Abstract
Inflammatory leiomyosarcoma (ILMS) is a malignant neoplasm showing smooth muscle differentiation, a prominent inflammatory infiltrate, and near-haploidization. These tumors have significant pathologic and genetic overlap with the recently described "inflammatory rhabdomyoblastic tumor (IRT)," suggesting that ILMS and IRT may belong to one entity. Herein, we describe two cases of ILMS/IRT with attention to new cytogenetic and sequencing findings. The tumors were composed of sheets and fascicles of variably pleomorphic tumor cells showing spindled and epithelioid to rhabdoid morphology and a prominent histiocyte-rich inflammatory infiltrate typical of ILMS/IRT. In case 1, chromosomal microarray analysis showed a near-haploid pattern with loss of heterozygosity resulting from loss of one copy of all autosomes except for chromosomes 5, 20, 21, and 22. Case 2 showed areas with high-grade rhabdomyosarcomatous transformation. In this case, the low-grade tumor component revealed a hyper-diploid pattern with loss of heterozygosity for most of autosomes but with a normal diploid copy number state except for chromosomes 5, 20, and 22, which showed a relative gain. The high-grade tumor component showed a similar pattern of copy-neutral loss of heterozygosity with additional abnormalities, including mosaic segmental gains at 1p, 5p, 8q, 9p, 20q, and segmental loss at 8p. Next-generation sequencing identified sequence variants in NF1, TP53, SMARCA4, KRAS, and MSH6. MSH6 variant was confirmed as germline, consistent with the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome in one of our study patients and suggestive that ILMS/IRT might be part of the HNPCC cancer spectrum.