Effectiveness of automated cervical cytology rescreening using the AutoPap® 300 QC System

This study assesses the performance of the AutoPap® 300 QC System in identifying false-negative (FN) smears in a slide population previously screened as normal and compares the detection rate to that achieved with a random rescreen of the same slide population. A total of 1,840 “normal” smears were rescreened both manually and by the AutoPap® 300 QC System. Overall, a total of 7 FN slides were detected. At QC selection rates of 30% and 20% the device achieved sensitivities for detection of FN smears of 57.19% (4/7) and 42.8% (3/7), respectively. This represents a three- to fourfold enrichment in the number of FN smears over that obtained by a random rescreen of a similar proportion of cases. None of the FN slides were identified by either method at a 10% rescreening rate. The ability of the device to detect slides previously classified as abnormal (n = 139) and FN (n = 40) was also studied. The overall sensitivity to abnormal smears at QC selection rates of 10%, 20%, and 50% was 61.9%, 77.0%, and 94.2%, respectively. Improved sensitivity to smears classified as LSIL or worse (n = 112) was obtained for corresponding selection rates (61.6%, 75.9%, and 93.8%). Sensitivity to FN slides classified as LSIL or worse (n = 17) for QC selection rates of 10%, 20%, and 50% was 29.4%, 70.6%, and 88.2%, respectively. The sensitivity and specificity of the device to an adequate squamous and endocervical cell component was also determined. At predetermined thresholds, the overall sensitivity to slides with an inadequate squamous cell component (n = 55) and to those smears with an endocervical cell component (n = 1,587) was 81.8%, and 82.7% respectively. The study demonstrated that the AutoPap® 300 QC System is superior to human random rescreen for the identification of FN smears although only a marginal improvement was noted due to the small sample. Further studies are required using a larger number of smears to fully assess the value of the device in quality control mode. The device also has the potential to improve the accuracy of specimen adequacy determinations and to serve as a useful adjunct to existing quality control measures designed to monitor individual performance and reporting accuracy. Diagn. Cytopathol. 16:505–512, 1997. © 1997 Wiley-Liss, Inc.     

Routine Pap smears for the diagnosis of bacterial vaginosis.

This study investigated the role of Papanicolaou (Pap) smears in determining the presence of bacterial vaginosis (BV). Pap results, vaginal Gram stains, signs, symptoms, and wet mounts were evaluated. Vaginal smears for Gram stain and routine Pap smears were collected from 420 consecutive patients. Ninety-three percent of patients with Pap smears showing only coccobacilli had a corresponding BV-positive Gram stain. Pap smears with mixed bacterial patterns had 22-71% positive Gram stains depending on the types of bacteria present. Only 10 of 70 symptomatic patients and 13 of 132 with cervicitis or discharge had a positive Gram stain and/or an altered bacterial pattern. All positive wet mounts had positive Gram stains and coccobacilli only on Pap smears. The most specific diagnosis of BV with Pap smears requires coccobacilli only. This reiterates the Bethesda system criteria. Clinical signs, physical symptoms, and wet-mount examinations were noncontributory in this study.     

Undetected invasive lobular carcinoma of the breast: review of false-negative smears

Analysis of a series of 34 fine-needle aspirations (FNA) from 28 patients with invasive lobular carcinoma (ILC) was undertaken. The false-negative smears were reviewed to reveal the cause of such a relatively frequent error. This was a retrospective study and comparison between the cytological and pathological findings in a series of 34 FNA. Three cases were excluded without sufficient material. Twelve cases were positive, nine suspicious of malignancy, and 10 were considered false-negatives. In a second analysis of this later group, one was reclassified as carcinoma, two reconsidered without sufficient material for diagnosis, and the remaining seven, still considered negatives, constituted the core of this study. Of these seven, there were none with hypercellular smears and in six there was a predominance of fat-tissue fragments. The scarce epithelial component showed honeycomb-flat sheets in four, loose clusters in three, small and tight clusters with irregular limits in six, and more than 10% of isolated epithelial cells (noncohesive cells) in one case. "Staghorns" were undetected and myoepithelial cell nuclei were very scarce in all cases. Some nuclear enlargement was detected in one, angulated nuclear contour in three, and nuclear crowding was present in five. All seven had fine, homogeneous chromatin, without prominent nucleoli. Cytoplasmic limits were undefined in all but one (6/7) and occasional cytoplasmic vacuolization was detected in two. Hypocellular smears with few, small, and dense groups (but always with more than 10 groups in at least one smear) can be related with ILC. In these cases, further studies are recommended to exclude malignancy. The loose cluster and flat sheets identified in four cases represent a benign epithelial hyperplasia mixed with the ILC.     

