外阴上皮内肿瘤形成20例临床病理学观察

Vulvar intraepithelial neoplasia： a clinicopathologic study of twenty cases

目的探讨外阴上皮内肿瘤形成（VIN）的临床、病理和免疫组织化学特征。方法按国际外阴阴道疾病研究学会（ISSVD）2004年的分类标准，从2009年2月至2011年12月问在北京五洲女子医院行外阴活检的女性患者中选取VIN患者，分为普通性VIN（u—VIN）和分化性VIN（d-VIN）两组进行研究，并进行Ki-67、p16和p53免疫组织化学MaxVision法染色。结果237例中有20例VIN，占同期所有外阴活检病例的8．4％（20／237）。u—VIN患者17例，平均年龄29．6岁，表现为全层或接近全层出现不典型细胞，类似于宫颈高级别鳞状上皮内肿瘤形成。Ki-67和p16免疫组织化学染色呈弥漫强阳性，高危型HPV阳性。d—VIN比u—VIN少见，本组仅3例，均发生于50岁以上女性，平均年龄53．7岁，多有硬化性苔藓背景，病变上皮增厚、上皮脚延长和角化不全，不典型性局限于鳞状上皮的基底和副基底部，病变细胞增大，具有丰富的嗜酸性胞质，核仁突出，伴有细胞成分增加或轻度核深染，形成发育不全的角化珠。d-VIN的p53免疫组织化学染色呈强阳性，Ki-67和少数p16反应仅局限于基底层少数细胞。结论VIN是外阴鳞状细胞癌的癌前病变，新的ISSVD分类将VIN均归为高级别病变，明确的组织病理学诊断对于及时治疗和预防外阴鳞状细胞癌具有重要意义。

Objective To investigate the clinical, pathological and immunohistochemical features of vulvar intraepithelial neoplasia （VIN）. Methods According to the 2004 modified terminology of International Society for the Study of Vulvovaginal Diseases （ISSVD） , the cases were diagnosed as VIN from patients who had performed vulvar biopsy in Beijing Wuzhou Women＇s Hospital from February 2009 to December 2011, which were reclassified as usual VIN and differentiated VIN. The clinical and pathological studies were conducted respectively. MaxVision immunohistochemical staining was used to detect the expression of Ki-67, p16 and p53 proteins. Results There were 20 cases of VIN in 237 patients, and the incidence of VIN was 8.4% in all of contemporary vulvar biopsy. In 17 cases of usual VIN, mean age was 29.6 years, the lesion typically presented with atypical cells involving almost all layers of the epithelium, which was equivalent to the high-grade squamous intraepithelial neoplasia of cervix. Immunohistochemistry for Ki-67 and p16 was strongly positive in usual VIN. High risk human papillomavirus （HPV） detection was also positive. The incidence of differentiated VIN was less than usual VIN, and there were only 3 cases in this study. In differentiated VIN, patients aged over 50 years, with mean of 53.7 years, and the lesion most commonly presented with lichen sclerosis background. There were epithelial thickening and extending, and parakeratosis, and atypia was strictly confined to the basal and parabasal layers of the epithelium where the cells enlarged with abundant eosinophilic cytoplasm, presented with prominent nucleoli, increased cellularity and abnormal keratinization. In differentiated VIN, p53 was strongly positive, Ki-67 and pl6 immunohistochemical expression was confined to the basal layer only. Conclusions VIN is a precursor of invasive squamous cell carcinoma of the vulva. The modified terminology of ISSVD classifies VIN as highgrade lesions. Definitive pathological diagnosis of VIN plays an important role in its timely treatment and the prevention of vulvar carcinoma.