What is the diagnosis for a patient with a hypervascular tumor in the liver, supplied by the hepatic artery, with endothelial cell origin and positive for von Willebrand factor (vw)?

Hepatic Angiosarcoma: Diagnosis and Characteristics

The diagnosis is hepatic angiosarcoma, a rare and highly aggressive malignant tumor of vascular endothelial origin that presents as a hypervascular liver mass with endothelial markers (von Willebrand factor positive). 1, 2

A. Diagnosis Confirmation

Hepatic angiosarcoma is definitively diagnosed based on the combination of:

• Hypervascular tumor on angiography supplied by the hepatic artery, which is characteristic of this vascular malignancy 1, 3
• Endothelial cell origin confirmed by positive immunohistochemical staining for von Willebrand factor (vWF), along with CD34 and ERG markers 1, 2
• Clinical context of a patient with prior chemotherapy exposure (treated for Hodgkin lymphoma 10 years ago), which is a known risk factor 3

This tumor accounts for only 0.1-2% of primary liver malignancies and approximately 1% of all hepatic malignant tumors, making it exceptionally rare. 2, 3 The presentation with left upper quadrant pain in a patient with previous chemotherapy exposure is consistent with this diagnosis. 1

B. Carcinogenic Associations

The primary carcinogens linked to hepatic angiosarcoma include:

• Vinyl chloride monomer (occupational exposure in plastics industry) 3
• Thorotrast (thorium dioxide, a historical radiologic contrast agent) 3
• Arsenic (chronic exposure) 3
• Alkylating chemotherapeutic agents (particularly relevant in this case given the patient's history of Hodgkin lymphoma treatment) 1, 3

Approximately 75% of cases are idiopathic with no identifiable carcinogen exposure. 4 However, in this patient with prior chemotherapy for Hodgkin lymphoma, the alkylating agents used in treatment represent the most likely carcinogenic exposure. 1

C. Microscopic Appearance

The histopathologic features of hepatic angiosarcoma include:

• Malignant endothelial cells forming irregular, anastomosing vascular channels and sinusoidal spaces 1, 2
• Atypical epithelioid cells with vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm (in epithelioid variant) 5
• Hemorrhagic areas with blood-filled spaces lined by malignant endothelial cells 1, 3
• Positive immunohistochemistry for vascular markers: CD34, ERG, and von Willebrand factor (Factor VIII-related antigen), which are essential for definitive diagnosis 1, 2
• Multifocal growth pattern with infiltrative borders and frequent areas of necrosis and hemorrhage 3, 5

The tumor typically shows high-grade cytologic atypia with pleomorphic nuclei and increased mitotic activity. 5 The vascular channels are lined by malignant endothelial cells that project into the lumens, creating a characteristic "papillary" appearance in some areas. 3

Critical Clinical Pitfall

Do not confuse this with hepatocellular carcinoma (HCC) despite the hypervascular appearance on imaging. HCC shows arterial hyperenhancement with portal venous washout in cirrhotic patients and stains positive for hepatocyte markers (glypican-3), not endothelial markers. 6 Hepatic angiosarcoma has a grave prognosis with median survival of only 6 months, and most cases are already advanced at diagnosis with rapid progression and high metastatic potential. 1, 3