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.
An 84-year-old woman presented with a four-week history of dizziness, headaches, and vertigo. Her past medical history included hypercholesterolemia, hypothyroidism, depression and osteopenia, and her regular medication consisted of atorvastatin, levothyroxine, citalopram, calcium, and cholecalciferol. She was a nonsmoker and had no history of cardiac, pulmonary, or renal disease. There was a family history of HBT but no other hematological disorders. The patient was known to have HBT with steady Hb and hematocrit (Hct) values marginally below the lower limit of normal, on yearly check-ups until two years prior to her presentation. A routine complete blood count arranged by her primary care physician nine months prior to presentation had shown Hb 14 g/dL, Hct 45.6%, red cell count (RBC) 6.13 x 1012/L with microcytosis and normal white cell and platelet counts.\nPhysical examination revealed no remarkable findings. Her arterial oxygen saturation was 97%. Abdominal ultrasound examination showed a fatty liver and normal-sized spleen. Computerized brain tomography revealed changes of ischemic leukoencephalopathy. Blood tests showed RBC 7.01 x 1012/L, Hb 15.8 g/dL, Hct 50.4%, mean corpuscular volume (MCV) 69 fL, white cell count 6.76 x 109/L, and platelet count 236 x 109/L. Serum lactate dehydrogenase was 326 U/L (normal range 135-225 U/L), while the rest of her biochemistry profile was unremarkable. Serum levels of iron, ferritin, and vitamin B12 were normal. Hb electrophoresis showed an elevated HbA2 of 3.8% (reference range 1.8-3.2), fetal hemoglobin (HbF) of 0.5% (reference <2%) and no evidence of abnormal Hbs, which was compatible with HBT. Serum Epo levels were low at 3.0 mU/mL (reference range 4.3-29.0 mU/mL). Bone marrow biopsy appearances were compatible with a myeloproliferative neoplasm of the PV type, without excess fibrosis or increased numbers of immature cells. The diagnosis of PV was confirmed by identifying heterozygocity for the JAK2 V617F mutation in peripheral blood white cells, using a real-time polymerase chain reaction assay with hybridization probes and melting curve analysis.\nThe patient showed a good clinical and laboratory response to the administration of low-dose aspirin and hydroxyurea with a target Hct of 42%.