Comparison of cervical cytology and the polymerase chain reaction for HPV 16 to identify women with cervical disease in a general practice population.

A comparison of the ability of cervical cytology and the polymerase chain reaction (PCR) for human papilloma virus type 16 (HPV 16) to identify women with cervical disease has been performed in a general practice population of 249 women, none of whom were believed to have current cervical disease prior to examination. Within this population, 29 women were found by colposcopy and subsequent histopathology to have evidence of cervical disease [5 with cervical intraepithelial neoplasia (CIN) 3; 8 with CIN 2; and 16 with CIN 1]. The prevalence of HPV 16 in this population was 18.9% (CIN 3, 80%; CIN 2, 50%, CIN 1, 12.5%, normal, 16.8%). Women with severe disease (CIN 2 and CIN 3) had a significantly higher incidence of HPV 16 DNA than those with mild cervical disease (CIN 1) or no cervical abnormality (P = 0.001). There was no significant difference in the ability of either PCR for HPV 16 or cytology to identify women with cervical disease. The combination of screening by cytology and the presence of HPV 16 DNA resulted in the identification of a higher proportion of the women with disease, but this observation did not reach statistical significance. Although the failure to detect disease by the two screening methods was similar, HPV 16 DNA positivity was associated with a higher false-positive rate for disease detection than cytology (P less than 0.03). The PCR assay for detecting HPV 16 in this investigation was shown to have a false-positive rate of 2.4% and a false-negative rate of 10.4%. The prospect of screening women for cervical disease using PCR for HPV 16 is discussed.     

Usefulness of concurrent Papanicolaou smear at time of cervical biopsy

The reliability and cost-effectiveness of a repeat Papanicolaou (Pap) smear performed at the time of colposcopic biopsy is uncertain. To evaluate the usefulness of this practice, Pap smear and biopsy results of 718 patients were reviewed and compared: 619 patients had Pap smears performed prior to colposcopy with a 1.1% false-negative rate, 97.5% sensitivity, and 83.6% positive predictive value. Ninety-nine patients had Pap smears performed at the time of colposcopy with a 19.1% false-negative rate, 56.8% sensitivity, and 92.6% positive predictive value. Repeat Pap smear at the time of colposcopy resulted in significant changes in the management of only 2 patients (2%) and more careful follow-up in one (1%). Pap smears performed at colposcopic biopsy are less sensitive than those done prior to biopsy (P < 0.001). The clinical benefit of this practice is marginal, considering the added costs and potential detrimental effects to the colposcopic examination, provided patients receive adequate follow-up.     

The value of repeated cytology at the time of first colposcopy: a retrospective analysis of 1,087 cases

Papanicolaou tests are often repeated just before the procedure for women who have been referred for colposcopy. The validity and clinical usefulness of this practice, however, is unclear. We retrospectively assessed the value of repeated cytology in a cohort of 1,087 consecutive patients who underwent repeated Papanicolaou testing at first colposcopy. The repeated cytology was considered clinically useful if the results could conceivably have influenced the physician's decision about more invasive diagnostic/therapeutic evaluation based on contemporary practice guidelines. Repeated cytology provided potentially clinically useful information in only a small proportion (3.6%) of the cases analyzed overall, including 41% (26/63) and 1.8% of the high- and low-grade squamous intraepithelial lesions referral cytology cases, respectively. Our data indicate that repeated cytology provides potentially clinically useful information in only a small percentage of overall cases but a substantial proportion of high-grade squamous intraepithelial lesion referral cytology cases, suggesting that high-risk referral cytology case subsets can be defined wherein the routine performance of repeated cytology would be most efficacious.     

液基薄层细胞学结合阴道镜检查在宫颈病变筛查中的临床意义

目的探讨宫颈液基薄层细胞学(TCT)结合阴道镜检查在宫颈病变筛查中的临床意义。方法对854例已婚妇女进行宫颈液基薄层细胞学检测,对宫颈细胞学异常者行阴道镜检查及活组织检查。结果 854例TCT检测的患者中,宫颈病变发生率达81.9%,其中良性病变482例,占69%,宫颈上皮内病变217例,占25.4%,对217例宫颈细胞学异常者进行阴道镜下活检与组织病理学诊断比较,符合率为88.7%。宫颈上皮内病变高发年龄为30-40岁,占35.5%。结论 TCT技术在宫颈病变的诊断中,具有简便、实用,准确率高的特点,配合阴道镜检查能及时发现宫颈早期病变,是防止宫颈癌的关键。     

