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Two years ago, while on his honeymoon, a 36-year-old male presented with spontaneous splenic rupture and liver lesions concerning for angiosarcoma. He did not respond to doxorubicin. He was later diagnosed with hepatosplenic T-cell lymphoma (HSTCL) on repeat liver biopsy and responded to chemotherapy including hyper-CVAD. He underwent stem-cell transplant (SCT) that was complicated by graft-versus-host disease and CMV viremia, although he eventually achieved remission.
The patient presented with two months of increasing abdominal pain and distension. A CT scan was notable for hepatomegaly and numerous lesions involving the liver, ribs, vertebra, and sacrum (see Figure 1). Bone marrow biopsies were unrevealing for malignancy. His liver function declined, and he was referred for liver transplant evaluation.
On exam, the patient was jaundiced and demonstrated massive hepatomegaly and anasarca. Labs revealed renal insufficiency, anemia, thrombocytopenia and coagulopathy, total bilirubin 33 mg/dL, AST 1336, ALT 378, and alkaline phosphatase 134 (IU/L). His course was complicated by rapid deterioration due to a large perihepatic hematoma with hemoperitoneum (requiring hepatic artery embolization), toxic epidermal necrolysis, disseminated intravascular coagulation, and, ultimately, multiorgan failure with septic shock. Given concerns for an aggressive malignancy, he was not deemed to be a candidate for transplant.
Postmortem analysis revealed a liver measuring 30 x 25 x 20 cm, weighing 7.0 kilograms with 90 percent of hepatic parenchyma composed of blood-filled vascular masses and confluent dark red hemorrhagic tumor nodules. Review of previously obtained biopsies by multiple pathology specialists diagnosed a malignant vascular tumor of the liver, representing either a hepatic angiosarcoma or hemangioendothelioma.
Malignant vascular tumors of the liver include hepatic angiosarcomas (HAS), epithelioid hemangioendotheliomas (HE), and hemangiopericytomas. HAS is a high-grade tumor that can progress rapidly with metastases to areas including the spleen, lymph nodes, lungs, bone, and adrenals. It typically presents in patients 50 to 70 years of age and is more common in men. HAS is characterized by poorly defined hemorrhagic and necrotic nodules that are hypodense and do not enhance with contrast on imaging. These tumors may be associated with certain exposures, such as vinyl chloride, arsenic, and thorium. Clinical presentation may vary, and possible symptoms include abdominal pain, jaundice, ascites, and, rarely, Budd-Chiari syndrome. Fifteen percent of HAS patients present initially with acute spontaneous hemoperitoneum due to nodule rupture. Causes of death include liver failure and intra-abdominal bleeding. Microangiopathic hemolytic anemia and thrombocytopenia may result from damage when blood cells pass through tumor vasculature. On pathology, characteristic findings include variably differentiated tumor endothelial cells with severe nuclear atypia and frequent mitoses along dilated sinusoids. HAS and HE can have positive immunostaining for vascular markers, including ERG transcription factor, CD31, CD34, and Factor VIII antigen.
Surgical resection may be performed for HAS, but even with complete resection, patient survival is less than one year. Because of a high recurrence rate and poor survival posttransplant, liver transplantation is not recommended. Various chemotherapy regimens have been tested (including doxorubicin, ifosfamide, and paclitaxel), but there has been no proven effectiveness with these therapies.
Epithelioid hemangioendotheliomas (EH) are less common (incidence of less than 0.1 per 100,000) than HAS and are low-grade, although they frequently metastasize to the lungs, lymph nodes, peritoneum, bone, and spleen. Most commonly, EH affects individuals 40 to 50 years of age and is characterized by cellular infiltration of tumor cells in sinusoids and intrahepatic veins. Presentation can range from absence of symptoms to portal hypertension or hepatic failure with slow or rapidly progressive disease, however, a multifocal tumor with varying sized nodules is typical. In contrast to HAS, the tumor periphery may enhance with contrast and may retract the liver capsule with calcifications in 20 percent of cases. Pathology is characterized by neoplastic cellular infiltration with epithelioid-type cells of sinusoids and intrahepatic veins. Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive tumor more frequently seen in children. KHE may be associated with Kasabach-Merritt phenomenon, or consumptive coagulopathy with intravascular fibrin deposition with thrombocytopenia and purpura.
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