Angiomatoid (malignant) fibrous histiocytoma: a peculiar low-grade tumor showing immunophenotypic heterogeneity and ultrastructural variations.

To clarify the cellular differentiation features and facilitate diagnosis of angiomatoid (malignant) fibrous histiocytoma (AFH), four cases of AFH were examined by clinicopathologic, immunohistochemical and ultrastructural analyses. The age of the patients ranged from 10 to 24 years (mean, 17 years) and the sex distribution was equal. All cases were of subcutaneous origin: three arose in the trunk and one in the upper extremity. All patients presented with systemic symptoms, including inflammatory signs and anemia. After a mean follow up of 11 years 3 months, all patients were alive and well, although one patient twice developed local recurrence after surgery. All cases presented as multinodular, cystic and hemorrhagic tumors ranging in size from 4 to 11 cm (mean, 8 cm) and were characterized by sheets of bland spindle or round cells with oval nuclei within a circumscribed nodule often surrounded by a lymphocytic cuff. One tumor showed predominantly round cell morphology similar to Ewing's sarcoma/primitive neuroectodermal tumor. All cases (100%) exhibited immunoreactivity for vimentin, desmin, CD68 and CD57 (Leu-7). Three cases (75%) were positive for synaptophysin, and reactivity for alpha-smooth muscle actin, epithelial membrane antigen, neuron-specific enolase and CD99 (O-13) was present in two cases (50%) each. The three cases examined by electron microscopy had a mixture of fibrohistiocytic, myofibroblastic and undifferentiated cells containing cytoplasmic processes and dense-core granules. It is important for accurate diagnosis of this peculiar soft-tissue tumor to recognize that it has a variety of immunophenotypes, such as histiocytic, myofibroblastic, epithelial and neural, and may occasionally have a predominantly round cell morphology.