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Myeloproliferative neoplasms: contemporary diagnosis using histology and genetics

Nature Reviews Clinical Oncology volume 6, pages 627–637 (2009)Cite this article

Abstract

The 2008 WHO classification system for hematological malignancies is comprehensive and includes histology and genetic information. Myeloid neoplasms are now classified into five categories: acute myeloid leukemia, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN, and myeloid and/or lymphoid malignancies associated with eosinophilia and PDGFR or FGFR1 rearrangements. MPN are subclassified into eight separate entities: chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia, primary myelofibrosis, systemic mastocytosis, chronic eosinophilic leukemia not otherwise specified, chronic neutrophilic leukemia, and unclassifiable MPN. The diagnosis of chronic myelogenous leukemia requires the presence of BCR-ABL1, while its absence is required for all other MPN. Additional MPN-associated molecular markers include mutations of JAK2, MPL, TET2 and KIT. JAK2 V617F is found in most patients with polycythemia vera, essential thrombocythemia, or primary myelofibrosis and is, therefore, useful as a clonal marker in those settings. The diagnostic utility of MPL and TET2 mutations is limited by low mutational frequency. In systemic mastocytosis, presence of KIT D816V is expected but not essential for diagnosis. Chronic eosinophilic leukemia not otherwise specified should be distinguished from both PDGFR-rearranged or FGFR1-rearranged neoplasms and hypereosinophilic syndrome. We discuss histologic, cytogenetic and molecular changes in MPN and illustrate their integration into practical diagnostic algorithms.

Key Points

  • The 2008 WHO classification system for hematologic malignancies includes new genetic information to complement histology for both disease classification and diagnosis

  • The presence of BCR-ABL in a chronic myeloid neoplasm is pathognomonic for chronic myelogenous leukemia and its absence is essential for the diagnosis of other myeloproliferative neoplasms

  • Diagnosis of polycythemia vera is unlikely if JAK2 exons 12 and 14 lack mutations, and excluded when exon 14 mutations are absent and serum erythropoietin levels are normal or elevated

  • Bone marrow histology is often helpful to distinguish clonal from reactive myeloproliferation and essential thrombocythemia from prefibrotic primary myelofibrosis

  • Diagnostic evaluation of nonreactive eosinophilia should always include screening for FIP1L1-PDGFRA and PDGFRB rearrangements; patients with these mutations can be treated with imatinib mesylate

  • The presence of a KIT mutation is expected in systemic mastocytosis but is not required for its diagnosis

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Figure 1: Photomicrographs of a bone marrow biopsy sample from a 52-year-old woman who presented with a platelet count of 790 × 109/l.
Figure 2: Photomicrographs of bone marrow biopsy samples from a 35-year-old man who initially presented with a platelet count of 900 × 109/l.
Figure 3
Figure 4: A genetic and histology-based diagnostic algorithm for CML, polycythemia vera, essential thrombocythemia and primary myelofibrosis.
Figure 5: A contemporary approach to diagnosis of secondary polycythemia.
Figure 6: Current diagnostic approach to chronic myeloid neoplasms associated with eosinophilia, monocytosis or bone marrow mastocytosis.

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, 55905, MN, USA

    Ayalew Tefferi

  2. Department of Research, University Hospital Basel, Hebelstrasse 20, Basel, CH-4031, Switzerland

    Radek Skoda

  3. Department of Pathology, University of Chicago, 5841 S. Maryland Avenue, MC0008, Chicago, 60657, IL, USA

    James W. Vardiman

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Correspondence to Ayalew Tefferi.

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Tefferi, A., Skoda, R. & Vardiman, J. Myeloproliferative neoplasms: contemporary diagnosis using histology and genetics. Nat Rev Clin Oncol 6, 627–637 (2009). https://doi.org/10.1038/nrclinonc.2009.149

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