Epithelioid hemangioendothelioma of soft tissue: a proposal for risk stratification based on 49 cases

Epithelioid hemangioendothelioma (EHE) of soft tissue is a distinctive vascular tumor that has been variously considered a tumor of borderline malignancy and low-grade angiosarcoma. The majority of cases are associated with low mortality, but some metastasize and cause patient death. We analyzed 49 cases of EHE to determine if a method for stratifying risk for mortality could be developed. Fifty-one cases of EHE diagnosed during the period of 1989 and 2005 were retrieved. Tumors were evaluated with respect to location, size, cytologic atypia, mitotic activity, tumor cell spindling, and necrosis. Follow-up information was obtained for all cases. For actuarial analysis, disease-specific overall survival was evaluated using univariate and multivariable analysis. Most tumors occurred in adults (range, 9 to 93 y) and affected women predominantly (21 M:28 F). They developed in the head and neck (6), extremities (32), mediastinum (4), trunk (4), genitals (2), and retroperitoneum (1) and ranged in size from 0.5 to 18 cm. Clinical follow-up was obtained for all patients and ranged from 1.5 to 170 months (mean, 57.9 mo); 31 patients were alive without disease, 5 patients were alive with disease, 9 patients died of disease and 4 died of other causes. Overall 5-year disease-specific survival was 81%. Eleven patients (22%) had metastatic disease affecting lung (6), lymph node (4), liver (2), and bone, retroperitoneum, and soft tissue (1 each). Two patients had metastases to multiple sites. Treatment modality was known for 46 patients: 31 were treated surgically and 15 were treated with surgery and chemotherapy and/or radiation therapy. By univariate analysis, mitotic activity and size were associated with higher mortality (P=0.007 and 0.004, respectively). By multivariable analysis, increasing mitotic activity (P=0.00827, hazard ratio 10.03) and size (P=0.01, hazard ratio 2.26) were associated with decreased survival. Tumor site, cytologic atypia, the presence of necrosis, and tumor spindling were not significant. Those tumors with >3 mitotic figures/50 high power fields and size >3.0 cm had the worst prognosis (P=0.0002). Patients with high-risk tumors had a 5-year disease-specific survival of 59%; no patients with low-risk tumors died. In conclusion, we report that EHE can be stratified into 2 risk groups with markedly different clinical courses.