevitable by about 40, so prophylactic colectomy is performed. gardner syndrome adds osteomas, desmoid tumours and epidermoid cysts; TURCOT syndrome adds brain tumours

Colorectal Carcinoma — Pathogenesis

Adenoma–carcinoma sequence — about 80% → Normal mucosa → loss of APC → hyperproliferative epithelium → DNA hypomethylation and KRAS mutation → adenoma enlarges → Loss of SMAD2/4 (18q) → advanced adenoma → Loss of p53 (17p) → carcinoma → microsatellite instability pathway — about 15%; defective mismatch repair (MLH1, MSH2); sporadic or as LYNCH syndrome; right-sided, mucinous, better prognosis, responds to immunotherapy

Morphology and Spread

Feature	Right (proximal) colon	Left (distal) colon and rectum
Growth	Polypoid, exophytic, fungating	Annular, encircling — the "napkin-ring" constriction giving an "apple-core" defect on barium enema
Lumen	Wide; contents fluid	Narrower; contents solid
Presentation	Iron deficiency anaemia, fatigue, occult bleeding, a mass; obstruction is late	Obstruction, altered bowel habit, tenesmus, frank rectal bleeding

CLINICAL PEARL

An older adult with unexplained iron deficiency anaemia has a right-sided colonic carcinoma until proved otherwise. The caecum is capacious and its contents liquid, so a tumour there bleeds slowly for months without obstructing and without visible blood. Colonoscopy is mandatory — treating the anaemia with iron and stopping there is a well-recognised and serious error.

Staging and Applied Aspects

DUKES staging — A: confined to the bowel wall; B: through the wall, nodes negative; C: lymph nodes involved; D: distant metastases. Now largely replaced by TNM
Depth of invasion and nodal status are the strongest prognostic factors
Spread — direct; lymphatic to regional nodes; haematogenous by the portal vein to the liver; transcoelomic
CEA is used for monitoring and detecting recurrence, not for diagnosis
Screening from age 45 to 50 — faecal immunochemical testing or colonoscopy; removing an adenoma prevents the cancer, which makes this one of the most effective cancer screening programmes available
Solitary liver metastases may be resected with curative intent, and long-term survival is achievable

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