[Erdheim-Chester disease initially discovered at extraskeletal locations: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features of Erdheim-Chester disease (ECD) initially diagnosed at extraskeletal locations. Methods: Clinical and pathological data of four cases of ECD diagnosed initially in extraskeletal locations were collected at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2013 to June 2023. BRAF V600E gene was detected by reverse transcription polymerase chain reaction (RT-PCR). Pertinent literatures were reviewed. Results: Four ECD patients included two males and two females ranging in ages from 2 years 11 months to 69 years. The lesions located in the lung (two cases), central nervous system (one case), and the testicle (one case) were collected in the study. One patient had occasional fever at night, one had nausea and vomiting, and two were asymptomatic. Radiologically, the two pulmonary ECD showed diffuse ground-glass nodules in both lungs, and the lesions in central nervous system and testicle both showed solid masses. Microscopically, there were infiltration of foamy histiocyte-like cells and multinucleated giant cells in a fibrotic background, accompanied by varying amounts of lymphocytes and plasma cells. The infiltration of tumor cells in pulmonary ECD was mainly seen in the subpleural area, interlobular septa, and perivascular and peribronchiolar areas. The fibrosis was more pronounced in the pleura and interlobular septa, and less pronounced in the alveolar septa. Immunohistochemical staining showed that all tumor cells expressed CD68, CD163 and Fô€ƒ¼a; one case showed S-100 expression; three cases were positive for BRAF V600E; all were negative for CD1α and Langerin. RT-PCR in all four cases showed BRAF V600E gene mutation. Conclusions: Extraskeletal ECD is often rare and occult, and could be easily misdiagnosed, requiring biopsy confirmation. The radiologic findings of pulmonary ECD is significantly different from other types of ECD, and the histopathological features of pronounced infiltration in the subpleura area, interlobular septa, perivascular and peribronchiolar areas can be helpful in the differential diagnosis from other pulmonary diseases. Detection of BRAF V600E gene mutation by RT-PCR and its expression by immunohistochemical staining are also helpful in the diagnosis.

Let-7 derived from endometrial extracellular vesicles is an important inducer of embryonic diapause in mice.

Embryonic diapause is a maternally controlled phenomenon. The molecule controlling the onset of the phenomenon is unknown. We demonstrated that overexpression of microRNA let-7a or incubation with let-7g-enriched extracellular vesicles from endometrial epithelial cells prolonged the in vitro survival of mouse blastocysts, which developed into live pups after having been transferred to foster mothers. Similar to in vivo dormant blastocysts, let-7-induced dormant blastocysts exhibited low level of proliferation, apoptosis, and nutrient metabolism. Let-7 suppressed c-myc/mTORC1 and mTORC2 signaling to induce embryonic diapause. It also inhibited ODC1 expression reducing biosynthesis of polyamines, which are known to reactivate dormant embryos. Furthermore, the overexpression of let-7 blocked trophoblast differentiation and implantation potential of human embryo surrogates, and prolonged survival of human blastocysts in vitro, supporting the idea that embryonic diapause was an evolutionary conserved phenomenon. In conclusion, let-7 is the main factor inducing embryonic diapause.