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Two cases of mycosis fungoides with large cell transformation with KMT2A rearrangements

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Abstract

Cutaneous T-cell lymphomas (CTCL) are a clinically and molecularly heterogeneous class of lymphomas of the skin-homing T cell, and their genetic profiles are not fully characterized. Previously, rearrangements of the Lysine Methyltransferase 2A (KMT2A) gene have been identified as driver mutations only in acute leukemias. KMT2A plays a role in epigenetic regulation, and cancers with such rearrangements are responsive to epigenetic therapy including hypomethylating agents. Here, we report two cases of CTCL with novel genetic profiles. KMT2A rearrangements were identified in two aggressive cases of mycosis fungoides with large cell transformation. A KMT2A::DSCAML1 gene rearrangement was seen in Case 1, while a KMT2A::MAPRE1 fusion was identified in Case 2. These cases demonstrate that KMT2A rearrangements can be found in primary CTCLs rather than solely acute leukemias, illustrating the importance of correlating molecular findings with clinical and histologic features in diagnosis. Additionally, this finding suggests that the subset of CTCLs driven by aberrancy of the KMT2A pathway may be responsive to therapy with hypomethylating agents or menin inhibitors, as seen in acute leukemias.

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Author notes

  1. Lauren Lawrence

    Present address: Guardant Health, Redwood City, CA, 94063, USA

Authors and Affiliations

  1. Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA

    Paul A. Wadsworth, Lauren Lawrence, Carlos J. Suarez, Atif Saleem, Kerri E. Rieger & Sebastian Fernandez-Pol

  2. Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Michael S. Khodadoust

  3. Department of Dermatology, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Youn H. Kim & Kerri E. Rieger

Authors
  1. Paul A. Wadsworth
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  2. Lauren Lawrence
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  3. Carlos J. Suarez
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  4. Atif Saleem
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Corresponding author

Correspondence to Sebastian Fernandez-Pol.

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Evaluation and reporting of these cases were performed under research protocols approved by the institutional review board of Stanford University.

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Wadsworth, P.A., Lawrence, L., Suarez, C.J. et al. Two cases of mycosis fungoides with large cell transformation with KMT2A rearrangements. J Hematopathol 16, 227–234 (2023). https://doi.org/10.1007/s12308-023-00567-2

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  • DOI: https://doi.org/10.1007/s12308-023-00567-2

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