15 393例宫颈液基细胞学与组织病理学的对照分析

目的探讨宫颈液基细胞学诊断与组织病理学诊断的符合情况。方法对15393例做SurePath宫颈液基细胞学检查,结果异常者依次做Hybrid Capture-Ⅱ肿瘤相关人乳头状瘤病毒（HPV）-DNA检测、5％醋酸宫颈染色肉眼观察并拍照、阴道镜检查及宫颈多点活检行组织病理学检查。细胞学诊断采用TBS（2001）分级报告系统,阳性诊断包括意义不明的不典型鳞状细胞（ASC-US）以上病变;本组细胞学阳性病例有组织病理诊断结果,并对两者进行了对照分析。结果15393例宫颈细胞学检查与组织病理学对照结果显示：7例鳞状细胞癌（SCC）均符合,高级别鳞状上皮内病变（HSIL）为93．6％（103／110）、低级别鳞状上皮内病变（LSIL）为82．0％（443／540）。HPV—DAN阳性检出率与细胞学TBS分级及组织病理学分级正相关。结论应用液基细胞学制片方法、准确掌握TBS的诊断标准可确保宫颈细胞学检查的准确性。     

1747例宫颈阴道病变筛查结果分析

目的 探讨膜式液基薄层细胞学检测(ThinPrep cytology test，TCT)技术在宫颈病变筛查中的价值。方法 对1747例门诊及住院患者行TCT检测。细胞学检查阳性者行阴道镜检查及多点活检，并行病理组织学检查。结果 1747例中51例不满意，不满意率2．92％，剩余1696例中1455例(85．79％)在正常范围内；139例(8．20％)为良性反应性改变；101例属非典型鳞状上皮细胞(atypical squamous cells，ASC)及其以上病变，检出率5．96％，其中ASC52例(3．07％)，鳞状上皮内病变(squamous intraepithelial lesion，SIL)及鳞状细胞癌(squamous cell carcinoma，SCC)共40例(2．36％)，二者之比为1．30：1；低度鳞状上皮内病变(low grade squamous intraepithel iallesion，LSIL)33例(1．95％)；高度鳞状上皮内病变(high grade squamous intraepithel iallesion，HSIL)7例(0．41％)；宫颈鳞状细胞癌(SCC)4例(0．24％)。不典型腺细胞(atypical glandular cells，AGC)4例(0．24％)，腺癌(Adenocareinomal)4例(0．06％)。在微生物检测中，霉菌52例，检出率3．07％，滴虫4例，检出率0．24％。与病理组织学对照，细胞学检出15例中的LSIL11例；检出7例HSIL中的6例；检出了全部4例鳞状细胞癌；组织学证实的1例腺癌被检出。结论 TCT技术制作的薄片，细胞结构清晰，背景清朗，可明显提高标本的满意率；且具有较高的阳性检出率，与组织学对照的诊断符合率亦较高，是临床宫颈病变筛查的好方法。     

计算机辅助阅片与单纯人工阅片在宫颈液基细胞学诊断中对比观察

目的 探讨计算机辅助阅片系统(ThinPrep imaging system,TIS)在宫颈液基细胞学诊断中的应用价值.方法 对10 000例宫颈液基细胞学标本运用TIS辅助阅片+人工阅片进行诊断,记录阅片时间及诊断结果,并分别与2011年同期10 000例单纯人工阅片的阅片时间及诊断结果进行比较.结果 单纯人工阅片平均时间为4.8 min/片,TIS辅助阅片后的人工阅片平均时间为2.6 min/片,阅片速度提高84.62%,二者差异有统计学意义(P＜0.001).两种阅片方法对比鳞状上皮细胞异常标本检出率显示:使用TIS后非典型鳞状上皮细胞(atypical squamous cells,ASC)以上的细胞增加9.82%,其中未明确诊断意义的非典型鳞状上皮细胞(atypical squamous cells-undetermined significance,ASC-US)增加12.01%;低级别鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)增加6.71%;高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)增加22.73%,不除外高级别鳞状上皮内病变的非典型鳞状上皮细胞(atypical squamous cells-cannot exclude HSIL,ASC-H)降低27.78%,两组相比差异无显著性(P＞0.05).两种阅片方法对比细胞学与组织学的诊断符合率显示:细胞学诊断为LSIL以上的与组织学诊断为子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)的符合率分别为90.32%和91.47%,使用TIS后诊断为LSIL的、组织学诊断为CIN1的符合率由71.59%升至74.45%,HSIL组织学诊断为CIN2以上的符合率由77.78%升至82.05%,差异无统计学意义(P＞0.05).结论 TIS能显著提高阅片速度,降低诊断医师的劳动强度,提高工作效率,并具有与单纯人工阅片相似的病变检出率,是一种具有较高应用价值的子宫颈癌筛查技术手段.TIS对HSIL的高敏感性,有待探讨.     

