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Chronic mast cell leukemia (MCL) with KIT S476I: a rare entity defined by leukemic expansion of mature mast cells and absence of organ damage

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Abstract

Mast cell leukemia (MCL) is a rare, life-threatening malignancy defined by a substantial increase in neoplastic mast cells (MCs) in bone marrow (BM) smears, drug-resistance, and a poor prognosis. In most patients, the survival time is less than 1 year. However, exceptional cases may present with a less malignant course. We report on a 49-year-old female patient with MCL diagnosed in 2013. In February 2013, first symptoms, including flushing, headache, and diarrhea, were recorded. In addition, mild anemia was detected. The disease was characterized by a massive increase in well-granulated, mature, and often spindle-shaped MCs (80 %) in BM smears. The serum tryptase level amounted to 332 ng/mL. Like in most other MCL patients, no skin lesions were detected. However, unlike in other patients, tryptase levels remained stable, and no other signs or symptoms of MCL-induced organ damage were found. Sequencing studies revealed an isolated S476I point mutation in KIT but no mutation in codon 816. The patient received histamine receptor blockers but refused cytoreductive therapy. After 9 months, still no progression or organ damage was detected. However, progression with transformation to acute MCL occurred after 12 months. We propose that the chronic type of MCL with stable conditions, absence of organ damage, and a mature MC morphology is recognized as a distinct entity that should be distinguished from the acute variant of MCL.

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Acknowledgments

We would like to thank Daniela Berger, Gabriele Stefanzl, and Susanne Herndlhofer for their skillful technical assistance. This study was supported by a Mastocytosis Grant of the Medical University of Vienna and the Austrian National Science Fund (FWF) grant no. SFB-F4704.

Contributions

P.V. and M.A. designed the study and wrote the paper. S.C.R., L.M. and H.P.H. contributed histomorphological, histopathological, and immunohistochemical studies. G.H. and C.M. provided molecular studies and KIT sequencing analyses. P.V., J.B., M.S., and M.A. contributed patients and provided patient-derived material. B.P. performed in vitro proliferation studies using patient-derived cells and KIT-targeting tyrosine kinase inhibitors. G.E. and P.B. performed flow cytometry studies. P.V., P.B., and M.A. contributed cytomorphological studies. All authors approved the final version of the manuscript.

Conflict of interest

P.V. and H.P.H. are Novartis-Consultants in a global trial examining the effects of PKC412 (midostaurin) in advanced systemic mastocytosis. P.V. received a research grant from Novartis and a research grant from The Mastocytosis Society.

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Authors and Affiliations

  1. Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

    Peter Valent, Sabine Cerny-Reiterer, Barbara Peter & Gregor Eisenwort

  2. Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

    Peter Valent, Sabine Cerny-Reiterer, Barbara Peter & Gregor Eisenwort

  3. Hospital Schwarzach, Internal Medicine Section, Pongau, Austria

    Jörg Berger

  4. Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria

    Gregor Hoermann & Christine Mannhalter

  5. Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria

    Leonhard Müllauer

  6. Division of Hematology and Oncology, Innsbruck Medical University, Innsbruck, Austria

    Michael Steurer

  7. Division of Hematology and Oncology, Elisabethinen Hospital Linz, Linz, Austria

    Peter Bettelheim

  8. Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany

    Hans-Peter Horny

  9. LBPA CNRS UMR8113, Ecole Normale Supérieure de Cachan, Cachan, France

    Michel Arock

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  1. Peter Valent
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  11. Hans-Peter Horny
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Correspondence to Peter Valent.

Additional information

This study was supported by the Austrian Science Fund (FWF) grant no. SFB-F4704

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Valent, P., Berger, J., Cerny-Reiterer, S. et al. Chronic mast cell leukemia (MCL) with KIT S476I: a rare entity defined by leukemic expansion of mature mast cells and absence of organ damage. Ann Hematol 94, 223–231 (2015). https://doi.org/10.1007/s00277-014-2207-9

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  • DOI: https://doi.org/10.1007/s00277-014-2207-9

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