Improvement of diagnostic accuracy and screening conditions with liquid-based cytology

The aim of this population-based study was to compare the histological follow-up diagnoses of cervicocytological neoplasia (dysplasia, carcinoma in situ and carcinoma) in conventional Papanicolaou (CP) smear and ThinPrep PapTest samples (TP).All cytological samples from the County of Funen, Denmark, in the periods 2000 (n = 34,832) and 2002 (n = 29,995) were included in the study. In 2000 and 2002, the specimens were CP and TP, respectively. The detection rate of > or = mild dysplasia was 0.8% in CP and 1.4% in TP, showing a 75% increase in TP when compared with CP (p < 0.001). Histological follow-up of > or = moderate dysplasia revealed a neoplastic lesion in 77.1% and 87.9% in CP and TP, respectively (P < 0.001).The present study indicates that the diagnostic accuracy of cervical cytology is improved with liquid-based cytology. In addition, we focus on the optimized cellular material that shows the diagnostic details very clearly to the microscopist and leads to radically improved screening conditions.     

Reducing "atypical squamous cells" overdiagnosis on cervicovaginal smears by diligent cytology screening

The frequency of possible reasons for "atypical squamous cells" (ASC) overdiagnosis on Papanicolaou (Pap) smears was analyzed. Pap smears of 199 women with negative biopsy outcome after an ASC diagnosis were reviewed. Special attention was paid to presence of reproductive tract infections (RTIs), perimenopausal cells (PM cells), immature metaplastic cells, hormone-related alterations, and drying artefacts. Comparisons were made using χ(2) test between the two ASC qualifiers and also between premenopausal and peri/postmenopausal women. Possible reasons for ASC overdiagnosis could be assigned on Pap smear review in 88/199 (44.2%) negative biopsies. Overall, PM cells were the most frequent reason for ASC overdiagnosis, being present in 35/199 (17.6%) smears. RTIs were the next most common cause (14.6%). PM cells were the most significant confounding factors for persistent ASC undetermined significance (ASC-US) over interpretation (20.2%) while in none of the cases these were interpreted as ASC-H (P = 0.004). Of these, 32 smears belonged to peri/postmenopausal women while only three to premenopausal women (P < 0.001). Immature metaplastic cells were significantly more frequent cause of ASC-H rather than ASC-US interpretation (P = 0.007). RTIs and drying artefacts were more frequently overcalled as ASC-US (in premenopausal women) while hormonal changes were interpreted as ASC-H. Hormone related changes, immature metaplastic cells and drying artefacts more commonly resulted in ASC interpretation in peri/ postmenopausal smears. The results of this study suggest that diligent screening can substantially reduce ASC overdiagnosis, thereby reducing the referrals/ follow ups.     

Outcome of "Atypical squamous cells" in a cervical cytology screening program: implications for follow up in resource limited settings

(1) To study the incidence and outcome of "Atypical squamous cells (ASC)" diagnosis in a hospital based cytology screening programme. (2) To work out a feasible strategy for follow up of Atypical squamous cells-undetermined significance (ASC-US) and Atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H) in resource limited settings. A total of 29,475 women were screened cytologically through Pap tests. The epithelial cell abnormalities (ECA) detected on screening were reviewed by the cytopathologists and classified according to Bethesda 2001 system. The women with ASC-US reports were followed up by two repeat cytology tests at 3 and 6 months of the initial visit. The persistent ASC-US cases or the cases which revealed squamous intraepithelial lesion (SIL) on follow up smears; as well as all ASC-H and above cases were referred for coloposcopic evaluation. ASC diagnosis comprised 3.6% of all reports. These were qualified as ASC-US (3.36%) and ASC-H (0.22%). On follow up, only 7 CIN 2 or worse (3.2%) lesions were detected on 218 biopsies in ASC-US category while in ASC-H qualifier 16 CIN 2 and above lesions (30.8%) were picked up on 52 colposcopic biopsies. The difference between ASC-US and ASC-H categories for a CIN 2 or worse outcome was highly significant (P < 0.001). ASC-H qualifier has a high likelihood for an ominous histological outcome and warrants an immediate colposcopic evaluation. On the other hand, ASC-US cases can be managed conservatively by repeat cytology tests at regular intervals without a significant risk of missing a high grade lesion. Diligent screening of cervical smears can judiciously downgrade some cases overcalled as ASC because of inflammatory atypia and thereby reduce referrals in geographic settings with high prevalence of reproductive tract infections. High risk HPV (HR HPV) testing may be a useful adjunct to further reduce referrals by selecting the women who require colposcopic evaluation.     

