A 17-year-old Caucasian male, a high school student from Missouri was referred for evaluation of unexplained erythrocytosis. He reported a myriad of symptoms including nausea, vomiting, abdominal pain, weight loss, fatigue, headaches, cold hands and feet with numbness and tingling, hyperhidrosis, palpitations, and pruritus. He was a non-smoker without illicit drug or hormone use. Family history was unremarkable. On physical examination, no cutaneous, abdominal or neurological abnormalities were noted. A review of serial blood counts showed a consistent elevation in Hgb >16.5 g/dl, with peak Hgb/Hct of 18.3 g/dl/52.4% and normal leukocyte and platelet counts. PV was excluded with a negative JAK2V617F/exon 12 mutation screen and elevated EPO at 22.6 mIU/mL (normal range; 2.6–18.5 mIU/mL). Bone marrow aspirate/biopsy was without features of a MPN. Hereditary erythrocytosis evaluation did not reveal high-affinity Hgb variants or mutations in 2,3-Bisphosphoglycerate Mutase (BPGM)(exons 1–4), EPOR (exon 8), or oxygen-sensing pathway proteins, including hypoxia-inducible factor 2 α (HIF2A) encoded by endothelial PASS domain protein 1 (EPAS1) (exons 9 and 12), prolyl hydroxylase 2 (PHD2) encoded by egl-9 family hypoxia-inducible factor 1(EGLN1)(exons 1-5), von Hippel Lindau (VHL) (three coding exons and intron/exon boundaries). Chest/abdominal imaging, arterial blood gas, transthoracic echocardiogram with shunt study, urinary catecholamines/metanephrines were unremarkable. Interestingly, MRI brain/spine revealed multiple cerebrovascular malformations; both developmental venous anomalies and cavernous hemangiomas in the frontal and temporal regions. Accordingly, the cerebrovascular malformations were hypothesized to be a plausible link to the patient’s erythrocytosis. Surgical intervention was not feasible due to the presence of multiple anomalies. He was initiated on phlebotomies with marked improvement in symptoms; thereafter, need for periodic phlebotomies was determined by symptoms rather than a target Hct value. This previously published case underscores the importance of a systematic diagnostic approach to JAK2 unmutated erythrocytosis [].
A 79-year old woman with beta-thalassemia minor and IgG+ monoclonal gammopathy of undetermined potential presents with stable Hb levels and a steady increase of platelet count (Hb = 13.2 g/dL; Hct = 43.5%; WBC = 14.2 × 109/L [N 9.67]; Plt = 866 × 109/L; LDH levels within normal ranges, Epo not assessed). JAK2 mutation is detected on peripheral blood (VAF not known). A BM biopsy (g–i) is hypercellular, with erythroid precursor expansion, megaloblastosis, and clustering of megakaryocytes, ranging in morphology from small, hypolobulated forms (including naked nuclei) to giant, hyperlobulated (“staghorn”) cells. No increase in reticulin fibers and CD34+ blasts is observed; the lympho-plasmacytic infiltrate is unremarkable.\nThe global picture strongly favors a diagnosis of MPN, but the differential diagnosis between ET and PV cannot be definitively settled. The former is favored by thrombocytosis and by prominent ET-type megakaryocyte morphology, and the latter is supported by the coexistence of neutrophilia alongside with normal Hb levels (possible effect of the concurrent thalassemic trait) [].