Head and Neck Mesenchymal Neoplasms with GLI1 Gene Alterations: A Pathologic Entity with Distinct Histologic Features and Potential for Distant Metastasis

Bin Xu, Koping Chang, Andrew L. Folpe, Yu Chien Kao, Shiuan Li Wey, Hsuan Ying Huang, Anthony J. Gill, Lisa Rooper, Justin A. Bishop, Brendan C. Dickson, Jen Chieh Lee, Cristina R. Antonescu

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)729-737
Number of pages9
JournalAmerican Journal of Surgical Pathology
Issue number6
Publication statusPublished - 2020


  • ACTB
  • GLI1 amplification
  • GLI1 fusion
  • MALAT1
  • pericytoma
  • PTCH1
  • Oncogene Fusion/genetics
  • Gene Amplification/genetics
  • Humans
  • Middle Aged
  • Soft Tissue Neoplasms/genetics
  • Child, Preschool
  • Head and Neck Neoplasms/genetics
  • Infant
  • Male
  • Young Adult
  • Zinc Finger Protein GLI1/genetics
  • Adolescent
  • Adult
  • Female
  • Aged
  • Child

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine


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