Gastrointestinal: hereditary diffuse gastric cancer: practice question

A Pathology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pathology · Gastrointestinal: hereditary diffuse gastric cancer

Sample item

A 32-year-old woman's mother and maternal aunt both died of gastric cancer in their thirties. Endoscopy of the patient shows pale mucosal patches, and biopsy shows signet-ring cells. Mutation of which gene is most likely?

ASMAD4BAPCCMLH1DCDH1 encoding E-cadherin

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

D. CDH1 encoding E-cadherin

Hereditary diffuse gastric cancer is an autosomal dominant syndrome caused by germline CDH1 mutations. Loss of E-cadherin removes cell adhesion, producing discohesive signet-ring cells that infiltrate the wall and cause a rigid stomach (linitis plastica). Affected carriers are also at risk of lobular breast cancer, and prophylactic gastrectomy is considered.

Option by option

A. SMAD4
SMAD4 mutation causes juvenile polyposis, which carries a risk of hamartomatous polyps.
B. APC
APC mutation causes familial adenomatous polyposis, with hundreds of colonic polyps.
C. MLH1
MLH1 mutation causes Lynch syndrome and intestinal-type gastric cancer with mismatch repair deficiency.
D. CDH1 encoding E-cadherin (correct)
Correct. CDH1 loss accounts for the discohesive diffuse-type gastric cancer.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

Questions about this Pathology question

What is the answer to this Pathology question?

The best answer is D, CDH1 encoding E-cadherin. Hereditary diffuse gastric cancer is an autosomal dominant syndrome caused by germline CDH1 mutations.

Why is "SMAD4" not the answer?

SMAD4 mutation causes juvenile polyposis, which carries a risk of hamartomatous polyps.

Why is "APC" not the answer?

APC mutation causes familial adenomatous polyposis, with hundreds of colonic polyps.

Why is "MLH1" not the answer?

MLH1 mutation causes Lynch syndrome and intestinal-type gastric cancer with mismatch repair deficiency.

What concept does this question test?

It tests Gastrointestinal: hereditary diffuse gastric cancer in Pathology. Loss of E-cadherin removes cell adhesion, producing discohesive signet-ring cells that infiltrate the wall and cause a rigid stomach (linitis plastica). Affected carriers are also at risk of lobular breast cancer, and prophylactic gastrectomy is considered.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Gastrointestinal: hereditary diffuse gastric cancer?

Learn each disease as a bundle: cause, key histology, markers, and the clinical hallmark. Then use the flashcards and the other Pathology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.