Liver transplantation for cryptogenic liver failure caused by diffuse hepatic angiosarcoma: case report

Cryptogenic liver failure remains an important cause of liver transplantation (LT) despite technical advances in imaging modalities and laboratory examinations [1, 2]. Hepatic angiosarcoma is a rare and aggressive malignancy with a poor prognosis and is difficult to diagnose in the absence of exposure to environmental carcinogens, such as thorotrast, polyvinyl chloride monomer, and arsenic [3, 4]. Diffuse type hepatic angiosarcoma is extremely rare and is very difficult to diagnose pre-operatively. Because these patients have a very poor prognosis after LT, owing to high rates of local recurrence and distant metastasis, LT is contraindicated in patients with these tumors [5]. As liver biopsy for patients with liver failure is risky, hepatic angiosarcoma is usually diagnosed by post-operative histopathological examination. This report describes two patients who underwent LT for cryptogenic liver failure and were found to have hepatic angiosarcoma on pathological examination of the explanted livers.

About 2–3% of soft-tissue sarcomas in adults are angiosarcomas. Primary hepatic angiosarcoma is a rare malignancy, accounting for about 1.8% of all primary hepatic tumors and fewer than 5% of angiosarcomas [6, 7]. The peak age at onset is 60–70 years old, with a male-to-female predominance as high as 3:1. Although the main cause of hepatic angiosarcoma is exposure to environmental carcinogens, causes remain unknown in many patients [3, 4, 8]. Its symptoms are nonspecific and can include abdominal pain, weakness, fatigue, weight loss, anorexia, and abdominal enlargement. There is no relationship between hepatic angiosarcoma and portal hypertension. In the patient 1, however, the patient presented with esophageal varices. There are some case reports of hepatic angiosarcoma had associated with idiopathic portal hypertension, but the frequency is not high. The relationship is not clear. Diffuse hepatic angiosarcomas are especially difficult to diagnose by imaging modalities, although a blocky contrast effect of the whole liver in enhanced CT may be an indicator. These findings may suggest angiosarcomas, but they look very much alike hyperplastic nodules in liver cirrhosis. FDG-PET in one patient showed extensive diffuse abdominal accumulation throughout the whole liver, suggesting a malignant tumor [9, 10]. Histopathologically, these tumors are characterized by dilated sinusoids lined by hypertrophied endothelial cells with atypical and hyperchromatic nuclei. Immunohistochemistry has shown that these tumors are usually positive stains for endothelial markers, such as HHV-8, CD31, CD34, and ERG [10, 11]. About 7.7% of primary hepatic angiosarcomas are diffuse hepatic angiosarcomas [4]. Of 59,462 patients diagnosed with liver tumors from 1987 through 2003 in the UNOS database, seven (0.0117%) with diffuse hepatic angiosarcoma underwent liver transplantation and were pathologically diagnosed post-operatively. Their mean duration of survival after transplantation was 262 ± 146 days [12]. Owing to their poor prognosis and high recurrence rate, LT is contraindicated for patients with hepatic angiosarcomas, especially those with diffuse hepatic angiosarcomas [7]. In both cases, addition of chemotherapy such as IL-2 might be necessary after the established diagnoses.

Liver biopsies are difficult to obtain from patients with cryptogenic liver failure. Nevertheless, pre-transplant liver biopsy may be necessary to distinguish diffuse hepatic angiosarcomas from tumors of other origin in patients with atypical cryptogenic liver failure.