9012例子宫颈液基细胞学诊断结果分析

目的探讨液基薄层细胞(TCT)检查在宫颈癌及癌前病变筛查中的应用价值。方法回顾分析开县人民医院9 012例宫颈液基细胞学检测结果和伯塞斯达系统(TBS)分类系统结果,其中12例ASC-US、10例ASC-H、35例低度鳞状上皮内病变(LSIL)、72例高度鳞状上皮内病变(HSIL)、2例鳞状上皮细胞癌(SCC)和6例腺细胞异常做阴道镜下病理活检,对细胞学异常结果与阴道镜下活组织检查病理诊断结果进行比较。结果 9 012例液基细胞学检测中,筛查出非典型鳞状细胞(ASC-US)以上病例285例,阳性率3.2%。液基细胞学检测与阴道镜下病理活检结果的符合率为91.24%。结论 TCT制片技术和TBS报告能较全面反映宫颈病变的情况,通过定期正规的筛查,能早期发现宫颈癌及癌前病变,从而早期治疗,阻止病变升级是预防宫颈癌的关键。     

细胞免疫化学p16/Ki-67双染预测子宫颈上皮内高级别瘤变

目的 探讨细胞免疫化学p16/Ki-67双染预测子宫颈上皮内高级别瘤变及其意义。方法 随机收集行细胞学检查标本123例,其中不明意义的非典型鳞状上皮细胞(atypical squamous cell of undetermined significance,ASC-US)及以上病例(合计103例)同时行高危人乳头瘤病毒(high risk-human papillomavirus,HR-HPV)检测且具有活检结果,20例液基细胞学检查未见恶性细胞和上皮内病变细胞(negative for intraepithelial lesion or malignancy,NILM),通过细胞免疫化学双染检测p16/Ki-67结果。结果 20例液基细胞学NLIM的标本中p16/Ki-67双染结果均阴性,ASC-US病例中预测CIN2+的敏感性66.67%、特异性95.92%、阳性预测值50.00%、阴性预测值97.92%,低级别鳞状上皮内病变(low-grade squamous intraepithelial lesions,LSIL)病例中预测CIN2+的敏感性91.67%、特异性95.00%、阳性预测值91.67%、阴性预测值95.00%,高级别鳞状上皮内病变(high-grade squamous intraepithelial lesions,HSIL)病例中预测CIN2+的敏感性92.86%、特异性0、阳性预测值92.86%、阴性预测值0;ASC-US及以上病例预测CIN2+的敏感性89.66%、特异性94.28%、阳性预测值86.67%、阴性预测值95.65%。结论 HR-HPV阳性的ASC-US和LSIL病例中进行p16/Ki-67双染检测,可以明显提高CIN2+检出的预测值,细胞免疫化学p16/Ki-67双染有望成为HPV筛查的有效辅助方法。     

