Department of Pathology, Istanbul Education and Research Hospital, Istanbul, Turkey.
Arch Pathol Lab Med. 2012 Nov;136(11):1347-58. doi: 10.5858/arpa.2011-0447-OA.
There are virtually no data in the literature regarding the incidence, patterns, and clinicopathologic characteristics of mucinous carcinomas (MCs) of the gallbladder (GB).
To determine the incidence of mucinous differentiation in invasive GB carcinomas and the clinicopathologic characteristics of those that qualify as MC.
Primary invasive GB carcinomas (n = 606) were reviewed for mucinous differentiation. Some degree of mucin production was identified in 40 cases (6.6%); however, only 15 (2.5%) were qualified for the World Health Organization definition of MC (stromal mucin deposition constituting >50% of the tumor).
The mean age was 65 years, and the female to male ratio was 1.1 (versus 3.9 for conventional pancreatobiliary-type GB adenocarcinomas; P = .04). A significant proportion of the cases (8 of 12, 67%) presented with the clinical picture and intraoperative findings that were interpreted as acute cholecystitis. Mean and median tumor sizes were larger than those of conventional adenocarcinomas (4.8 and 3.4 cm versus 2.9 and 2.5 cm, respectively; P = .01). Most (13 of 15, 87%) cases presented with pT3 tumors (versus 48% for ordinary GB carcinomas; P = .01). Two cases had almost an exclusive colloid pattern (>90% composed of well-defined stromal mucin nodules that contained scanty carcinoma cells, most of which were floating within the mucin). Eight cases were of mixed-mucinous type, showing a mixture of colloid and noncolloid patterns. Five others had prominent signet-ring cells, both floating within the mucin (which constituted >50% of the tumor by definition) and infiltrating into the stroma as individual signet-ring cells in some areas. Immunohistochemical analysis performed on the 7 cases that had available tissue revealed CK7 in 4 of 7 (57%), CK20 in 2 of 7 (29%), MUC1 in 4 of 7 (57%), MUC2 in 6 of 7 (86%), CDX2 in 1 of 7 (14%), MUC5AC in 6 of 7 (86%), MUC6 in 0 of 7 (0%), and loss of E-cadherin in 6 of 7 (86%). The MLH1 and MSH2 were retained in 6 of 7 cases (100%). Follow-up information was available for 13 cases: 11 (85%) died of disease (1-37 months) and 2 (15%) were alive (23 months and 1 month). Overall survival of MCs was significantly worse than that of conventional adenocarcinomas (13 versus 26 months; P = .01); however, that did not seem to be independent of stage.
Mucinous carcinomas constitute 2.5% of GB carcinomas. They present with an acute cholecystitis-type picture. Most MCs are a mixed-mucinous, not pure colloid, type. They are typically large and advanced tumors at the time of diagnosis and thus exhibit more-aggressive behavior than do ordinary GB carcinomas. Immunophenotypically, they differ from conventional GB adenocarcinomas by MUC2 positivity, from intestinal carcinomas by an often inverse CK7/20 profile, from pancreatic mucinous carcinomas by CDX2 negativity, and from mammary colloid carcinomas by a lack of MUC6. Unlike gastrointestinal MCs, they appear to be microsatellite stable.
关于胆囊（GB）的黏液性癌（MC）的发生率、模式和临床病理特征，文献中几乎没有数据。
确定浸润性胆囊癌中出现黏液分化的发生率，以及符合 MC 标准的病例的临床病理特征。
对 606 例原发性浸润性胆囊癌进行了黏液分化的复习。在 40 例（6.6%）中发现了一定程度的黏液产生，但仅有 15 例（2.5%）符合世界卫生组织关于 MC 的定义（间质黏液沉积构成肿瘤的>50%）。
平均年龄为 65 岁，女性与男性的比例为 1.1（而传统的胰胆管型 GB 腺癌为 3.9；P = .04）。相当一部分病例（8 例中的 12 例，67%）表现为急性胆囊炎的临床表现和术中所见。平均和中位肿瘤大小大于传统腺癌（分别为 4.8 和 3.4 厘米与 2.9 和 2.5 厘米；P = .01）。大多数（13 例中的 15 例，87%）病例为 pT3 肿瘤（而普通 GB 癌为 48%；P = .01）。2 例几乎全部为胶样型（>90%由定义明确的间质黏液结节组成，其中含有少量癌细胞，大多数漂浮在黏液中）。8 例为混合黏液型，表现为胶样和非胶样模式的混合。另外 5 例有明显的印戒细胞，既漂浮在黏液中（定义为黏液构成肿瘤的>50%），又在某些区域以单个印戒细胞的形式浸润到间质中。对 7 例有可用组织的病例进行了免疫组织化学分析，7 例中有 4 例（57%）显示 CK7，2 例（29%）显示 CK20，4 例（57%）显示 MUC1，6 例（86%）显示 MUC2，1 例（14%）显示 CDX2，6 例（86%）显示 MUC5AC，0 例（0%）显示 MUC6，6 例（86%）显示 E-cadherin 缺失。6 例中的 MLH1 和 MSH2 均保留（100%）。有 13 例可获得随访信息：11 例（85%）死于疾病（1-37 个月），2 例（15%）存活（23 个月和 1 个月）。MC 的总生存率明显差于传统腺癌（13 个月与 26 个月；P = .01）；然而，这似乎并不是独立于分期的。
MC 占 GB 癌的 2.5%。它们表现为急性胆囊炎样表现。大多数 MC 是混合黏液型，而不是纯胶样型。在诊断时，它们通常是大的和晚期肿瘤，因此表现出比普通 GB 癌更具侵袭性的行为。在免疫表型上，它们与常规 GB 腺癌的区别在于 MUC2 阳性，与肠型腺癌的区别在于 CK7/20 模式通常相反，与胰腺黏液性癌的区别在于 CDX2 阴性，与乳腺胶样癌的区别在于缺乏 MUC6。与胃肠道 MC 不同，它们似乎是微卫星稳定的。
