{'fraction_non_alphanumeric': 0.05929702173329756, 'fraction_numerical': 0.052320901529380195, 'mean_word_length': 4.81591263650546, 'pattern_counts': {'":': 0, '<': 2, '<?xml version=': 0, '>': 6, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Masked polycythemia vera: analysis of a single center cohort of 2480 red cell masses

Classical Philadelphia-negative myeloproliferative neoplasms (MPN) are characterized by the presence of driver mutations (JAK2, CALR or MPL) and comprise polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Recently masked PV (mPV) was defined in the 2016 World Health Organisation classification of MPN as a new JAK2V617F-positive entity with a phenotypic presentation mimicking ET (apparently isolated thrombocytosis) but associated to endogenous erythroid colony formation (EEC) as found in PV or histological findings of PV (initially described as latent or inapparent PV). Distinguishing ET from mPV is impossible based on hemoglobin or hematocrit values but is of the utmost importance since patients with mPV may have a high risk of thrombosis. If mPV is misdiagnosed as ET, therapy is based on antiaggregating agents (AA) only whereas phlebotomy + AA or cytoreductive therapy + AA would be more adequate. We previously showed that another proportion of JAK2+ ET patients have early-stage polycythemia when red blood cell measurement (RCM) is systematically measured. Recently, Alvarez-Larran et al. and others showed that mPV could be identified using red blood cell mass (RCM) measurement (masked PV presenting an increased RCM above 125%) in place of bone marrow histology. This study included a small number of patients (83 overt PV and 68 mPV) and did not compare mPV to ET patients with hematocrit levels within the same order of magnitude and thus failed to explain why mPV present sub-normal hematocrit and hemoglobin levels. To further analyze these novel World Health Organisation entities and the role of RCM in their diagnosis, we retrospectively analyzed 2,480 consecutive patients in whom a RBCM was performed in our center for suspected polycythemia during the last 7 years. We first compared JAK2V617F positive and negative patients (Online Supplementary Table S1). Then, we analyzed the characteristics at diagnosis of the following groups of patients: “PV” (RCM >125%, presence of JAK2V617F mutation, hemoglobin higher than 18.5/16.5g/dL [male/female]; “masked PV” (presence of JAK2V617F mutation, RCM >125% and hemoglobin 16.5-18.5/1516.5g/dL [male/female]; “JAK2V617F ET with hemoglobin level identical to mPV” (presence of JAK2V617F mutation, RCM<125%, hemoglobin 16.5-18.5/15-16.5g/dL [male/female]). We note that in this cohort 37.3% of the 2480 patients had an RCM >125% confirming polycythemia. All but one JAK2V617F-positive patients with hemoglobin >16.5/18.5g/dL (female/male) (n=117) had a RCM >125%. Patients with lower hemoglobin levels (1516.5g/dL (56 females) and 16.5-18.5g/dL (112 males)) could be further classified according to the RCM level between masked PV (n= 113) when RCM was > 125% or JAK2V617F-positive ET (n=55) when RCM was <125% of predicted value (Figure 1). Variables were summarized as frequencies and percentages or means ± standard deviation, min-max or median and lowest datum still within the 1.5 interquartile range of the lower quartile, and the highest datum still within the 1.5 interquartile range of the upper quartile (Tukey boxplot), as appropriate. Comparisons were performed using Student t-test. Mean ages (min-max) were 63.8 years (y) (32.1-91.1) in PV, 60.3y (18.3-96.9) in mPV (p PV vs. mPV=not significant (NS)) and 56.6y (18.3-87.6) in ET (PV vs. mPV P=0.003; ET vs. mPV P=NS). Characteristics of patients are represented in Figure 2. According to the definitions of patients subgroups, mean hemoglobin levels were statistically different between PV and mPV or ET: 18.6g/dL (16.5-22.3) in PV versus 16.6g/dL (15-18.4) in mPV and