Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, PR China.
Department of Hepatopancreatobiliary Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, PR China.
Diagn Pathol. 2020 Jun 2;15(1):66. doi: 10.1186/s13000-020-00981-5.
Undifferentiated carcinomas of the gallbladder are extremely rare. Most undifferentiated carcinomas are accompanied by adjacent foci of other conventional carcinomas, and a transition zone is shared between them. However, genetic alterations of undifferentiated gallbladder carcinoma and the similarities or differences between the undifferentiated carcinoma and the foci conventional carcinoma are unknown.
Herein, we report a case of undifferentiated gallbladder carcinoma with osteoclast-like giant cells with invasion into the liver, duodenum, and stomach in a 56-year-old man. The tumor was microscopically formed from the tubular adenocarcinoma (< 5% of the entire tumor), the undifferentiated carcinoma, and a transition zone between them. Four somatic mutations (TP53, TERT, ARID2, and CDH1), three amplifications (CCND1, FGF19, and MET), and a tumor mutation burden (TMB) of 3.45 muts/Mb were detected in the undifferentiated component using targeted gene sequencing, whereas 102 somatic mutations (including TP53, TERT, ARID2, and CDH1), one amplification (CCND1), and a higher TMB of 87.07 muts/Mb were detected in the tubular component. This patient died of tumor recurrence 2 months after the surgery.
The undifferentiated gallbladder carcinoma had its unique molecular alterations. The similarities in the genetic alterations of the undifferentiated carcinoma and adenocarcinoma provide evidence of a common origin at the genetic level. The occurrence of an undifferentiated carcinoma may be due to heterogeneity-associated branched evolution from the tubular adenocarcinoma.
胆囊未分化癌极为罕见。大多数未分化癌伴有相邻的其他常规癌灶，且其间存在过渡区。然而，未分化胆囊癌的遗传改变以及未分化癌与常规癌灶之间的相似性或差异性尚不清楚。
本研究报告了 1 例 56 岁男性肝、十二指肠和胃浸润性未分化胆囊癌伴破骨样巨细胞的病例。肿瘤显微镜下由管状腺癌（<5%的肿瘤）、未分化癌和其间的过渡区组成。采用靶向基因测序检测到未分化成分中有 4 个体细胞突变（TP53、TERT、ARID2 和 CDH1）、3 个扩增（CCND1、FGF19 和 MET）和 3.45 muts/Mb 的肿瘤突变负荷（TMB），而管状成分中检测到 102 个体细胞突变（包括 TP53、TERT、ARID2 和 CDH1）、1 个扩增（CCND1）和更高的 87.07 muts/Mb 的 TMB。该患者术后 2 个月因肿瘤复发死亡。
未分化胆囊癌具有独特的分子改变。未分化癌和腺癌在遗传改变上的相似性为其在遗传水平上具有共同起源提供了证据。未分化癌的发生可能是由于管状腺癌的异质性相关分支进化所致。
