Research Article

European Clinical Laboratory, Molecular and Pathological (ECMP) criteria for prefibrotic JAK2V617F-Thrombocythemia and Polycythemia Vera versus MPL515- and CALR-Thrombocythemia and Myelofibrosis: From Dameshek to Michiels 1950-2018

Jan Jacques Michiels*, Zwi Berneman, Wilfried Schroyens, Fibo W J ten Kate, King Lam and Hendrik De Raeve

Published: 03/01/2019 | Volume 2 - Issue 1 | Pages: 001-017


The broad spectrum of heterozygous versus homozygous JAK2V617F mutated MPN consists ET, ET with early features of PV (prodromal PV), classical PV, masked PV, advanced PV and post-PV myelofibrosis. Combined use of bone marrow histology and increased erythrocyte counts above 5.8x1012/L can replace increased red cell mass at time of presentation as the pathognomonic clue for the correct diagnosis of hetero/homozygous or homozygous mutated PV. Erythrocyte counts are in the normal range below 5.8x1012/L in heterozygous JAK2V617F mutated ET and prodromal PV but above 5.8x1012/L in heterozygous-homozygous or homozygous mutated PV. The bone marrow cellularity and morphology in pre-fibrotic ET, prodromal PV and PV carrying the JAK2V617F mutation are overlapping showing clustered increase of large mature pleomorphic megakaryocytes (M) with no increase of cellularity (<60%) in ET. The bone marrow is hypercellular (60%-80%) due to increased erythropoiesis megakaryopoiesis (EM) in prodromal and classical PV and trilinear hypercellular (80%-100% due increased megakaryopoiesis, erythropoiesis and granulopoiesis (EMG) in advanced PV and masked PV. Bone marrow cellularity ranging from normal (<60%) in ET to increased erythropoiesis (EM) in prodromal PV to hypercellular (80-100%) in advanced PV and masked PV largely depends on increasing JAK2V617F mutation load from low to high on top of other biological MPN variables like constitutional symptoms during long-term follow-up. MPL515 mutated ET is featured by an increase of clustered small and giant megakaryocytes with hyper-lobulated staghorn-like nuclei in a normal cellular bone marrow. The third entity of pronounced JAK2/MPL wild type ET associated with primary megakaryocytic granulocytic myeloproliferation (PMGM) without PV features proved to be caused by calreticulin (CALR) mutation. CALR mutated thrombocythemia is characterized by dual proliferation of megakaryocytic and granulocytic bone marrow proliferation of dense clustered large to giant immature dysmorphic megakaryocytes with bulky (bulbous) hyperchromatic nuclei, which are not seen in MPL515-mutated Thrombocythemia and JAK2V617F-Thrombocythemia, prodromal PV and classical PV.

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