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Intrasinusoidal Spread of Hepatic Epithelioid Hemangioendothelioma: Implications for the Diagnosis in Minimal Samples.

Epithelioid hemangioendothelioma (EHE) is an angiocentric tumor that, when arising in liver, is centered around hepatic/portal veins. However, EHE cells can also track along sinusoids, which is not well recognized or studied. We identified 18 cases of hepatic EHE and 6 nonhepatic EHEs. For all cases, we recorded EHE multifocality and maximum size. When tumor cells were identified apart from the main mass, we recorded their location, maximum distance from the main tumor, density per high-power field, and cytomorphology. Immunohistochemical staining for CAMTA1, ERG, and CAM5.2 was performed on all cases. Lesional cells were present apart from the main mass in 17 of 18 (94%) liver cases, always within sinusoids and occasionally (4/17, 24%) in central veins. They appeared intensely hyperchromatic with vaguely cerebriform nuclei and multinucleation in 6 (35%) of cases. CAMTA1 and ERG positivity was seen in all 17 cases. Two cases (12%) demonstrated focal CAM5.2 positivity. Sinusoidal EHE cells ranged from 0.1 to 0.8 cm away from the main tumor. There were no statistically significant associations between histologic findings and patient outcome. In the 6 nonhepatic cases, tumor cells did not extend beyond the main EHE. Lesional cells in hepatic EHE often extend beyond the main lesion into sinusoids, where they demonstrate an unusual, somewhat distinctive morphology. Care should be taken to identify such cells in limited biopsies; immunohistochemistry for CAMTA1, a specific and sensitive marker for EHE, can be confirmatory.

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