宫颈脱落细胞miR-125b与宫颈病变关系及其在HR-HPV 阳性患者分层筛查中的作用研究

比较正常宫颈、宫颈上皮内瘤变及宫颈癌患者宫颈脱落细胞中miR-125b表达水平差异,探讨宫颈脱落细胞miR-125b表达水平检测在HR-HPV阳性患者分层筛查中的作用及其与宫颈病变的关系。方法 采用第二代杂交捕获技术进行HR-HPV初筛,HR-HPV阳性患者行宫颈液基薄层细胞学检查及miR-125b检测。液基细胞学检查结果异常者直接阴道镜下活检行病理学检查,液基细胞学检查正常者行阴道镜检查,阴道镜检查下发现异常者行阴道镜下活检取材,余视作宫颈组织学正常,不做宫颈活检。RT-qPCR检测正常宫颈及不同级别宫颈病变中miR-125b表达水平,比较不同组织学分组之间的宫颈脱落细胞miR-125b表达水平,绘制ROC曲线,探讨miR-125b、液基细胞学检查在宫颈病变中的诊断作用。结果 宫颈脱落细胞miR-125b水平随着宫颈病变程度加重逐渐升高（P＜0.05）;在HR-HPV阳性患者分层筛查中,宫颈液基细胞学诊断宫颈高级别上皮内病变的敏感性、特异性分别为64.90%、80.70%,AUC为0.728（95%CI:0.657~0.779,P＜0.001）。与液基细胞学检查相比,宫颈脱落细胞miR-125b检测诊断宫颈高级别上皮内病变的灵敏性、特异性更高（87.30% vs 64.90%;69.20% vs 80.70%）,AUC为 0.864（95%CI:0.800~0.928,P＜0.001）。结论 miR-125b水平随着宫颈病变加重逐渐升高,检测宫颈脱落细胞miR-125b水平可有效分流HR-HPV阳性患者,敏感性高于细胞学检查,可能成为一种有效的分层筛查方法。     

TCT联合HPV检测与多基因甲基化检测在宫颈病变诊断中应用价值分析

目的 分析液基薄层细胞学检测(TCT)联合人乳头瘤病毒(HPV)检测与多基因甲基化检测在宫颈病变诊断中的应用价值.方法 将2018年6月至2020年5月于成都医学院第二附属医院核工业四一六医院妇科就诊的298例宫颈病变高风险患者作为研究对象,均进行TCT联合HPV检测、多基因甲基化检测和阴道镜下宫颈病理活检,以病理结果为金标准,进行统计学分析,比较TCT联合HPV检测、多基因甲基化检测在宫颈病变中的诊断价值.结果 298例宫颈病变高风险患者中宫颈上皮正常90例,炎症84例,低级别鳞状上皮内病变(LSIL)47例,高级别鳞状上皮内病变(HSIL)50例,宫颈癌27例;TCT联合HPV检测对HSIL及宫颈癌诊断的灵敏度、特异性、阳性预测值和阴性预测值分别为90.91％、90.95％、77.78％和96.63％;多基因甲基化检测对HSIL及宫颈癌诊断的灵敏度、特异性、阳性预测值和阴性预测值分别为98.70％、97.29％、92.68％和99.54％;多基因甲基化检测对HSIL和宫颈癌的诊断结果与病理结果一致性分析显示Kappa值= 0.940,一致性极高.结论 相较于TCT联合HPV检测,多基因甲基化检测对HSIL及宫颈癌的诊断效能更高.     

血性/炎性涂片背景对宫颈液基细胞学诊断的影响

目的 探讨宫颈薄层液基细胞学涂片背景及其对细胞学诊断的影响.方法 回顾性分析北京市石景山医院病理科进行薄层液基细胞学检查的病例,并与活检病理诊断进行对比分析.结果绝大多数宫颈上皮病变背景干净,约8.72%的病例出现重度炎症背景,约3.15%的病例出现血性背景.鳞癌(squmaous carcinoma,SC)和腺癌(adenocarcinoma,AC)(100.00%)组、鳞状上皮内高度病变(high-grade squamous intraepithelial lesion,HSIL)(32.00%)组和非典型鳞状上皮、不除外高度病变(atypical squamous cells,cannot exclude high-grade squamous intraepithelial lesion,ASC-H)组(33.30%)血性/炎性背景发生率明显高于非典型鳞状上皮、意义不明确(atypical squamous cells of undetermined significance,ASCUS)组(6.30%)和鳞状上皮内低度病变(low-grade squamous intraepithelial lesion,LSIL)(4.76%).结论血性/炎性背景是导致宫颈上皮病变低诊断甚至漏诊的主要原因.冰醋酸溶液处理可有效清除血性背景,提高涂片质量.     

