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Abstract：
BACKGROUND: 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.
METHODS: 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.
CONCLUSIONS: 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.
METHODS: 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.
CONCLUSIONS: 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.
摘要：
背景：未分化的胆囊癌极为罕见。大多数未分化癌伴有其他常规癌的邻近病灶，它们之间共享一个过渡区。然而,未分化型胆囊癌的遗传改变以及未分化型胆囊癌和常规病灶癌之间的相似性或差异性尚不清楚。
方法：这里，我们报告了一例未分化的胆囊癌，伴有侵入肝脏的破骨细胞样巨细胞，十二指肠,还有一个56岁的男人的肚子.肿瘤在显微镜下由管状腺癌（<整个肿瘤的5％）形成，未分化癌,和它们之间的过渡区。四种体细胞突变（TP53，TERT，ARID2和CDH1)，三个扩增（CCND1，FGF19和MET），使用靶向基因测序在未分化成分中检测到3.45muts/Mb的肿瘤突变负荷（TMB），而102个体细胞突变(包括TP53、TERT、ARID2和CDH1)，一次扩增（CCND1），在管状组件中检测到较高的TMB，为87.07muts/Mb。该患者在手术后2个月死于肿瘤复发。
结论：未分化胆囊癌有其独特的分子改变。未分化癌和腺癌的遗传改变的相似性提供了在遗传水平上共同起源的证据。未分化癌的发生可能是由于肾小管腺癌的异质性相关分支演变所致。
方法：这里，我们报告了一例未分化的胆囊癌，伴有侵入肝脏的破骨细胞样巨细胞，十二指肠,还有一个56岁的男人的肚子.肿瘤在显微镜下由管状腺癌（<整个肿瘤的5％）形成，未分化癌,和它们之间的过渡区。四种体细胞突变（TP53，TERT，ARID2和CDH1)，三个扩增（CCND1，FGF19和MET），使用靶向基因测序在未分化成分中检测到3.45muts/Mb的肿瘤突变负荷（TMB），而102个体细胞突变(包括TP53、TERT、ARID2和CDH1)，一次扩增（CCND1），在管状组件中检测到较高的TMB，为87.07muts/Mb。该患者在手术后2个月死于肿瘤复发。
结论：未分化胆囊癌有其独特的分子改变。未分化癌和腺癌的遗传改变的相似性提供了在遗传水平上共同起源的证据。未分化癌的发生可能是由于肾小管腺癌的异质性相关分支演变所致。
