Primary Liver Carcinoma with Biphenotypic Differentiation: 22 Cases of Combined Hepatocellular Carcinoma-Cholangiocarcinoma
James Mathews, William Chapman, Benjamin Tan, Neeta Vachharajani, Elizabeth Brunt. Washington University School of Medicine, St. Louis
Background: Combined hepatocellular carcinoma-cholangiocarcinoma (HCC-CCa) is an uncommon tumor accounting for 1 to 5% of primary liver malignancies. By definition, the diagnosis includes tumors with unequivocal elements of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCa). The 2010 WHO recognized subtypes including the classic type and those with stem-cell features. Several studies show survival intermediate between HCC and CCa. Reported one and three year survival rates are 92% and 77% for HCC, 82% and 47% for HCC-CCa and 44% and 18% for CCa.
Design: Potential cases of biphenotypic primary liver cancer (HCC-CCa) were identified in our Pathology database from 1994 to present. Re-reviewed cases were included only if they showed morphologic and immunohistochemical (IHC) evidence of biphenotypic (HCC-CCa) differentiation. 22 cases met inclusion criteria. IHC included the following antibodies: EpCAM, NCAM, K7, K19 and polyclonal CEA. Staining properties were scored for intensity and proportion of reactive cells. Demographic and retrospective outcome data were collected from medical records.
Results: Cases had a mean follow-up of 25 months; the median overall survival (OS) was 1.3 years. One and three year survival rates were 56% and 33%. 23% of cases occurred in patients with cirrhosis; the remainder did not have underlying liver disease. Average AFP at presentation was modestly elevated (mean 30 ± 53 ng/mL). All tumors showed canalicular staining for pCEA. All tumors expressed EpCAM, K7 and K19 either diffusely or in a mosaic pattern. Significant NCAM expression was seen in only 3 tumors. Poor histopathologic prognostic features were cholangiolar differentiation (median OS 11.3 versus 25.7 months) and diffuse, strong reactivity for EpCAM, K7 and K19 (median OS 10.9 versus 27.4 months).
Conclusions: Primary liver cancer with biphenotypic differentiation (HCC-CCa) is an entity of growing recognition that has different prognostic implications than either HCC or CCa. Similar to prior studies, our study showed a prognosis that was intermediate between those reported for HCC and CCa. Strong expression of EpCAM, K7 and K19 as well as cholangiolar differentiation were associated with a shorter median OS. Without an IHC panel, hepatocellular or cholangiolar differentiation may be under-appreciated in primary liver carcinomas. Additional studies are needed to further examine these findings.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 265, Monday Morning