Pap smears of patients with extramammary Paget's disease of the vulva

Extramammary Paget's disease (EMPD) of the vulva is a rare entity. The diagnosis is almost always made on biopsy. Tumor cells are seen rarely in Papanicolaou (Pap) smears. We encountered three cases of EMPD that were detected in Pap smears. One patient had vulvar and vaginal involvement and the abnormal cells seen in the vaginal smear initially were interpreted as high-grade squamous intraepithelial lesion. Retrospective review showed scattered single atypical cells with enlarged hyperchromatic nuclei, coarse chromatin, inconspicuous nucleoli, high nuclear/cytoplasmic (N:C) ratio, and scanty basophilic cytoplasm. Rare signet ring cells and cells within cells were present. In the other two patients who had cervical involvement, the correct diagnosis was made on Pap smears. The slides showed both single and cohesive sheets of glandular cells with enlarged round to oval nuclei, coarse chromatin, prominent nucleoli, and abundant basophilic cytoplasm containing prominent vacuoles with signet ring-cell appearance. Cells within cells were abundant. EMPD has distinct cytomorphological features. Although infrequently encountered, EMPD can be diagnosed on Pap smears with adequate clinical history.     

Automated screening for quality control using PAPNET: A study of 638 negative Pap smears

To determine if the PAPNET screening system can be used for quality control to lower false-negative rates for Pap smears 638 manually screened. “negative” Pap smears were subjected retrospectively to the PAPNET screening system. Twenty-nine of the smears came from 18 patients who subsequently had biopsy-proven high-grade squamous intraepithelial lesions (SIL). The remaining 609 negative smears were arbitrarily selected as controls. One hundred twenty-eight (128) of the retrospectively reviewed smears (20%) were selected by PAPNET for microscopic referral because of potential abnormalities. Abnormalities were confirmed on 14 of these smears upon microscopic evaluation. Five of these 14 smears were from smears obtained from four of the 18 women with high-grade SIL. The incidence of manually screened false-negatives detected by PAPNET rescreening was 14/638 or 2.2% for the entire patient population in this study and 5/29 or 17.24% for the targeted patients known to have subsequently developed high-grade lesions. The 2.2% decrease in the false-negative rate in this experiment may be partly artificial as this study group was seeded with false-negative cases at high risk for containing missed abnormalities. The implementation of the PAPNET system for quality control may lower false-negative rates for Pap smears. Diagn Cytopathol 1996;14:316–320. © 1996 Wiley-Liss, Inc.     

Improved detection of Mycobacterium spp. using the Bactec MGIT 960 system

Until 1987, the notification rate for mycobacterial infection was on the decline; however, it now appears to be increasing once more. The reason for this may be multifactoral and include improved reporting of diagnosed cases, increased infection of an ageing population, homelessness, immunosuppression (e.g. due to human immunodeficiency virus infection), and immigration of people from countries where tuberculosis is endemic. This rising incidence and the increasing importance of resistant organisms mean that rapid identification by the clinical microbiology laboratory is required, and this is where an automated detection system can be an advantage. Over a two-year period, 2743 clinical specimen were examined for Mycobacterium spp. using the Bactec MGIT 960, and 286 were positive. Time to detection ranged from three to 14 days (mean: 9.3 days), and M. tuberculosis was recovered from 214 (75.5%). Contamination rate was higher (8.6%) than with manual methods, however. On balance, the Bactec MGIT 960 system proved a valuable tool in the routine microbiology laboratory.     

