Gastric Polyps, GIST, MALT Lymphoma & Ménétrier

Ménétrier disease

Mechanism. Ménétrier disease is a rare hypertrophic gastropathy caused by excess TGF-α signaling through EGFR. Surface mucous (foveolar) cells proliferate massively in the body and fundus, raising giant, brain-like rugal folds while the antrum is usually spared. The oxyntic glands atrophy and parietal cells are lost, so acid output falls (hypochlorhydria).

Clinical picture. Protein leaks across the hyperplastic mucosa, producing a protein-losing gastropathy with hypoalbuminemia and peripheral edema, plus epigastric pain, vomiting, and weight loss. Adults, typically men aged 30 to 60, have a chronic course and an increased risk of gastric adenocarcinoma; children develop a transient form linked to CMV. Severe disease is treated with the anti-EGFR antibody cetuximab or with gastrectomy.

Giant folds have four main causes: Ménétrier disease (foveolar hyperplasia, low acid, low albumin), Zollinger-Ellison syndrome (parietal-cell hyperplasia, high acid), lymphoma, and diffuse-type adenocarcinoma (linitis plastica with signet-ring cells). Ménétrier mimics linitis plastica on imaging, so a deep, full-thickness mucosal biopsy is needed.

Gastric polyps

Fundic gland polyps are the most common gastric polyps in Western countries, usually small and multiple in the body and fundus. Adenomas are the only true neoplasms of the three; they are resected completely, and because the surrounding mucosa remains at risk, the stomach stays under surveillance.

Gastrointestinal stromal tumor

Origin and genetics. GIST is the most common mesenchymal tumor of the GI tract and arises most often in the stomach (~60%). It derives from the interstitial cells of Cajal, the pacemaker cells of peristalsis. About 75–80% carry activating mutations of KIT, the receptor tyrosine kinase for stem cell factor, and a smaller subset PDGFRA mutations. Tumors stain for CD117 (KIT) and DOG1, whereas desmin marks smooth-muscle tumors such as leiomyoma.

Behavior and treatment. Older adults present with a submucosal mass that may ulcerate and bleed. Most tumors are spindle-cell, and risk depends on size, mitotic rate, and site. Spread goes to liver and peritoneum, rarely to lymph nodes. Resection is primary; imatinib, a tyrosine kinase inhibitor of KIT, PDGFRA, and BCR-ABL, treats unresectable, metastatic, or high-risk disease, and sunitinib follows imatinib resistance. Syndromic GISTs occur in Carney triad (gastric GIST, pulmonary chondroma, paraganglioma) and NF1 (multiple small-bowel GISTs).

Gastric MALT lymphoma

Pathogenesis. The normal stomach has little lymphoid tissue; chronic H. pylori gastritis creates it. H. pylori–specific T cells then drive a marginal-zone B-cell clone (CD20+, CD5−, CD10−) whose cells invade and destroy glands, forming lymphoepithelial lesions. Early tumors are low-grade and localized.

Treatment logic. Because early tumors still depend on antigen-driven T-cell help, H. pylori eradication makes most regress. The t(11;18) API2-MALT1 fusion constitutively activates NF-κB, making growth antigen-independent; these tumors resist eradication and receive radiation or rituximab. Any MALT lymphoma can transform to diffuse large B-cell lymphoma. Other antigen-driven MALT lymphomas arise with Sjögren syndrome (salivary gland), Hashimoto thyroiditis (thyroid), and Chlamydia psittaci (ocular adnexa).

Keep the translocations apart: t(11;18) MALT, t(14;18) follicular (CD10+), t(11;14) mantle cell (CD5+), t(8;14) Burkitt lymphoma.

Gastric neuroendocrine tumors

Cell of origin. Gastric NETs arise from enterochromaffin-like (ECL) cells, the histamine-secreting cells of the body and fundus, which proliferate under the trophic effect of gastrin. All stain for chromogranin A and synaptophysin.