Head and neck mesenchymal neoplasms with GLI1 gene alterations: A pathologic entity with distinct histologic features and potential for distant metastasis Journal Article
| Authors: | Xu, B.; Chang, K. P.; Folpe, A. L.; Kao, Y. C.; Wey, S. L.; Huang, H. Y.; Gill, A. J.; Rooper, L.; Bishop, J. A.; Dickson, B. C.; Lee, J. C.; Antonescu, C. R. |
| Article Title: | Head and neck mesenchymal neoplasms with GLI1 gene alterations: A pathologic entity with distinct histologic features and potential for distant metastasis |
| Abstract: | Soft tissue tumors with GLI1 gene fusions or amplifications have been recently described as a unique pathologic entity with an established risk of malignancy. We herein expand these findings by investigating a cohort of 11 head and neck lesions with GLI1 alterations, including 8 from the tongue, for their clinicopathologic and molecular features. The tumors commonly affected males in their 30s (male:female ratio 2.7:1; range: 1 to 65). Tumors showed a multinodular growth pattern, nested architecture separated by a delicate, arborizing vascular network, monotonous round to ovoid nuclei, and clear cytoplasm. Tumor protrusion into vascular spaces was common. Genetic alterations were investigated by fluorescence in situ hybridization and/or targeted RNA sequencing. Seven tumors harbored GLI1 fusions with the following partners: ACTB (n=4), PTCH1 (n=2), or MALAT1 (n=1). The remaining 4 cases showed coamplifications of GLI1 with CDK4 and MDM2 genes. Tumors were commonly positive for S100 protein and CD56. CDK4, MDM2, and STAT6 were positive in GLI1-amplified tumors. Two of 6 patients with available follow-up (1 each with GLI1 amplification and PTCH1-GLI1 fusion) developed distant metastases. Both tumors showed a high mitotic index and tumor necrosis. The head and neck region, particularly tongue, is a common location for GLI1-related mesenchymal tumors. Although a morphologic overlap was noted with the previously reported "pericytoma with t(7,12) translocation," often occurring in the tongue, our findings expand the original findings, to include a more variable immunophenotype, propensity for late distant metastases, and alternative mechanisms of GLI1 oncogenic activation, such as various GLI1 fusion partners or GLI1 coamplifications with MDM2 and CDK4 genes. |
| Keywords: | tumor; expression; malat1; ptch1; actb; pericytoma; actb-gli1 fusion; t(7/12); gli1 amplification; gli1 fusion |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 44 |
| Issue: | 6 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2020-06-01 |
| Start Page: | 729 |
| End Page: | 737 |
| Language: | English |
| ACCESSION: | WOS:000536254200002 |
| DOI: | 10.1097/pas.0000000000001439 |
| PROVIDER: | wos |
| PMCID: | PMC7225037 |
| PUBMED: | 31934916 |
| Notes: | Article -- Source: Wos |
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