Novel TERT::PDLIM7 Gene Fusion in a Skull-Based Soft Tissue Myoepithelial Carcinoma

Introduction

Soft tissue myoepithelial carcinoma (MECA) represents an uncommon malignancy showing overlapping histomorphologic, immunophenotypic and genetic features with its salivary and cutaneous counterparts. Most MECAs harbor rearrangements. Genetic aberrations of TERT have only rarely been documented in soft tissue neoplasms, including myxoid and spindle cell liposarcoma and chordoma, but not MECA.

Material and methods

A 67-year-old male with a history of pancreatic neuroendocrine tumor metastatic to the liver and skeletal bones, presented with a large, bone-destructive, skull-base tumor of the left pterygopalatine fossa with extension into the orbit, optic canal, cavernous sinus and sinonasal cavity presumed to represent new metastases. An endoscopic biopsy was performed.

Results

Histopathologic examination disclosed an infiltrative malignant neoplasm composed of spindle cells arranged in short intersecting fascicles and immersed in a dense fibrocollagenous stroma. Lesional cells featured plump, ovoid or elongated, open-face nuclei with coarse chromatin, rich eosinophilic cytoplasm, and indistinct cell membrane borders. Nuclear pleomorphism and cytologic atypia were minimal, and mitoses were infrequent. By immunohistochemistry, the neoplastic cells were strongly and diffusely positive for CAM5.2 and SMA with focal reactivity for CK7, EMA, AE1/AE3, ERG and SATB2. Lesional cells were negative for p40, INSM1, S100, SOX10, GFAP, Desmin and STAT6. Ki-67 was approximately 30-45% by manual quantitation. SMARCB1 was retained. The overall histopathologic and immunophenotypic features were considered diagnostic of MECA. Genomic profiling of the tumor identified an intrachromosomal fusion and an inactivating mutation. The patient was treated with definitive chemoradiation and remains asymptomatic with significant tumor volume reduction 6 months post-treatment.

Conclusions

Herein, we report a unique case of a clinically aggressive skull-based MECA with novel gene fusion and expand the molecular landscape of non-rearranged MECA. The biologic significance of the above gene fusion remains, hitherto, unknown.