Epithelioid hemangioendothelioma of the anterior mediastinum. Clinicopathologic, immunohistochemical, and ultrastructural analysis of 12 cases.

Twelve cases are reported of primary epithelioid hemangioendothelioma of the anterior mediastinum. Patient ages ranged from 19 to 62 years (mean, 49.4); three were women and nine were men. Seven patients presented with symptoms due to compression of surrounding structures; the remainder were asymptomatic and the lesions were discovered on routine chest x-ray films. The tumors measured from 4.5 to 13.5 cm in greatest diameter; they were encapsulated and well-circumscribed in seven cases and locally infiltrative in five. Histologically, a spectrum of features was observed ranging from those classically described for low-grade epithelioid hemangioendothelioma at other locations--including cells with abundant eosinophilic cytoplasm showing prominent vacuolization and intracellular lumen formation, few mitotic figures, and myxoid changes in the stroma--to more pronounced cytologic atypia, increased mitotic activity, and areas of necrosis. Metaplastic bone formation and osteoclast-type giant cells were observed in five cases, and four tumors displayed focally a prominent intravascular papillary endothelial component. Immunohistochemical studies showed positive staining of the neoplastic cells with factor VIII-related antigen and vimentin and focal staining in most cases with Ulex europaeus lectin. Stains for broad-spectrum keratin, CAM-5.2, S-100 protein, CD34, actin, and desmin were negative. Electron microscopic examination in three cases showed features distinctive for epithelioid vascular endothelial cells, including abundant cytoplasmic intermediate filaments, basal lamina material, marked pinocytotic activity, and primitive intracytoplasmic lumen formation. All cases were treated by surgical excision. Follow-up information was available in nine patients; seven patients were alive and well without evidence of disease 2-21 years after diagnosis (mean follow-up, 8 years); one patient had a recurrence after 1 year and died due to complications of surgery, and another patient died after 1 year of undetermined causes. Despite their often ominous clinical, radiological, and pathological features, epithelioid hemangioendotheliomas arising in the anterior mediastinum appear to behave as low-grade malignant neoplasms that may be adequately controlled in most instances by surgery alone.