A 32-year old male with unremarkable past clinical history presents with persistent thrombocytosis (Hb = 15.6 g/dL; Hct = 46.1%; WBC = 6.76 × 109/L; Plt = 745 × 109/L; Epo and LDH levels within normal ranges). JAK2 mutation is detected (VAF = 10.1%) on peripheral blood granulocytes. A BM biopsy (a–c) features striking hypocellularity without morphologic atypia. A slight decrease in the myeloid-to-erythroid ratio is noted with mildly increased, polymorphic megakaryocytes consisting of mature-looking to giant, hyperlobulated forms. There is no evidence of BM fibrosis and CD34+ blasts are not increased. The clinicopathologic synopsis supports MPN, but the very unusual morphologic picture favors a provisional diagnosis of MPN-U. Hypocellularity is uncommon in clonal myeloid disorders in general and barely reported in both early and chronic phase MPN. It may nonetheless be encountered in late-stage disease with the classical picture of MF with myeloid metaplasia. In this setting, the BM niche is overwhelmed by the stromal component with consequent peripheralization of hematopoietic cells. In the current case, the diagnosis of MPN is strongly supported by the laboratory findings, by the presence of a driver mutation, and by megakaryocyte morphology. Even though most clues point towards ET, the relative increase in the erythroid progenitors and Hb levels at the upper limit of normal cannot definitively rule out early phase PV with ET-like presentation and very atypical BM morphology.
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.