Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Pathology, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.
Mod Pathol. 2020 Feb;33(2):206-216. doi: 10.1038/s41379-019-0338-1. Epub 2019 Aug 2.
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.
胃黏膜内（A 组，8 例）和黏膜下浸润（A 组，8 例）的 26 例肿瘤被分析和分类为胃泌素分泌腺肿瘤。后者进一步分为具有典型组织学特征的肿瘤（B 组，14 例）和不典型特征的肿瘤，包括高级别核或结构异常和存在不典型细胞分化（C 组，4 例）。A 组和 B 组肿瘤具有相似的组织学特征，表现为以主细胞增生为主的模式，或以主细胞和壁细胞混合为特征的分化良好的混合细胞模式，类似于胃底腺。此外，C 组肿瘤显示出不典型的细胞分化，包括粘颈细胞和滤泡上皮。C 组肿瘤中观察到中度或甚至显著的细胞学异型性，而在其他组中除了 3 例 B 组肿瘤存在局灶性中度异型性外，通常为轻度异型性。仅在 C 组中发现超过 1000μm 的黏膜下浸润和淋巴管浸润。突变分析发现 C 组中 1 例肿瘤存在 KRAS 突变，A 组和 B 组中各 1 例肿瘤存在 GNAS 突变。黏膜内肿瘤在生物学上似乎表现为良性，应归类为“胃泌素分泌腺腺瘤”。那些有黏膜下浸润的肿瘤也具有低恶性潜能；然而，一部分肿瘤具有与侵袭性组织学特征相关的不典型特征，应被指定为“胃底腺型腺癌”。特别是，我们建议将具有黏膜下浸润和不典型细胞分化的肿瘤命名为“胃底腺黏膜型腺癌”，因为该特征可能是侵袭性表型的标志。