TCT查验子宫颈涂片中HPV感染的研究

目的评价液基薄层细胞检测技术(TCT)检测宫颈涂片中人乳头状瘤病毒(human papilloma virus,HPV)感染的敏感性与准确性。方法对1030例外阴尖锐湿疣患者的子宫颈涂片,采用TCT检测技术进行细胞病理学诊断,其诊断标准依据The Bethesda System(TBS)分类法。同期行阴道镜指引下的子宫颈活组织检查和聚合酶链反应(PCR)技术检测宫颈拭子中的HPVDNA。结果应用PCR检测1030例宫颈拭子HPVDNA,阳性者37例(35.92%)。宫颈活组织学检查结果为ASCUS57例(5.53%);上皮内病变CIN11例,占总数的1%;占HPV( )百分率为29.73;占57例为非典型麟状细胞阳性的19.3。结论TCT作为一种细胞病理学检测技术,用于诊断宫颈HPV感染或亚临床感染,有临床应用价值。     

Endometrial cells and the AutoPap System for primary screening of cervicovaginal Pap smears

In 1998, the AutoPap 300 received FDA approval for primary screening of conventional cervical smears. As approved, smears categorized as "no further review" and comprising up to 25% of the smears screened by the AutoPap 300 can be reported as negative for malignant and dysplastic cells without screening by a cytotechnologist. We studied 106 conventional cervical smears in which glandular endometrial cells had been identified by manual screening to assess the ability of the AutoPap System (TriPath Imaging, Inc., Burlington, NC) to (1) designate conventional Papanicolaou smears that contain endometrial cells for "review," and (2) stratify smears that contain endometrial cells as more or less likely to be abnormal. Although the number of cases in our study was small, our findings indicate that (1) the AutoPap System is slightly less sensitive than manual screening by experienced cytotechnologists for the detection of endometrial cells in conventional smears, as the System designated for "review" 94.3% of all smears containing endometrial cells, 92.9% of smears reported as atypical glandular cells of undetermined significance (AGUS) or endometrial adenocarcinoma, and 100% of the four smears with subsequently confirmed endometrial adenocarcinomas, (2) ranking of smears into quintiles by the AutoPap System did not provide additional diagnostically useful information with respect to endometrial pathology, (3) the number of endometrial cells in the smears did not correlate with quintile assignment, and (4) for most patients, routine use of the AutoPap System for primary screening of conventional cervical smears is unlikely to contribute to delay in the diagnosis of clinically significant endometrial lesions.     

Clinical significance of identifying candida on cervicovaginal (Pap) smears.

This study was undertaken to determine the clinical significance of detecting candida on Pap smear. Clinical information was obtained from a questionnaire sent to the health care provider whenever candida was identified during the study period. Candida was identified in 309 (3.0%) of the 10,370 Pap smears examined. Completed questionnaires were returned on 137 (44.3%) patients. All 137 smears were reviewed. Ninety-nine (72%) patients were asymptomatic, 29 (21%) had symptoms typical of candida infection, and nine (7%) had nonspecific symptoms. Forty-four (32%) patients had been treated for candida during the original clinic visit. After the Pap smear reported candida, 19 (20%) of the 93 nontreated patients were contacted and treated, while 10 (11%) were scheduled for further evaluation. No action was taken on the remaining 64 (69%) patients. There was a significant association between having initial symptoms and receiving immediate treatment (P < 0.001) and undergoing subsequent treatment or further evaluation after the Pap smear report (P < 0.001). Marked inflammation was statistically associated with symptoms (P = 0.014), but the form or number of candida organisms was not. In conclusion, the identification of Candida on Pap smear does not necessarily indicate a symptomatic infection, although the Pap smear results had a direct impact on the treatment of 21% of patients in this study and served as a confirmation for clinical treatment in another 32% who had received such treatment at the time of the original visit.     

