Utility and limitations of Albumin RNA in situ hybridization in the diagnosis of hepatobiliary lesions and metastatic carcinomas to the liver.

Albumin messenger RNA in situ hybridization (RISH) is a sensitive and specific marker for hepatocellular carcinoma (HCCs). Intrahepatic cholangiocarcinoma (ICC) shows variable sensitivity, whereas extrahepatic cholangiocarcinomas (ECCs) and metastatic carcinomas are usually negative. We studied the clinical utility and limitations of albumin RISH in a cohort of HCCs, ICCs, ECCs, bile duct adenomas (BDAs), bile duct hamartomas (BDHs) and metastatic carcinomas to the liver; and investigated the variability in sensitivity observed for this marker in ICCs.We identified 122 cases (40 resections and 82 biopsies) of hepatobiliary lesions and metastatic carcinomas. Albumin RISH was performed using the RNAscope (Leica Biosystems, Buffalo Grove, IL), the Bond III autostainer and probe Hs-ALB-01 (ACD, Newark, CA) with negative (DapB) and positive probes (PPIB) for RNA. ICCs were categorized according to the classification proposed by Hayashi et al. in small duct (SD), large duct (LD) and indeterminate (IND) subtypes.Albumin RISH was positive in all 17 HCCs, and focally in 75% of BDAs. All 28 non-hepatic carcinomas, 13 BDHs and 9 ECCs were negative. 35/47 (74.4%) ICCs expressed albumin with 35/37 (94.6%) being of SD subtype, 2/3 (66.6%) of the IND subtype and 1/7 (14.2%) of the LD subtype, P<0.003.Albumin RISH performed on resection specimens or on small core biopsies is a sensitive and specific marker for HCCs. It is highly sensitive and moderately specific in the diagnosis of ICC with small gland morphology, but not in ICCs with large duct morphology and in metastatic carcinoma. The variability in sensitivity of albumin RISH in ICCs may depend on the subtypes of ICCs.