Inhibin-positive hepatic carcinoma: proposal for a solid-tubulocystic variant of intrahepatic cholangiocarcinoma

Inhibin-positive hepatic carcinoma is a rare primary liver neoplasm that resembles sex cord-stromal tumor and thyroid follicular tumors. The term "cholangioblastic variant of intrahepatic cholangiocarcinoma" has been proposed. This study describes the clinicopathologic, immunophenotypic, and molecular features of a small series (n = 6) of this rare tumor. Albumin in situ hybridization (ISH) and capture-based next-generation sequencing (NGS) were also performed. All tumors occurred in young women (mean age 32.5 years, range 19-44 years) as a solitary large mass (mean 15.8 cm, range 6.9-23.5 cm). All tumors showed a highly distinctive morphology with sheets and large nests of tumor cells alternating with tubular and cystic areas imparting a sex cord-like or thyroid follicle-like morphology. Cytologic atypia was mild, and mitotic activity was low. All cases were positive for inhibin, as well as pancytokeratin, CK7, CK19, and albumin ISH. Synaptophysin and chromogranin showed focal or patchy staining, whereas INSM1 was negative. Markers for hepatocellular differentiation, thyroid origin, and sex cord-stromal tumor were negative. There were no recurrent genomic changes based on capture-based NGS of ∼500 cancer genes. Recurrence and/or metastasis was seen in three (50%) cases (follow-up time range for all cases: 5 months to 2 years). In conclusion, this series describes the distinctive morphology, immunophenotypic features, and diffuse albumin staining in six cases of a rare inhibin-positive primary liver carcinoma that runs an aggressive course similar to intrahepatic cholangiocarcinoma. Genomic changes typical of cholangiocarcinoma or hepatocellular carcinoma were not identified, and there were no recurrent genetic abnormalities. We propose the term "solid-tubulocystic variant of intrahepatic cholangiocarcinoma" to reflect the spectrum of morphologic patterns observed in this tumor.