Oxyntic gland neoplasm of the stomach: expanding the spectrum and proposal of terminology.

Gastric neoplasms exhibiting oxyntic gland differentiation typically are composed of cells with mild cytonuclear atypia differentiating to chief cells and to a lesser extent, parietal cells. Such tumors with atypical features have been reported also and terminology for this entity remains a matter of considerable debate. We analyzed and classified 26 tumors as oxyntic gland neoplasms within mucosa (group A, eight tumors) and with submucosal invasion. The latter was divided further into those with typical histologic features (group B, 14 tumors) and atypical features, including high-grade nuclear or architectural abnormality and presence of atypical cellular differentiation (group C, four tumors). Groups A and B tumors shared similar histologic features displaying either a chief cell predominant pattern characterized by monotonous chief cell proliferation, or a well-differentiated mixed cell pattern showing admixture of chief and parietal cells resembling fundic gland. In addition, group C tumors displayed atypical cellular differentiation, including mucous neck cell and foveolar epithelium. Moderate or even marked cytological atypia was noted in group C, whereas it was usually mild in the other groups except for three group B tumors with focal moderate atypia. More than 1000 μm submucosal invasion and lymphovascular invasions were recognized only in group C. Mutation analyses identified KRAS mutation in one group C tumor as well as GNAS mutation in in one group A and group B tumors. Intramucosal tumors appear to behave biologically benign and should be classified as "oxyntic gland adenoma". Those with submucosal invasion also have low malignant potential; however, a subset will have atypical features associated with aggressive histologic features and should be designated as "adenocarcinoma of fundic gland type". Especially, we suggest "adenocarcinoma of fundic gland mucosa type" for tumors with submucosal invasion exhibiting atypical cellular differentiation, because the feature is likely to be a sign of aggressive phenotype.