HPV阳性宫颈细胞学标本及活检组织中L1蛋白表达及意义

目的 探讨HPV L1衣壳蛋白在HPV阳性的宫颈细胞学标本和活检组织标本中的表达及意义.方法 运用免疫组化SP法检测L1蛋白在宫颈细胞学和组织学标本中表达.结果 52例细胞学标本中,L1蛋白在非典型鳞状细胞(ASCUS)、低级别鳞状上皮内病变(LSIL)、高级别鳞状上皮内病变(HSIL)中阳性表达率分别为43.8%(7/16)、28.5%(10/26)、0(0/10);100例组织学标本中,L1蛋白在炎症、CIN1、CIN2、CIN3中阳性表达率分别为55.6%(15/27)、43.8%(14/32)、15.4%(4/26)、0(0/15);两组资料L1蛋白阳性表达率的差异均具有统计学意义(χ2=9.149,P=0.01;χ2=23.555,P=0.00).结论 早期检测HPV L1蛋白,有助于判断宫颈病变程度及其恶性进展趋势,为宫颈病变患者提供更合理的治疗流程.     

宫颈腺癌伴CIN3及双侧卵巢Brenner瘤1例并文献复习

目的探讨宫颈腺癌(uterine cervix adenocarcinoma)伴宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)3的临床与病理学特征。方法对1例宫颈腺癌伴CIN3进行液基细胞学、组织学检查及免疫组化染色,并复习相关文献。结果患者50岁,宫颈液基细胞学检查发现原位腺癌(ade-nocarcinoma in situ,AIS)及高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)结构。宫颈活检结果为高分化腺癌伴CIN3,术后病理显示宫颈高分化腺癌伴CIN3,双侧卵巢Brenner瘤。免疫组化标记宫颈腺癌及CIN3两种病变p16、Ki-67均强阳性。结论宫颈腺癌伴CIN3是一种十分少见的恶性肿瘤,液基细胞学普查对宫颈肿瘤的早期发现具有重要价值。     

Chromosome in situ hybridisation, Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology

AIMS: To assess the potential value of chromosome in situ hybridisation (CISH), Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology to help detect carcinoma cells and precursors. METHOD: Sixty ThinPrep processed cervical cytology samples were studied: 23 cases within the normal limit, 13 low grade squamous intraepithelial lesions (LSILs), 10 high grade squamous intraepithelial lesions (HSILs), six squamous cell carcinomas, three endocervical adenocarcinomas, two cervical adenosquamous cell carcinomas, and three endometrial adenocarcinomas. CISH was performed with DNA probes specific for the pericentromeric regions of chromosome 11 and 16. Hybridisation signals were visualised with the streptavidin-biotin peroxidase technique. The monoclonal MIB1 and polyclonal TRT-H231 antibodies were used to detect Ki-67 and telomerase immunoreactivity, respectively. RESULTS: Non-specific background staining was almost absent in CISH slides. Normal squamous and glandular cells showed a diploid chromosomal pattern. A relative gain in chromosomes 11 and 16 (aneusomy) was seen in HSIL and the carcinomas (p<0.0001). In MIB1 stained smears, normal cells and koilocytes showed inconspicuous immunoreactivity, whereas strongly immunoreactive nuclei were found in cancer cells and HSIL (p<0.0001). Not only carcinoma and HSIL cells, but also some normal cells, showed cytoplasmic staining for telomerase. CONCLUSIONS: These preliminary results indicate that ThinPrep processed cervical smears are suitable for CISH and immunocytochemical studies. The neoplastic squamous and glandular cells were easily identified based on nuclear aneusomy and strong Ki-67 immuoreactivity in the context of abnormal nuclear morphology. This is the first study to apply CISH in cervical cytology using an immunoenzymatic approach.     

