Liver Tumor Post Liver Transplantation for Hepatitis C Cirrhosis: An Unusual Cause

Abstract

Question: A 60-year-old African American man with a history of hepatitis C virus (HCV) cirrhosis underwent orthotopic liver transplantation in 2009. The explant showed chronic HCV with mild activity and cirrhosis (grade 2, stage 4) without evidence of malignancy. The post-transplant course was complicated by recurrent HCV treated 5 years later with simeprevir and sofosbuvir with a sustained viral response. However, the patient developed fibrosing cholestatic hepatitis with rapid progression to fibrosis and portal hypertension demonstrated by small varices and ascites. A liver biopsy in August 2010 revealed mild to moderated inflammatory activity and incipient bridging fibrosis grades 2–3, stages 2–3. Due to worsening renal function and new-onset proteinuria, the dose of the calcineurin inhibitor was reduced and mycophenolate mofetil was added. He was lost to follow-up from 2014 to 2016. Magnetic resonance imaging in February 2017 for screening showed numerous masses in the liver with arterial enhancement and incomplete but progressive washout, some with an enhancing capsule (Figure A–C). At the time, his laboratory tests showed excellent graft function. What is the diagnosis and strategy for treatment? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Given the history of HCV infection and transplantation, there was concern for hepatocellular carcinoma. An ultrasound-guided core biopsy showed a vascular tumor positive for CD34 and negative for pancytokeratin and CK7, consistent with epithelioid hemangioendothelioma (HEHE) (Figure D-F). Low-power image on with hematoxylin and eosin staining (Figure D) shows upper core with normal liver, and lower core with replacement by vascular lesion (black arrow) with hemorrhage (thick black arrows). Figure E shows high power image with multiple diminutive vascular channels replacing liver parenchyma (black arrowheads), and Figure F with vascular channels replacing liver parenchyma on CD34 stain (black arrows). Figures A-C demonstrate HEHE lesions as target shaped lesion on a T1-weighted volumetric interpolated breath-hold examination sequence (Figure A), with largest lesion in a postcontrast sequence (Figure B), and multiple lesions seen on venous phase sequence (Figure C). Retransplantation was considered; however, given the indolent nature of the lesions, he was referred to oncology and interventional radiology for treatment. He did not make those appointments, and the latest blood tests in August 2020 showed stable graft function with no decompensation. He developed dementia and has not been able to follow-up with further imaging. HEHE was first described in 1984 and is a rare indolent malignant tumor with unclear etiology with vague presentations including abdominal discomfort, nausea, and vomitting.1Ishak K.G. Sesterhenn I.A. Goodman M.Z.D. et al.Epithelioid hemangioendothelioma of the liver: A clinicopathologic and follow-up study of 32 cases.Hum Pathol. 1984; 15: 839-852Crossref PubMed Scopus (382) Google Scholar HEHE rarely involves the vasculature, causing Budd–Chiari Syndrome, veno-occlusive disease, and portal hypertension. At diagnosis, extrahepatic involvement is reported in 36.6% of patients involving lungs, regional lymph nodes, and peritoneum.2Mehrabi A. Kashfi A. Fonouni H. et al.Primary malignant hepatic epithelioid hemangioendothelioma: a comprehensive review of the literature with emphasis on the surgical therapy.Cancer. 2006; 107: 2108-2121Crossref PubMed Scopus (343) Google Scholar Although the etiology is unknown, reported associations include oral contraceptive use, alcohol consumption, liver trauma, sarcoidosis, Crohn’s disease, viral hepatitis, and vinyl chloride or asbestos exposure.2Mehrabi A. Kashfi A. Fonouni H. et al.Primary malignant hepatic epithelioid hemangioendothelioma: a comprehensive review of the literature with emphasis on the surgical therapy.Cancer. 2006; 107: 2108-2121Crossref PubMed Scopus (343) Google Scholar Treatment options include a combination of liver resection, transarterial chemoembolization, liver transplantation, and the possible addition of chemotherapy.2Mehrabi A. Kashfi A. Fonouni H. et al.Primary malignant hepatic epithelioid hemangioendothelioma: a comprehensive review of the literature with emphasis on the surgical therapy.Cancer. 2006; 107: 2108-2121Crossref PubMed Scopus (343) Google Scholar,3Brahmbhatt M. Prenner S. Bittermann T. Liver transplantation for hepatic epithelioid hemangioendothelioma is facilitated by exception points with acceptable long-term outcomes.Transplantation. 2020; 104: 1187-1192Crossref PubMed Scopus (13) Google Scholar HEHE should be considered in the differential diagnosis of de novo liver masses after liver transplantation.