PA23.1-9 | Gastrointestinal Tract — Case Study

CLINICAL SCENARIO

A 62-year-old male presents with a 4-month history of fatigue, progressive exertional dyspnoea, and a 6 kg weight loss. He reports no per-rectal bleeding. Investigations reveal haemoglobin 7.8 g/dL (microcytic hypochromic), serum ferritin 6 ng/mL, and a positive faecal occult blood test. Colonoscopy reveals a 4 cm fungating, friable mass in the caecum. Biopsy is taken. CT abdomen shows a soft-tissue mass in the right colon with two hypoechoic lesions in the right lobe of the liver.

You are the pathology resident assigned to this case. Work through the clinico-pathological reasoning systematically.

Section 1: Clinical Reasoning — Why No Rectal Bleeding?

This patient has iron-deficiency anaemia (IDA) as the presenting complaint, yet denies per-rectal bleeding. Explain why right-sided colorectal carcinoma typically presents with occult rather than overt bleeding, in contrast to left-sided carcinoma. What anatomical and tumour-growth differences account for this?

Guidance: Address: (a) caecal/ascending colon lumen diameter and faecal consistency; (b) tumour growth pattern (fungating/exophytic vs annular/napkin-ring); (c) why the right colon favours a polypoid mass that oozes rather than obstructs; (d) how chronic occult loss → IDA. A brief note on left-sided vs right-sided clinical signatures is expected (~80 words).

Section 2: Pathogenesis — The Adenoma-Carcinoma Sequence

Most sporadic colorectal carcinomas arise via the adenoma-carcinoma sequence. Outline the molecular steps involved, identifying the key tumour suppressor genes and oncogenes implicated (in order of acquisition). State whether the right colon or left colon is more commonly associated with microsatellite instability (MSI) and explain why.

Guidance: Expected pathway: APC mutation → loss of Wnt brake → adenoma growth → KRAS → SMAD4/DPC4 → TP53 → invasive carcinoma. Mention the alternative serrated/MSI pathway (BRAF, MLH1 silencing). Right colon is more commonly MSI-H; link to HNPCC/Lynch syndrome and sporadic MLH1 hypermethylation. Avoid listing gene names without explaining their function (~150 words).

Section 3: Gross and Histological Pathology

The caecal mass is resected (right hemicolectomy). Describe the expected gross and microscopic features of a well-to-moderately differentiated colorectal adenocarcinoma. How does gross morphology differ between right-sided and left-sided tumours? What specific histological feature is most characteristic of colorectal adenocarcinoma?

Guidance: Gross: right-sided = fungating, polypoid, soft, often necrotic/ulcerated centre; left-sided = annular, napkin-ring, obstructive. Microscopy: gland-forming (tubular/acinar) adenocarcinoma; columnar cells; central necrosis in glandular lumina ('dirty necrosis' / luminal necrosis is a hallmark); desmoplastic stroma; goblet cell loss. Mention signet-ring and mucinous variants as poorly differentiated subtypes. Histological grade (well/moderate/poor) and its prognostic significance (~150 words).

Section 4: Staging — Dukes and TNM

The histopathology report states: tumour invades through the muscularis propria into pericolorectal tissues; 3 of 14 lymph nodes are positive; the two liver lesions are confirmed metastatic adenocarcinoma on biopsy. Stage this tumour using both the Dukes classification and the current AJCC TNM system (8th edition). What is the prognostic significance of this stage?

Guidance: Dukes D = distant metastases (some classifications use C2 for positive nodes + distant Mets; clarify Dukes vs Astler-Coller if used). TNM: T3 (through muscularis propria into pericolorectal fat), N1b (3 regional nodes positive), M1a (liver only) → Stage IVA. 5-year survival for Stage IV colorectal carcinoma ~14%. Mention that resectability of liver metastases influences prognosis (~100 words).

Section 5: Tumour Marker — CEA

The oncology team orders a serum CEA (carcinoembryonic antigen). Define CEA, state its normal range, and explain its clinical utility and limitations in this patient. Is it diagnostic of colorectal carcinoma? How is it used in post-surgical surveillance?

Guidance: CEA: oncofetal glycoprotein, normal <5 ng/mL (non-smokers); elevated in colorectal, gastric, pancreatic, lung, breast carcinomas — not specific. NOT diagnostic; no role in screening general population. Utility: (1) pre-operative baseline — high CEA correlates with advanced stage and poorer prognosis; (2) post-operative surveillance — rise after curative resection is first sign of recurrence; (3) monitor treatment response in metastatic disease. Mention that poorly differentiated tumours may not produce CEA (~120 words).

Section 6: Mechanism of Hepatic Metastasis

Explain why the liver is the most common site of colorectal carcinoma metastasis. Describe the route of spread and the characteristic gross appearance of hepatic colorectal metastases. How does this differ from haematogenous spread to the lungs?

Guidance: Portal venous drainage of the colon → first-pass filtration by the liver (sinusoidal seeding) → hepatic metastases. Gross: multiple, discrete, pale/white nodules with central umbilication ('crater' appearance) due to central necrosis outgrowing blood supply. Lung = second filter (via hepatic veins → IVC → right heart → pulmonary circulation), hence second most common site. Contrast with rectal carcinoma — low rectal tumours drain via systemic veins (inferior rectal/pudendal → IVC), bypassing portal circulation, hence more likely to metastasise to lungs first. (~120 words).

PEER REVIEW

After your submission deadline, you will be assigned one classmate's response anonymously.

Your task: Use the rubric above to score each criterion (0–5 or 0–6 as marked). For each criterion, write 1–3 sentences of specific, constructive feedback — identify what was done well and one concrete improvement. Then write a 2–3 sentence overall comment.

Standards for a good peer review:
- Be specific: quote or paraphrase the passage you are commenting on.
- Be constructive: 'The staging was incorrect — T3 means invasion into pericolorectal fat, not through the serosa (that is T4a)' is more useful than 'Staging needs work'.
- Be respectful and objective.

Anti-patterns to avoid: Empty praise ('Great job!'), scoring without justification, or penalising a classmate for using different but correct terminology.

Peer reviews are graded on quality of feedback, not on whether your scores match the faculty key.