Identifying Common Pathogenic Features in Deep Endometriotic Nodules and Uterine Adenomyosis

Increasing imaging data point to a link between deep endometriotic nodules (DENs) and uterine adenomyosis (AD). The study aimed to investigate this link at the histological level and detect potential features shared by the two diseases. We collected formalin-fixed paraffin-embedded tissue (endometrium and lesions) from women with DENs of the rectovaginal septum (n = 13), AD (n = 14), and control subjects (n = 14). Immunohistochemical analyses of CD41 and CD68 were conducted to explore the roles of platelets and macrophages, respectively. Picrosirius red staining was carried out to gather evidence of fibrosis. Vascular endothelial growth factor (VEGF) was assessed, and total numbers of CD31-positive vessels were calculated to investigate the mechanism governing angiogenesis. Double immunohistochemistry for CD31 and alpha smooth muscle actin (αSMA) was performed to discern stable vessels. Platelet aggregation was significantly decreased in both types of lesions compared to their corresponding eutopic endometrium and healthy controls. Macrophage numbers were higher in both lesions than in their corresponding endometrium and healthy subjects. Significantly higher rates of collagen accumulation were detected in DENs and AD lesions compared to their corresponding eutopic and healthy endometrium. VEGF expression was downregulated in the stromal compartment of AD lesions compared to the healthy endometrium. The total number of vessels per area was significantly higher in DENs and AD lesions than in the healthy endometrium. Rates of αSMA-surrounded vessels were decreased in DENs and AD lesions compared to their corresponding eutopic and healthy endometrium. We report common pathogenic mechanisms between DENs and AD, namely excessive macrophage accumulation, fibrosis, and irregular angiogenesis. Our results further support the notion of DENs and AD being linked at the histological level.