Spindle Cell Rhabdomyosarcoma of Oral Cavity With TCF12::VGLL3 Fusion, Expanding on a Recently Described Entity With...

Recently, a distinct, bland spindle cell neoplasm with rhabdomyoblastic phenotype, and VGLL3 rearrangement has been described. These tumors have a striking predilection for the head and neck area and so far, followed an indolent course. It remains unclear whether these tumors are best classified as true rhabdomyosarcomas. There are 11 reports of such tumors with limited follow-up. Here, we report an additional case with local recurrence, long-term follow-up and spatial profiling. The tumor occurred in the right buccal mucosa/oral commissure of a 47-year-old man. On clinical examination, the mass was firm, measuring ~1.5 cm. Biopsy and subsequent wedge excision were performed. Histologically, the tumor was composed of bland, small, spindle to ovoid cells, arranged in short fascicles and vaguely storiform architecture. The tumor cells diffusely infiltrated into skeletal muscle. There was a background of inflammatory cells including small lymphocytes and histiocytes. Neoplastic cells were positive for SMA, demsin, PAX7, myogenin and MyoD1. Whole transcriptome sequencing revealed a TCF12::VGLL3 fusion. Digital spatial profiling (DSP) identified pan-AKT expression, differential expression in the MAPK pathway, and revealed that the tumor attracted a dense T-cell rich inflammatory infiltrate. The patient had a lesion in the same location 6 years prior that underwent incisional biopsy, showed intense inflammatory infiltrate, and was interpreted as benign. FISH for VGLL3 on this tissue was positive for rearrangement. No additional adjuvant treatment was given, and the patient is alive without disease, 8 months after the major resection. Long term follow-up of 6 years with only local recurrence lends further support to the notion that these neoplasms are a class of indolent/low-grade rhabdomyoblastic tumors that are biologically and clinically distinct from fully malignant spindle cell rhabdomyosarcomas.