An 80-year old male presents with longstanding monocytosis and progressive thrombocytosis without anemia (Hb = 13.4 g/dL; Hct = 41.3%; WBC 5.9 × 109/L [monocytes 1.42 × 109/L, 24%]; Plt = 1.348 × 109/L). Epo levels are within normal limits, while LDH levels are increased (290 U/L; range: 135–225). Morphologic assessment of a BM smear is not informative due to absent cellularity, whereas a BM biopsy (d–f) features hypercellularity with increased myeloid-to-erythroid ratio, myeloid left shifting, and a well-represented CD14+ monocyte component. The megakaryocytes display clustering with frequent giant hyperlobated forms. Small megakaryocytes with maturation defects are also present. Reticulin stain and blast count are unremarkable. Targeted next generation sequencing (NGS) on the peripheral blood cells documents mutations of TET2 (VAF = 37%), JAK2 (VAF = 26%) and CALR (VAF = 28%); the karyotype is normal.The clinic-pathologic picture is consistent with a myeloid neoplasm with monocytosis and poses the differential diagnosis between PMF and chronic myelomonocytic leukemia. While the overall histological picture is more in keeping with MPN, the left shifting of the myeloid series and the maturation defects of the megakaryocytes may, in contrast, suggest multi-lineage dysplasia. However, the mutational profile favors a JAK2/CALR-driven MPN. TET2 mutations are of little value, as they can be present (likely as early clonal events) both in MPN, MDS/MPN, and in clonal hematopoiesis of indeterminate potential (CHIP) [,,,,]. As to the unusual coexistence of driver gene mutations, a JAK2/CALR double-mutated genotype has been reported rarely in MPNs and does not correlate with specific clinical phenotypes [,]. Finally, it should be stressed that monocytosis in MPNs is mostly observed alongside fibrotic progression and may be assumed as an indicator of accelerated phase disease [,]. This was not the case for our patient.
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 [,,].