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PA23.1-9 | Gastrointestinal Tract — PBL Case

CLINICAL SETTING

Rajan Kumar, a 34-year-old auto-rickshaw driver from a small town in Chhattisgarh, is brought to the district hospital by his wife and elder brother. Over the past eight months, he has been eating progressively less — not because he lacks appetite, but because even a small meal makes him feel unbearably full within minutes. He has lost 14 kg. His wife says he looks like a different person. At the PHC level three months ago, the doctor attributed his symptoms to acidity and prescribed antacids; there was no improvement. He has never used tobacco or alcohol. There is no family history of cancer. His father died of tuberculosis twenty years ago. On examination he is cachectic, with conjunctival pallor. His abdomen is slightly distended. A vague firmness is felt in the epigastrium. His wife mentions he also complains of pain in both knees — a symptom that seems unrelated but has worried the family greatly.

Trigger 1: Initial Presentation

Rajan is a 34-year-old male who presents with 8 months of progressive early satiety, anorexia, and a 14 kg weight loss. There is no haematemesis or melaena. He has no history of tobacco, alcohol, or NSAID use. His father died of pulmonary tuberculosis. At the PHC, he was treated empirically for peptic ulcer disease with no benefit. On examination: BMI 16.8 kg/m², pulse 98/min, BP 100/68 mmHg. Abdomen: mild epigastric fullness; no hepatomegaly; no ascites detected clinically. He also complains of bilateral knee joint pain with no swelling or erythema. Blood investigations: Haemoglobin 9.2 g/dL (normocytic normochromic), total leucocyte count 9,800/µL, ESR 62 mm/hr, serum albumin 2.8 g/dL.

DISCUSSION POINTS

What is your differential diagnosis for an 8-month history of progressive early satiety and weight loss in a young Indian male? Rank the possibilities and justify your reasoning.
How does the absence of risk factors (no tobacco, no alcohol, no NSAID use, no H. pylori history) affect your probability estimate for peptic ulcer disease versus gastric carcinoma?
What is the pathophysiological basis of early satiety, and which diseases involving the stomach wall directly cause this symptom through a structural mechanism rather than a secretory one?
The bilateral knee pain without joint inflammation — what paraneoplastic or metastatic process could link this to a GI malignancy, and what would you look for on examination?

Click to reveal Trigger 2: Investigations (discuss previous trigger first!)

Trigger 2: Investigations

Upper GI endoscopy is performed. The stomach does not distend normally on air insufflation. The mucosa looks diffusely rigid and thickened throughout the body and antrum, described by the endoscopist as a 'leather-flask' appearance. Multiple biopsies are taken from the antrum, body, and fundus. There is no discrete ulcer or polypoid mass. Barium meal confirms a small, non-distensible stomach with a fixed 'leather-bottle' appearance. CT abdomen: diffuse gastric wall thickening (up to 2.4 cm), no discrete mass, no obvious regional lymphadenopathy, no liver lesions. Bone scan: increased uptake in bilateral distal femoral metaphyses. Biopsy histology (antrum): The surface epithelium is disrupted. Beneath it, the lamina propria is densely infiltrated by discohesive individual cells, each containing a large mucin vacuole that pushes the nucleus to the periphery, giving the cell a 'signet ring' appearance. There is abundant stromal fibrosis (desmoplasia). No gland formation is seen. No granulomas. CEA: 28 ng/mL; CA 19-9: 186 U/mL.

DISCUSSION POINTS

What histological diagnosis do these biopsy findings confirm? Explain the term 'linitis plastica' — what structural change in the gastric wall produces the leather-bottle appearance, and which cell type is responsible at the microscopic level?
Using the Lauren classification, categorise this tumour. How does the diffuse type differ from the intestinal type in terms of: (a) epidemiology and age of onset, (b) precursor lesions, (c) E-cadherin expression, (d) mucin production, and (e) prognosis?
How does the pathogenesis of diffuse-type gastric carcinoma differ from intestinal-type in terms of molecular mechanisms? Which hereditary syndrome is caused by germline CDH1 mutation, and why is this relevant to Rajan's age?
Explain the bone scan findings. What is the pathological mechanism by which signet-ring cell carcinoma metastasises to bone — and how does it differ from the haematogenous spread pattern of intestinal-type carcinoma?

