Early-Polycythemia Vera (e-PV) with Thrombocytosis: Clinical Characteristics, Morphological Features and JAK2^V617F Mutational Status Contributing to the Differential Diagnosis with Essential Thrombocythemia.

According to the recently published WHO classification, two well-defined stages of PV, known as polycythemic phase and post-polycythemic myelofibrosis, are clearly recognizable. A few years ago, it has been reported that erythrocytosis may develop in the course of ET, and that PV may present in the early stage of the disease with an elevated platelet count, mimicking ET. Recently, it has been suggested that PV could be preceded by an “early” phase of the disease (Thiele et al, 2005), in which the increase in the red cell mass or hemoglobin level are lower than requested for the diagnosis either by the updated diagnostic criteria of the Polycythemia Vera Study Group (PVSG) or by the WHO classification. Very recently, the European Clinical and Pathological (ECP) criteria for the diagnosis of the “early” PV have been published (Michiels et al, 2006).

The aim of this study is to examine the clinical features, the bone marrow biopsies (BMBs) and the JAK2^V617F mutational status of 17 e-PV patients. All presented, at diagnosis, the clinical and morphological features of ET, and manifested a well-developed polycythemic phase of PV during the course of the follow-up (median 8.6 yrs; range 2–17 yrs). We compared the study group with 19 cases of PV and 14 cases of ET (according to WHO) as controls. Clinically, e-PV patients revealed at diagnosis increased levels of Hb (e-PV: 15.5g/dl; ET: 13.8g/dl; PV: 16.9g/dl), Hct (e-PV: 45.9%; ET: 41%; PV: 51.8%) and Ptl count (e-PV: 854×10⁹/l; ET: 877×10⁹/l; PV: 691×10⁹/l), splenomegaly (e-PV: 43%; ET: 0%; PV: 61%) and hepatomegaly (e-PV: 53%; ET: 14%; PV: 61%). Morphological examination of the BMBs in e-PV patients demonstrated moderate to marked increase of the BM cellularity (e-PV: 65%; ET: 0%; PV: 73%) and pleiomorphic (i.e. clusters of small to giant) megakaryocytes (e-PV: 83%; ET: 20%; PV: 100%). Moreover, increased (e-PV: 100%; ET: 14%; PV: 100%) and left shifted erythropoiesis (e-PV: 82%; ET: 0%; PV: 79%), and increased (e-PV: 65%; ET: 14%; PV: 100%) and left-shifted granulopoiesis (e-PV: 65%; ET: 0%; PV: 58%) were also found. Mutational status analysis revealed that 15/15 e-PV cases (100%) carried the JAK2^V617F mutation (6 homozygous and 9 heterozygous), in comparison to 7/13 (54%) ET (1 homozygous, 6 heterozygous) and to 17/19 (89%) PV (5 homozygous, 12 heterozygous). In conclusion, the results of our study confirm the existence of a “early” phase of PV that may mimic ET. A diagnostic algorithm, useful to differentiate e-PV from ET, may be obtained considering altogether the clinical, morphological and molecular characteristics of each patient.