Massive Foveolar-Gland Polyposis of the Stomach: Clinicopathologic, Histologic, and Molecular Analysis of Three Cases with Gastrectomy
Raul S Gonzalez, Juan M Sarmiento, Neal Osborn, Steven Keilin, James R Spivey, Michael Rossi, Charles Hill, Pelin Bagci, Volkan Adsay. Emory, Atlanta
Background: A distinctive syndrome characterized by massive transformation of the gastric mucosa into innumerable hyperplastic/hamartomatous-like polyps has been sporadically described in the gastroenterology and surgical literature, but its pathologic features have not been fully characterized, and nomenclature has varied.
Design: Clinicopathologic and molecular characteristics of three such patients who underwent gastrectomy are described.
Results: Two men and one woman, aged 37, 50, and 53, had massive polyposis replacing the entire gastric mucosa (Image 1). The polyps ranged from a few mm to 9 cm in size. Microscopically, they had hyperplastic features with foveolar-type lining. They appeared to originate and protrude from surface epithelium, with lower aspects of the mucosa typically unremarkable. Cystically dilated glands were often present, suggesting a hamartomatous nature. All patients had fewer than five inflammatory-type colon polyps. One patient, with a history of microsatellite-stable right-sided colorectal carcinoma, had a 3 mm gastric invasive adenocarcinoma of diffuse-infiltrative (“poorly cohesive cell”) type. The other patients had focal dysplastic changes but no carcinoma. The patient with cancer and her sister both had a heterozygous c.1139G>A SMAD4 germline mutation. Copy number variation analysis performed on tissue from another patient showed a gain in chromosome 18 at the locus containing SMAD4, again implicating the gene in the pathogenesis of this syndrome. Immunostaining for SMAD4 was noncontributory. All patients are alive at 43, 16, and 8 months.
Conclusions: Massive gastric polyposis is emerging as a distinct syndrome. Based on morphologic characteristics in this study, we propose the name Massive Foveolar-gland Polyposis Syndrome (MFPS). Germline SMAD4 mutation appears to be the key event, and this entity may be related to the subset of Juvenile Polyposis Syndrome (JPS) cases associated with SMAD4 mutation, which occasionally show malignant transformation. Unlike in JPS, polyps in MFPS are largely restricted to the stomach, with only rare non-adenomatous polyps in the lower GI tract. Appropriate genetic evaluation should be performed MFPS patients.
Monday, March 19, 2012 1:00 PM
Poster Session II # 97, Monday Afternoon