Ectomesenchymal Chondromyxoid Tumor

Abstract

Ectomesenchymal chondromyxoid tumor is a rare and benign neoplasm with a predilection for the anterior dorsal tongue. Despite morphologic heterogeneity, most cases are characterized by a proliferation of bland spindle cells with a distinctive reticular growth pattern and myxoid stroma. The immunophenotype of these neoplasms is likewise variable; most cases express glial fibrillary acid protein and S100 protein, with inconsistent reports of keratin and myoid marker expression. The molecular pathogenesis is poorly understood; however, a subset of cases has been reported to harbor EWSR1 gene rearrangement. Following identification of an RREB1-MKL2 fusion gene by RNA Sequencing in an index patient, a retrospective review of additional cases of ectomesenchymal chondromyxoid tumors was performed to better characterize the clinical, immunohistochemical, and molecular attributes of this neoplasm. A total of 21 cases were included in this series. A marked predisposition for the dorsal tongue was confirmed. Most cases conformed to prior morphologic descriptions; however, hypercellularity, hyalinized stroma, and necrosis were rare attributes not previously emphasized. The neoplastic cells frequently coexpressed glial fibrillary acid protein, S100 protein, keratin, smooth muscle actin, and/or desmin; a single case was found to contain significant myogenin expression. An RREB1-MKL2 fusion product was identified in 19 tumors (90%), a single tumor (5%) had an EWSR1-CREM fusion product, and the remaining case lacked any known fusion gene by RNA Sequencing. The latter 2 cases subtly differed morphologically from many in the cohort. This series illustrates that recurrent RREB1-MKL2 fusions occur in most, perhaps all, cases of ectomesenchymal chondromyxoid tumor.

Ectomesenchymal chondromyxoid tumor with a significant proliferative index: A case report

“…25 The immunohistochemical profile of ECT is highly variable. However, as in previous studies, the present tumor was positive for S100 and GFAP, 4,6,7,12,15,19,23,26,27 demonstrating an origin from the neural crest, as well as for CD10, 28 NSE 20,29 and cyclin D1. 4,17,28 Regarding this last protein, strong nuclear ex-pression was detected, but no translocation of CCND1/IGH or amplification of the CCND1 gene was found.…”

Brain tumor with an ATXN1-NUTM1 fusion gene expands the histologic spectrum of NUTM1-rearranged neoplasia

“…Initially associated with NUT midline carcinomas, NUTM1 fusions have now been described in a broad spectrum of tumors ranging from carcinoma to sarcoma and leukemia [2, 3, 7]. The most common fusion partner gene in carcinoma and sarcoma is BRD4 followed by BRD3 and NSD3 .…”

“…The most common fusion partner gene in carcinoma and sarcoma is BRD4 followed by BRD3 and NSD3 . Various new partners have been recently described [2, 3, 5]. The prognosis of these tumors is generally poor, although NUT-associated leukemias appear to be associated with a better prognosis and YAP1-NUTM1 is associated with benign skin adnexal gland tumors [3, 5].…”

“…Excluding CIC-NUTM1 fused tumors, only one NUTM1 rearranged brain tumor has been previously reported, namely a cytokeratin negative BRD4-NUTM1 PNET-like parietal lobe tumor in a 3-year old boy with GFAP and synaptophysin positivity. On methylation profiling, this neoplasm did not cluster with tumors of the CNS Ewing Family Tumor CIC group [2].…”

“…Whether the strong GFAP positivity of our specific case is indicative of a glial tumor or of a sarcoma with myoepithelial differentiation cannot be assessed due to the lack of positive staining and specificity for other markers tested. GFAP positivity has been described in 3 out of 4 NUTM1 rearranged soft tissue or visceral sarcomas, this is in contrast to the CNS Ewing Family Tumor CIC group which fails to express any differentiation markers [2, 6]. We recommend performing NUT immunohistochemistry followed by RNA sequencing to identify any potential NUTM1 fusion partner genes in GFAP+/olig2- unclassified glioma, particularly those with myxoid and/or chondroid features.…”