Analytical and clinical performances of a restriction fragment mass polymorphism assay for detection and genotyping of a wide spectrum of human papillomaviruses

Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry-based restriction fragment mass polymorphism (RFMP) assay was adapted to human papillomavirus (HPV) genotyping. The analytical sensitivity and the clinical utility were evaluated by testing defined HPV genome equivalents and a total of 426 specimens composed of normal cytology, atypical squamous cells of undetermined significance, low grade squamous intraepithelial lesion, high grade squamous intraepithelial lesion and invasive squamous cell carcinoma. The RFMP assay was able to detect 38.4-114.6 genomic equivalents of a wide variety of HPV types. The RFMP assay detected 34 different HPV genotypes in cervical samples of which 8% were found to be multiple-type infections. The high-risk HPV positivity rate according to the histological diagnosis was 7.9% (8/101), 31.7% (38/120), 50% (55/110), 86% (37/43), 96.2% (50/52) in normal, atypical squamous cells of undetermined significance, low grade squamous intraepithelial lesion, high grade squamous intraepithelial lesion and squamous cell carcinoma subgroups, respectively. Diagnostic sensitivities/specificities for the cervical lesions of squamous cell carcinoma and high grade squamous intraepithelial lesion or worse histology were found to be 96.2%/92.1% and 91.6%/92.1%, respectively. The sensitivity, accuracy, wide range of genotype identification and high-throughput capacity with cost-effectiveness of the test consumables make the RFMP assay suitable for mass screening and monitoring of HPV-associated cervical cancer.     

Comparison of p16INK4a and ProEx™ C immunostaining on cervical ThinPrep® cytology and biopsy specimens

ProEx? C and p16^INK4a staining of cytology/histology specimens have recently been explored to help distinguish high‐grade squamous intraepithelial lesions (HSIL) from benign mimics. The goal of this study was to evaluate the performance characteristics of p16 and ProEx C in tissue and patient matched ThinPrep® liquid‐based cytology specimens. Residual cervical ThinPrep cytology specimens and tissue blocks (N = 64) from 63 patients were stained with p16 and ProEx C. Review of immunostained material, Papanicolaou and H&E stained slides was performed by two cytopathologists. The cytology slides were evaluated for the presence or absence of squamous atypia as well as immunoreactivity. Histologic specimens were interpreted as negative, indeterminate, or positive for each immunostain. There was 86% agreement (55/64) between the p16 and ProEx C stains on tissue specimens. Eleven specimens were interpreted as positive for both stains. All had a low‐ or high‐grade squamous lesion on the corresponding H&E section. ProEx C was able to identify four low‐grade squamous intraepithelial lesion specimens that were interpreted as negative by p16. All four HSIL specimens demonstrated p16 and ProEx C staining. However, 84% of cytology negative specimens demonstrated false‐positive staining. Clinical utilization of both stains, combined with morphologic features, may be beneficial for confirming HSIL on histologic specimens. ProEx C and/or p16 immunostains may lead to a false‐positive result in cytology specimens due to staining of normal appearing cells. Diagn. Cytopathol. 2010;38:564–572. 2009 Wiley‐Liss, Inc.     

The p16INK4a protein: a cytological marker for detecting high grade intraepithelial neoplasia of the uterine cervix

