Rhabdomyosarcoma Arising in Inflammatory Rhabdomyoblastic Tumor: A Genetically Distinctive Subtype of Rhabdomyosarcoma

“Inflammatory rhabdomyoblastic tumor” (IRMT) is a recently coined name for a distinctive soft tissue neoplasm characterized by slow growth, a dense histiocytic infiltrate, scattered, bizarre-appearing tumor cells with morphologic and immunohistochemical evidence of skeletal muscle differentiation, a near-haploid karyotype with retained biparental disomy of chromosomes 5 and 22, and usually indolent behavior. There are 2 reports of rhabdomyosarcoma (RMS) arising in IRMT. We studied the clinicopathologic and cytogenomic features of 6 cases of IRMT with progression to RMS. Tumors occurred in the extremities of 5 men and 1 woman (median patient age, 50 years; median tumor size, 6.5 cm). Clinical follow-up (6 patients: median, 11 months; range 4-163 months) documented local recurrence and distant metastases in 1 and 5 of 6 patients, respectively. Therapy included complete surgical resection (4 patients) and adjuvant/neoadjuvant chemo/radiotherapy (6 patients). One patient died of disease, 4 were alive with metastatic disease, and one was without evidence of disease. All primary tumors contained conventional IRMT. Progression to RMS appeared as follows: (1) overgrowth of monomorphic rhabdomyoblasts with diminished histiocytes, (2) monomorphic spindle cell morphology with variably pleomorphic rhabdomyoblasts and low mitotic activity, or (3) morphologically undifferentiated spindle cell and epithelioid sarcoma. All but one were diffusely desmin-positive, with more limited MyoD1/myogenin expression. All RMS arising in IRMT, either primary or metastatic, demonstrated widespread loss of heterozygosity with retained heterozygosity of chromosomes 5 and 20, and all but one displayed additional gains and losses involving loci containing oncogenes/ tumor suppressor genes, most often CDKN2A and CDKN2B. RMS arising in IRMT have unique clinicopathologic and cytogenomic features, warranting classification as a distinct, potentially aggressive RMS subtype. It should be distinguished from other RMSs, particularly fusion-driven spindle cell RMS and pleomorphic RMS.