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Increased microvessel density contributes to abnormal BM and spleen microenvironment in myelofibrosis (MF). Taking advantage of the JAK2V617F mutation as a marker of malignancy, in the present study, we investigated whether splenic endothelial cells (ECs) obtained from capillaries by laser microdissection or from fresh spleen tissue by cell culture or cell sorting harbored such mutation in patients bearing the mutation in their granulocytes and undergoing splenectomy for therapeutical reasons. To extend the analysis to the ECs of large vessels, endothelial tissue from the splenic vein was also studied. We found JAK2V617F+ ECs in 12 of 18 patients also bearing the mutation in their granulocytes. In 3 patients, the mutation was found in at least 2 different EC samples obtained by laser microdissection, cell culture, or cell sorting. The mutation was detected in the splenic vein ECs of 1 of 6 patients investigated. In conclusion, we provide evidence that some ECs from the spleen and splenic veins of patients with MF bear the JAK2V617F mutation. We suggest that splenic ECs are involved in the process of malignant transformation in MF.

Introduction The purpose of the study was to evaluate the differences in individual histopathologic placental lesions in pregnancies complicated by early‐onset (<32 weeks at diagnosis) and late‐onset (≥32 weeks at diagnosis) fetal growth restriction (FGR). Material and methods A cohort study of 440 singleton pregnancies complicated by FGR, diagnosed according to standard ultrasonographic criteria, followed up and delivered at the same institution between 2010 and 2016. Placental lesions were classified according to the Amsterdam Placental Workshop Consensus Criteria. Pathologic examination of placentas from 113 healthy singleton term pregnancies served as controls. Binary and multinomial logistic regression models were used to evaluate the independent association of placental lesions with the type of FGR. Results In our cohort the prevalences of early and late FGR were 37.3% (164/440) and 62.7% (276/440), respectively. The overall rates of preeclampsia (69/164 vs 59/276, P < 0.01) and absent/reversed umbilical artery pulsatility indices (61/164 vs 14/276, P < 0.001) were higher among early FGR than late FGR. Placental characteristics from early and late FGR pregnancies differed mainly in regard to maternal vascular malperfusion scores rather than fetal scores, with preeclampsia found to be a cofactor modulating the rates and severity of associated lesions. In the binary logistic analysis, recent infarcts (OR 2.44, 95% CI 1.2‐5), distal villous hypoplasia (OR 1.8, 95% CI 1.0‐3.2), atherosis (OR 2.71, 95% CI 1.35‐5.47), persistent endovascular trophoblasts (OR 1.67, 95% CI 1.03‐2.7), and a reduced fetal/placental weight score (OR 0.27, 95% CI 0.2‐0.38) were independently associated with an increased likelihood of early FGR compared with late FGR. The sensitivity, specificity, and area under the curve of the model were 60% (95% CI 51.2‐66.2), 89.1% (95% CI 84.9‐92.3), and 0.81 (95% CI 0.77‐0.85), respectively, suggesting a fair to good predictive value. Conclusions Individual placental lesions suggestive of increased rates of ischemia, defective remodeling of spiral arteries, peripheral hypoxia interfering with villus development, and reduced placental efficiency were significantly more common in early FGR than late FGR.