The identification of a small percentage of high grade cervical intraepithelial neoplasia (HGCIN) among patients with a diagnosis of atypical squamous cells of undetermined significance (ASC-US) and low grade squamous intraepithelial lesion (LSIL) is one of the difficulties in cytology based cervical cancer screening. p16INK4a is a surrogate marker for the initiation of HPV mediated cervical carcinogenesis. This article describes the detection of the protein p16INK4a by immunocytochemistry coupled with the use of a nuclear score to differentiate abnormal basal cells from metaplastic or atrophic cells. The results of a pilot series of 210 liquid based cytology (LBC) specimens of which 108 were considered normal, 52 with a diagnosis of LSIL and 50 with a diagnosis of high grade SIL are described. The second series includes 137 LBC specimens with an ASC-US diagnosis and 88 with a LSIL diagnosis with an histological correlation. The overall sensitivity for the diagnosis of HGCIN using for the labeled squamous cells a nuclear score superior to 2 was 96% and the specificity was 83%. The sensitivity in the ASC-US was 95% and the specificity was 84%, in the LSIL group 100% and 81%, respectively. These data suggest to study a large series of LBC smears with a diagnosis of ASC-US and LSIL to confirm its efficacy of predicting the presence of an HGCIN.     

Differentiating between endocervical glandular neoplasia and high grade squamous intraepithelial lesions in endocervical crypts: Cytological features in ThinPrep and SurePath cervical cytology samples

A recent audit at our institution revealed a higher number of cases diagnosed as endocervical glandular neoplasia on ThinPrep (TP) cervical cytology samples (9 cases) as opposed to SurePath (SP) (1 case), which on histology showed only high‐grade cervical intraepithelial neoplasia (CIN) with endocervical crypt involvement (CI). We attempted to ascertain the reasons for this finding by reviewing the available slides of these cases, as well as slides of cases diagnosed as glandular neoplasia on cytology and histology; cases diagnosed as high‐grade squamous intraepithelial lesions (HSIL) on cytology which had CIN with CI on histology and cases with mixed glandular and squamous abnormalities diagnosed both cytologically and histologically. Single neoplastic glandular cells and short pseudostratified strips were more prevalent in SP than TP with the cell clusters in glandular neoplasia 3–4 cells thick, in contrast to the dense crowded centre of cell groups in HSIL with CI. The cells at the periphery of groups can be misleading. Cases with HSIL and glandular neoplasia have a combination of the features of each entity in isolation. The diagnosis of glandular neoplasia remains challenging and conversion from conventional to liquid based cervical cytology requires a period of learning and adaptation, which can be facilitated by local audit and review of the cytology slides in cases with a cytology–histology mismatch. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Performance of a fluid-based, thin-layer papanicolaou smear method in the clinical setting of an independent laboratory and an outpatient screening population in New England.

BACKGROUND: A patented, fluid-based, thin-layer method for preparation of Papanicolaou (Pap) smears (ThinPrep Pap test) has been reported to be significantly more effective than the conventional smear invented by George Papanicolaou. We tested this position by comparing the cytologic diagnosis and specimen adequacy results obtained using the ThinPrep method with data from conventional Pap smears obtained from a similar population. METHODS: Test results of 56 339 ThinPrep specimens were compared with results from 74 756 conventional smear cases obtained from the same sources in a corresponding period of the previous year. RESULTS: The use of ThinPrep for cervicovaginal cytology produced a 75.14% increase in the detection of low-grade squamous intraepithelial lesions and higher diagnoses. Detection of low-grade squamous intraepithelial lesions increased by 71.65% (from 1.58% to 2.71%), and detection of high-grade squamous intraepithelial lesions increased by 102.54% (from 0.26% to 0.52%). There was a 39.11% decrease in the atypical squamous cells of undetermined significance-intraepithelial lesion ratio (from 2.07 to 1.26). There were also marked decreases in the number of specimens categorized as "satisfactory but limited," owing to obscuring inflammation (-94.34%), obscuring blood (-99.84%), and poor fixation (-99.25%). CONCLUSION: ThinPrep produced increased detection of premalignant precursors while improving specimen adequacy.     

p16(INK4a) as a complementary marker of high-grade intraepithelial lesions of the uterine cervix. I: Experience with squamous lesions in 189 consecutive cervical biopsies

