The Significance of Bone Marrow Biopsy andJAK2^V617FMutation in the Differential Diagnosis Between the “Early” Prepolycythemic Phase of Polycythemia Vera and Essential Thrombocythemia

Abstract

It has been suggested that polycythemia vera (PV) could be preceded by an "early" phase of the disease (e-PV), in which the increase in the red cell parameters is lower than required for a PV diagnosis. In this study, we compared the clinicopathologic and molecular features of 17 patients with e-PV with those of 14 patients with essential thrombocythemia (ET) and 19 with PV. The results for e-PV were more similar to those for PV than for ET. In fact, patients with e-PV were characterized by an increase in the red cell parameters, splenomegaly (P<.05), and hepatomegaly (P=.038), together with hypercellular bone marrow due to increased erythropoiesis and granulopoiesis, associated with megakaryocytic hyperplasia, with pleomorphic aggregates (P<.001). The frequency of the JAK2V617F mutation was similar in e-PV (16 cases tested [100%]) and PV (18/19 [95%]) but was significantly lower (7/13 [54%]) in ET (P=.0007). We propose a diagnostic algorithm helpful to distinguish ET from the early prepolycythemic phase of PV.

Reproducibility of the WHO histological criteria for the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms

“…[15][16][17][18] In this study, aimed to evaluate the inter-observer reproducibility of the morphological parameters considered for the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms, we found an overall high level of agreement (470%) for about all these features. Interestingly, the percentage of agreement ranged among reviewers in relation to the individual pathological entity and to the different categories of each morphological feature.…”

“…The four reviewers were instructed to classify the quantitative morphological variables (numbered 1, 2, 4, 6, 7) with three possible categories ('reduced', 'normal' or 'increased') and the qualitative variables (numbered 3,5,[8][9][10][11][12][13][14][15][16][17][18] with two ('absent' or 'present'). 12 To register a qualitative variable as 'present', the reviewer had to identify that specific morphological features at least two times in the same slide.…”

Prodromal myeloproliferative neoplasms: The 2008 WHO classification

“…As shown by an elaborate epidemiological study in 88 patients with an confirmed high hematocrit level (women >0.48, men >0.51) after an observation time of 5 years progression into manifest PV [5,7] occurred in three patients [71]. These prodromal stages may occasionally present with an excess in platelets (Table I) and clinically mimic ET [72], particularly when the outdated PVSG criteria [5,21] were applied [70]. In the original series of the PVSG trial differentiation between PV and ET seemed to be difficult in several cases that apparently exhibited a transition between these two entities [21].…”

“…Although it is certainly difficult to tackle the very beginning of PV, it is tempting to assume that in the series of patients previously described to present idiopathic (pure, benign) erythrocytosis or an occult/smouldering PV, a considerable number may be consistent with initial disease manifestations [63][64][65][66][67], but particularly those with positive JAK2V617F mutation status and high allele burden [3,10,15,28,29,[68][69][70]. As shown by an elaborate epidemiological study in 88 patients with an confirmed high hematocrit level (women >0.48, men >0.51) after an observation time of 5 years progression into manifest PV [5,7] occurred in three patients [71].…”

“…Altogether persuasive evidence has been produced that even in prodromal stage PV histopathology plays a prominent role for establishing the diagnosis [58] in combination with JAK2V617F and related mutation studies [3,8,10,17,69,70,77,78], the determination of the Epo level [64,[79][80][81] and/or the laboratory intensive as well as timeconsuming cell culture studies [82,83] that are neither absolutely specific for PV [84][85][86] nor standardized for clinical use [87]. All patients developed overt polycythemic PV about 6 months to 2 years later, at the beginning 35 patients may be clinically mimic ET when applying the PVSG criteria [5,7,21].…”