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 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.