AIM: To test the usefulness of p16(INK4a) immunostaining for improving the diagnostic accuracy of cervical punch biopsies referred to a routine laboratory setting during the investigation of women with abnormal Papanicolaou smears. METHODS: A total of 188 consecutive and unselected colposcopically directed cervical biopsies and a single contemporaneous cervical polyp were accessioned prospectively over a 3-month period, step-serially sectioned and examined by H&E and immunostained for p16(INK4a). The clinical context, results of concurrent Papanicolaou smears/ThinPrep slides and Digene hybrid capture tests for high-risk human papillomavirus (HPV) subtypes, as well as follow-up cervical smears/ThinPrep, biopsies and loop excisions of transformation zones or cone biopsies were all correlated with the morphological and immunohistochemical findings. RESULTS: Seventy-seven biopsies (40.7%) displayed a high-grade squamous intraepithelial lesion (HGSIL; cervical intraepithelial neoplasia [CIN] 2-3), 27 (14.3%) showed a low grade squamous intraepithelial lesion (HPV +/- CIN1) and 85 (45%) showed a range of non-dysplastic (inflammatory or reactive) changes. Diffuse strong parabasal immunostaining for p16(INK4a), suggestive of integrated high-risk HPV DNA into the host genome, was observed in 81 biopsies (42.9%, including the cervical polyp) and correlated (>90%) with HGSIL in the H&E sections. Only one case revealed irreconcilable discordance between the histological features and this strong parabasal immunostaining pattern. Focal and weaker midzonal or superficial p16(INK4a) immunostaining, suggestive of episomal HPV infection, was noted in 19 biopsies (10%) and these biopsies exhibited a range of histological changes but predominantly low grade squamous intraepithelial lesion (LGSIL). No staining of the squamous epithelium was seen in 89 biopsies (47.1%). Again, only one case revealed irreconcilable discordance between the histological features and this negative immunostaining pattern. On review of all cases where discordant results were noted between the H&E appearances and expected p16(INK4a) immunostaining, we found 26 cases (13.7%) in which this discordance prompted justifiable modification of the original diagnosis. CONCLUSIONS: Thus, within a routine diagnostic laboratory, p16(INK4a) immunostaining appears to be a very useful adjunctive test in the examination of colposcopically directed cervical biopsies, in the diagnostic cascade of women investigated for abnormal Papanicolaou smears. It is possible, as further data accumulate concerning the importance of integration of high-risk HPV DNA into the host cell genome and the reliability with which this can be identified by p16(INK4a) immunostaining, that this will become the diagnostic 'lesion of interest', replacing the subjective histological grading of cervical dysplasia, in the management of such patients; i.e., the discriminatory watershed between continued surveillance and active intervention.     

Rapid prescreen of cervical liquid-based cytology preparations: results of a study in an academic medical center

A rapid prescreening or rapid rescreening method for quality assurance in cervical cytology has been used in Europe and in Canada but has not been accepted in the United States. The rapid prescreen method was tested in a cytology laboratory that serves an academic medical center with a high‐risk population for cervical cancer. For a period of 3 months, a tray of 20 sequentially numbered Surepath? liquid‐based preparations, randomly selected from the cervical cytology daily workload, were each prescreened in a random fashion for 1 minute. Experienced cytotechnologists performed the rapid prescreen. Results were recorded as negative, further review needed, or epithelial cell abnormality, category specified. The 20 cervical cytology preparations were then replaced in their same position in the daily workload for routine screening performed by another cytotechnologist. Final interpretation was by a cytopathologist as requested or required by Clinical Laboratory Improvement Amendments of 1988. The rapid prescreen data was tabulated and compared with data for a similar time period using the laboratory's normal quality assurance program. Seven hundred and twelve cases underwent rapid prescreen. Six hundred and forty‐two were interpreted as negative. Twenty‐six cases were interpreted as low‐grade squamous intraepithelial lesion (LGSIL) or higher. Forty‐four cases were classified as needing further review. For the 642 negative cases by rapid prescreening, routine screening reported 537 as negative and 105 as either abnormal or needed cytopathologist review. The error rate for the rapid prescreen is 50 of 712 (7.0%); for LGSIL and above 19 of 712 (2.6%). Of the 105 abnormal cases or those submitted for cytopathologist review, 31 were interpreted as atypical squamous cells of undermined significance (ASCUS), 41 cases as reactive/repair, 17 as LGSIL, 4 as unsatisfactory, 1 as atypical squamous cells, cannot rule out high‐grade squamous intraepithelial lesion (ASC‐H), 8 as the presence of endometrial cells in a women aged >40, 1 as malignant melanoma, and 2 as within normal limits with the presence of Actinomyces. The laboratory's routine quality assurance program selects cases, 10% of initially interpreted negative cases plus any gynecologic cytology on patients with a prior abnormal cervical cytology, or history of cervical epithelial cell abnormality. This quality assurance program averages 29% of cases, 4,045 of a total of 13,767, in 2008. Thirty‐seven (0.9%) cases were detected in this rescreen (ASCUS, 16 cases; LGSIL, 13 cases; 1 high‐grade squamous intraepithelial lesion; 4 ASC‐H; and 3 atypical glandular cells of undetermined significance). Eliminating ASCUS cases, eight significant cases were detected, with an error rate of 0.2%. In this cytology laboratory, the rapid prescreen did not prove as reliable as routine quality assurance program for cervical cytology cases. Diagn. Cytopathol. 2012. © 2010 Wiley Periodicals, Inc.     

