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A case of vasculogenic mesenchymal tumor in the mediastinum: whole-exome sequencing reveals origin from pre-existing germ cell tumor

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Abstract

Vasculogenic mesenchymal tumor (VMT), a primitive mesenchymal neoplasm enriched by various-sized atypical vessels, is a new entity that develops in mediastinal germ cell tumors (GCTs) with yolk sac tumor (YST) components after chemotherapy. Notably, patients with VMT in the residual GCT have increased risk of developing sarcomas or hematopoietic malignancies. Here, we report a late-teenage male patient with residual teratoma and high-grade VMT after chemotherapy for a mediastinal mixed GCT, including YST. Whole-exome sequencing revealed biallelic inactivation of TP53 and extensive copy number alterations that suggested whole-genome doubling. The biopsy tissue of the mixed GCT before chemotherapy exhibited overlapping genetic alterations to those in the VMT. Immunohistochemical analyses of the VMT showed that the abnormal vessels were positive for cytokeratin, glypican 3, EZH2, and IMP3. The findings that VMT inherits the genetic alterations of pre-existing mixed GCT and exhibits a partly YST-like immunophenotype might contribute to its clinical aggressiveness.

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Data Availability

The datasets used during the current study are available from the corresponding author upon reasonable request.

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Funding

Yosuke Yamada is currently receiving a grant, JSPS KAKENHI Grant Number JP21K06902.

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Authors and Affiliations

  1. Department of Diagnostic Pathology, Kyoto University Hospital, 54 Shogoin Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan

    Hirotake Fujii, Yosuke Yamada, Marina Tsujimura & Hironori Haga

  2. Department of Dermatology, Kyoto University Hospital, Kyoto, Japan

    Kentaro Yamamura & Yoshihiro Ishida

  3. Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan

    Kazuhisa Matsumoto, Satona Tanaka & Hiroshi Date

  4. Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan

    Tadaaki Nishikawa

  5. Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan

    Yukihiro Yoshida

  6. Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan

    Jumpei Kashima & Yasushi Yatabe

  7. Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Seishi Ogawa

  8. Institute of Pathology, Mannheim and Medical Faculty Mannheim, University Medical Centre, Heidelberg University, Mannheim, Germany

    Alexander Marx

  9. Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA

    Thomas M. Ulbright

Authors
  1. Hirotake Fujii
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  2. Yosuke Yamada
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  3. Kentaro Yamamura
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  12. Yasushi Yatabe
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  13. Seishi Ogawa
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  14. Alexander Marx
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  15. Thomas M. Ulbright
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  16. Hironori Haga
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Contributions

Drafting the manuscript: TF and YY. Acquisition and analysis of pathological data: TF, YY, MT, JK, YY, AM, TU, and HH. Acquisition and analysis of genetic data: KY, YI, and SO. Acquisition and analysis of clinical data: KM, ST, HD, TN, and YY. Correction and approval of the manuscript: all authors.

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Correspondence to Yosuke Yamada.

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Fujii, H., Yamada, Y., Yamamura, K. et al. A case of vasculogenic mesenchymal tumor in the mediastinum: whole-exome sequencing reveals origin from pre-existing germ cell tumor. Virchows Arch 482, 923–927 (2023). https://doi.org/10.1007/s00428-023-03529-2

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  • DOI: https://doi.org/10.1007/s00428-023-03529-2

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