The tumor is made by cords, strands, and solid aggregates of epithelioid, round to slightly spindle-shaped endothelial cells with abundant pale eosinophilic cytoplasm and round vesicular nucleus with minimal pleomorphism embedded in a fibromyxoid or sclerohyaline stroma (Fig. 36.2). Intracytoplasmic vacuolization with occasional intraluminal erythrocytes reminiscent of primitive vessels is a diagnostic clue (Figs. 36.3 and 36.4). The so-called high-risk EHE demonstrates classic histopathologic features and a size larger than 3 cm or >3 mitotic figures per 50 high-power fields. Cases are always positive for at least one vascular endothelial marker (factor VIII-related antigen, CD31, CD34), but not usually all. Podoplanin and FLI-1 may also be positive. The cytokeratin is expressed in one fourth of patients and CD10 and actin positivity may be found. Electron microscopy reveals the endothelial nature of the tumor cells surrounded by basal lamina, dotted with surface pinocytotic vesicles and intracytoplasmic lumina, and occasionally containing Weibel-Palade bodies. The chromosomal translocation involving chromosomes 1 and 3 (t[1;3][p36.3;q25]) and resulting in the WWTR1-CAMTA1 fusion gene is known to occur in EHE.