A 41-year old male presents with a 5-year history of erythrocytosis and high hematocrit levels. Laboratory test at presentation disclose high Hb (17.8 g/dL) and Hct (54%), normal WBC (6.7 × 109/L) and platelet counts (203 × 109/L), and erythropoietin (Epo) levels below local laboratory ranges (3.9 mU/mL [4.3–29]). A JAK2 mutation with 2.8% variant allele frequency (VAF) is detected on peripheral blood granulocytes (data on exon 12 and/or additional exon 14 mutations not available). The overall clinical presentation is suspected for PV and prompts a BM evaluation. A BM biopsy () features cellularity within age-related limits, preserved maturation of erythroid and myeloid lineages, and only a minor increase in megakaryocytes. The latter are sparse in distribution, with predominant mature-type morphology and only rare, scattered large forms. Thus, the lack of clear-cut major criterion 2 () does not allow a diagnosis of PV and warrants a provisional characterization as MPN-U.\nIn the present case, the histology is not inconsistent with the clinical diagnosis of PV, but it is not robust (particularly, some clustering of megakaryocytes with scattered large forms are disputable). A pre-morphologic diagnosis of MPN (i.e., a diagnosis made without full-blown MPN histology) is not common []. Indeed, it may occur in clinical settings where awareness of early phase MPNs suggests comprehensive laboratory and molecular screening, including quantitative PCR for low-burden driver gene mutations []. In such a context, it is worth noting that low VAF of JAK2 may be due to multiple base mutations in exon 14, which may hamper primer annealing and affect the quantification of the mutational burden []. Thus, searching for additional exon 14 mutations may be justified in cases with inexplicably low burdens of JAK2.
Sixty-six-year-old lady from Minnesota with history of mild asthma, recurrent generalized anxiety, and episodic hypertension with possible right subclavian steal, was referred for evaluation of erythrocytosis. Complete blood count revealed Hgb of 19.3 g/dL, Hct of 58%, leukocytes 6.5 × 109/l, and platelet count of 349 × 109/l. Historical blood count review noted Hgb of 18.6 g/dl four years prior with progressive rise in Hgb >19 g/dl. Family history was unremarkable, and the patient was a non-smoker, without history of thrombosis, or aquagenic pruritus. Her dominant symptoms included severe headaches and fatigue. Physical exam revealed hypertension, normal oxygen saturation, without palpable hepatosplenomegaly. EPO level was in the normal range at 13.9 mIU/mL and JAK2V617F/exon 12 mutation analyses were negative. Bone marrow examination lacked features of MPN. Abdominal ultrasound did not reveal renal or hepatic lesions or evidence for renal artery stenosis. CT head was without intracranial abnormalities. Sleep apnea was excluded by overnight oximetry. Monoclonal protein studies and pheochromocytoma evaluation with urinary catecholamines/metanephrines were also obtained and unrevealing. In addition, hereditary erythrocytosis workup including high-oxygen affinity Hgb variants, EPOR, BPGM, VHL, PHD2, HIF2A mutation testing was unrevealing. In the absence of a specific etiology for erythrocytosis, our working diagnosis was “idiopathic” erythrocytosis or erythrocytosis not otherwise specified. She was recommended aspirin 81 mg daily and initiated on phlebotomy due to her symptoms and labile hypertension. The need for periodic phlebotomy was based upon symptoms. At six-month follow-up, Hgb remained below 16 g/dl without phlebotomy, along with resolution of headaches and hypertension. We recommended close monitoring of blood counts every 3–6 months.