Diagnosis Of Chronic Myeloproliferative Neoplasms.Pdf

Mini-SyMpoSiuM: pathology of bone Marrow diSorderS

Diagnosis of chronic myeloproliferative neoplasms with special emphasis on early stages
hans Michael Kvasnicka Juergen thiele

Introduction
The revision of the diagnostic criteria for Philadelphia chromosome-negative (Ph1−) chronic myeloproliferative neoplasms (MPN) by the World Health Organization (WHO) was driven by new scientificfindings, particularly the discovery of the JAK2 V617F mutation.1 The mandate for this classification was to correlate molecular genetics with clinicopathological findings, implying the explicit appreciation that histological bone marrow (BM) patterns are associated with the clinical presentation.2,3 In contrast, the aim of the Polycythemia Vera Study Group (PVSG) was to investigate the natural historyof polycythaemia vera (PV), establish diagnostic guidelines and conduct clinical trials based on uniform diagnostic criteria.4 The PVSG criteria focus primarily on the exclusion of other causes of erythrocytosis, thrombocytosis and myelofibrosis, and do not emphasize BM findings or acknowledge prodromal stages in Ph1− MPN.4–8 Clinical studies have shown that MPN usually follow a relatively stablecourse for many years, until complications occur, such as life-threatening thromboembolic or haemorrhagic events, overt myelofibrosis (MF) with myeloid metaplasia (MMM) or transformation into acute leukaemia.9 In clinical practice, the diagnosis of MPN is generally established by a set of criteria that have mostly derived from the PVSG.4,6–8,10–14 However, PVSG diagnostic guidelines were based onhaematological parameters characterizing overt disease manifestations rather than early prodromal stages. Controversy persists concerning these initial stages of MPN that may eventually progress into full-blown and easily identifiable manifestations.15 These prodromal stages pose a number of problems, because they may not meet the classical clinical criteria for diagnosis and can only berecognized by scrutinized BM examinations in combination with biological tests and a positive JAK2 V617F mutation status.1,16 In this context, epidemiological studies and retrospective evaluations have elucidated the early stages of PV, primary myelofibrosis (PMF) and essential thrombocythaemia (ET), which often precede the overt MPN disease manifestations by several years.17–27 The diagnostic algorithmsfor PV, ET and PMF have been substantially changed to incorporate the JAK2 V617F status and similar activating mutations.1–3 As a consequence, clinicians are becoming increasingly aware that a positive mutation status28–31 may help to discriminate reactive from neoplastic conditions, even in the initial stages of disease. However, a JAK2 V617F mutation is neither specific for any MPN nor does itsabsence exclude an MPN.1,3 Taking all these considerations into account, a synoptical approach to the categorization of Ph1− MPN in order to include the whole spectrum of disease manifestations has been proposed in the new WHO diagnostic criteria (Table 1).2,3 Diagnosis of early stages of the major entities of MPN (PV, ET and PMF) can only be accomplished by a close correlation of morphology withclinical data, preferably including biological and molecular markers, and continued follow-up.

Abstract
in the interdisciplinary approach to the diagnosis of chronic myeloproliferative neoplasms (Mpn), bone marrow (bM) histopathology, clinical findings and molecular genetic abnormalities play a pivotal role. the recognition of the early stages of Mpn requires long-term follow-up studies,including sequential bM examinations in combination with biological tests and the JAK2 V617F mutation status. based on these rationales, the early stages of Mpn, including polycythaemia vera (pV), essential thrombocythaemia (et) and primary myelofibrosis (pMf), are described with corresponding haematological data. with reference to relevant complications (thromboembolic and haemorrhagic events and...