Diagnosis of chronic myeloproliferative neoplasms with special emphasis on early stages

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 myelofibrotic transformation) and ensuing therapeutic options, the diagnostic value of a proper evaluation of the initial BM biopsies can not be overemphasized. Pre-polycythaemic stage PV, which often presents with a low but increasing haemoglobin level at onset, can be diagnosed from a positive JAK2 V617F mutation status, the characteristic BM features of panmyelosis (trilineage increase in erythro-, granulo- and megakary-opoiesis) and a serum erythropoietin level below the normal range. Early manifestations of ET can be recognized by lowering the platelet count (>600 x 10⁹/litre) to 450 × 10⁹/litre, BM morphology (predominance of large to giant megakaryocytes without abnormalities of maturation), as well as relevant complications (haemorrhage and vascular events). Histopathological characteristics and accompanying clinical features play a distinctive role in the establishment of pre-fibrotic early PMF. Due to their significant differences in progression to myelofibrosis and outcome, an important issue is the discrimination between pre-fibrotic PMF, which frequently presents with thrombocytosis, and ET. Up-to-date diagnostic criteria, originally established by the World Health Organization (WHO) and recently revised by a panel of experts, should be generally applied and validated in prospective clinical trials to achieve a consensus-based working diagnosis.

Keywords: bone marrow features, chronic myeloproliferative neoplasms, essential thrombocythaemia, JAK2 V617F mutation, myelofibrotic transformation, myeloid metaplasia, polycythaemia vera, primary myelofibrosis, prodromal stages, prognosis