GLI1-fusion neoplasm of the tongue: report of a pediatric case associated with SHOX deficiency disorder

GLI1-altered soft tissue tumor is a recently recognized entity featuring GLI1 fusions or amplifications, with predilection for the head and neck region and potential for metastasis. We report an additional case arising in the tongue of a 9-year-old boy with growth hormone insufficiency and epilepsy. Imaging showed an enhancing midline dorsal tongue lesion. Incisional biopsy revealed a multilobulated submucosal proliferation of monomorphic epithelioid-to-ovoid cells with prominent perivascular distribution around branching vessels and focal protrusion into vascular spaces. Tumor cells were GLUT-1 positive and negative for S100, GFAP, pan-cytokeratin, SMA, WT-1, CD31, CD34, STAT6, β-catenin, and HMB-45, with Ki-67 nuclear staining of 10–15% of cells. Next Generation Sequencing of the tumor confirmed ACTB::GLI1 fusion. In light of his neurodevelopmental disorders, further genetic evaluation was performed revealing SHOX deletion within PAR1 with complex Y-chromosomal rearrangement. Although GLI1-altered neoplasms have a distinctive morphology, lack of defining immunophenotype makes molecular confirmation of GLI1-altered soft tissue tumors essential in most cases. These tumors are low-grade sarcomas which are treated with complete local excision and long-term follow-up.