Angiomatoid "malignant" fibrous histiocytoma: a clinicopathologic study of 158 cases and further exploration of the myoid phenotype.

Angiomatoid "malignant" fibrous histiocytoma (AMFH) has been considered to be a low-grade sarcoma of childhood, and, with its fibrous pseudocapsule, angiomatoid change, dense lymphoplasmacytic response, and proliferation of spindled or round cells, has been classified as a fibrohistiocytic neoplasm. We wanted to study the clinicopathologic and immunophenotypic features of a large number of these tumors and to especially further explore their myoid differentiation. Cases coded as AMFH from 1979 to 1995 were retrieved from the Soft Tissue Registry of the AFIP. Only cases that met the criteria for AMFH by light microscopy were included, a total of 158 cases. Immunohistochemistry was obtained on 98 cases. Clinical history on 92% of all cases revealed a gender ratio of 1.3 females: males, age range of 2 to 71 years, median size of 2.0 cm, and a distribution of extremities > trunk > head and neck, with 66% lesions occurring in areas of normal lymphoid tissue. All tumors with available margins were well-circumscribed. Eighty percent of cases had some degree of lymphoplasmacytic infiltration; 50% cases had pseudovascular spaces filled with blood. Fifty-two percent had predominantly round cell morphology; 48% had a predominantly spindle cell pattern. Desmin positivity was noted in 51% cases and occurred in both predominantly round cell and spindle cell tumors. Most of the desmin-positive cases with adjacent lymphoid infiltrate (67%) showed scattered similar, desmin-positive cells in the surrounding lymphoid infiltrate, adjacent to the tumor. Muscle-specific and smooth-muscle actins were seen in 14% cases. Heavy-caldesmon was strongly positive in 3%, and calponin was focally positive in 73% and extensively positive in 12% cases. MyoD1, myoglobin, and myogenin (myf4) were negative in all tumors studied. Forty-five percent of cases were positive for CD99; 52% of these had round cell morphology. Fifteen percent of cases were positive for KP-1. All tumors were positive for vimentin and negative for CD21, CD35, S100 protein, CD34, keratins 8/18, and lysozyme. Clinical follow-up on 86 patients indicated that only 1 patient was alive with a local nodal metastasis (1% frequency of metastasis) within 1 year, and 2 others had local recurrence, all over a mean follow-up period of 6 years. The myoid, primarily myofibroblastic, phenotype of these lesions is supported by desmin, calponin, and occasional actin positivity. The occasional heavy-caldesmon and smooth muscle actin additionally suggest rare smooth muscle phenotype; however, lack of skeletal muscle markers indicate no relationship of AMFH to skeletal muscle tumors. The resemblance of these lesions to lymph nodes, clinically and morphologically, the finding of similar desmin positive cells in the adjacent lymphoid infiltrate, and the fact that 66% cases were found in sites of normal lymphoid tissue raise the possibility that some of these lesions may arise from or be related to myoid cells of lymphoid tissue. AMFH has an almost invariably benign behavior, but the 1% metastatic rate warrants its classification as low-grade "malignant." The predominantly round cell, CD99-positive and desmin positive AMFH cases, respectively, should not be confused with Ewing's sarcoma/PNET or rhabdomyosarcoma, respectively.