Osman İlhami ÖZCEBE, İbrahim Celalettin HAZNEDAROĞLU, Salih AKSU, Nilgün SAYINALP, Hakan GÖKER, Elifcan ALADAĞ, Haluk DEMİROĞLU, Yahya BÜYÜKAŞIK

Unclassifiable non-CML classical myeloproliferative diseases with microcytosis: findings indicating diagnosis of polycythemia vera masked by iron deficiency

Background/aim: Polycythemia Vera (PV) is a myeloproliferative disorder characterized by overproduction ofmorphologically normal red blood cells (RBCs), granulocytes, and platelets, a phenotype that is caused by a mutation(V617F) in Janus kinase 2 (JAK2). However, JAK2 V617F is also found in approximately 50% of patients with essentialthrombocytosis and primary myelofibrosis, rendering its presence nonspecific as a diagnostic test. An increased red cellmass is a major criterion for the diagnosis of PV according to World Health Organization (WHO) 2016 criteria. Highhemoglobin (Hgb) or Hematocrit (Hct) are universally used as indicators of an increased red cell mass for the diagnosisof PV. However, conditions such as iron deficiency (ID) with decreased mean cell volume may mask the diagnosis due tononelevated Hct level. The aim of this study was to investigate the clinical characteristics of the patients with unclassifiablenon-CML classical myeloproliferative disease with microcytosis (MPD/M) and nonelevated Hgb and Hct levels at diagnosisand to determine if some of these cases could be real PV cases masked due to ID-related microcytosis.Materials and methods: There were 23 MPD/M cases among 208 non-CML classical MPD cases (11%). Among 22 patientswho had adequate test results related to the cause of microcytosis, ID and beta-thalassemia trait (TT) were the apparentcauses of microcytosis in 15 and 1 cases, respectively.Results: Clinicopathological correlations revealed consistently positive JAK2 V617F mutation status (20/20, 100%),frequently elevated RBC count (17/23, 73.9%), and PV-compatible bone marrow findings (10/12, 83.3%). These findingsare compatible with PV instead of essential thrombocytopenia or primary myelofibrosis. In spite of frequent cytoreductivetreatment, 3 patients developed increased Hgb/Htc levels during median 58.2 (279–63) months’ follow-up.Conclusion: These data show that the majority of MPD/M cases are PV patients masked due to ID-related microcytosis.

PDF

___

1. Barbui T, Thiele J, Gisslinger H, Finazzi G, Vannucchi AM et al. The 2016 revision of WHO classification of myeloproliferative neoplasms: Clinical and molecular advances. Blood Reviews 2016; 30: 453-459.
2. Büyükaşik Y, Al IR, Ar C, Turgut M, Yavuz S et al. Polycythemia vera: diagnosis, clinical course, and current management. Turkish Journal of Medical Science 2018; 48: 698-710.
3. Sirhan S, Tefferi A. Red cell mass measurement in polycythemia: Evaluation of performance and added value. Blood 2004; 104: 427a-428a.
4. Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 2007; 110: 1092-1097.
5. Alvarez-Larran A, Angona A, Ancochea A, Garcia-Pallarols F, Fernandez C et al. Masked polycythaemia vera: presenting features, response to treatment and clinical outcomes. European Journal of Haematology 2016; 96: 83-89.
6. Arber DA, Orazi A, Hasserjian R. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia (vol 127, pg 2391, 2016). Blood 2016; 128: 462-463.
7. Barbui T, Carobbio A, Rumi E, Finazzi G, Gisslinger H et al. In contemporary patients with polycythemia vera, rates of thrombosis and risk factors delineate a new clinical epidemiology. Blood 2014; 124: 3021-3023.
8. Silver RT, Chow W, Orazi A, Arles SP, Goldsmith SJ. Evaluation of WHO criteria for diagnosis of polycythemia vera: a prospective analysis. Blood 2013; 122: 1881-1886.
9. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127: 2391-2405.
10. Keohane C, McMullin MF, Harrison C. The diagnosis and management of erythrocytosis. BMJ 2013; 347: f6667.
11. Alvarez-Larran A, Perez-Encinas M, Ferrer-Marin F, Hernandez-Boluda JC, Ramirez MJ et al. Risk of thrombosis according to need of phlebotomies in patients with polycythemia vera treated with hydroxyurea. Haematologica 2017; 102: 103-109.