研究背景: 先天性生殖道梗阻畸形指子宫至阴道下段不同水平发生流出道梗阻的少见解剖学异常，常见类型包括阴道斜隔综合征，单角子宫合并残角子宫等。其具体发病机制尚不明确，现主要认为与胚胎发育过程中苗勒氏管发育异常相关。子宫腺肌症为患者常见的合并症，已有研究提示其致病与苗勒氏管残余和子宫干细胞异常分化相关，泌乳素通路的局部异常调控亦参与疾病的发生发展过程。但受限于病例数少且多为散发，系统性的疾病特点报道十分有限，且缺少深入的致病机制研究。材料与方法: 本研究回顾了1990年1月至2022年12月期间北京协和医院病理科确诊的两类代表性生殖道梗阻畸形（阴道斜隔综合征、单角子宫合并功能性残角子宫）合并子宫腺肌症患者共17例，收集并统计临床表现、治疗方式及生育结局等临床资料。利用免疫组化法对患者病理组织进行测定，探究苗勒氏管发育、子宫干细胞及泌乳素通路相关标记物的局部表达模式，与不同对照组比较后寻找可能的异常调控，以提示可能的致病相关因素。研究结果: 纳入的17例患者中共包括10例单角子宫合并功能性残角子宫、7例阴道斜隔综合征。梗阻畸形合并子宫腺肌症患者的临床表现最常为进行性加重的痛经，其次为月经量异常、甚至可表现为经量减少，与正常发育者子宫腺肌症存在一定差异。子宫内膜异位症为最常见的合并症，且卵巢型内异症均发生于梗阻同侧。腺肌症主要发生于梗阻同侧（94.1%），且弥漫型腺肌症发病率远高于局灶型。经手术解除梗阻并切除腺肌症病灶后，患者多有良好的生育结局。免疫组化测定表明，梗阻畸形腺肌症患者病灶局部的苗勒氏管来源标记物（PAX8、PAX2、GATA3）、子宫干细胞标记物（β-catenin、SSEA-1、CD146）、泌乳素通路相关因子（PRL、PRLR、DRD2）表达模式与正常腺肌症无显著差异。子宫腺肌症患者普遍存在病灶局部PRLR和DRD2的异常表达。结论: 生殖道梗阻畸形合并子宫腺肌症患者具有较为独特的临床表现，且具有腺肌症及合并的卵巢型子宫内膜异位症多发生于梗阻侧的特点。经手术解除梗阻后，可显著改善其生育结局。生殖道梗阻畸形合并腺肌症患者在苗勒氏管来源和子宫干细胞标记物及泌乳素通路相关因子表达方面可能与正常腺肌症无明显差异，提示流出道梗阻可能并非腺肌症致病的关键环节。泌乳素通路的异常调控可能参与子宫腺肌症的致病。

Background: Congenital obstructive reproductive tract anomaly is a rare anatomic malformation occurring at different levels from the uterus to the lower vagina, resulting in outflow obstruction. Common types of the disease include Herlyn-Werner-Wunderlich syndrome (HWWS) and unicornuate uterus with a rudimentary horn. Though the pathogenesis remains unclear, it is now generally considered that the anomaly is correlated with deficiency of Mullerian duct development during embryogenesis. Adenomyosis is a common complication of obstructive reproductive tract anomaly. Researches have suggested that the lesions originate from differentiation of pluripotent Mullerian remnants or adult uterine stem cells, meanwhile abnormal local regulation of prolactin and relevant receptors may also be involved. However, due to limited cases and the sporadic characteristic of the disease, systematic reports summarizing clinical features and intensive researches on pathogenesis are quite few. Materials and Methods: In this retrospective study, 17 cases of two types of representative obstructive reproductive tract anomaly (HWWS and unicornuate uterus with a functional rudimentary horn) complicated with adenomyosis, diagnosed by Department of Pathology, Peking Union Medical College Hospital, were included. Clinical data including manifestations, treatment and fertility outcomes were collected. Samples of uterine tissue of patients were obtained. Immunohistochemistry was used to localize a series of markers indicating Mullerian-derived tissue, uterine stem cells and prolactin pathway expression. Comparing with different control groups, expression patterns of these markers were determined, in order to find similarities and differences between patients and normal control. Results: All 17 patients include 10 cases of unicornuate uterus with a functional rudimentary horn and 7 cases of HWWS. All patients with obstructive reproductive tract anomaly complicated with adenomyosis were most presented with progressive dysmenorrhea, followed by abnormal uterine bleeding, and some cases may report reduced menstrual flow, which is different from the clinical features of adenomyosis in patients with normal reproductive tract. Endometriosis is the most common complication, and ovarian endometrial cysts all occurred at the same side of obstruction. Adenomyotic lesion most occurred at the obstructive side (94.1%), and the incidence of diffuse adenomyosis is significantly higher than that of focal adenomyosis. Satisfactory fertility outcomes could be achieved after correction of obstruction and excision of adenomyotic lesions by surgery. Immunohistochemistry showed no significant difference between adenomyosis with obstructive reproductive tract and with normal reproductive tract in local expression of Mullerian-derived tissue markers (PAX8, PAX2, GATA3), uterine stem cell markers (β-catenin, SSEA-1, CD146) and prolactin pathway markers (PRL, PRLR, DRD2). However, all adenomyotic uterine expressed abnormal localization of PRLR and DRD2 compared with normal uterine tissue. Conclusions: Patients with obstructive reproductive tract anomaly complicated with adenomyosis have unique clinical symptoms, characterized by adenomyotic lesion and ovarian endometrial cyst commonly occurring at the obstructive side. Surgery correcting the obstruction could improve patients’ fertility outcome. No significant differences were found between adenomyosis with obstructive reproductive tract and with normal reproductive tract in expression of markers representing Mullerian-derived tissues, uterine stem cells and prolactin pathway, suggesting that outflow obstruction might not play a decisive role in pathogenesis of adenomyosis. However, abnormal local regulation of prolactin receptors is likely to participate in the mechanism of adenomyosis.