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 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) [].