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

Abstract

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.