Angiomatoid "malignant" fibrous histiocytoma: A clinicopathologic study of158 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, a ngiomatoid change, dense lymphoplasmacytic response, and proliferation of s pindled or round cells, has been classified as a fibrohistiocytic neoplasm. We canted to study the clinicopathologic and immunophenotypic features of a large number of these tumors and to especially further explore their myoi d differentiation. Cases coded as AMFH from 1979 to 1995 were retrieved fro m the Soft Tissue Registry of the AFIP. Only cases that met the criteria fo r AMFH by light microscopy were included, a total of 158 cases. Immunohisto chemistry was obtained on 98 cases. Clinical history on 92% of ail cases re vealed a gender ratio of 1.8 females: males, age range of 2 to 71 years, me dian size of 2.0 cm, and a distribution of extremities > trunk > head and n eck, with 66%, lesions occurring in areas of normal lymphoid tissue. All tu mors with available margins were well-circumscribed. Eighty percent of case s had some degree of lymphoplasmacytic infiltration; 50X cases had pseudova scular spaces filled with blood Fifty-two percent had predominantly round c ell morphology; 48% had a predominantly spindle cell pattern. Desmin positi vity was noted in 51% cases and occurred in both predominantly round cell a nd spindle cell tumors. Most of the desmin-positive cases with adjacent lym phoid infiltrate (67%) showed scattered similar, desmin-positive cells in t he surrounding lymphoid infiltrate, adjacent to the tumor, Muscle-specific and smooth-muscle actins were seen in 14% cases. Heavy-caldesmon was strong ly 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 posi tive for KP-I. 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 m etastasis (1% frequency of metastasis) within 1 year, and 2 others had loca l recurrence, all over a mean follow-up period of 6 years. The myoid, prima rily myofibroblastic, phenotype of these lesions is supported by desmin, ca lponin, and occasional actin positivity. The occasional heavy-caldesmon and smooth muscle actin additionally suggest rare smooth muscle phenotype; how ever, lack of skeletal muscle markers indicate no relationship of AMFH to s keletal muscle tumors. The resemblance of these lesions to lymph nodes, cli nically and morphologically the finding of similar desmin positive cells in the adjacent lymphoid infiltrate, and the fact that 66% cases were found i n 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. AMF H has an almost invariably benign behavior, but the 1% metastatic rate warr ants its classification as low-grade "malignant." The predominantly round c ell, CD99-positive and desmin positive AMFH cases, respectively, should tro t be confused with Ewing's sarcoma/PNET or rhabdomyosarcoma, respectively. Copyright (C) 1999 by W.B. Saunders Company.