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Poorly differentiated extra-axial extraskeletal chordoma diagnosed by methylation profiling: case report and analysis of brachyury expression in SWI/SNF-deficient tumors

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Abstract

Chordoma is a rare malignant tumor with notochordal differentiation, usually affecting the axial skeleton of young patients. We report a case of a high-grade epithelioid tumor involving the synovium and soft tissues of the knee in a 74-year-old male patient. The preliminary biopsy was inconclusive, but a diagnosis of metastatic clear-cell carcinoma of unknown origin was suggested. However, imaging studies did not reveal any primary lesions. The resection specimen consisted of nests and sheets of oval to polygonal cells with discernible cell borders, clear or lightly amphophilic cytoplasm, and round to oval nuclei with occasional well-visible eosinophilic nucleoli. Rare atypical mitoses, necrotic areas, and bizarre nuclei were noted. The biopsy and resection specimens underwent a wide molecular genetic analysis which included methylation profiling. The DKFZ sarcoma classifier assigned the methylation class chordoma (dedifferentiated) with a calibrated score of 0.96, and additionally, a loss of SMARCB1 locus was noted in the copy number variation plot. To verify these findings, T-brachyury and SMARCB1 immunostaining was performed afterward, showing diffuse nuclear positivity and complete loss in the tumor cells, respectively. To assess the prevalence of T-brachyury immunopositivity among SWI/SNF-deficient tumors and to evaluate its specificity for poorly differentiated chordoma, we analyzed a series of 23 SMARCB1- or SMARCA4-deficient tumors, all of which were negative. After incorporating all the available data, including the absence of any morphological features of conventional chordoma, the case was diagnosed as poorly differentiated chordoma. As illustrated herein, the utilization of methylation profiling in the diagnostic process of some carefully selected unclassifiable soft tissue neoplasms may lead to an increased detection rate of such extremely rare soft tissue tumors and enable their better characterization.

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Data Availability

Data supporting the findings of this study are available within the article. The complete datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the study grant SVV 260652 from the Ministry of Education, Czech Republic (Natálie Klubíčková); by the Cooperatio program, research area SURG (Natálie Klubíčková, Michael Michal); and by the Cooperatio Program, research area Medical Diagnostics and Basic Medical Sciences (Jindra Brtková).

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Authors and Affiliations

  1. The Sikl Department of Pathology, Faculty of Medicine and University Hospital in Pilsen, Charles University, Prague, Czech Republic

    Natálie Klubíčková, Michael Michal, Michal Michal & Marián Švajdler

  2. Bioptical Laboratory, Ltd., Pilsen, Czech Republic

    Natálie Klubíčková, Michael Michal, Zdeněk Kinkor, Veronika Hájková, Nikola Ptáková, Michal Michal & Marián Švajdler

  3. The Fingerland Department of Pathology, Faculty of Medicine and University Hospital, Charles University, Hradec Kralove, Czech Republic

    Jiří Soukup & Aleš Ryška

  4. Department of Pathology, Military University Hospital, Prague, Czech Republic

    Jiří Soukup

  5. Department of Radiology, Faculty of Medicine and University Hospital, Charles University, Hradec Kralove, Czech Republic

    Jindra Brtková

  6. Department of Orthopedic Surgery, Faculty of Medicine and University Hospital, Charles University, Hradec Kralove, Czech Republic

    Martin Lutonský

  7. Onco Team Diagnostic, București, Romania

    Mihaela Farkas

Authors
  1. Natálie Klubíčková
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  2. Michael Michal
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  3. Zdeněk Kinkor
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  8. Veronika Hájková
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  9. Nikola Ptáková
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  10. Michal Michal
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  11. Mihaela Farkas
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  12. Marián Švajdler
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Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Natálie Klubíčková, Marián Švajdler, and Jiří Soukup. The first draft of the manuscript was written by Natálie Klubíčková, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Natálie Klubíčková.

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Ethics approval

The study was approved by the institutional review board of the Faculty of Medicine in Pilsen, Charles University. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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No patient consent was required for this study.

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The authors declare no competing interests.

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Klubíčková, N., Michal, M., Kinkor, Z. et al. Poorly differentiated extra-axial extraskeletal chordoma diagnosed by methylation profiling: case report and analysis of brachyury expression in SWI/SNF-deficient tumors. Virchows Arch 484, 621–627 (2024). https://doi.org/10.1007/s00428-023-03620-8

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  • DOI: https://doi.org/10.1007/s00428-023-03620-8

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