Depatment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
J Clin Pathol. 2020 Jan;73(1):23-29. doi: 10.1136/jclinpath-2019-206055. Epub 2019 Aug 17.
The histological distinction of intrahepatic cholangiocarcinoma (ICC) from metastatic adenocarcinoma remains a challenge. The primary goal was to evaluate the diagnostic value of morphology and albumin expression in the diagnosis of ICC.
We evaluated morphological patterns in 120 ICCs and 677 non-hepatic adenocarcinomas and performed in situ hybridisation (ISH) stain for albumin in the former cohort (retrospective cohort). We also identified 119 samples from primary and metastatic lesions, the validation cohort, in which albumin ISH was performed as part of the diagnostic workup. Targeted sequencing was performed on selected cases. We also mined existing expression profiling data including cases from The Cancer Genome Atlas (TCGA) (41 760 unique samples).
In the retrospective cohort, 45% of ICCs and <1% of non-hepatic adenocarcinomas showed a cholangiolar pattern; albumin ISH was positive in 93% of ICCs with significant intratumorous heterogeneity. In the validation cohort, 29% of ICCs showed a cholangiolar pattern and 88% expressed albumin, while all metastatic non-hepatic neoplasms were negative (n=37) (sensitivity 88% and specificity 100%). Targetable genetic alterations ( mutations and fusions) were identified in 31% of ICCs (10 of 32). An analysis of the TCGA data validated the specificity of the albumin assay.
The cholangiolar pattern and albumin RNA ISH distinguishes ICC from metastatic adenocarcinoma with high specificity. Given the high prevalence of targetable mutations in ICC, albumin RNA ISH is an essential component in the workup of tumours of uncertain origin. A specific diagnosis of ICC could trigger molecular testing and uncover targetable genetic alterations.
肝内胆管细胞癌（ICC）与转移性腺癌的组织学鉴别仍然具有挑战性。主要目的是评估形态学和白蛋白表达在 ICC 诊断中的诊断价值。
我们评估了 120 例 ICC 和 677 例非肝性腺癌的形态学模式，并对前者进行了白蛋白原位杂交（ISH）染色（回顾性队列）。我们还在验证队列中鉴定了来自原发性和转移性病变的 119 个样本，其中白蛋白 ISH 是诊断工作的一部分。对选定病例进行了靶向测序。我们还挖掘了现有的表达谱数据，包括来自癌症基因组图谱（TCGA）的病例（41760 个独特样本）。
在回顾性队列中，45%的 ICC 和<1%的非肝性腺癌显示出胆管样模式；93%的 ICC 中白蛋白 ISH 阳性，且存在明显的肿瘤内异质性。在验证队列中，29%的 ICC 显示胆管样模式，88%表达白蛋白，而所有转移性非肝性肿瘤均为阴性（n=37）（敏感性 88%，特异性 100%）。在 31%的 ICC 中发现了可靶向的遗传改变（突变和融合）（10 of 32）。对 TCGA 数据的分析验证了白蛋白测定的特异性。
胆管样模式和白蛋白 RNA ISH 可高度特异性地区分 ICC 与转移性腺癌。鉴于 ICC 中可靶向突变的高发生率，白蛋白 RNA ISH 是不确定起源肿瘤检查的重要组成部分。ICC 的明确诊断可能会引发分子检测并揭示可靶向的遗传改变。
