[Pathological characteristics of megakaryocytes in myeloproliferative neoplasms and their correlation with driver...

Objective: To investigate the pathological characteristics of megakaryocytes in myeloproliferative neoplasms(MPN)and their correlations with driver gene mutations. Methods: Trephine specimens administered for 160 patients with MPN from February 2012 to October 2017 were reevaluated according to the World Health Organization(WHO)'s(2016)diagnostic criteria. Results: This cohort of patients included 72(45.0%)men, with the median age of 59(range, 13-87)years, comprising 39 with polycythemia vera(PV), 33 with essential thrombocythemia(ET), 37 with prefibrotic/early-primary myelofibrosis(pre-PMF), 37 with overt PMF, 1 with post-ET MF, 2 with post-PV MF, and 11 with MPN-unclassifiable(MPN-U)after the re-diagnosis. With PV, ET, pre-PMF, and overt PMF changes, proportions of dense clusters, hypolobulated nuclei, and naked nuclei of megakaryocytes gradually increased, whereas erythropoiesis gradually decreased. Proportions of reticulin, collagen, and osteosclerosis grades of ≥1 also increased. Dense clusters, hypolobulated nuclei, and naked nuclei of megakaryocytes were negatively correlated with erythropoiesis and positively correlated with granulopoiesis and fibrosis. In patients with pre- and overt PMF, dense clusters and naked nuclei of megakaryocytes were positively correlated with fibrosis. Patients with JAK2V617F MPN had significantly increased erythropoiesis(P=0.022). Patients with CALR-mutated MPN were characterized by increased loose and dense clusters; paratrabecular distribution and naked nuclei of megakaryocytes(P=0.055, P=0.002, P=0.018, P=0.008); and increased reticulin, collagen, and osteosclerosis(P=0.003, P<0.001, P=0.001). In patients with pre- and overt PMF, patients with JAK2V617F had increased cellularity(P=0.037). CALR-mutated patients had increased dense clusters and giant sizes of megakaryocytes, collagen, and osteosclerosis(P=0.055, P=0.059, P=0.011, P=0.046). Conclusion: Megakaryocytes showed abnormal MPN morphology and distribution, which were related to fibrosis. CALR mutation was probably associated with abnormal morphology and distribution of megakaryocytes and fibrosis.