Sporadic and Familial Adenomatous Polyposis-associated Foveolar-type Adenoma of the Stomach

Abstract

Gastric foveolar-type adenoma (FA) is a rare benign neoplasm occurring either sporadically or in patients with familial adenomatous polyposis (FAP). However, the molecular features of FA and the relationship between sporadic and syndromic lesions remain unclear. In this study, we performed clinicopathological, immunohistochemical, and genetic analyses of 18 sporadic and 30 FAP-associated FAs. Most sporadic and FAP-associated FAs were located in the upper or middle third of the stomach, on a background of fundic gland mucosa. Most lesions were low-grade, but 3 lesions had a high-grade component. Sporadic FAs included 2 morphologically distinct subtypes, that is, flat and raspberry-like FAs, which we distinguished based on the endoscopic features. Seven lesions were regarded as flat FAs, appearing as large, slightly elevated lesions and measuring 11 to 87 mm in size. Conversely, 10 raspberry-like FAs were small bright-red polyps, measuring 2 to 8 mm in size. FAPassociated FAs, particularly larger lesions, exhibited morphologic features resembling flat FAs but varied significantly in size (2 to 103 mm). Mutation analysis identified APC and KRAS mutations in all flat FAs but never in raspberry-like FAs. Remarkably, somatic APC and KRAS mutations were also detected in 19 (63%) and 27 (90%) of FAP-associated FAs, respectively. This indicates that they are genetically equivalent to sporadic, flat FAs. This study showed that sporadic FA includes at least 2 morphologically and genetically distinct subtypes: flat and raspberry-like FA. Furthermore, flat FA represents a sporadic counterpart of FAP-associated FA.

Prevalence of Raspberry-type Gastric Foveolar-type Tumor in Individuals Undergoing Medical Checkups

“…Recently, Kushima suggested that gastric foveolar-type tumors of H. pylori-uninfected cases should be called "foveolar-type adenoma", since those are clinically and molecularpathologically different from the tumors of H. pyloripositive cases. (28,29). Therefore, the present study was conducted to analyze the prevalence of raspberry-type gastric foveolar-type tumor without division into adenocarcinoma or adenoma.…”

Clinicopathologic differences of gastric neoplasms between Helicobacter pylori-infected and naïve patients

“…An FGA is an epithelial polyp consisting of neoplastic foveolar epithelium that occurs in the oxyntic compartment, and positive for MUC5AC (gastric foveolar mucin, gastric phenotype marker). This tumor primarily shows small reddish protrusions (raspberry type) and rarely those with a whitish at form ( at type) [5,7,18,19]. An IGD is an epithelial neoplasm consisting of dysplastic intestinalized epithelium that occurs as a depressed lesion in the pyloric-gland mucosa, and positive for CDX2 (intestinal differentiation marker), MUC2 (goblet cell mucin, intestinal phenotype marker), and/or CD10 (glycosylated transmembrane protein, intestinal phenotype marker) [6].…”

KLF4 c.A1322C Mutation Is a Consistent and Specific Genetic Feature of Raspberry-like Foveolar-type Adenoma of the Stomach

“…We have previously reported that sporadic foveolar-type adenoma (FA) occurring on nonatrophic mucosa includes 2 distinct subtypes, namely, flat FA and raspberry-like FA, with each exhibiting a characteristic appearance on endoscopy. 1 These 2 subtypes are clinicopathologically and genetically different; specifically, while flat FAs consistently harbor APC and KRAS mutations, raspberry-like FA lacks them. Remarkably, despite distinct clinical backgrounds, familial adenomatous polyposis (FAP)-associated FAs share genetic features with sporadic, flat FAs.…”

“…1). 1 Histologic diagnoses of intestinal-type adenoma or pyloric gland adenoma were based on the WHO classification 5,6. Dysplasia and intramucosal adenocarcinoma were diagnosed according to the previously reported criteria,7 and dysplasia was further classified as foveolar-type, intestinal-type, or hybrid-type based on previously described morphologic features 8.…”