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GLI1-altered mesenchymal tumor: a clinicopathological and molecular analysis of ten additional cases of an emerging entity

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Abstract

We report 10 additional cases of GLI1-altered mesenchymal tumor to further delineate its clinicopathological and molecular spectrum. There were seven males and three females with a median age of 31 years (range 1.3 ~ 75 years). Five tumors arose in the oral cavity, one each in the stomach, uterine cervix, elbow, groin, and thigh. Histologically, all cases except one were composed of monomorphic round to epithelioid cells showing an infiltrative multinodular growth pattern. The neoplastic cells were surrounded by a rich network of capillary vessels. Vessel invasion or subendothelial protrusion into the vascular space was commonly present. One tumor developed regional lymph node metastasis. The remaining case showed a predominantly spindle cell tumor. By immunohistochemistry, most tumors showed diffuse staining of CD56 (8/8) with variable expression of S100 protein (7/8). In three tumors harboring amplified genes, strong and diffuse nuclear staining of MDM2 (2/3) and CDK4 (3/3) were noted. Next-generation sequencing (NGS) studies revealed GLI1 fusions in 7 cases and GLI1 amplification in 2 cases, which were validated by fluorescence in situ hybridization (FISH) analysis in the majority of cases. One case did not show fusion gene by RNA-seq, but FISH revealed both amplification and break-apart of GLI1 gene. Follow-up information showed local recurrences in two patients. All other patients remained disease-free at the last follow-up. Our study further demonstrates that mesenchymal tumors with GLI1 alterations represent a distinctive clinicopathological entity. Although the tumor has a propensity for the tongue, it can also arise in somatic soft tissues as well as in visceral organs. Based on the characteristic morphological features and genomic profiles, we propose the term “GLI1-altered mesenchymal tumor” to describe this emerging entity.

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Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from the Shanghai Science and Technology Development fund (19MC1911000).

This study has been approved by the institutional review board (IRB) of both institutions. Informed consent was obtained from the patients or guardians.

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  1. Jiahan Liu and Rongjun Mao contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Jiahan Liu, I Weng Lao, Lin Yu, Qianming Bai, Xiaoyan Zhou & Jian Wang

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Jiahan Liu, I Weng Lao, Lin Yu, Qianming Bai, Xiaoyan Zhou & Jian Wang

  3. Department of Pathology, Foshan Hospital of Chinese Traditional Medicine, Guangdong Province, Foshan, 528000, China

    Rongjun Mao

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Contributions

Jiahan Liu performed the sample collection and research and wrote the paper. Rongjun Mao, I Weng Lao, and Lin Yu contributed to the research design. Qianming Bai and Xiaoyan Zhou did FISH and NGS analyses. Jian Wang designed the research and gave the final approval of the manuscript. All the authors critically reviewed and approved the manuscript.

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Correspondence to Jian Wang.

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Liu, J., Mao, R., Lao, I. et al. GLI1-altered mesenchymal tumor: a clinicopathological and molecular analysis of ten additional cases of an emerging entity. Virchows Arch 480, 1087–1099 (2022). https://doi.org/10.1007/s00428-021-03224-0

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