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PA23.8 | Colorectal Carcinoma — SDL Guide (Part 3)

Histopathology — Microscopic Features and Grading

A histopathology teaching diagram compares conventional colorectal adenocarcinoma features, WHO grading by gland formation, and mucinous and signet-ring subtypes. — **Panel A:** Conventional adenocarcinoma with irregular tumour glands, nuclear pleomorphism, prominent nucleoli, mitotic activity, dirty necrosis, and desmoplastic stroma.. **Panel B:** Well-differentiated G1 adenocarcinoma showing more than 95% gland formation and better prognosis.. **Panel C:** Moderately differentiated G2 adenocarcinoma showing 50–95% gland formation and intermediate prognosis.. **Panel D:** Poorly differentiated G3 adenocarcinoma showing less than 50% gland formation, solid tumour sheets, and worse prognosis.. **Panel E:** Mucinous adenocarcinoma with more than 50% extracellular mucin pools, floating tumour glands, MSI-H/Lynch association, and right-sided predominance.. **Panel F:** Signet-ring cell carcinoma with isolated mucin-filled tumour cells, peripheral displaced nuclei, Lynch association, and poorest prognosis..

Conventional adenocarcinoma (most common)
- Gland-forming tumour cells with nuclear pleomorphism, prominent nucleoli, and mitotic activity.
- "Dirty necrosis" — a distinctive feature: necrotic cellular debris within the tumour gland lumina (intraluminal necrosis), producing a characteristic dirty appearance on H&E. This helps distinguish colorectal from other gland-forming metastases.
- Desmoplastic stroma surrounds the glands.

Grading (WHO):

Grade	Gland formation	Behaviour
Well-differentiated (G1)	>95% glandular	Better prognosis
Moderately differentiated (G2)	50–95% glandular	Intermediate
Poorly differentiated (G3)	<50% glandular	Worse prognosis

Special subtypes:
- Mucinous adenocarcinoma (>50% extracellular mucin pools): associated with MSI-H/Lynch; right-sided predominance; classified G3 by default.
- Signet-ring cell carcinoma (<10% of CRC): single cells with intracytoplasmic mucin displacing the nucleus to periphery; poorest prognosis; associated with Lynch syndrome.

Tumour budding (isolated single cells or clusters of <5 cells at the invasive front) is an independent adverse prognostic feature now reported routinely.

Spread and Routes of Metastasis

Diagram showing the four major routes of colorectal carcinoma spread: direct invasion, lymphatic spread, haematogenous spread, and peritoneal seeding. — **Panel A:** Colon mucosa, submucosa, muscularis propria, pericolorectal fat, adjacent organ, invasive colorectal carcinoma, direct/local extension, T-stage determinant. **Panel B:** Primary colorectal carcinoma, pericolorectal lymph nodes, intermediate lymph nodes, principal central lymph nodes, mesenteric vessels, lymphatic spread, N-stage determinant. **Panel C:** Portal vein, liver metastases, lung metastases, adrenal metastases, bone metastases, rectal carcinoma, inferior haemorrhoidal veins, systemic venous circulation, direct lung metastases. **Panel D:** Peritoneal cavity, exfoliated tumour cells, peritoneal carcinomatosis, malignant ascites, bilateral ovaries, Krukenberg tumour, mucin-secreting colorectal carcinoma, CEA monitoring inset.

CRC spreads by four classical routes:

Direct/local extension: Through the bowel wall layers (mucosa → submucosa → muscularis propria → pericolorectal fat → adjacent organs). Determines the T-stage.

Lymphatic spread: To pericolorectal lymph nodes → intermediate nodes → principal (central) nodes. Number of involved nodes is a major prognostic determinant (N-stage).

Haematogenous spread: Via the portal vein → liver (most common distant metastatic site). Subsequently, pulmonary, adrenal and osseous metastases. Rectal carcinoma may also spread via the inferior haemorrhoidal veins to the systemic circulation, bypassing the liver (direct lung metastases).

Transcoelomic (peritoneal) spread: Seeding of the peritoneal cavity → peritoneal carcinomatosis; malignant ascites; Krukenberg tumour (bilateral ovarian metastases from mucin-secreting CRC).

Clinical implication: At time of diagnosis, ~25% of patients have synchronous liver metastases. CEA level correlates with metastatic burden and is used post-operatively to monitor for recurrence.

Staging — Dukes and TNM

A three-panel colorectal cancer staging diagram comparing tumour wall invasion, Dukes stages, and TNM categories with lymph node and metastasis status. — **Panel A:** Transverse colorectal wall cross-section showing mucosa, submucosa, muscularis propria, visceral peritoneum or serosa, pericolorectal fat, adjacent organ, and T1, T2, T3, T4a, T4b invasion depth.. **Panel B:** Dukes staging comparison showing Dukes A, Dukes B, Dukes C, Dukes D, extent of tumour spread, lymph node status, distant metastasis, and 5-year survival.. **Panel C:** TNM staging map showing colon tumour, regional lymph nodes, N0, N1, N2, M0, M1, distant liver metastasis, and visual correlation with Dukes A-D..

Two staging systems are used in parallel — you must know both.

Dukes Staging (original + modified Astler-Coller):

Stage	Extent	5-Year Survival
Dukes A	Confined to bowel wall (not beyond muscularis propria)	>90%
Dukes B	Through bowel wall into pericolorectal fat; nodes negative	65–75%
Dukes C	Any wall depth; lymph node positive	30–40%
Dukes D	Distant metastases (added by later modifications)	<5%

TNM Staging (AJCC/UICC):
- T (Tumour): T1 = submucosa; T2 = muscularis propria; T3 = pericolorectal tissues; T4a = visceral peritoneum; T4b = adjacent organs.
- N (Nodes): N0 = none; N1 = 1–3 regional nodes; N2 = ≥4 regional nodes.
- M (Metastasis): M0 = none; M1 = distant.
- Stages I–IV roughly correspond to Dukes A, B, C, D.

Key prognostic factors beyond stage: grade, margin status (R0/R1), vascular invasion, perineural invasion, tumour budding, MSI status.

A three-panel colorectal carcinoma staging diagram correlating Dukes A to D with TNM stages, wall invasion depth, nodal spread, metastasis, and approximate 5-year survival. — **Panel A:** Cross-sectional colon wall layers labeled mucosa, submucosa, muscularis propria, pericolorectal fat, serosa/adventitia; arrows showing T1, T2, T3, and T4 depth of invasion.. **Panel B:** Comparative table showing Dukes A/B/C/D, equivalent TNM stages I, IIA-IIC, IIIA-IIIC, IV, node/metastasis status, and approximate 5-year survival percentages.. **Panel C:** Clinical application showing T3 tumor invasion into pericolorectal fat, metastatic regional lymph nodes, absence of distant metastasis, and final staging as Dukes C / Stage III with 30-40% 5-year survival..

SELF-CHECK

A resected colorectal carcinoma invades through the muscularis propria into pericolorectal fat. Three of twelve harvested lymph nodes contain metastatic carcinoma. No distant metastasis. What is the Dukes stage and approximate 5-year survival?

A. Dukes A; >90% survival

B. Dukes B; 65–75% survival

C. Dukes C; 30–40% survival

D. Dukes D; <5% survival

Reveal Answer

Answer: C. Dukes C; 30–40% survival

Lymph node involvement at any depth of wall invasion = Dukes C. The wall invasion (through muscularis propria into pericolorectal fat = T3) is less important for the Dukes classification than the presence of nodal metastases. No distant metastases rules out Dukes D. Five-year survival for Dukes C is 30–40%, compared with >90% for Dukes A (confined within the wall, node-negative).