A 46-year-old woman presents with a long-lasting history of thrombocytosis (mean platelets: 500 × 109/L) and a putative clinical diagnosis of ET treated with low-dose aspirin. A BM biopsy () is performed 20 years after clinical onset and shows hypercellular, trilinear hematopoiesis with normal myeloid-to-erythroid ratio, mildly left shifted granulopoiesis, and increased, mature-looking megakaryocytes. Blasts account for 3–4% of the hematopoietic cells and reticulin fibrosis is not increased. Driver mutations of JAK2, CALR and MPL are not detected, but targeted NGS documents the L56S RUNX1 variant. The overall morphological and molecular findings exclude ET and suggest an alternative diagnosis of RUNX1-mutated myeloid neoplasm with thrombocytosis.\nGermline RUNX1 mutations are reported in inherited forms of platelet disorders with a predisposition to myeloid malignancies []. Acquired RUNX1 derangements are instead relatively common in MDS, MDS/MPN, AML, and in contexts akin to CHIP []. In the present case, the unremarkable family history, the clinical presentation, and the histological findings exclude such diagnoses and favors MPN-U. Of note, rare cases of MPN feature RUNX1 mutations and typically undergo myelofibrotic and/or blastic progression [,]. This and 3 similar cases published by Cattaneo and colleagues [] disclose the unique features of an MPN with “high risk” genetics and an indolent, ET-like clinical course.
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%.