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Current diagnostic criteria for the chronic myeloproliferative disorders (MPD) essential thrombocythemia (ET), polycythemia vera (PV) and chronic idiopathic myelofibrosis (CIMF)

2006; Elsevier BV; Volume: 55; Issue: 2 Linguagem: Inglês

10.1016/j.patbio.2006.06.002

1768-3114

Jan Michiels, Z. Bernema, Dirk Van Bockstaele, Hendrik De Raeve, Wilfried Schroyens,

Eosinophilic Disorders and Syndromes

The clinical criteria for the diagnosis of essential thrombocythemia (ET) according to the polycythemia vera study group (PVSG) do not distinguish between ET and thrombocythemia associated with early stage PV and prefibrotic chronic idiopathic myelofibrosis (CIMF). The clinical criteria of the PVSG for the diagnosis of polycythemia vera (PV) only detects advanced stage of PV with increased red cell mass. The bone marrow criteria of the World Health Organization (WHO) are defined by pathologists to explicitly define the pathological criteria for the diagnostic differentiation of ET, PV, and prefibrotic and fibrotic CIMF. As the clinical PVSG and the pathological WHO criteria show significant shortcomings, an updated set of European Clinical and Pathological (ECP) criteria combined with currently available biological and molecular markers are proposed to much better distinct true ET from early PV mimicking ET, to distinguish ET from thrombocythemia associated with prefibrotic CIMF, and to define the various clinical and pathological stages of PV and CIMF that has important therapeutic and prognostic implications. Comparing the finding of clustered giant abnormal megakaryocytes in a representative bone marrow as a diagnostic clue to MPD, the sensitivity for the diagnosis of MPD associated with splanchnic vein thrombosis was 63% for increased red cell mass, 52% for low serum EPO level, 72% for EEC, and 74% for splenomegaly indicating the superiority of bone marrow histopathology to detect masked early and overt MPD in this setting. The majority of PV and about half of the ET patients have spontaneous EEC, low serum EPO levels and PRV-1 over-expression and are JAK2 V617F positive. The positive predictive value for the diagnosis of PV of spontaneous growth of endogenous erythroid colonies (EEC) of peripheral blood (PB) and bone marrow (BM) cells is about 80–85% when either PB or BM EEC assays, and up to 94% when BM and PB EEC assays were performed. The diagnostic impact of low serum EPO levels (ELISA assay) in a large study of 186 patients below the normal range (< 3.3 IU/l) had a sensitivity specificity and positive predictive value of 87%, 97% and 97.8%, respectively, for the diagnosis of PV. There is a significant overlap of serum EPO levels in PV versus control and controls versus SE. The specificity of a JAK2 V617F PCR test for the diagnosis of MPD is high (near 100%), but only half of ET and MF (50%) and the majority of PV (up to 97%) are JAK2 V617F positive. The use of biological markers including JAK2 V617 PCR test, serum EPO, PRV-1, EEC, leukocyte alkaline phosphatase score and peripheral blood parameters combined with bone marrow histopathology has a high sensitivity and specificity (almost 100%) to diagnose the early and overt stages of ET, PV and CIMF in JAK2 V617F positive and negative MPDs. Les critères cliniques de diagnostic de la thrombocytémie essentielle (TE) développés par le PVSG ne permettent pas de distinguer les TE des formes débutantes avec thrombocytose de PV et de MFI. Ces critères ne permettent par ailleurs que le diagnostic de formes patentes de PV, avec une claire augmentation du volume globulaire. Les critères OMS de diagnostic des SMP incluent la biopsie médullaire, avec des critères définis par les pathologistes pour clairement différencier TE, PV, MFI au stade préfibrotique ou fibrotique. Nous proposons une mise à jour des critères diagnostiques utilisant les marqueurs biologiques et moléculaires actuellement disponibles, dans le but de distinguer des TE pures les formes débutantes de PV et de MFI mimant les TE, et de définir les stades cliniques et anatomopathologiques de PV et MFI, ce qui a d'importantes conséquences pronostiques et thérapeutiques. Sont notamment discutés, la valeur des données morphologiques sur la biopsie de moelle osseuse, du dosage d'érythropoïétine, de l'existence de colonies érythroïdes ou mégacaryocytaires spontanées, de l'hyperexpression du gène PRV-1, et de la mutation V617F de JAK2. L'utilisation de ces marqueurs en association avec les données morphologiques de la moelle osseuse permet de diagnostiquer avec une haute sensibilité et spécificité (proches de 100 %) les stades patents mais aussi précoces de TE, PV et MFI, qu'ils soient V617F JAK2 positifs ou négatifs.