Morphology and genetics of pyloric gland adenomas in familial adenomatous polyposis

Abstract

Background Gastric pyloric gland adenomas (PGAs) are rare epithelial polyps that are more commonly found in autoimmune atrophic gastritis and familial adenomatous polyposis. Little is known about the morphology and genetics of PGAs in familial adenomatous polyposis. Aims PGAs in familial adenomatous polyposis are studied morphologically and genetically. Findings in FAP associated PGAs are compared to sporadic PGAs and related lesions such as oxyntic gland adenoma (OGA) to increase our understanding of these rare polyps. Methods 7 PGAs and 18 FGPs from FAP patients were collected. KRAS and GNAS mutations we determined in 6 PGAs and 18 FGPs. Immunohistochemistry was applied on 5 PGAs to provide further confirmation of the histologic subtypes and genetic alterations. Morphology of all PGAs was studied and compared to literature on sporadic PGAs and related lesions. Results All successfully sequenced PGAs (6/6) carried a GNAS mutations and half of the successfully sequenced PGAs carried a KRAS mutation (3/6). Nuclear β-catenin was only seen in one PGS with focal high-grade dysplasia. Morphologically, PGAs in FAP showed overlapping features with OGA. Conclusion FAP associated PGAs have a similar genetic background, i.e. KRAS and GNAS mutation. Based on morphological findings in FAP associated PGAs it is hypothesized that PGAs and OGAs are closely related lesions.

Gastric pyloric gland adenoma: a multicentre clinicopathological study of 67 cases

“…PGA can be difficult to distinguish from foveolar‐type adenoma and OGA . In this regard, immunohistochemical stains for MUC6 and MUC5AC can be helpful.…”

“…PGA can be difficult to distinguish from foveolartype adenoma 1,15,17 and OGA. 16,18 In this regard, immunohistochemical stains for MUC6 and MUC5AC can be helpful. MUC6 expression is the more specific marker for PGA, as both foveolar-type adenoma and PGA can express MUC5AC.…”

“…2 Although gastric PGAs are known to occur more commonly in older females in the setting of autoimmune gastritis (AIG), they can be seen in the setting of familial adenomatous polyposis (FAP), Lynch syndrome or juvenile polyposis syndrome. [2][3][4][5][11][12][13][14][15][16] The precancerous nature of PGA is well established, and the reported rate of association with adenocarcinoma ranges from 12% to 47%. 2,3,5,17 Histologically, PGA is composed of tightly packed tubular glands (with occasional cystic dilatation) lined by cuboidal to low columnar cells demonstrating round basal nuclei and eosinophilic cytoplasm with a ground-glass quality.…”

“…1,17 PGA can be labelled with markers of gastric pyloric gland differentiation, including mucin apoprotein 6 (MUC6) and MUC5AC, 1,[3][4][5]15,17 but MUC6 expression is the more specific marker for the diagnosis, as foveolartype adenoma shows MUC5AC positivity but is negative for MUC6. 1,[3][4][5]15,17 However, if a significant population of chief and parietal cells is present in the lesion, 16 it can also be difficult to differentiate PGA from oxyntic gland adenoma (OGA) which, like PGA, shows diffuse MUC6 expression. 16,18 In an earlier study, PGA was divided into three categories: those without conventional histological dysplasia, low-grade dysplasia (LGD) and high-grade dysplasia (HGD).…”

“…1,[3][4][5]15,17 However, if a significant population of chief and parietal cells is present in the lesion, 16 it can also be difficult to differentiate PGA from oxyntic gland adenoma (OGA) which, like PGA, shows diffuse MUC6 expression. 16,18 In an earlier study, PGA was divided into three categories: those without conventional histological dysplasia, low-grade dysplasia (LGD) and high-grade dysplasia (HGD). 17 PGAs without dysplasia are composed of uniform tubular glands surrounded by a monolayer of small round nuclei without noticeable atypia, whereas low-grade PGAs show irregularly shaped glands with elongated nuclei and mild cytological atypia.…”