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.
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.