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

Area of Science:

• Oncology
• Pathology
• Genetics

Background:

• A distinct spindle cell neoplasm with rhabdomyoblastic phenotype and VGLL3 rearrangement has been described, primarily affecting the head and neck with an indolent course.
• Classification as true rhabdomyosarcomas remains unclear, with limited follow-up data available from previous reports.

Purpose of the Study:

• To report an additional case of this rare neoplasm, including long-term follow-up and spatial profiling.
• To further elucidate the biological and clinical characteristics of these tumors and their distinction from malignant rhabdomyosarcomas.

Main Methods:

• Histological examination and immunohistochemistry (SMA, demsin, PAX7, myogenin, MyoD1) of tumor tissue.
• Whole transcriptome sequencing to identify gene fusions (TCF12::VGLL3).
• Digital spatial profiling (DSP) to analyze protein expression (pan-AKT, MAPK pathway) and tumor microenvironment (T-cell infiltrate).

Main Results:

• The tumor, located in the buccal mucosa, exhibited bland spindle cells with a rhabdomyoblastic phenotype and a TCF12::VGLL3 fusion.
• DSP revealed pan-AKT expression, MAPK pathway involvement, and a dense T-cell infiltrate.
• A 6-year history of a prior lesion with VGLL3 rearrangement and intense inflammation, initially interpreted as benign, was noted. The patient experienced only a local recurrence after resection and remains disease-free at 8 months post-surgery.

Conclusions:

• This case, with long-term follow-up, supports the classification of these neoplasms as indolent/low-grade rhabdomyoblastic tumors.
• These tumors are biologically and clinically distinct from fully malignant spindle cell rhabdomyosarcomas.
• The presence of VGLL3 rearrangement and specific molecular pathways warrants further investigation in this distinct tumor category.