The correlation of inflammation and epithelial changes in the Pap smears of cervix uteri

A modification of The Bethesda System classification of cytologic findings of uterine cervix named Zagreb 1990 has been accepted in Croatia as a unique classification, the use of which has begun after the publication and printing of the new, uniform method of cytologic examination. AIM: The aim of this study was to assess the number and type of cytologic abnormalities of uterine cervix classified according to Zagreb 1990, on routinely examined Pap smears during the 6-year period, and to investigate the connection of these abnormalities with lower genital tract infections. MATERIAL AND METHODS: The retrospective study included Pap smears from the City of Zagreb and from the town of Imotski. A total of 59901 Pap smears (patients aged 17-79) were routinely examined: the cytopathologic diagnosis of CIN I or higher recorded in 3664 (6.12%) of them. The control group consisted of 401 Pap smears of age-matched women referred by the same gynecologists and free from cytologic abnormalities. The most frequently diagnosed epithelial change was CIN 1 (84.57% of all epithelial changes, and 5.17% of total study population), followed by CIN II (10.92%; 0.67%), CIN III (3.11%; 0.19%), and invasive squamous carcinoma (1.31%; 0.08%). Endocervical adenocarcinoma was cytologically diagnosed in only 0.0055% of all Pap smears examined. Inflammation was significantly more common in the group with epithelial dysplasia/carcinoma than in the control group (p < 0.01). Of specific causative agents HPV and Chlamydia trachomatis were significantly more frequently found in the group with epithelial dysplasia/carcinoma than in the control group (p < 0.05 both), however, Gardnerella vaginalis, Trichomonas vaginalis or Candida yielded no significant differences. It is concluded that inflammation very likely contributes to the development of precancerous lesions of the cervix, HPV and Chlamydia showing strongest correlation, at least in a part of our population.     

Non-isotopic detection of HPV DNA in cervical smears using dot-blot hybridization

Infection of the cervix with specific types of the human papillomavirus (HPV) results in condylomatous, dysplastic and/or neoplastic epithelial changes. To enable routine screening of premalignant cervical lesions for HPV DNA, we have developed a sensitive method of detecting HPV -6, -11, -16, -18 and -33 in cervical scrapes using a non-isotopic, dot-blot hybridization assay. Cloned, genomic HPV DNA is labelled with biotin-11-dUTP by nick translation, and used to screen for HPV types under high stringency conditions. DNA is extracted from cervical cells and spotted on nitrocellulose membranes. Cervical cells, from 20 patients attending colposcopy were screened for HPV types. All patients had a dysplasia or condyloma. HPV DNA was isolated from 80%. The method visualized an amount of target DNA as low as 1 pg without background. Compared with Southern blot hybridization utilizing radiolabelled probe, this assay is equally sensitive and specific. The technique is easy to do, and may significantly contribute to the management of cervical dysplasia.     

Clinicopathological study of Papanicolaou (Pap) smears for diagnosing of cervical infections

Cervical infections are not uncommon in our population especially in young and sexually active women. One thousand samples of married women, aged between 20 and 70 years, were studied by conventional Papanicolaou smears. These samples were examined in the Department of Pathology, King Edward Medical University, Lahore from January 2007 to June 2009. Only cases without (pre)neoplastic cytology were included. Six types of infections were diagnosed cytologically. The overall frequency of normal, inadequate, neoplastic, and infective smears was 50%, 1.8%, 10.2%, and 38.3%, respectively. Most of the patients (67%) were in the reproductive age group with mean age 34.7 ± 2.6 years. The commonest clinical sign seen in 354/383 (92%) cases and symptom in (349/383; 91%) cases were vaginal discharge and pruritis vulvae. Among the infective smears, 290 cases (75.7%), the cytologic diagnosis was nonspecific inflammation. Most of these 290 smears contained clue cells (indicating Gardnerella infection) and a lack of lactobacilli. Such smears are predominant in patients suffering from bacterial vaginosis (BV). Twenty-eight smears (7.3%) were positive for Trichomonas vaginalis, 27 cases (7%) were smears with koilocytic change pathognomonic of human papilloma virus infection. Twenty-five smears (6.5%) were positive for fungal infection. Seven cases (1.8%) were diagnosed as herpes simplex virus infection. Finally, there were six cases (1.5%) with atrophic vaginitis. We conclude that the cervical smear is well suited for diagnosing cervical infections. It is clear that Gardnerella, known to be associated with bacterial vaginosis, is a major problem in our Pakistani population.     