Cytohistological correlation in patients with atypical glandular cells on Papanicolaou test in a Chilean population

The standard screening test for detecting cervical lesions and cancers is a Papanicolaou (Pap) smear. While squamous cell abnormalities remain the most common positive Pap test result, cytologic findings of glandular cell abnormalities have become more frequent in recent decades. The 2014 Bethesda System for reporting cervical cytology includes the classification “atypical glandular cells” (AGC). AGC have morphological abnormalities that fall outside the range of reactive changes, but are insufficient for a diagnosis of invasive adenocarcinoma. In several histologic follow‐up studies, most AGC cases were found to represent a benign condition. In the current study, we evaluate the significance of AGC cytology findings by analyzing the histologic follow‐up results of a large number of patients with AGC. Most patients with AGC in this study were found to have a significant lesion on follow‐up (63.9%), with negative histologic results in only 36.1% of patients. Among patients with significant lesions, the most common result was low‐grade squamous intraepithelial lesion (26.6%), followed by high‐grade squamous intraepithelial lesion (23.2%). This provides further evidence to support the Chilean Clinical Guidelines for Cervical Cancer, which recommends diagnostic follow‐up studies in all women with AGC to minimize the chance of undetected serious cervical disease.     

Comparison of the sensitivity of conventional cytology and the ThinPrep Imaging System for 1,083 biopsy confirmed high‐grade squamous lesions

Liquid‐based cytology continues to be utilized as an adjunct to conventional cytology in most Australian laboratories, even though a direct‐to‐vial ThinPrep protocol has been introduced in many countries with established cervical screening programs. Manual screening of ThinPrep slides has been widely practiced for more than 10 years and the recent introduction of the ThinPrep Imaging System (TPI) has been reported as being more sensitive than the conventional smear (CS) in the identification of high‐grade cervical disease. We report our experience with ThinPrep Imaging since its introduction into our routine gynecological cytology service. 87,284 split sample pairs reported using the Imaging System demonstrated a decrease in unsatisfactory reports (3.65% for CS and 0.87% for TPI) and an increase in possible high grade and definite high‐grade squamous reports (1.57% for CS and 1.62% for TPI). For 1,083 biopsy confirmed high‐grade lesions, the correct diagnosis of high grade or possible high‐grade squamous disease was made on the ThinPrep imaged slide in 61.0% (661/1,083) of cases and on the CS in 59.4% (643/1,083). This was not statistically significant. When all abnormalities identified on cytology were considered, including possible low grade and definite low‐grade abnormalities, the difference in sensitivity for Thinprep imaged slides of 96.0% (1,040/1,083) and CSs of 91.6% (992/1,083) was statistically significant. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.