Metastatic malignant melanoma of the uterine cervix: first diagnosed on liquid-based cytology

Malignant melanomas of the female genital tract are uncommon lesions. The first case of vulvar melanomas with a subsequent malignant melanoma of the cervix diagnosed based on liquid-based cytology without evidence of gross pathology is described.     

Usefulness of NMP22 as an adjunct to a typical urine cytology and low‐grade urothelial carcinoma

The usefulness of urine cytology combined with NMP22 was evaluated for the primary diagnosis of urothelial carcinoma. Of 53 clinically suspected patients, histopathological diagnoses were low‐grade urothelial carcinoma (25), high‐grade urothelial carcinoma (13), and inflammatory lesions (15). Cytology was positive in 25 and negative in 14 patients. Fourteen of 25 low‐grade urothelial carcinoma and 11/13 high‐grade urothelial carcinoma were diagnosed correctly on urine cytology. Atypical cells seen in 14 patients were categorized as inconclusive for malignancy. The overall sensitivity of urine cytology was 65.8%, whereas specificity was 100%. NMP22 was positive in 33 patients. Of these 30, 18 low‐grade and 12 high‐grade lesions were true positive. Of the 20 NMP22, eight negative cases were false‐negative. Ten of 15 with negative histopathology were also negative for NMP22, three were false‐positive, and two showed erratic results. Nine of 14 cases with atypical urine cytology were positive for NMP22. Eight of these showed low‐grade carcinoma on histopathology. The sensitivity of BladderChek NMP22 test was 79%, whereas specificity was 80%. NMP22 BladderChek test is a useful adjunct to urine cytology in atypical and low‐grade carcinoma. Diagn. Cytopathol. 2010;38:788–790. © 2009 Wiley‐Liss, Inc.     

Improved sensitivity over time with rapid prescreening in gynecologic cytology

Rapid prescreening (RPS) is a powerful tool to measure and improve performance in the cytology laboratory. Long‐term use of RPS has been shown to result in improved sensitivity and precision in routine screening. The effect of long‐term RPS on RPS itself is not known. We compared the sensitivity of 100% RPS of Surepath? liquid‐based cytology over a 4‐year period in a laboratory of 11 cytotechnologists (CTs). In comparison with the first 2 years, RPS for the laboratory showed a significant increase in sensitivity for all abnormalities (72.2% vs. 67.3%, P < 0.001) and ASCUS + LSIL (68.5% vs. 62.1%, P < 0.001). For individual CTs s, the lowest sensitivity for all abnormalities increased from 59.0 to 63.2%, whereas, for HSIL, it increased from 71.4% to 75.0%. We conclude that long‐term use of RPS leads to significant increase in the sensitivity of RPS. Diagn. Cytopathol. 2011;39:428–430. © 2010 Wiley‐Liss, Inc.     

液基薄层细胞学检测及TBS分类在宫颈病变诊断中的应用

目的探讨液基薄层细胞学（TCT）检测在宫颈病变诊断中的价值。方法对648例宫颈异常的患者进行液基薄层细胞学检测，将诊断意义不明的不典型细胞（ASCUS）以上病变者行阴道镜下活检，将细胞学检测结果与活检结果作对比分析。结果648例TCT检测的患者中，宫颈病变发生率达81．9％，其中良性病变348例，占53．7％，宫颈上皮内病变183例，占28．2％，对183例异常者进行阴道镜下活检与组织病理学诊断比较，符合率为83．6％。宫颈上皮内病变高发年龄为30～40岁，占37．8％。结论TCT技术在宫颈病变的诊断中，具有简便、实用，准确率高的特点，配合阴道镜检查能及时发现宫颈早期病变，是防止宫颈癌的关键。     

Usefulness of lavage cytology during endoscopic transpapillary catheterization into the gallbladder in the cytological diagnosis of gallbladder disease

