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.
A 79-year old woman with beta-thalassemia minor and IgG+ monoclonal gammopathy of undetermined potential presents with stable Hb levels and a steady increase of platelet count (Hb = 13.2 g/dL; Hct = 43.5%; WBC = 14.2 × 109/L [N 9.67]; Plt = 866 × 109/L; LDH levels within normal ranges, Epo not assessed). JAK2 mutation is detected on peripheral blood (VAF not known). A BM biopsy (g–i) is hypercellular, with erythroid precursor expansion, megaloblastosis, and clustering of megakaryocytes, ranging in morphology from small, hypolobulated forms (including naked nuclei) to giant, hyperlobulated (“staghorn”) cells. No increase in reticulin fibers and CD34+ blasts is observed; the lympho-plasmacytic infiltrate is unremarkable.\nThe global picture strongly favors a diagnosis of MPN, but the differential diagnosis between ET and PV cannot be definitively settled. The former is favored by thrombocytosis and by prominent ET-type megakaryocyte morphology, and the latter is supported by the coexistence of neutrophilia alongside with normal Hb levels (possible effect of the concurrent thalassemic trait) [].