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Peripheral T-cell lymphoma emerging in a patient with aggressive polymyositis: molecular evidence for neoplastic transformation of an oligoclonal T-cell infiltrate

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Abstract

We report a rare case of peripheral T-cell lymphoma arising in a 52-year-old man with biopsy-proven aggressive polymyositis, who had cardiac involvement, progressive bulbar symptoms, and died 11 months post diagnosis due to multiorgan failure. Using a multimodality approach including immunohistochemistry, genome-wide single nucleotide polymorphism (SNP)-array analysis, and high-throughput sequencing of the complementary determining region 3 (CDR3) of T-cell receptor beta (TCRβ) genes, our study demonstrates a molecular link between polymyositis and T-cell lymphoma, and provides evidence of the rapid and possibly late occurrence of genomic instability during neoplastic transformation of an oligoclonal T-cell population. Immunohistochemical analysis revealed loss of CD5, CD7, and CD8 antigen expression in autopsy tissue samples, as well as the occurrence of aberrant CD56 expression, not seen in pre-mortem biopsies, supporting the emergence of a neoplastic T-cell population. Multiplex polymerase chain reaction and next-generation sequencing of the TCRβ CDR3 region displayed two unique T-cell clones in both the diagnostic biopsy confirming polymyositis and the autopsy muscle tissue exhibiting T-cell lymphoma, linking the two pathological processes. SNP-array analysis revealed complex genomic abnormalities at autopsy but not in the pre-mortem muscle biopsies displaying polymyositis, confirming malignant transformation of the oligoclonal T-cell infiltrate. Our findings raise the possibility that clinically aggressive polymyositis might represent a preneoplastic condition in some instances, similar to certain other autoimmune and inflammatory disorders.

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Acknowledgments

We thank Dr. James Goldman and Dr. Jean Paul Vonsattel for their helpful critique of the manuscript and David Hamm from Adaptive Biotechnology Corp. for help with analysis of the TCRβ deep sequencing data.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Neuropathology, Department of Pathology and Cell Biology, Columbia University Medical Center and New York Presbyterian Hospital, 630 W. 168th Street, PH15-124, New York, 10032, USA

    Nadejda M. Tsankova & Kurenai Tanji

  2. Department of Neurology, Columbia University Medical Center and New York Presbyterian Hospital, New York, 10032, USA

    Carolyn Bevan, Lewis P. Rowland & Kurenai Tanji

  3. Department of Medicine, Columbia University Medical Center and New York Presbyterian Hospital, New York, 10032, USA

    Elizabeth W. Mayer

  4. Department of Pathology and Cell Biology, Columbia University Medical Center and New York Presbyterian Hospital, New York, 10032, USA

    Vaidehi Jobanputra, Yen Chen Kevin Ko, Jay H. Lefkowitch & Mahesh Mansukhani

  5. Division of Hematopathology, Department of Pathology and Cell Biology, Columbia University Medical Center and New York Presbyterian Hospital, New York, 10032, USA

    Govind Bhagat

Authors
  1. Nadejda M. Tsankova
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  2. Carolyn Bevan
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  3. Vaidehi Jobanputra
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  4. Yen Chen Kevin Ko
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  5. Elizabeth W. Mayer
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  6. Jay H. Lefkowitch
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  7. Mahesh Mansukhani
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  8. Lewis P. Rowland
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  9. Govind Bhagat
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  10. Kurenai Tanji
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Correspondence to Nadejda M. Tsankova.

Additional information

G. Bhagat and K. Tanji contributed equally/co-senior authors.

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Tsankova, N.M., Bevan, C., Jobanputra, V. et al. Peripheral T-cell lymphoma emerging in a patient with aggressive polymyositis: molecular evidence for neoplastic transformation of an oligoclonal T-cell infiltrate. Acta Neuropathol 126, 595–601 (2013). https://doi.org/10.1007/s00401-013-1164-z

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  • DOI: https://doi.org/10.1007/s00401-013-1164-z

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