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Diagnostic challenges in the work up of hypereosinophilia: pitfalls in bone marrow core biopsy interpretation

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Abstract

The FIP1L1-PDGFRA (FP) fusion gene is identified in a substantial proportion of patients with eosinophilia-associated myeloproliferative neoplasms (MPN-eo) who subsequently achieve rapid and durable remissions on imatinib. In the initial diagnostic work-up of hypereosinophilia (HE), histologic and immunohistochemical evaluation of a bone marrow (BM) core biopsy is considered essential for the differentiation between reactive hypereosinophilia (HER), MPN-eo and hypereosinophilic syndrome (HES). We therefore retrospectively analysed the initial reports of BM core biopsies from 116 patients who were subsequently identified as FP positive (FP+, n = 56) or FP negative/corticosteroid-responsive HER or HES (n = 60). Compared to HER or HES, detection of FP was more frequently associated with increased numbers of blasts (11/56 vs. 2/60, p = 0.007) and mast cells (23/33 vs. 7/23, p = 0.006; with expression of CD25 [11/18 vs. 2/13, p = 0.025]), and/or fibrosis (25/35 vs. 1/23, p < 0.0001). In FP+ patients, HE was correctly associated with an underlying clonal haematologic disorder in only 36/56 (64 %) of cases, but final BM diagnoses included a variety of diagnoses such as MPN-eo (n = 15), acute myeloid leukaemia (n = 8), systemic mastocytosis (n = 6), chronic myeloid leukaemia (n = 5) or unclassified MPN (n = 2). We conclude that the final evaluation of BM core biopsies in the diagnostic work-up of HE should include comprehensive morphologic (stains for myeloid blast cells, mast cells and fibres) and genetic analyses before a final diagnosis is established.

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Acknowledgments

This work was supported by the “Deutsche José Carreras Leukämie-Stiftung e.V.” (H11/03 and R13/05), Germany.

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    Authors and Affiliations

    1. III. Medizinische Klinik, Hämatologie und Onkologie, Universitätsmedizin Mannheim, Mannheim, Germany

      Juliana Schwaab, Mohamad Jawhar, Nicole Naumann, Alice Fabarius, Wolf-Karsten Hofmann, Andreas Reiter & Georgia Metzgeroth

    2. Institut für Pathologie, Universitätsklinikum Freiburg, Freiburg, Germany

      Annette Schmitt-Graeff

    3. Pathologisches Institut, Ludwig-Maximilians-Universität München, München, Germany

      Hans-Peter Horny

    4. Wessex Regional Genetics Laboratory, Salisbury, UK

      Nicholas C. P. Cross

    5. Faculty of Medicine, University of Southampton, Southampton, UK

      Nicholas C. P. Cross

    Authors
    1. Juliana Schwaab
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    2. Mohamad Jawhar
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    3. Nicole Naumann
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    4. Annette Schmitt-Graeff
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    5. Alice Fabarius
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    8. Wolf-Karsten Hofmann
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    9. Andreas Reiter
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    Corresponding author

    Correspondence to Andreas Reiter.

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    The authors declare that they have no conflict of interest.

    Authorship and disclosure

    JS, MJ, NN, AF and GM performed the data analysis. AR, GM and WKH provided patient material. ASG and HPH reviewed the bone marrow biopsies. JS, NCPC, AR and GM wrote the paper. NCPC, WKH and AR revised the manuscript.

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    Andreas Reiter and Georgia Metzgeroth contributed equally to this work.

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    Schwaab, J., Jawhar, M., Naumann, N. et al. Diagnostic challenges in the work up of hypereosinophilia: pitfalls in bone marrow core biopsy interpretation. Ann Hematol 95, 557–562 (2016). https://doi.org/10.1007/s00277-016-2598-x

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    • DOI: https://doi.org/10.1007/s00277-016-2598-x

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