Click to reveal Trigger 3: Diagnosis & Management (discuss previous trigger first!)

Trigger 3: Diagnosis & Management

The multidisciplinary team confirms a diagnosis of diffuse-type gastric adenocarcinoma (signet-ring cell carcinoma), with bone metastases and an elevated tumour marker profile. The tumour is staged as T4a N1 M1 (Stage IV, TNM 8th edition). The team reviews treatment options. Because of metastatic disease, curative surgical resection is not feasible. The oncology team proposes palliative chemotherapy (FLOT regimen considered, but patient's performance status is ECOG 3). A district-level palliative care referral is initiated. The family asks the team: "Could this have been detected earlier? Are his children at risk?" The gastroenterologist also asks the pathology resident to describe what would be seen on gross examination had a gastrectomy specimen been available, and to distinguish the morphology from a peptic ulcer of the stomach on both gross and microscopic grounds.

DISCUSSION POINTS

Compare the gross and microscopic features of diffuse-type gastric carcinoma (linitis plastica) with a benign chronic peptic ulcer. What are the five key differentiating features on gross examination, and how does the histological four-zone floor of a peptic ulcer contrast with the diffuse desmoplastic infiltrate of signet-ring carcinoma?
Describe the routes of spread of gastric carcinoma: (a) direct extension to adjacent structures, (b) lymphatic spread (Virchow's node, Irish node), (c) transcoelomic spread (Krukenberg tumour) — why does this occur preferentially in the ovary, and what is the mechanism? (d) haematogenous spread to liver versus bone.
Evaluate the role of H. pylori in gastric carcinoma. The WHO classifies H. pylori as a Group 1 carcinogen for intestinal-type gastric carcinoma. Discuss why H. pylori eradication is a public health priority in India, and why it is less relevant to Rajan's diffuse-type tumour.
Advise the family on hereditary risk. What percentage of diffuse gastric carcinoma cases are hereditary? What is the recommended surveillance strategy for first-degree relatives of a CDH1-mutation carrier, and at what age should prophylactic gastrectomy be considered?

Group Task Assignments

Group 1: Etiology and Molecular Pathogenesis of Gastric Carcinoma

Construct a comparative table of intestinal-type versus diffuse-type gastric adenocarcinoma covering: epidemiology, precursor lesions, key molecular events (APC, TP53, CDH1/E-cadherin loss), H. pylori association, Lauren gross pattern, and 5-year survival.
Prepare a 3-minute case-linked summary explaining why Rajan's young age, diffuse histology, and absence of classic risk factors points toward the sporadic diffuse subtype and how germline CDH1 testing changes family counselling.

Competencies: PA23.4

Group 2: Pathology of Peptic Ulcer Disease vs Malignant Ulcer

Draw and label: (a) the four histological zones of a chronic peptic ulcer (fibrinopurulent exudate, fibrinoid necrosis, granulation tissue, fibrosis); (b) the signet-ring cell infiltrate with desmoplastic stroma seen in Rajan's biopsy. Highlight the absence of gland formation and the discohesive cell pattern.
List five gross morphological features that help distinguish a benign peptic ulcer from a malignant gastric ulcer at endoscopy/gross examination. For each feature, state whether it points toward benign or malignant and explain the underlying pathological basis.

Competencies: PA23.3, PA23.4, PA23.9

Group 3: Routes of Spread and Staging

Using Rajan's case, map each of the four routes of spread for gastric carcinoma (direct, lymphatic, transcoelomic, haematogenous) to specific clinical or imaging findings already present in his workup. For each route, name a specific anatomical site of secondary involvement and explain why that site is targeted.
Apply the TNM staging system (8th edition) to Rajan's findings and confirm the Stage IV assignment. Then explain the Dukes staging system for colorectal carcinoma and discuss why a similar staging convention does NOT apply to gastric carcinoma — what is used instead?

