Liver Transplantation for Small Solitary Cholangiocellular Carcinoma in Cirrhosis: A Medical Mistake or a New Indication?

Abstract

The differential diagnosis of primary liver tumors in cirrhosis is essential for therapy planning. This is especially important given that the only indication for liver transplantation (LTx) in the setting of active malignancy is hepatocellular carcinoma (HCC). In the rare instances where tumor markers alpha-fetoprotein and carbohydrate antigen 19-9 are not elevated and biopsy results are indeterminate, imaging techniques such as computed tomography or magnetic resonance imaging remain as the sole diagnostic methods. However, their accuracy for small tumors in end-stage cirrhotic livers is poor (1, 2). A 54-year-old man with alcoholic induced liver cirrhosis, Child-Turcotte-Pugh class B, and a 2.1-cm solitary mass in segment VIII of the liver presented to our department. A diagnosis of HCC was made, based on hyperdensity of the tumor in the early arterial phase of computed tomography. A percutaneous liver biopsy was consistent with malignancy but could not provide further characterization. Alpha fetoprotein, carbohydrate antigen 19-9 and carcinoembryonic antigen were all within normal laboratory range. Further tumor staging by thoracic computed tomography and bone scintigraphy was negative for extrahepatic metastases. The patient was listed for LTx, and received a single session of transarterial chemoembolization as bridging therapy. After a waiting period of 158 days, he was transplanted with a deceased donor liver allocated through Eurotransplant. MELD score at the time of LTx was 12. The patient recovered uneventfully and was discharged on postoperative day 21. Histology showed a well differentiated, partially necrotic, 4-cm solitary cholangiocellular carcinoma with no vascular invasion. Initial immunosuppression was with calcineurin inhibitors, and was switched to sirolimus after the sixth postoperative month, because of its antiproliferative action which is presumed to be of benefit in malignancy. However, due to side effects (pleural effusion), calcineurin-inhibitor-based immunosuppresion had to be restarted. Follow-up studies showed no evidence of tumor recurrence. Our patient currently remains in very good general condition 27 months posttransplantation. It is generally believed that, except in cases of primary sclerosing cholangitis, cholangiocellular carcinomas are not encountered in cirrhotic livers. Given the reported rising incidence of cholangiocellular carcinoma in hepatitis C induced cirrhosis this concept seems to need reconsideration (3, 4). These findings could change the therapeutical management of cholangiocellular carcinoma in cirrhosis in the future and maybe set off a discussion about an indication of LTx in cases of small solitary cholangiocellular carcinoma in cirrhosis. Furthermore, selected cases of solitary cholangiocellular carcinoma in the setting of cirrhosis could represent an extended indication for living donor liver transplantation (5). Five-year survival rates of 42% after LTx for peripheral cholangiocellular carcinoma are already being reported in the literature (6). Although our case could be characterized as a “medical mistake,” its outcome justifies and rewards it. Georgios C. Sotiropoulos Eirini I. Brokalaki Ernesto P. Molmenti Susanne Beckebaum Andrea Frilling Massimo Malagó Christoph E. Broelsch Department of General Surgery and Transplantation University Hospital Essen Essen, Germany