GLI1-altered epithelioid soft tissue tumor: a newly defined entity with characteristic genetic profile

Introduction

GLI1-altered epithelioid soft tissue tumor is a recently recognized entity featuring GLII-1 fusions or amplifications. It has a predilection for the head and neck area, particularly in the tongue, and appears to have a malignant potential. Herein we report an additional case of GLI1-altered soft tissue tumor of the tongue in a patient with growth retardation and epilepsy.

Materials and Methods

A 9-year-old boy presented with a lobulated sessile reddish nodule at the dorsum of the tongue of unknown duration. His medical history was significant for growth hormone insufficiency and epilepsy with centrotemporal spikes. Magnetic resonance imaging showed an avidly enhancing lesion at the midline dorsum of the tongue. An incisional biopsy of the lesion was performed.

Results

Microscopic examination of the lesion revealed a multilobulated submucosal mass of epitheloid to ovoid cell proliferation with a perivascular distribution around delicate and branching blood vessels. The tumor cells are small to medium with clear to amphophilic cytoplasm. They are arranged in fascicles, cords, and reticular patterns and separated by richly vascular stroma with frequent prominent capillary-sized vasculature. Protrusion of tumor cells into vascular spaces is focally seen. Immunohistochemistry showed cytoplasmic positivity of the tumor cells to GLUT-1 and B-Catenin and negativity to S100, GFAP, Pan-CK, SMA, WT-1, CD-31, CD-34, and HMB-45. Ki-67 is around 10-15%. RNA-sequencing confirmed the presence of ACTB::GLI1 fusion.

Conclusion

GLI1-altered epithelioid soft tissue tumor is a unique neoplasm with unknown lineage and variable immunoreactivity. Therefore, molecular testing is indicated to confirm the diagnosis. GLI1-altered epithelioid soft tissue tumors have the potential for local recurrence and distant metastases; thus, it is best regarded as low-grade sarcoma and warrants a long-term follow-up after surgical excision.