宫颈/阴道液基细胞学假阴性诊断的影响因素分析

Analysis of factors influencing the false-negative diagnosis of cervical/vaginal liquid based cytology

目的探讨宫颈/阴道液基细胞学假阴性诊断的可能影响因素,进一步提高宫颈/阴道细胞学检测的灵敏度。方法回顾性分析2015年7月至2018年12月北京大学第一医院妇产科门诊及住院患者的宫颈/阴道细胞学标本检测结果,将6个月内活检病理诊断为宫颈上皮内瘤变(CIN)2或阴道上皮内瘤变(VAIN)2及以上病变,且细胞学检测结果为未见上皮内细胞病变及恶性(NILM)视为细胞学假阴性。细胞学假阴性涂片的复阅,由2位高年资(主治以上)细胞学医师共同完成。采用二分类Logistic回归评估年龄、病变位点、病变程度3个因素对细胞学检测假阴性诊断的影响,并结合复阅结果分析假阴性诊断不一致的原因。结果1009例CIN2+和VAIN2+病变中,180例(17.8%)细胞学结果为NILM。复阅涂片后,123例(68.3%)判读为NILM;57例(31.7%)判读为细胞学异常。患者年龄≤30岁组的假阴性率最高(20.8%),其风险是31~60岁年龄组的8.85倍(P<0.001),是年龄≥60岁组的9.26倍(P<0.001)。以宫颈多点病变为参照,宫颈息肉或宫颈管内病变的细胞学假阴性率最高为50.0%;阴道壁或阴道断蒂的假阴性率为13.0%;宫颈单点病变的假阴性率为22.3%。高级别鳞状上皮内病变(HSIL)和宫颈原位腺癌的假阴性率为13.7%,恶性肿瘤的假阴性率为3.9%。复阅结果为细胞学异常病例,细胞类型以中表层鳞状细胞(38.6%)及外底层鳞状细胞(24.6%)异常为主,异常细胞全部散在分布最常见(59.7%),涂片中异常细胞数量<10个多见(31.6%),核增大浅染常见(42.2%),背景有炎性病变或伴角化性改变最多见(59.7%)。结论患者的年龄、病变位点和病变程度等因素可导致细胞学假阴性诊断的发生,总结取样经验和提升取样技巧,将有利于减少假阴性病例的发生。细胞学阅片医师更加细致地鉴别涂片中一些轻微异常形态学的改变,不断积累阅片经验,将有助于减少假阴性诊断的发生。

Objective To investigate the possible influencing factors of false-negative diagnosis of cervical/vaginal liquid based cytology,and further improve the sensitivity of cervical/vaginal cytology.Methods The results of cervical/vaginal cytology of outpatients and inpatients in Department of Obstetrics and Gynecology,Peking University First Hospital from July 2015 to December 2018 were analyzed retrospectively.Cytological false-negative cases were defined as the patients whose cytological results showed no intraepithelial neoplasia and malignant(NILM),but whose biopsy was diagnosed as cervical intraepithelial neoplasia(CIN)2 or vaginal intraepithelial neoplasia(VAIN)2 or above within 6 months of the diagnosis.The review of false-negative cytology smear was completed by two senior cytologists.Two-class logistic regression was used to evaluate the influence of age,location or number of lesion,and degree of lesion on the false-negative diagnosis of cytology.The reasons for the inconsistency of false-negative diagnosis were analyzed with the review results.Results Among 1009 cases of CIN2+and VAIN2+lesions,180 cases(17.8%)showed NILM.After reviewing the smear,123 cases(68.3%)were identified as NILM and 57 cases(31.7%)as abnormal.The false-negative rate was the highest(20.8%)in the patients with age≤30 years,and the risk was 8.85 times higher than the patients aged 31 to 60 years(P<0.001),9.26 times than the patients aged≥60 years(P<0.001).The highest cytological false-negative rate was 50.0%for cervical polyps or intraductal lesions.The false-negative rate of vaginal wall or vaginal pedicle rupture was 13.0%;that of single cervical lesion was 22.3%;that of high-grade squamous intraepithelial lesion(HSIL)and adenocarcinoma in situ of cervix(AIS)was 13.7%and that of malignant lesions was 3.9%.The most common cell types in the reviewed abnormal cases were squamous cells in the middle surface layer(38.6%)and squamous cells in the outer bottom layer(24.6%).The abnormal cells in all smears was the most common distribution(59.7%),the number of abnormal cells in the smear was less than 10(31.6%),nuclear enlargement and light staining were common(42.2%),and inflammatory lesions or keratotic changes in the background were most common(59.7%).Conclusions Age of the patient,location or number of lesion,and degree of lesion are associated with false-negative diagnosis of cytology.Summarizing sampling experience and improving sampling skills will help reduce the occurrence of false-negative cases.Cytopathologists should examine slightly abnormal changes more carefully and learn how to further reduce the false-negative rate procactively.