Departments of *Anatomic Pathology §Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University †Department of Pathology, Fukuoka Red Cross Hospital, Fukuoka ‡Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Am J Surg Pathol. 2017 Mar;41(3):343-353. doi: 10.1097/PAS.0000000000000785.
Duodenal neoplasm of gastric phenotype (DNGP) is very rare, and details of its histopathologic, genetic, and biological features are still unclear. Frequent gene mutations in GNAS, KRAS, and APC have been reported in pyloric gland adenomas and fundic gland-type neoplasms (initially reported as low-grade adenocarcinomas) of the stomach. Here we retrospectively analyzed 16 cases of extra-ampullary DNGP (benign to malignant), and we examined the mucin immunoprofile and oncogene mutations (GNAS, KRAS, APC, BRAF, and CTNNB1). The 16 DNGPs were histologically classified into adenomas (5 pyloric gland adenomas and 2 foveolar-type adenomas), neoplasms of uncertain malignant potential (NUMPs, n=6), and invasive adenocarcinomas (n=3). NUMPs consisted of slightly atypical epithelial cells with pale, eosinophilic, or basophilic cytoplasm growing in an anastomosing or branching glandular pattern, often with expansive submucosal extension. In contrast to invasive adenocarcinomas, NUMPs lacked significant nuclear irregularity, desmoplastic stromal reaction, lymphovascular invasion, and metastasis; their features were reminiscent of fundic gland-type neoplasms of the stomach. Immunophenotypically, most of NUMPs were predominantly positive for MUC6 with variable expressions of pepsinogen-I, HKATPase, human gastric mucin, and MUC5AC. Molecular analyses revealed the gene mutations of GNAS in 6 (38%) of 16 DNGPs (4 [57%] adenomas, 1 [16%] NUMP, and 1 [33%] invasive adenocarcinoma) and APC in 4 of 15 (27%) DNGPs: no adenomas, 2 (33%) NUMPs, and 2 (67%) invasive adenocarcinomas. BRAF mutation was present in only 1 (16%) NUMP, and KRAS and CTNNB1 mutations were absent. In conclusion, gastric-phenotype adenomas and NUMPs of the duodenum are similar to their counterparts of the stomach, in terms of histologic, genetic, and clinicopathologic features. We propose the term "NUMP" as an intermediate category between adenoma and definitely invasive adenocarcinoma. Our findings may provide novel insights into the classification of undescribed but distinctive duodenal tumors showing similarity to gastric-phenotype neoplasms of the stomach.
胃表型十二指肠肿瘤（DNGP）非常罕见，其组织病理学、遗传学和生物学特征尚不清楚。胃幽门腺腺瘤和胃底腺型肿瘤（最初报道为低级别腺癌）中经常报道 GNAS、KRAS 和 APC 的基因突变。在这里，我们回顾性分析了 16 例非壶腹 DNGP（良性至恶性），并检查了粘蛋白免疫组化和癌基因突变（GNAS、KRAS、APC、BRAF 和 CTNNB1）。16 例 DNGP 的组织学分类为腺瘤（5 例幽门腺腺瘤和 2 例滤泡型腺瘤）、不确定恶性潜能的肿瘤（NUMP，n=6）和浸润性腺癌（n=3）。NUMP 由轻度非典型上皮细胞组成，胞质淡染、嗜酸性或嗜碱性，呈吻合或分支腺管状生长，常有扩张性黏膜下延伸。与浸润性腺癌不同，NUMP 缺乏明显的核不规则、纤维组织反应、脉管侵犯和转移；其特征类似于胃底腺型肿瘤。免疫表型上，大多数 NUMP 主要表达 MUC6，胃蛋白酶原-I、HKATPase、人胃粘蛋白和 MUC5AC 的表达可变。分子分析显示，16 例 DNGP 中有 6 例（38%）存在 GNAS 基因突变（4 例[57%]腺瘤、1 例[16%] NUMP 和 1 例[33%]浸润性腺癌）和 15 例 DNGP 中有 4 例（27%）存在 APC 基因突变：无腺瘤，2 例（33%）NUMP 和 2 例（67%）浸润性腺癌。BRAF 突变仅存在于 1 例（16%）NUMP 中，KRAS 和 CTNNB1 突变不存在。总之，十二指肠的胃表型腺瘤和 NUMP 与胃的对应物在组织学、遗传学和临床病理学特征上相似。我们提出“NUMP”一词作为腺瘤和明确浸润性腺癌之间的中间类别。我们的发现可能为未描述但具有独特特征的十二指肠肿瘤的分类提供新的见解，这些肿瘤与胃的胃表型肿瘤相似。
