Molecular and Cytogenomic Profiling of Hepatic Adenocarcinoma Expressing Inhibin, a Mimicker of Neuroendocrine Tumors: Proposal to Reclassify as “Cholangioblastic Variant of Intrahepatic Cholangiocarcinoma”

Publication date: Available online 21 February 2017
Source:Human Pathology
Author(s): David R. Braxton, Debra Saxe, Nevena Damjanov, Kristen Stashek, Stuti Shroff, Jennifer D. Morrissette, Rashmi Tondon, Emma E. Furth
Only a single case report exists in the literature of hepatic adenocarcinoma expressing InhibinA in a young woman in which the authors proposed it to be a rare variant of intrahepatic cholangiocarcinoma (iCCA). We present novel molecular and histologic findings in our series of three cases occurring in young women and show these tumors may mimic well differentiated neuroendocrine tumors (NET). Immunohistochemical (IHC) profiling was performed along with next generation sequencing (NGS) 47 gene solid tumor panel, and cytogenomic profiling via SNP microarray. IHC for InhibinA, Chromogranin A (ChrA), and synaptophysin (Syn) was surveyed in liver tumors and in fetal liver. Two of the three patients recurred with metastatic disease with two confirmed deaths. Histological patterns present in the tumors included solid, trabecular, organoid, microcystic, and blastemal-like. IHC was positive for cytokeratin 7 in 3/3, cytokeratin 19 in 3/3, inhibinA in 3/3, ChrA in 3/3, Syn in 3/3, Sox9 2/3 and HepPar1 in 0/3. NGS was negative for pathogenic mutations. Recurrent cytogenomic abnormalities included gain of 17q, and loss of 6q. InhibinA was strong and diffusely expressed in 0/10 (0%) iCCA, 0/15 (0%) Hepatocellular carcinomas (HCC), in the biliary component of 1/4 (25%) Combined HCC-iCCA, 0/4 hepatoblastomas, 1/8 (13%) metastatic NET, and in 1/8 fetal liver tissues. We propose a classification of "cholangioblastic variant of intrahepatic cholangiocarcinoma" and molecular pathogenesis for this rare malignancy. Accurate identification on core biopsy is crucial for clinical management as it may mimic neuroendocrine neoplasms.



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