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Gastric adenocarcinoma of fundic gland type (GA-FG). A new entity 1. Process of establishing this entity and clinicopathological features of GA-FG 2. Progressive variant of GA-FG 3. Genetic events of GA-FG 4. Differential diagnosis 53 Differential diagnosis • (Atypical) chief cell hyperplasia • Fundic gland polyp • Adenoma of pyloric gland type • Carcinoid tumor • Parietal cell carcinoma • Oncocytic adenocarcinoma Chief cell hyperplasia ? •Müller-Höcker J, et al. Chief cell proliferation of the gastric mucosa mimicking early gastric cancer: an usual variant of fundic gland polyp. Virchow Archiv 442: 496-500, 2003. •Matsukawa A, et al. Chief cell hyperplasia with structural and nuclear atypia: a variant of fundic gland polyp. Pathol Res Pract 200: 817-821, 2005 The lesions in these reports are the same as ACFG ARTICLE IN PRESS Pathology – Research and Practice 200 (2005) 817–821 www.elsevier.de/prp TEACH I NG CASE Chief cell hyperplasia with structural and nuclear atypia: a variant of fundic gland polyp Akihiro M atsukawaa, , Ryoichi K uranob, Takahiro Takemotoc, M otoko K agayamaa, Takaaki I toa The cytological feature is the same as the adenocarcinoma of fundic gland type Differential diagnosis • (Atypical) chief cell hyperplasia • Fundic gland polyp • Adenoma of pyloric gland type • Carcinoid tumor • Parietal cell carcinoma • Oncocytic adenocarcinoma Fundic gland polyp (FGP) • FGP is mainly composed of mature chief and parietal cells with scattered mucous cells. • Cytological feature of FGP is similar to GA-FG. • Lack of cytological and architectural atypa in FGP is different from GA-FG. Pyloric gland adenoma (PGA) PGA is positive for MUC6, which is the same as AG-FG, but is usually negative for pepsinongen I and H+/K+-ATPase. MUC6 Differential diagnosis • (Atypical) chief cell hyperplasia • Fundic gland polyp • Adenoma of pyloric gland type • Carcinoid tumor • Parietal cell carcinoma • Oncocytic adenocarcinoma A case submitted to some medical journal as “A case of gastric carcinoid” GA-FG is sometimes misdiagnosed as carcinoid Diagnosed as carcinoid by immunohistochemistry GA-FG can be misdiagnosed as carcinoid only by immunohistochemical results. Chromgranin A (CG-A)(-) CD56 (+) GA-FG is negative for CG-A. Synaptophysin (+) (a) (b) Histological features a little bit similar to carcinoid (c) Carcinoid is negative for pepsinogen I and MUC6 Pepsinogen I (+) MUC6 (+) Differential diagnosis • (Atypical) chief cell hyperplasia • Fundic gland polyp • Adenoma of pyloric gland type • Carcinoid tumor • Parietal cell carcinoma • Oncocytic adenocarcinoma Parietal cell carcinoma of gastric cardia: immunophenotype and ultrastructure. Only one case was reported, confirming parietal cell differentiation by H+/K+-ATPase positivity Yang GY, et al. Uitrastruct Pathol. 227:87-94, 2003. Oncocytic adenocarcinoma of the stomach: Parietal cell carcinoma. So-called “Parietal cell carcinomas”were oncocytic adenocarcinoma, which were positive for antimitochondrial antibody MAB 1273 Takubo K, et al. Am J Surg Pathol. 26:458–465, 2002. Summary • Gastric adenocarcinoma of fundic gland type (GAFG) is a new entity having distinct clinicopathological features. • GA-FG is not associated with H, plyori infection. • GA-FG was originally reported as low-grade malignancy, however, a progressive variant with aggressive biological behaviors, fundic gland mucosal type, has been found. • Carcinogenesis and/or progression of GA-FG is associated with Wnt/β-catenin signalling pathway and GNAS mutation in part. • Further study with collecting more cases is needed for clarifying its natural history. Thank you very much for your kind attention