Myeloproliferative neoplasms: contemporary diagnosis using histology and genetics
The 2008 WHO classification system for hematological malignancies is now in print and has effectively integrated clinical, histologic and genetic information
The ultimate purpose of disease classification is to streamline diagnostic and treatment approaches, enable accurate predictions of prognosis, and provide structure for pathogenetic studies. To be consistent with this mission, classification systems must evolve and undergo revision from time to time as new pathogenetic and therapeutic information accumulates. The 2008 WHO classification system for hematological malignancies is now in print and has effectively integrated clinical, histologic 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 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. 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. 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. 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.
In the November issue of Nature Review Clinical Oncology, Ayalew Tefferi of the Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, USA and colleagues discuss histologic, cytogenetic and molecular changes in MPN and illustrate their integration into practical diagnostic algorithms. In the context of MPN, this system has been extremely useful for the diagnosis of polycythemia vera and essential thrombocythemia in routine clinical practice. Similarly, the therapeutic relevance of genetic classification of eosinophilic disorders has been validated. In view of the current impetus of reports on the molecular pathogenesis of MPN and other hematological malignancies, the authors expect additional major revisions to the WHO document in the near future.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου