女性生殖道中肾腺癌临床病理及分子特征分析

Clinicopathological and molecular characterization of mesonephric adenocarcinoma in gynecologic tract.

目的:探讨女性生殖道中肾腺癌的临床特点、组织病理学形态及免疫表型和分子特征。方法:收集2014年1月至2023年12月于首都医科大学附属北京妇产医院确诊的女性生殖道中肾腺癌5例(宫颈中肾腺癌4例及阴道中肾腺癌1例),回顾分析其临床病理资料。结果:5例患者平均年龄55岁(49~63岁)。主要临床表现为异常阴道出血。4例宫颈中肾腺癌均在术前行宫颈活检,但未明确诊断为中肾腺癌。患者均行根治性全子宫切除+双侧附件切除+盆腔淋巴结清扫±腹主动脉旁淋巴结切除术,术前和(或)术后行以铂类为基础的化疗±放疗±抗血管生成治疗。4例宫颈中肾腺癌诊断为FIGOⅠb1~Ⅱb期,1例阴道中肾腺癌诊断为Ⅲ期。宫颈中肾腺癌肿瘤主体位于宫颈管壁深层,肿瘤周边存在中肾管残余/中肾管增生。5例中肾腺癌的免疫组化染色结果基本一致,阳性表达PAX8、GATA3、CD10,并阴性表达TTF-1、ER及PR,且4例为TP53野生型。1例宫颈中肾腺癌和1例阴道中肾腺癌均存在KRAS基因突变,突变位点分别为p.G12D及p.G12A。平均随访51个月(18~115月),1例阴道中肾腺癌患者在随访13个月时发生肺转移。结论:女性生殖道中肾腺癌是起源于中肾管残留或增生的罕见恶性肿瘤。中肾腺癌极易误诊,结合PAX8、GATA-3、CD10、ER、PR及TTF-1等免疫组化特征有助于明确诊断。中肾腺癌常与KRAS/NRAS的分子改变有关,为疾病的分子靶向治疗提供了依据。

Objective:To investigate the clinicopathological and molecular features of mesonephric adenocarcinoma of the gynecologic tract.Methods:Four cases of cervical mesonephric adenocarcinoma and 1 case of vaginal mesonephric adenocarcinoma diagnosed between January 2014 and December 2023 were collected and retrospectively analyzed.Results:The average age at diagnosis was 55(range 49 to 63 years).The main clinical presentation was abnormal vaginal bleeding.All 4 cases of cervical mesonephric adenocarcinoma were misdiagnosed before surgery.All patients underwent radical hysterectomy+bilateral salpingo-oophorectomy+pelvic lymphadenectomy±para-aortic lymphadenectomy,with neoadjuvant chemotherapy and/or platinum-based chemotherapy±radiation therapy±antiangiogenic treatment.4 cases of cervical mesonephric adenocarcinoma were diagnosed as FIGO stageⅠb1 toⅡb,and the vaginal mesonephric adenocarcinoma was diagnosed as stageⅢ.The cervical mesonephric adenocarcinoma cases were located in the cervical stroma,which demonstrated residual mesonephric ducts presented at the periphery.The histology staining results showed that all cases were positive for PAX8,GATA3,and CD10,and negative for TTF-1,ER,and PR,meanwhile four were TP53 wild type.According to NGS results,KRAS mutations were detected in 2 cases.All patients were followed for a mean period of 51 months(range 18~115).One patient with vaginal mesonephric adenocarcinoma developed lung metastasis at 13 months follow-up.Conclusion:Mesonephric adenocarcinoma is a rare tumor of the female genital tract,which originates from mesonephric duct remnants.Mesonephric adenocarcinoma is prone to misdiagnosed,and its diagnosis can be clarified with the help of immunohistochemical features.KRAS/NRAS mutation appear to be highly prevalent in mesonephric adenocarcinoma,and therapeutics that target this pathway are worthy of further study.