Cervical biopsy-based comparison of a new liquid-based thin-layer preparation with conventional Pap smears

The objective of this study is to compare the diagnostic efficacy of universal collection medium (UCM) liquid-based cytology (LBC) (Digene Corp., MD) and the conventional Pap smear in a comparative study, using histologic results as the gold standard. This was a cross-sectional study. Conventional Pap smears and UCM LBC specimens, obtained from women in a low socioeconomic outpatient population referred to a tertiary center for gynecologic care, were compared. For the purpose of this study, when cervical specimens were collected for cytology, all women underwent colposcopy and biopsy was done if a cervical abnormality was observed. Cytologic evaluation of UCM LBC and conventional Pap smears were carried out separately, masked to the results of the other method. Agreement beyond chance between the two cytologic methods was ascertained by means of the unweighted kappa statistic. Sensitivity, specificity, and predictive values with 95% confidence intervals were calculated for both methods. McNemar's test was used to determine the level of association between the two cytology procedures. A total of 800 women were evaluated. Assessment of the overall agreement between the two cytologic methods yielded a kappa of 0.777 (P < 0.0001). After adjustment for histologic diagnosis, the computed kappa in each stratum was as follows: normal = 0.733; CIN 1 = 0.631; CIN 2/3 = 0.735; cancer = 0.652. The sensitivity and specificity of UCM LBC for detection of cervical intraepithelial lesions and cancer were 75.3% and 86.4%, respectively, not statistically different from the 81.8% and 85.2% seen with the conventional method. This study demonstrates that the UCM LBC method is as accurate as the conventional Pap smear cytology in detecting cervical intraepithelial lesions and cancer even so the UCM samples were systematically prepared from a second sampling of the cervix.     

Improved fracture detection using the mammographic film-screen combination

Aim

The single emulsion or single screen system is usually reserved for mammography since its use in general radiography is limited. The purpose of this study is to compare the mammographic film-screen combination (MFC) and the standard film-screen combination (SFC) in terms of fracture and soft tissue injuries detection.

Patients, methods and materials

In this prospective study, 41 patients from Accident and Emergency suspected of having injury in the hands, wrists, ankles and feet regions were radiographed using both MFC and SFC. These were compared in terms of image quality, presence of fractures and soft tissue injuries. The two different film-screen combinations were also compared in terms of detection of bony fragments, film characteristics such as film speed, contrast and spatial resolution, dose and cost.

Results

The MFC gives statistically better image quality compared to SFC. In 10% of patients, fractures were detected only in the MFC, which also detects tiny bone fragments that may not be resolved by the SFC. The spatial resolution of the MFC is greater than the SFC. The film speed and contrast of the MFC are lower than that of the SFC. The doses of MFC were higher compared to SFC.

Conclusions

The MFC detects fractures better compared with SFC. However, the entrance skin dose for the mammographic film-screen combination was about 35% to 55% higher than the standard film-screen combination.     

Detection of false-negative Papanicolaou smears by rapid rescreening in a large routine cervical cytology laboratory

Rapid rescreening was established in our laboratory in 1995, following the publication of several studies indicating improved sensitivity for the detection of abnormalities in cervical smears. During the study period, 285,841 negative smears (representing 89.09% of the total workload) were rapidly rescreened. A total of 7,650 (2.68%) were identified as abnormal or suspicious and selected for full rescreening. Of these, 228 cases were considered abnormal following pathologist review and resulted in the issue of an amended report. This represents an increased detection rate for all abnormalities of 0.08%. Of the cases with histological follow-up, a high grade epithelial abnormality (HGEA) was confirmed in 31% of cases and a low grade epithelial abnormality (LGEA) in 42%. We conclude that rapid rescreening is easily incorporated into the daily workflow of a large routine cervical cytology laboratory, Our results support conclusions from previous studies that rapid rescreening is an effective quality control technique resulting in the detection of increased numbers of abnormal smears.