Inflammatory leiomyosarcoma/rhabdomyoblastic tumor: A report of two cases with novel genetic findings

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.

Inflammatory Rhabdomyoblastic Tumor of the Posterior Pharyngeal Wall

“…Tumors classified as ILMS, previously thought to be a tumor of smooth muscle origin, stained positive for the skeletal muscle markers desmin, myogenin, and MyoD1. Tumors with both smooth and skeletal muscle differentiation were subsequently reclassified as IRT, which is the designation given to the tumor in this report following expert soft tissue pathologic review.…”

Inflammatory rhabdomyoblastic tumor, pheochromocytoma, and pulmonary hamartoma in a patient with neurofibromatosis type 1: a case report

“…Although there is a known disposition to develop pheochromocytomas in NF1, the incidence of IRMT and pulmonary hamartomas remains obscure. Considering the relatively high percentage of NF1 patients in previously published case series of IRMT, and the frequency of NF1 mutations found, it is likely that the NF1 gene plays an important role in the pathogenesis of these tumors (Table 1 ) [ 4 – 7 , 15 , 16 ]. Germline or sporadic mutations in NF1, combined with the loss of heterozygosity (LOH) that occurs during haploidization events, could be the driving factors for tumorigenesis.…”

Intraoral Inflammatory Leiomyosarcoma: A Case Report and Literature Review

“…At the molecular level, ILMS is characterized by near-haploid loss of heterozygosity in most chromosomes but consistently maintained heterozygosity for chromosomes 5 and 22 and frequently for chromosomes 18, 20, and 21. In addition, NF1 and TP53 gene mutations have been reported [ 2 , 8 , 17 ]. Regrettably, the genetic test was not done in our case.…”