Department of Human Pathology, School of Medicine, Juntendo University.
Department of Pathology, Juntendo Urayasu Hospital.
Am J Surg Pathol. 2018 Sep;42(9):1237-1245. doi: 10.1097/PAS.0000000000001117.
Twenty-four surgically resected, gallbladder pyloric gland adenomas (GB-PGAs) were examined and their features were compared with the reported features of stomach, duodenum, and pancreatic PGAs to better understand GB-PGAs. Clinical information on background gallbladder lesions and histologic data, including tumor grade, existence of squamoid morules, intratumoral cholesterosis, and intracytoplasmic mucins were collected. Immunohistochemical staining for MUC2, MUC5AC, MUC6, CDX2, pepsinogen I, p53, and MIB-1/nuclear β-catenin were evaluated. Targeted mutational analyses of KRAS exon2, GNAS exon 7, and CTNNB1 exon 3 were conducted. We found that 29.2% of the GB-PGAs were histologically high-grade dysplasias/carcinomas; 70.8% were low grade; and 20.8% and 33.3% contained squamoid morules and intratumoral cholesterosis, respectively. In addition, 45.8% and 54.2% of GB-PGAs were mucin-rich and mucin-poor types, respectively. Immunohistochemically, MUC6 was diffusely positive in all GB-PGAs; MUC2, MUC5AC, and CDX2 were only focally positive, and no pepsinogen-I positive cells were observed. Nuclear β-catenin accumulation was observed in all cases; however, the ratio varied among cases. Mucin-poor types were significantly associated with high histologic grade dysplasias/carcinomas and high nuclear β-catenin labeling indices. Mutational analyses identified CTNNB1 mutations in 100% of GB-PGAs (21/21), KRAS in 4.2% (1/23), and GNAS in 0% (0/22). The present study clarified the unique histologic features, phenotypic differentiation, and molecular statuses frequently associated with GB-PGAs. Altogether, our data suggest that tumorigenesis of GB-PGA is distinct from that of stomach, duodenum, and pancreatic PGAs.
我们研究了 24 例经手术切除的胆囊幽门腺腺瘤（GB-PGA），并将其特征与已报道的胃、十二指肠和胰腺 PGA 的特征进行比较，以便更好地了解胆囊 PGA。收集了有关背景胆囊病变的临床信息和组织学数据，包括肿瘤分级、存在鳞样小体、肿瘤内胆固醇沉着和细胞内黏蛋白。评估了 MUC2、MUC5AC、MUC6、CDX2、胃蛋白酶原 I、p53 和 MIB-1/核 β-连环蛋白的免疫组织化学染色。对 KRAS 外显子 2、GNAS 外显子 7 和 CTNNB1 外显子 3 进行了靶向突变分析。我们发现，29.2%的 GB-PGA 组织学上为高级别发育不良/癌；70.8%为低级别；20.8%和 33.3%分别含有鳞样小体和肿瘤内胆固醇沉着。此外，45.8%和 54.2%的 GB-PGA 分别为富含黏蛋白和黏蛋白缺乏型。免疫组化显示，所有 GB-PGA 均弥漫性表达 MUC6；MUC2、MUC5AC 和 CDX2 仅局灶性阳性，未见胃蛋白酶原 I 阳性细胞。所有病例均观察到核 β-连环蛋白积聚；然而，病例之间的比例不同。黏蛋白缺乏型与高级别发育不良/癌和高核 β-连环蛋白标记指数显著相关。突变分析发现 100%（21/21）的 GB-PGA 存在 CTNNB1 突变、4.2%（1/23）存在 KRAS 突变和 0%（0/22）存在 GNAS 突变。本研究阐明了与胆囊 PGA 频繁相关的独特组织学特征、表型分化和分子状态。总的来说，我们的数据表明，GB-PGA 的肿瘤发生与胃、十二指肠和胰腺 PGA 不同。
