TY - JOUR
T1 - Head and Neck Mesenchymal Neoplasms With GLI1 Gene Alterations
T2 - A Pathologic Entity With Distinct Histologic Features and Potential for Distant Metastasis
AU - Xu, Bin
AU - Chang, Koping
AU - Folpe, Andrew L.
AU - Kao, Yu Chien
AU - Wey, Shiuan Li
AU - Huang, Hsuan Ying
AU - Gill, Anthony J.
AU - Rooper, Lisa
AU - Bishop, Justin A.
AU - Dickson, Brendan C.
AU - Lee, Jen Chieh
AU - Antonescu, Cristina R.
N1 - Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - ACTB
KW - GLI1 amplification
KW - GLI1 fusion
KW - MALAT1
KW - PTCH1
KW - pericytoma
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UR - http://www.scopus.com/inward/citedby.url?scp=85078158780&partnerID=8YFLogxK
U2 - 10.1097/PAS.0000000000001439
DO - 10.1097/PAS.0000000000001439
M3 - Article
C2 - 31934916
AN - SCOPUS:85078158780
SN - 0147-5185
VL - 44
SP - 729
EP - 737
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 6
ER -