RREB1::MRTFB fusion-positive extra-glossal ectomesenchymal chondromyxoid neoplasm of the palate

Introduction

Ectomesenchymal chondromyxoid tumor (EMCMT) is a rare benign tumor that typically occurs in the anterior tongue. This tumor is characterized by the RREB1::MTRFB (formerly RREB1::MKL2) fusion. A subset of cases has the EWSR1 gene rearrangement. The histogenesis of this tumor is unproven but thought to originate from either ectomesenchymal cells of the neural crest or myoepithelial cells. Recently, at least 10 molecularly confirmed cases of extra-glossal mesenchymal neoplasms have been reported with the RREB1::MTRFB fusion; the majority occurring in the head and neck region in patients with a median age of 36 years. These tumors express a wide range of morphological features.

Case Findings

An 80-year-old man presented with a painless 3 × 2.5 cm anterior palatal mass of unknown duration. The lesion was completely excised and submitted for pathological analysis. On gross examination, the bosselated cut surface was yellow-tan, rubbery, with zones having a gelatinous consistency.

Results

The specimen was comprised of a submucosal, unencapsulated, lobulated neoplasm. The tumor was variably cellular with a chondromyxoid stroma and no discrete architectural arrangement. The cells were spindled to stellate with ovoid nuclei and amphophilic to basophilic cytoplasm with rare mitoses. Immunohistochemically the tumor cells were positive for SMA and S100 (patchy). The cells did not stain with AE1.3, CD34, CD56, chromogranin, desmin, GFAP, MUC4, SOX-10, and synaptophysin. Genetic sequencing confirmed a RREB1::MTRFB fusion, with exon 8 of RREB1 fused to exon 11 of MRTFB.

Conclusions

These extra-glossal neoplasms with RREB1::MTRFB fusions are characterized by morphological and immunohistochemical variability. This case report adds to the evidence for extra-glossal sites of this tumor and highlights the variable demographics and morphology reported to date. Cases with molecular profiling confirm the phenotypic variation among these RREB1::MKL2 fusion tumors, thus refining our current understanding of these chondromyxoid neoplasms.