Performance of an imaging system vs. manual screening in the detection of squamous intraepithelial lesions of the uterine cervix

OBJECTIVE: To compare the ThinPrep Imaging System (Cytyc Corp., Boxborough Massachusetts, U.S.A) to manual screening in the detection of cervical squamous epithelial lesion (SIL). STUDY DESIGN: A total of 27,525 manually screened ThinPrep Pap tests were compared with 27,725 imaged ThinPrep Pap tests for: (1) diagnostic rates of atypical squamous cells of undetermined significance; atypical squamous cells of undetermined significance, cannot rule out high grade SIL (ASC-H); low grade SIL and high grade SIL (HSIL); (2) ASC/SIL ratio; (3) high-risk HPV positivity for ASC; and (4) biopsy follow-up for ASC-H and HSIL. RESULTS: There were significant increases in the percentage of cytologic diagnoses in all categories with the imager. The ASC/SIL ratios of both groups were comparable. There was a significant decrease in HPV positivity in the imager group of ASC. Biopsy results confirmed a significant increase in the detection of HSIL in both the ASC-H and HSIL groups of the imaged cohort. CONCLUSION: The ThinPrep Imaging System is significantly better than manual screening in the detection of cervical SIL.     

Evaluation of the AutoCyte SCREEN system in a clinical cytopathology laboratory

OBJECTIVE: To compare the AutoCyte SCREEN (AutoCyte, Burlington, North Carolina, U.S.A.) system with manual screening by experienced cytotechnologists using thin-layer preparations that had been previously extensively studied and their cytologic abnormalities well defined. STUDY DESIGN: AutoCyte PREP (AutoCyte) samples prepared for a previous split-sample study comparing thin-layer preparations to conventional smears were used. These 1,992 AutoCyte PREP samples were in a cohort the abnormal findings of which had been confirmed via independent review by two sets of pathologists. For the current study, these samples were remasked and evaluated by the AutoCyte SCREEN system in a clinical laboratory. The instrument scanned each slide and selected six overview fields and 120 single objects for storage and display. The computer classified each slide in one of the following categories: abnormal, uncertain, normal or unsatisfactory. Independently for each case, a cytotechnologist evaluated the six fields and 120 objects selected by the instrument as abnormal, normal or unsatisfactory. For those cases classified as uncertain by AutoCyte, the technologist then reexamined the cellular displays and entered a consensus classification. These results were then compared to those of an independent review by cytotechnologists of the identical set of slides using routine manual screening. RESULTS: The AutoCyte SCREEN selected 35% of slides for manual review. Technologist and computer rendered equivalent classifications in 79%. Of the total slides screened by the AutoCyte SCREEN, 57% were classified as "uncertain," and 88% of these were subsequently classified as normal by consensus. Using the well-defined abnormal values of the cellular sample as a basis for calculation, the AutoCyte SCREEN-assisted practice had a diagnostic sensitivity of 85% and diagnostic specificity of 97.6%. Comparable values for manual screening of the identical cellular sample were a diagnostic sensitivity of 80% and specificity of 97.4%. CONCLUSION: The AutoCyte SCREEN achieves comparable or greater sensitivity in detecting cervical abnormalities in comparison with manual screening. When combined with the substantial advantage of thin-layer preparations over conventional smears, the AutoCyte SCREEN provides a screening system of superior sensitivity over conventionally prepared and examined cervical smears.     

Effectiveness of liquid-based cytology and papanicolaou tests in a low risk population

OBJECTIVE: To compare sensitivity an effectiveness of ThinPrep vs. Pap Test and determine whether the Hybrid Capture System II (HCII) for detection of human papillomavirus (HPV) could increase the sensitivity and effectiveness of cervical screening in a low risk population. STUDY DESIGN: We present a comparative observer, blind, "split sample" study of ThinPrep and Papanicolaou staining in a population of 2026 consecutive women. RESULTS: Conventional Papanicolaou stain detected lesions in 62 cases (3.06%), including 1 atypical glandular cell of undetermined significance (AGUS), 34 atypical squamous cells of undetermined significance (ASCUS) (1.73% of atypias), 20 (0.99%) low grade squamous intraepithelial lesions (LSIL), and 7 (0.35%) high grade squamous intraepithelial lesions (HSIL). ThinPrep detected lesions in 63 cases (3.11%), including 26 (1.28%) ASCUS, 27 (1.33%) LSIL and 10 (0.49%) HSIL. Despite this overall similarity, only 35 had a coincident cytopathologic result by both methods. The kappa concordance index between ThinPrep and Pap was 0.546. Sensitivity and specificity were 74.6 and 45.0 in ThinPrep and 69.5 and 25.0 in Papanicolaou-stained smears. High risk HPV (HR-HP 17) was positive in 13 of ZOASCUS and in 21 of 22 SIL. CONCLUSION: Technologies now widely available such as Thin Prep and viral detection aim to improve accuracy of screening.     