Many studies have reported methods of cell collection involving percutaneous transhepatic cholangiodrainage (PTCD) and fine‐needle aspiration cytology for the diagnosis of gallbladder disease. However, few studies have described the use of a transpapillary approach, i.e., endoscopic transpapillary catheterization into the gallbladder (ETCG). In this study, we analyzed cells collected by ETCG to evaluate its usefulness in the cytological diagnosis of gallbladder disease. The subjects were 19 patients who had undergone ETCG for the diagnosis of gallbladder disease. Of these patients, 11 and 8 had gallbladder cancer and benign gallbladder disease, respectively. We also evaluated the diagnostic accuracy of PTCD cytology performed in 15 patients with gallbladder cancer. Specimens were cytologically diagnosed as normal or benign, indeterminate, suspected malignancy, malignant, and inadequate in 47% (9/19), 11% (2/19), 0% (0/19), 37% (7/19), and 5% (1/19) of patients, respectively. Specimens were diagnosed as malignant, indeterminate, normal or benign, and inadequate in 7, 2, 1, and 1, respectively, of the 11 patients diagnosed with gallbladder cancer. The sensitivity and specificity of ETCG cytology were 78 and 100%, respectively, whereas the diagnostic accuracy of PTCD cytology was 20% (3/15). None of the patients developed complications of ETCG. Despite its technical difficulty, ETCG for bile cytology allows the collection of adequate cell numbers from patients with benign disease or gallbladder cancer and facilitates a cytological diagnosis, making it a useful method for collecting cells. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

The impact of high risk human papillomavirus testing in an inner London colposcopy clinic

This is an audit of a new technique to improve the colposcopy service. Samples were tested for high risk HPV DNA using Digene Hybrid Capture II. Sixty-four percent of the sampled women under 30 had detectable high risk HPV DNA, decreasing to 44% in 30--39 year olds and to 27% in women over 40. High risk HPV prevalence increased with severity of cytology, although 22% with normal colposcopy had detectable high risk HPV. Of those women treated for cervical dysplasia, 83% had detectable high risk HPV prior to treatment, compared to only 32% afterwards. The audit has shown that high risk HPV testing has considerable discriminatory value. It has been integrated successfully into the service, particularly to manage low grade cervical abnormalities and to add valuable information following treatment for cervical dysplasia. Results need to be interpreted alongside colposcopy, cytology, and histology, and care must be taken in the interpretation of a single high risk HPV result.     

Application of impression cytology to the diagnosis of conjunctival neoplasms

Conjunctival impression cytology using cellulose acetate filter paper was employed to obtain multiple samples of conjunctival epithelium from 192 normal and abnormal eyes. Modifications of an established technique were used and the impressions were stained by the Papanicolaou method and mounted on glass slides. The impressions were examined for their effectiveness in demonstrating the morphological characteristics of normal epithelium and the features of the more common conjunctival neoplasms. The technique was found to be successful at both removing cells and preserving cytologic features. It also had several advantages over other collection techniques. Overlapping cells were not a detrimental feature of the preparations from this study. Diagn Cytopathol 1994;11:246–249. © 1994 Wiley-Liss, Inc.     

HPV检测在“不典型鳞状细胞-不除外宫颈高度上皮内病变”中的意义

目的探讨高危型人乳头状瘤病毒(HR-HPV)检测对细胞病理学诊断为不典型鳞状细胞-不除外宫颈高度上皮内病变的(ASC-H)患者的临床处理价值。方法 2004年6月～2007年4月于中日友好医院妇产科门诊进行宫颈细胞学检查的患者17 125例,选择其中细胞学诊断结果为不典型鳞状细胞的患者,应用第二代杂交捕获方法检测HR-HPV,观察HR-HPV检测对细胞学诊断结果为ASC-H进行分流的意义。结果 HR-HPV阳性的ASC-H患者中宫颈高度病变的检出率(48.1%)显著高于ASC-US(25.2%),(P<0.01)。13例HR-HPV阴性的ASC-H患者中1例宫颈活组织检查结果为CIN2(5.9%),与ASC-US(5.7%)相比无差异。在ASC-US和ASC-H患者中,HR-HPV检测对于宫颈高度病变的敏感性分别为82.8%、96.2%,阴性预告值分别为94.3%,92.3%。结论对于HR-HPV阴性的ASC-H患者可以考虑定期随诊细胞学和高危型HPV,减少阴道镜检查,HR-HPV检测可能对于ASC-H患者同样具有分流作用。     

Accuracy of a low priced liquid‐based method for cervical cytology in 632 women referred for colposcopy after a positive Pap smear

