Mesenchymal tumours with RREB1–MRTFB fusion involving the mediastinum: extra‐glossal ectomesenchymal chondromyxoid tumours?

Abstract

Aims: Ectomesenchymal chondromyxoid tumour (ECT) is a rare benign intraoral tumour which almost exclusively presents as a small mass of the anterior dorsal tongue. Recently, the RREB1-MRTFB (previously known as MKL2) fusion gene has been identified in 90% of ECTs, all located in the tongue, emphasising its genetic distinctiveness. Here, we report two mesenchymal tumours involving the superior mediastinum of adult women with RREB1-MRTFB fusions. Methods and results: Both tumours presented as wellcircumscribed paravertebral masses that were clinically suspected to be schwannoma. After fragmented resection, recurrence was not observed at 27 and 18 months. Although tumours were originally unclassifiable, nextgeneration sequencing detected identical RREB1 (exon 8)-MRTFB (exon 11) fusion transcripts, which were validated by reverse transcriptase-polymerase chain reaction, Sanger sequencing, and fluorescence in-situ hybridisation. Both tumours shared hyalinised areas with round cells embedded in a cord or reticular manner. The tumour cells showed mild nuclear atypia of possible degenerative type with very low mitotic activity, and were at least focally positive for S100, glial fibrillary acidic protein, smooth muscle actin and epithelial membrane antigen. Overall, these findings suggest that they may represent previously undescribed extra-glossal ECT involving the mediastinum. However, the histology was not classic for ECT, because that in case 2 was predominated by storiform growth of spindle cells, whereas the tumour in case 1 lacked myxoid change. Conclusions: We have provided the first evidence that RREB1-MRTFB fusion is not limited to tumours in the head region, and whether such tumours represent extra-glossal ECTs requires further research.

RREB1‐MKL2 fusion in a spindle cell sinonasal sarcoma: biphenotypic sinonasal sarcoma or ectomesenchymal chondromyxoid tumor in an unusual site?

“…Interestingly, Siegfried et al 10 showed in their case of biphenotypic “oropharyngeal” sarcoma that the RREB1‐MKL2 chimeric transcription factor encoded by this fusion gene produced an increase in MKL2 expression, thus mimicking the role of PAX3 in BSNS tumorigenesis. Just recently, a RREB1‐MKL2 fusion transcript was described in two cases of mesenchymal tumors involving the mediastinum 26 . These data suggest a potential role of RREB1 and MKL2 activation in oncogenesis leading to effects in the corresponding downstream pathways.…”

“…Just recently, a RREB1-MKL2 fusion transcript was described in two cases of mesenchymal tumors involving the mediastinum. 26 These data suggest a potential role of RREB1 and MKL2 activation in oncogenesis leading to effects in the corresponding downstream pathways.…”

RREB1::MRTFB fusion‐positive extra‐glossal mesenchymal neoplasms: A series of five cases expanding their anatomic distribution and highlighting significant morphological and phenotypic diversity

“…To date, very few cases of extra‐glossal EMCMT have been reported 10–16 . However, only five genuine extra‐glossal EMCMTs have been verified by molecular testing (Tables 1 and 2).…”

Expanding Awareness of the Distribution and Biologic Potential of Ectomesenchymal Chondromyxoid Tumor

“…More recently, Dickson et al detected a RREB1-MRTFB (formerly MKL2) fusion gene in 19/21 (90%) tumors by RNA-Seq and/or FISH as well as an EWSR1-CREM fusion product in a single tumor [2]. In addition to the ectomesenchymal chondromyxoid tumor, the RREB1-MRTFB fusion product has also been reported in a "biphenotypic oropharyngeal sarcoma" [14] as well as two mediastinal masses described as "extra-glossal ectomesenchymal tumors" [15]. The biphenotypic oropharyngeal sarcoma appears to be morphologically dissimilar to the current case; thus, the relationship of this report to ectomesenchymal chondromyxoid tumor remains uncertain.…”