Diagnostic value of the thin-layer, liquid-based Pap test in endometrial cancer: a retrospective study with emphasis on cytomorphologic features

OBJECTIVE: To examine the diagnostic value (sensitivity and specificity of the ThinPrep Pap test in the detection of endometrial cancer and assess the morphologic features of endometrial cancer in ThinPrep tests. STUDY DESIGN: In a retrospective, case-controlled study, we identified 60 Pap slides performed within 12 months of the tissue diagnosis of endometrial carcinoma and 56 comparison slides from patients without known carcinoma. The slides were blindly reviewed by the authors without knowledge of the surgical diagnosis. An independent diagnosis was given for the tests based on 14 diagnostic criteria from the 2001 Bethesda System and 6 additional criteria proposed by the authors. RESULTS: The sensitivity of detecting endometrial carcinoma was 88.3% (95% CI 77.8-94.2%) and specificity was 87.5% (95% CI 76.4-93.8%). The positive likelihood ratio was 7.067 (95% CI 3.513-14.217) and negative likelihood ratio was 0.133 (95% CI 0.066-0.269). Enlarged nuclei and the presence of nucleoli in endometrial cells were the most reliable indicators of endometrial cancer or atypical endometrial cells. CONCLUSION: The ThinPrep Pap test has high sensitivity and specificity in detecting or suggesting the presence of endometrial cancer. Certain cytomorphologic features are helpful in distinguishing benign and malignant endometrial lesions.     

Primary screening with liquid-based cytology in an unscreened population in rural China,with an emphasis on reprocessing unsatisfactory samples

OBJECTIVE: To determine the sensitivity and specificity of liquid-based cytology in a high-risk, unscreened population. STUDY DESIGN: A cross-sectional comparative trial of multiple screening techniques. This report focuses on the performance of liquid-based cytology using biopsy as the standard. RESULTS: In total, 1,997 women were screened. All subjects had a minimum of five cervical biopsies. Of the subjects, 4.3% had CIN 2 on biopsy. The ThinPrep Pap with ASCUS as positive had a sensitivity for CIN 2 of 94% and specificity of 78%; the sensitivity for CIN 3 was 98% and for cancer, 100%. The unsatisfactory rate due to bloody specimens was 7.9% (158/1,997). After reprocessing, the unsatisfactory rate was 0.15% (3/1,997). CONCLUSION: Reprocessing effectively recovers ThinPrep samples otherwise unsatisfactory due to blood and mucus. The ThinPrep Pap test is a highly sensitive screening test when used in a high-risk, unscreened population.     

A thin-layer,liquid-based pap test for mass screening in an area of China with a high incidence of cervical carcinoma. A cross-sectional,comparative study

OBJECTIVE: To confirm the accuracy of the ThinPrep Pap Test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) on the basis of histologic diagnosis by biopsy and the detection of human papillomavirus (HPV) DNA in mass screening. STUDY DESIGN: A total of 1,997 women residing in Xiangyuan County, Shanxi Province, P.R.C., an area with a high incidence of cervical carcinoma, were enrolled in this study. We collected exfoliative cervical samples from all subjects into a liquid buffer (Preserv-Cyt [Cytyc]) and utilized for both cytologic screening using the ThinPrep Pap Test and HPV DNA testing. Subsequent colposcopic biopsies were taken on all subjects. All the tests were performed in an independent and blinded fashion. We compared the ThinPrep Pap test with colposcopic biopsy and HPV test. RESULTS: High grade squamous intraepithelial lesions (HSIL) (CIN 2/3) were identified in 74 (3.7%) of 1,993 women adequately assessed, and there were 12 cases of squamous cell carcinoma (SCC). The false negative rate of ThinPrep cytology was 3.2% for biopsy-confirmed CIN 3 and 9.3% for CIN 2. Twenty-seven (87%) of the 31 women with biopsy-confirmed CIN 3 and 12 (100%) of 12 with biopsy-confirmed SCC had a diagnosis of either HSIL or greater abnormalities on ThinPrep cytology. In addition, the HPV DNA detection rates offered a good correlation between cytology and biopsy. CONCLUSION: The ThinPrep Pap performed extremely well in this primary screening trial. We found a good correlation between ThinPrep cytology and colposcopic biopsy on detection of HSIL and SCC; cervical specimens collected in ThinPrep liquid buffer serve as a direct test for HPV as well.     

