Epithelioid hemangioendothelioma (EHE) is a vascular tumor of intermediate malignant potential, which presents as infiltrative lesions involving multiple organs. We reviewed our institutional experience with the cytologic diagnosis of this neoplasm including the performance of rapid on-site evaluation (ROSE). From our institutional database, we identified 29 cytology specimens, obtained between 2012 and 2020, from 21 patients with biopsy confirmation of EHE. ROSE and final diagnosis were compared. All cytology slides were reviewed, and selected cytologic features were recorded. The cohort included 29 specimens comprising 17 (59%) from liver, 6 (21%) from lung, 2 (7%) from lymph node, and 4 (14%) from other sites. At ROSE, 8/27 (30%) were reported inadequate, yet on review, all cases contained scattered cells typical of EHE in the touch imprint air-dried slides including two cases reported with a final diagnosis of non-diagnostic. All cases contained epithelioid and plasmacytoid cells with ovoid nuclei, fine chromatin, delicate (or biphasic) cytoplasm, and scattered cells with delicate, elongated cytoplasmic tails. The majority 26/29 (90%) of cases had multi-nucleated and multi-lobated nuclei. Intracytoplasmic lumens/blister cells were in 17/29 (59%), and a subset had erythrocytes therein (4/29, 14%). Metachromatic fibromyxoid or fibrotic stroma fragments were commonly seen (23/29, 79%). Mitoses and necrosis were absent in all cases. Of 11 tested cases, WWTR1::CAMTA1 and YAP1::TFE3 fusions were detected in nine and two cases, respectively. EHE has distinctive cytologic features which are often under-recognized during ROSE.

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