Abstract
Blood and bone features in JAK2V617F mutated prefibrotic essential thrombocythemia (ET) and polycythemia vera (PV) are overlapping in terms of increased cellularity due to increased erythropoiesis and pleomorphic megakaryocytes indicating the need to measure red cell mass (RCM) according to PVSG and WHO criteria. The JAK2V617F mutated myeloproliferative neoplasms (MPN) appeared to be a broad biological continuum of normocellular ET, ET with features of polycythemia vera (prodromal PV), classical PV, advanced PV, Inapparent PV (IPV) with splenomegly, masked PV or hypercellular ET due to megakaryocytic granulocytic myeloproliferation (ET.MGM) when the 2013 WHO and European Clinical, Molecular and Pathological (WHO-CMP) criteria are applied. The megakaryocytes morphology may change from pleomorphic to dysmorphic in advanced PV, in IPV and in masked PV (ET.MGM) as bone marrow cellularity, the degree myelofibrosis and the JAK2V617F mutation load increase during long-term follow-up. Erythrocytes above the upper limit of normal (5.8×1012/L), but not hemoglobin and hematocrit is clearly correlated with increased red cell mass (RCM) above (30) ml/kg) and therefore diagnostic for PV and idiopathic erythrocythemia (IE) on top of pathognomonic MPN bone marrow histology in newly diagnosed PV patients with normal mean cell volume (MCV) of erythrocytes and no or minor of splenomegaly. Erythrocyte count remain above the upper limit of normal in PV and IE in complete hematological remission by phlebotomy alone as the consequence of iron deficiency induced microcytic erythrocytes that correct the blood volume (RCM), hemoglobin and hematocrit to normal. The combination of increased RCM, increased plasma volume, and normal or low erythrocyte counts is characteristic for IPV with significant splenomegaly as the only cause of increased blood volume without symptoms of hypervolumemia.
Highlights
According to Dameshek & Henthel a definite diagnosis of polycythemia vera (PV) can be made by the combined occurrence of plethoric appearance, splenomegaly, elevated erythrocyte count above 6×1012/L, elevated platelet count, and elevated hematocrit [1]
Between 1997 and 2013 we prospectively studied the presenting blood and bone marrow features during long-term follow-up in 10 cases of JAK2V617F mutated myeloproliferative neoplasms (MPN, 6 essential thrombocythemia (ET) and 4 PV patients) and could demonstrate the existence of sequential stages of JAK2V617F mutated MPN patients including normocellular ET, ET with PV features, classical PV and hypercellular ET associated with megakaryocytic granulocytic myeloproliferation (ET.megakaryocytic and granulocytic myeloproliferation (MGM)) when the integrated WHO and European Clinical, Molecular and Pathological (WHO-CMP) criteria are applied (Tables 2 and 3)
The megakaryocyte pleomorphic morphology were identical in appearance in symptomatic ET and PV patients
Summary
According to Dameshek & Henthel a definite diagnosis of polycythemia vera (PV) can be made by the combined occurrence of plethoric appearance, splenomegaly, elevated erythrocyte count above 6×1012/L, elevated platelet count, and elevated hematocrit [1]. We were able to prospectively document the prefibrotic stages of ET and PV in 30 cases by the combined use of the Rotterdam clinical and pathological (RCP) features for ET and PV (Table 1) [3,4]. Between 1997 and 2013 we prospectively studied the presenting blood and bone marrow features during long-term follow-up in 10 cases of JAK2V617F mutated myeloproliferative neoplasms (MPN, 6 ET and 4 PV patients) and could demonstrate the existence of sequential stages of JAK2V617F mutated MPN patients including normocellular ET, ET with PV features (prodromal PV), classical PV and hypercellular ET associated with megakaryocytic granulocytic myeloproliferation (ET.MGM) when the integrated WHO and European Clinical, Molecular and Pathological (WHO-CMP) criteria are applied (Tables 2 and 3). The 2013 WHO- CMP classification of the MPNs encompasses a wider scale of specific clinical, molecular and bone marrow histology features of JAK2V617F positive ET and PV, thereby making early diagnosis, proper staging, and timely initiation of targeted treatment options possible
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