The aim of this quality controlling study was to determine the accuracy of liquid‐based cytology (LBC) with the Turbitec® cytocentrifuge technique. Cervical smears of 632 women, who were referred to our CIN outpatient department, after at least two smears with ASCUS or higher were evaluated and compared with the histological outcome. In 592 cases the smears revealed abnormalities of squamous epithelium, and in 40 cases the abnormalities of glandular epithelium. In the group of squamous epithelium abnormalities, the sensitivity for LSIL was 39.7% and the specificity was 89.2%; for the LSIL+ group, these values were 89.4% and 91.4%, respectively. For HSIL the sensitivity was 68.3% and the specificity 92.8%, for the HSIL+ group 82.3% and 92.3%, respectively. The ASCUS rate was low (2.4%). The Turbitec cytocentrifuge method was proved to be a very good LBC method for cervical smears. Because of a comparable accuracy together with a lower price, this LBC method outweighs commercial alternatives. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Role of HPV DNA,HPV mRNA and cytology in the follow‐up of women treated for cervical dysplasia

The aim of this study was to assess the role of cytology, human papilloma virus (HPV) DNA and human papilloma virus messenger RNA (HPV mRNA) assays in detecting cervical intraepithelial neoplasia grade 2+ (CNi 2+) (recurrences/persistence) during the follow‐up of women after treatment of cervical intraepithelial lesion. This cross‐sectional study was performed among 43 women treated for cervical intraepithelial neoplasia (CIN) between January 2014 and January 2017 at the Department of Obstetrics and Gynecology of Spedali Civili's Hospital, Brescia, Italy. Pap smear and cervical samples for HPV tests were collected during the follow‐up visit. Furthermore, colposcopy was always performed in order to find out the persistence/recurrence of the disease. A cervical biopsy was collected when necessary. Cervical samples obtained were tested for HPV DNA using the INNO‐LiPa HPV assay and for HPV mRNA using the APTIMA assay. The mean age of enrolled women was 42.5 years. Among the treated patients, more than 50% of women revealed the absence of high risk HPV DNA and HPV mRNA. We found the persistence of the disease cervical intraepithelial neoplasia grade 2 (CIN 2) only in one woman. The sensitivity of cytology, HPV DNA and HPV mRNA in detecting disease was satisfactory (100%), while the specificity was quite different for the three tests: 64.2, 52.4 and 78.9%, respectively. The HPV mRNA test has higher specificity with respect to cytology and HPV DNA, avoiding the referral to unnecessary colposcopy with an improvement of costs/benefits for healthcare system. However, given the small size sample, this study should be considered as a pilot for future larger studies.     

Aspiration cytology of neuroendocrine tumors below the diaphragm

In a series of 630 transabdominal fine-needle aspirates, 24 neuroendocrine tumors (NETs) presenting below the diaphragm were encountered. Of these, 10 were classic small-cell undifferentiated carcinomas (SCUCs). Recognition of SCUC in abdominal aspirates has major directive value, pointing to bronchogenic origin, possibly unsuspected, in most cases (eight of 10 in this series). The other 14 NETs were 10 pancreatic islet-cell tumors and four intestinal carcinoids, both diagnosed more frequently in metastatic than in primary sites (10 of 14 in the liver in this series). The cytologic presentation of these non-SCUC neoplasms has received little literature attention, and it is described and illustrated here, with discussion of cytologic pitfalls and differential diagnoses. Diagnostic specificity was 100%, and sensitivity was also 100%, exclusive of two sampling errors. The purpose of this article is to establish a broader view of the range of morphological features of the extended neuroendocrine group of tumors in aspiration cytology.     

Fine-needle aspiration cytology of the thyroid gland: comparative analysis of experience at three hospitals

Fine-needle cytology is an effective and accurate diagnostic method for the assessment of thyroid lesions. The aim of the present study was to evaluate the role of thyroid cytology at a tertiary where cytopathologists with experience in thyroid cytology participate in the procedure and compare it with results in two community hospitals lacking pathology departments and on-site cytopathologists. A total of 1,770 specimens were diagnosed between 1998 and 2003. Of these, 425 were from the two local hospitals. The fraction of unsatisfactory specimens was 24% for submitted specimens and 9.5% for those taken in the presence of a cytopathologist. The percentage of malignant specimens was 4.1% at the tertiary center compared with 2.2% of submitted cases. These data highlight the need to centralize thyroid fine needle cytology to specialized centers with experienced cytopathologists.