原发性外阴Paget病36例临床分析

Analysis of clinical characters of female vulvar Paget disease

目的 探讨原发性外阴Paget病（VPD）的临床病理特点和诊治情况，进一步分析影响原发性VPD患者复发的相关因素。方法收集1983年1月-2017年12月中国医学科学院北京协和医院收治的经病理检查证实为原发性VPD的患者共36例，回顾性分析其临床病理特点、诊断、治疗、预后，并分析影响原发性VPD患者复发的相关因素。结果（1）临床病理特点：原发性VPD好发于绝经后妇女，占94％（34／36）；主要症状为外阴瘙痒，占86％（31／36）；主要体征为外阴皮损，常表现为溃疡（67％，24／36）、红斑（50％，18／36）、色素减退（42％，15／36）、硬结（31％，11／36）、色素沉着（17％，6／36），病变主要累及大阴唇（97％，35／36）、小阴唇（53％，19／36）、阴蒂（28％，10／36）、肛周（25％，9／36）、阴道口（3％，1／36）、尿道口（3％，1／36）。19％（7／36）的患者合并外阴或其他部位的上皮内瘤变或原发性恶性肿瘤。（2）诊断和治疗：36例患者均经病理检查确诊为原发性VPD。原发性VPD的治疗以手术治疗为主。36例原发性VPD患者中，34例（94％，34／36）患者行手术治疗，2例（6％，2／36）患者为非手术治疗。手术治疗方式包括病灶切除术、病灶扩大切除术、单纯外阴切除术、外阴广泛性切除术；非手术治疗方式包括放疗、化疗、激光治疗、光动力治疗等。（3）预后：36例原发性VPD患者中，4例失访，随访率为89％（32／36）。随访时间为术后1个月-31年，中位随访时间35．3个月。34例手术治疗的原发性VPD患者中30例有随访资料，其中2例患者随访时间未达到6个月无法判断是否复发，8例患者手术失败（即术后半年内症状再次出现，且经病理检查证实有Paget细胞），可评价是否复发的患者20例，其中9例复发，复发率为45％（9／20），中位复发时间为术后14个月。32例有随访资料的原发性VPD患者中，死亡1例，死亡率为3％（1／32）。（4）影响原发性VPD患者复发的相关因素：将患者年龄、确诊时间、病变是否局限于表皮、手术方式、切缘与病灶的距离、切缘有无浸润、病灶切除的长度及厚度纳人分析，结果显示，上述因素对VPD患者的复发均无明显影响（P〉0.05）。结论原发性VPD的恶性程度较低，常合并外阴或其他部位的上皮内瘤变或原发性恶性肿瘤。原发性VPD的治疗以手术治疗为主，但术后存在较高的复发率，故术后应密切随访，但复发后再次手术仍可获得良好的效果。

Objective To investigate the clinical and pathological features, diagnosis and treatment of primary vulvar Paget disease （VPD）, and analyze the related factors that may affect the recurrence. Methods A retrospective study was carried out on 36 patients diagnosed as VPD pathologically from January 1983 to December 2017 at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences. The clinical and pathological features, diagnosis, treatment and prognosis and the factors influencing recurrence rate of VPD were analyzed. Results （1） Totally 94% （34/36） of VPD occurred in postmenopausal women. Pruritus was counted 86% （31/36） of the main complaint. Lesions of vulvar were main symptom which had no specificity, acting as ulcer （67%, 24/36）, erythema （50%, 18/36）, depigmentation （42%, 15/36）, sclerosis （31%, 11/36）, and pigmentation （17%, 6/36）. The lesions invaded labium majus （97%, 35/36）, sometimes labium minus （53%, 19/36）, clitoris （28%, 10/36）, perianal （25%,9/36）, orificium vaginae （3%, 1/36）, and meatus urinarius （3%, 1/36）. Approximately 19%（7/36） of VPD coexisted with intraepithelial neoplasia or adenocarcinoma of vulvar or other part of body. （2） Diagnosis and treatment： diagnosis was confirmed histologically by biopsy or pathologies after surgery, and immunohisto- chemical results were helpful for differential diagnosis. Surgery was the mean treatment method, 34 of all the 36 patients （94%, 34/36） underwent surgery for at least once, while 2 patients （6%, 2/36） were performed non-operative treatment. The surgical treatment included excision of focus, wide local excision, simple vulvectomy, and extensive vulvectomy. The non-operative treatment included radiotherapy, chemotherapy, laser, photodynamic therapy, and so on. （3）Prognosis： among 36 VPD patients, 4 were lost to follow-up with a 89% （32/36） follow-up rate. Median follow-up was 35.3 months （range, 1 month to 31 years）. During the follow-up period, 2 patients were unable to judge whether they will relapse for the follow-up time did not reach half a year, 8 cases were unsuccessful operation, 20 cases succeeded, the achievement ratio was 71% （20/28）. Nine of twenty cases relapsed, the recurrence rate was 45% （9/20）. The median recurrence time was 14 months after operation. One patient of the 32 followed-up patients died, the mortality rate was 3% （1/32）. （4）The related factors affected the recurrence of VPD： t test was applied to the analysis of patients＇ age, rank test was used in the statistics of the time of confirmed diagnosis, the length and thickness of the resection focus. Fisher test was used to calculate whether the focus were limited to the epidermis, type of surgical procedures, distance between the margin and the focus, whether tumor cells infiltrated the margin. The results showed that none of the above terms in the first operation had significant contribution to recurrence （all P〉0.05）. Conclusions VPD may be a low potential malignancy, which could slowly progress into deep invasive disease. VPD is often associated with intraepithelial neoplasia or primary tumors of the vulva or somewhere else. Operations is the first choice for VPD, but consider for its high recurrence rate after operation, close follow-up should be strongly suggested.