Competencies: PA23.4, PA23.8

Group 4: H. pylori, Mucosal Defense, and PUD Complications

Explain the aggressive-versus-defensive factor imbalance model of peptic ulcer pathogenesis. For each aggressive factor (H. pylori virulence factors, NSAIDs, acid hypersecretion) and each defensive factor (mucus-bicarbonate barrier, prostaglandins, mucosal blood flow), describe the specific mechanism of action at the cellular level.
List the four major complications of peptic ulcer disease. For each complication, state: (a) the anatomical basis (e.g., which vessel is eroded in posterior duodenal ulcer haemorrhage), (b) the clinical presentation, and (c) the gross/micro pathological finding.

Competencies: PA23.3

Group 5: GI Morphology — Practical Slide Interpretation

Given H&E slide descriptions of: (a) peptic ulcer with four-zone floor, (b) signet-ring cell carcinoma with desmoplastic stroma, (c) intestinal-type gastric adenocarcinoma with irregular gland formation and 'dirty necrosis', and (d) normal gastric mucosa — practice applying the systematic five-step reading approach (site → gross pattern → architecture → benign/malignant determination → diagnosis) to each description.
Describe how you would distinguish between a Krukenberg tumour in the ovary and a primary ovarian carcinoma on histology. What is the mechanism of transcoelomic spread, and what characteristic cellular feature of the metastatic deposit confirms the gastric primary?

Competencies: PA23.9, PA23.4, PA23.3

Learning Issues

Research these questions and bring your findings to the discussion.

[PA23.1] What are the common premalignant lesions of the oral cavity, and how does their malignant transformation risk compare? What features in a biopsy distinguish leukoplakia with dysplasia from invasive squamous cell carcinoma?
[PA23.2] Describe the two histological types of oesophageal carcinoma. What is Barrett's oesophagus, what type of metaplasia defines it histologically, and how does it progress through the metaplasia–dysplasia–carcinoma sequence to adenocarcinoma?
[PA23.3] Explain the pathogenesis of peptic ulcer disease as an imbalance between aggressive and defensive mucosal factors. Describe the four histological zones of a chronic peptic ulcer, its common complications, and the gross and microscopic features that distinguish it from a malignant gastric ulcer.
[PA23.4] Describe the etiology, pathogenesis, Lauren classification (intestinal vs diffuse type), gross pathology (including linitis plastica), microscopic features (signet-ring cells, desmoplasia, gland formation in intestinal type), and routes of spread of gastric adenocarcinoma. What molecular event characterises the diffuse type?
[PA23.5] Describe the two morphological forms of intestinal tuberculosis (ulcerative and hyperplastic), their diagnostic microscopic features, and the clinico-pathological features that distinguish intestinal TB from Crohn's disease — particularly in the Indian context.
[PA23.6] Compare and contrast Crohn's disease and ulcerative colitis in terms of: distribution, gross morphology (skip lesions vs continuous; cobblestoning vs pseudopolyps), depth of inflammation (transmural vs mucosal), granulomas, and major complications including risk of colorectal carcinoma.
[PA23.7] Enumerate the major causes of malabsorption syndrome. Describe the pathological changes in coeliac disease (villous atrophy, crypt hyperplasia, intraepithelial lymphocytes). What laboratory tests confirm fat malabsorption, and which specific serological and genetic markers diagnose coeliac disease?
[PA23.8] Describe the adenoma-carcinoma sequence in colorectal carcinoma, the Vogelstein molecular pathway (APC → K-RAS → SMAD4 → TP53), and how right-sided versus left-sided CRC differ in gross morphology and clinical presentation. What are the Dukes staging criteria and their prognostic significance?
[PA23.9] Identify the microscopic features of peptic ulcer, intestinal ulcers (TB, Crohn's, UC), and GI tumours (oral/oesophageal SCC, gastric diffuse adenocarcinoma, colorectal adenocarcinoma with dirty necrosis) using a systematic five-step reading approach: site → gross pattern → architecture → benign/malignant determination → final diagnosis.