A 44-year old female with unremarkable past clinical history refers to the Hematology Clinic for persistent thrombocytosis (Hb = 15.2 g/dL; Hct = 44.8%; WBC = 12.65 × 109/L [N = 9.58 × 109/L]; Plt = 742 × 109/L). Epo levels are close to the lower limit of normal (4.29 mU/mL; range: 4.3–29), LDH is not increased (206 U/L, range: 135–214) and JAK2 mutation is detected (VAF = 5.5%). Splenomegaly is not documented at clinical examination and sonography. BM biopsy (d–f) discloses a hypercellular marrow with features of panmyelosis, maturing erythroid and myeloid lineages and polymorphous, and loosely clustering megakaryocytes with frequent giant hyperlobated forms. A minor increase in reticulin fibers is observed, consistent with MF-1 according to WHO criteria. This case displays borderline features between a pre-polycythemic phase of PV (highly supported by the very typical morphologic pattern) and pre-fibrotic PMF.\nA diagnosis of ET is ruled out by BM histology. In contrast to case 1, the still low JAK2 allele burden could be responsible for the blood count, which is not fully consistent with PV. In similar cases, concurrent hematopoiesis-modifying factors (e.g., thalassemic trait, vitamin deficiencies, malabsorption, etc.) should be investigated. In addition, a minor increase in fibrosis should warrant closer monitoring.
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.