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Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant, with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling
Primary intracranial spindle cell sarcoma is an extremely rare mesenchymal tumor, the molecular pathogenesis of which is poorly understood. Because of the lack of specific markers, diagnosis sometimes relies on ruling out all possible differential diagnoses, often making it difficult to reach a defi...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580084/ https://www.ncbi.nlm.nih.gov/pubmed/36277904 http://dx.doi.org/10.1177/11795476221131189 |
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author | Nejo, Takahide Takayanagi, Shunsaku Tanaka, Shota Shinozaki-Ushiku, Aya Kohsaka, Shinji Nagata, Keisuke Yokoyama, Munehiro Sora, Shigeo Ushiku, Tetsuo Mukasa, Akitake Aburatani, Hiroyuki Mano, Hiroyuki Saito, Nobuhito |
author_facet | Nejo, Takahide Takayanagi, Shunsaku Tanaka, Shota Shinozaki-Ushiku, Aya Kohsaka, Shinji Nagata, Keisuke Yokoyama, Munehiro Sora, Shigeo Ushiku, Tetsuo Mukasa, Akitake Aburatani, Hiroyuki Mano, Hiroyuki Saito, Nobuhito |
author_sort | Nejo, Takahide |
collection | PubMed |
description | Primary intracranial spindle cell sarcoma is an extremely rare mesenchymal tumor, the molecular pathogenesis of which is poorly understood. Because of the lack of specific markers, diagnosis sometimes relies on ruling out all possible differential diagnoses, often making it difficult to reach a definitive diagnosis. In this case study, we report a 69 year-old female patient for whom the integration of multi-layered molecular analyses contributed to making the diagnosis. The disease exhibited aggressive clinical behavior, requiring two sequential surgeries because of rapid regrowth within a short period. Primary and recurrent tumors exhibited similar histological features, in which spindle-shaped cells arranged in interlacing fascicles without any specific architectures, implicating sarcomatous tumors. In immunohistochemistry testing, tumor cells were immunopositive for vimentin but lacked any specific findings that contribute to narrowing down the differential diagnoses. Seeking further diagnostic clues, we performed DNA methylation-based analysis. The copy number analysis revealed MDM2 gene amplification and loss of heterozygosity of 22q. Moreover, dimension reduction clustering analysis implicated a methylation pattern comparable to aggressive types of sarcomas. In addition, an in-house next-generation sequencing panel (“Todai-OncoPanel”) analysis identified somatic mutations in DICER1, NF2, and ATRX genes. Taken all together, we finally made the diagnosis of primary intracranial spindle cell sarcoma, DICER1-mutant, with MDM2 gene amplification. This case report suggests that even for the tumors with insufficient morphological and immuno-histological diagnostic clues, integration of multi-layered molecular analyses can contribute to making the diagnoses as well as to understanding the rare tumors by elucidating unexpected genetic and epigenetic features. |
format | Online Article Text |
id | pubmed-9580084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-95800842022-10-20 Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant, with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling Nejo, Takahide Takayanagi, Shunsaku Tanaka, Shota Shinozaki-Ushiku, Aya Kohsaka, Shinji Nagata, Keisuke Yokoyama, Munehiro Sora, Shigeo Ushiku, Tetsuo Mukasa, Akitake Aburatani, Hiroyuki Mano, Hiroyuki Saito, Nobuhito Clin Med Insights Case Rep Case Report Primary intracranial spindle cell sarcoma is an extremely rare mesenchymal tumor, the molecular pathogenesis of which is poorly understood. Because of the lack of specific markers, diagnosis sometimes relies on ruling out all possible differential diagnoses, often making it difficult to reach a definitive diagnosis. In this case study, we report a 69 year-old female patient for whom the integration of multi-layered molecular analyses contributed to making the diagnosis. The disease exhibited aggressive clinical behavior, requiring two sequential surgeries because of rapid regrowth within a short period. Primary and recurrent tumors exhibited similar histological features, in which spindle-shaped cells arranged in interlacing fascicles without any specific architectures, implicating sarcomatous tumors. In immunohistochemistry testing, tumor cells were immunopositive for vimentin but lacked any specific findings that contribute to narrowing down the differential diagnoses. Seeking further diagnostic clues, we performed DNA methylation-based analysis. The copy number analysis revealed MDM2 gene amplification and loss of heterozygosity of 22q. Moreover, dimension reduction clustering analysis implicated a methylation pattern comparable to aggressive types of sarcomas. In addition, an in-house next-generation sequencing panel (“Todai-OncoPanel”) analysis identified somatic mutations in DICER1, NF2, and ATRX genes. Taken all together, we finally made the diagnosis of primary intracranial spindle cell sarcoma, DICER1-mutant, with MDM2 gene amplification. This case report suggests that even for the tumors with insufficient morphological and immuno-histological diagnostic clues, integration of multi-layered molecular analyses can contribute to making the diagnoses as well as to understanding the rare tumors by elucidating unexpected genetic and epigenetic features. SAGE Publications 2022-10-17 /pmc/articles/PMC9580084/ /pubmed/36277904 http://dx.doi.org/10.1177/11795476221131189 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Case Report Nejo, Takahide Takayanagi, Shunsaku Tanaka, Shota Shinozaki-Ushiku, Aya Kohsaka, Shinji Nagata, Keisuke Yokoyama, Munehiro Sora, Shigeo Ushiku, Tetsuo Mukasa, Akitake Aburatani, Hiroyuki Mano, Hiroyuki Saito, Nobuhito Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant, with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling |
title | Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant, with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling |
title_full | Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant, with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling |
title_fullStr | Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant, with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling |
title_full_unstemmed | Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant, with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling |
title_short | Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant, with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling |
title_sort | primary intracranial spindle cell sarcoma, dicer1-mutant, with mdm2 amplification diagnosed on the basis of extensive molecular profiling |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580084/ https://www.ncbi.nlm.nih.gov/pubmed/36277904 http://dx.doi.org/10.1177/11795476221131189 |
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