A 41-year old male presents with a 5-year history of erythrocytosis and high hematocrit levels. Laboratory test at presentation disclose high Hb (17.8 g/dL) and Hct (54%), normal WBC (6.7 × 109/L) and platelet counts (203 × 109/L), and erythropoietin (Epo) levels below local laboratory ranges (3.9 mU/mL [4.3–29]). A JAK2 mutation with 2.8% variant allele frequency (VAF) is detected on peripheral blood granulocytes (data on exon 12 and/or additional exon 14 mutations not available). The overall clinical presentation is suspected for PV and prompts a BM evaluation. A BM biopsy () features cellularity within age-related limits, preserved maturation of erythroid and myeloid lineages, and only a minor increase in megakaryocytes. The latter are sparse in distribution, with predominant mature-type morphology and only rare, scattered large forms. Thus, the lack of clear-cut major criterion 2 () does not allow a diagnosis of PV and warrants a provisional characterization as MPN-U.\nIn the present case, the histology is not inconsistent with the clinical diagnosis of PV, but it is not robust (particularly, some clustering of megakaryocytes with scattered large forms are disputable). A pre-morphologic diagnosis of MPN (i.e., a diagnosis made without full-blown MPN histology) is not common []. Indeed, it may occur in clinical settings where awareness of early phase MPNs suggests comprehensive laboratory and molecular screening, including quantitative PCR for low-burden driver gene mutations []. In such a context, it is worth noting that low VAF of JAK2 may be due to multiple base mutations in exon 14, which may hamper primer annealing and affect the quantification of the mutational burden []. Thus, searching for additional exon 14 mutations may be justified in cases with inexplicably low burdens of JAK2.
A 32-year old pregnant woman refers to the Emergency Unit for abdominal pain. Sonography reveals SVT of the splenic-portal axis and blood tests disclose anemia (Hb = 10.5 g/dL; Hct = 32%), leukocytosis (WBC = 18.2 × 109/L), and thrombocytosis (Plt = 596 × 109/L) with low Epo levels (3.3 mU/mL [4.3–29]), and JAK2 mutation. A BM biopsy (a–c) discloses PV changes with hypercellularity, expansion of the three hematopoietic lineages, clustering of polymorphic megakaryocytes, and no fibrosis. Despite this, the lack of the first major criterion hampers a formal diagnosis of PV.\nThe present case depicts the prototypic features of “masked PV”, presenting with SVT. A further bias is the concurrent pregnancy, which itself favors deep vein thrombosis. Such a clinical event may occur in any subtype of MPN, either at diagnosis or during the course of the disease. A higher thrombotic risk is related to a hyperinflammatory state and neutrophilia, which are more commonly experienced in PV []. Besides the diagnostic issues, it should be stressed that thrombotic events pose the highest threat for patients with early phase MPN. Despite the risk factors for vascular events are only partially defined, major determinants include JAK2 status, age, neutrophil count, and a positive history of thrombosis [,,].