Analysis of urine cytology tests in 120 paired cases

OBJECTIVE: To evaluate the smear quality and diagnostic accuracy of ThinPrep processing in comparison to conventional Cytospin technique for urinary cytology. STUDY DESIGN: ThinPrep and Cytospin techniques were retrospectively evaluated by 2 observers in a double-blinded, randomized fashion. Each quality parameter was scored using a semi-quantitative score of 1-3. Diagnostic accuracy indices were calculated with biopsy histology as the gold standard. RESULTS: Quality of cellular distribution and cell preservation were better with Cytospin preparations, whereas ThinPrep smears were superior in terms of stain distribution and cleaner slide background. However, the only significant differences observed were in cellular distribution and a clean background (p < 0.05). Sensitivity and positive and negative predictive values were higher with Cytospin than the ThinPrep technique (90.0%, 94.7% and 71.4% vs. 80.0%, 94.1% and 55.6%, respectively). Conversely, the specificity of both techniques was comparable. CONCLUSION: The Cytospin smears were of better quality than those prepared by the ThinPrep technique. Although both techniques resulted in similar diagnostic accuracies in negative cases, the ThinPrep preparations were not found to be superior to Cytospin smears in diagnosing positive urinary cytology.     

A new look at cervical cytology. ThinPrep multicenter trial results.

The objective of this study was to compare the sensitivity of a new test method with the smear method for detection of neoplasia of the uterine cervix. The new procedure, the ThinPrep process, is an automated, fluid-based technique for the collection and preparation of exfoliated and aspirated cytologic specimens. A single sample from each patient was split and prepared both with the smear and test methods. The diagnostic results from the two slides were compared in this blind study. Among a total of 2,655 patients, diagnoses concurred in 92% of cases and were within one diagnostic level of each other 98% of the time. The ThinPrep method facilitated the detection of more low-grade lesions (P less than .001, McNemar's test). In addition, the test method decreased the number of ambiguous interpretations. The ThinPrep method appears to improve the cervical cytologic smear quality by the harvest of a random and reproducible sample, with a reduction in artifacts. The new method improves the sensitivity of the cervical cytologic screening test.     

Bile duct brushings cytology – improving sensitivity of diagnosis using the ThinPrep® technique: a review of 113 cases

OBJECTIVE: Common bile duct (CBD) brushings have been recognized as a technique of moderate sensitivity and high specificity in identifying carcinoma of the ampulla and pancreatico-biliary regions. This study evaluated the increase in sensitivity of this technique using the ThinPrep technique of specimen preparation when compared with conventional cytology smears. METHODS: A total of 113 bile duct brushings were included in the study (38 conventional smears and 75 slides prepared using the ThinPrep technique). All slides were reviewed by one cytologist. Five categories of reporting were used: inadequate, negative, atypia, suspicious and malignant. RESULTS: The inadequate category of reporting disappeared in the ThinPrep group with improved specimen fixation and preparation and hence reduced artefact. Sensitivity of diagnosis of malignancy increased from 39% in conventional smears to 53% in the ThinPrep group. Specificity, positive and negative predictive values and accuracy were 100%, 100%, 60% and 68% for conventional smears and were 100%, 100%, 60% and 72%, respectively, for ThinPrep specimens. CONCLUSIONS: ThinPrep technique was associated with increased sensitivity of diagnosis, in part due to improved specimen fixation and reduced artefact. Cytology of bile duct brushings is an important diagnostic tool for sites from which it can be difficult to obtain a histology biopsy. It may therefore provide the only opportunity for tissue diagnosis of carcinoma from these sites, hence the importance of optimizing sensitivity.     

Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast

X. Jing, E. Wey and C. W. Michael Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast Objective: To evaluate the utility of ThinPrep® as an optional specimen processing method for the detection of axillary lymph node metastasis of invasive breast carcinoma. Methods: A computer SNOMED search from the file at our institution between January 2003 and August 2011 retrieved a total of 209 fine needle aspiration (FNA) specimens of axillary lymph nodes prepared by ThinPrep and followed by axillary lymph node biopsy and/or dissection. Original cytological diagnoses and corresponding histological diagnoses were documented. Using the histological diagnoses as the gold standard, the diagnostic parameters including sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and diagnostic accuracy were calculated. Both cytology and histology slides from cyto‐histologically discrepant cases were reviewed. Results: Out of a total of 209 specimens, 193 (92%) had adequate diagnostic material while the remaining 16 specimens (8%) were inadequate for cytological assessment. The diagnostic specimens included 168 invasive ductal carcinomas (IDC), 15 invasive lobular carcinomas (ILC) and 10 mixed carcinomas (IDC and ILC). Excluding 19 cases with malignant cells on FNA in which no residual tumour was found in fibrotic lymph nodes after neoadjuvant therapy (cytology and histology confirmed on review) ThinPrep detected nodal metastasis with an overall sensitivity of 77.5%, specificity of 100%, PPV of 100% and NPV of 53.7%. Diagnostic accuracy was 82.2%. There was no difference in Bloom–Richardson grade or the number or size of metastases between tumours with true‐positive and false‐negative cytology. Sampling error was the sole factor contributing to cyto‐histological discrepancy. Conclusions: ThinPrep is a good alternative to the conventional smear for cytological assessment of axillary lymph node status in patients with invasive breast carcinoma, particularly when specimens are collected at remote sites or when cytologists are not available for assistance during FNA.     

Use of the ThinPrep Imaging System for internal quality control of cervical cytology

T. Heard, A. Chandra, G. Culora, S.S. Gupta, A. Herbert and M. Morgan
Use of the ThinPrep Imaging System for internal quality control of cervical cytology Objective: To audit the use of the ThinPrep Imaging System (TIS) for internal quality control (IQC) in the place of rapid review (RR), and to compare its performance with routine primary screening. Method: During 9 months, 16 462 ThinPrep slides were processed by TIS. Slides were initially reviewed using the TIS review scope, as recommended by the manufacturer: 22 fields of view were observed and, if considered abnormal, a full microscopic review was conducted using the review scope. Different biomedical scientists (BMSs), working on each procedure in rotation, performed batches of TIS‐assisted quality control and routine primary screening independently on unmarked slides. Any slides with abnormalities detected by either method were referred to a consultant pathologist or advanced BMS practitioner for a final report. TIS results were compared with both previous records of RR and routine primary screening carried out on the same slides. We used the UK terminology in which ‘dyskaryosis’ is equivalent to squamous intraepithelial lesion (SIL) and borderline to atypical (including squamous and glandular cells). Results: TIS preview detected significantly more high‐grade dyskaryosis compared with RR during the previous 4 years: 2.0–4.2 compared with 0.1–1.8 detected per 1000 slides (P = 0.0001). TIS and routine screening were equivalent in sensitivity and specificity for the final cytology result, but BMSs were significantly more likely to classify slides as dyskaryotic rather than borderline when using TIS compared with routine screening. Referrals for potentially high‐grade abnormalities detected by TIS‐assisted IQC alone found 28 biopsies of at least cervical intraepithelial neoplasia grade 2 (CIN2+), whereas 15 CIN2+ biopsies were found on routine screening but missed using TIS. There was no significant change in the rates of inadequate tests, high‐ or low‐grade cytological abnormalities, or positive predictive value for CIN2+ when TIS was in use. Conclusions: Screening with TIS was more sensitive than RR for IQC, providing a rescreening method equivalent to routine primary screening in overall accuracy.     

Concordance between original screening and final diagnosis using imager vs. manual screen of cervical liquid-based cytology slides

OBJECTIVE: To compare agreement of pathologists and cytotechnologists and technologist productivity before and after implementation of the Cytyc ThinPrep Imager. STUDY DESIGN: Using the Cytyc ThinPrep Imaging System, a retrospective analysis was conducted, from the first 6 months in 2004 and in 2005. Total cases in January through June were 79,791 in 2004 and 76,887 in 2005. Data on the number and type of changes from one impression to another were collected in a "confusion matrix". The chi2 test with 1 degree of freedom was used to calculate the significance of the difference between the groups. RESULTS: Changes in diagnosis were most frequently seen in negative for intraepithelial lesion, atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion. Interobserver agreement before the imager (weighted kappa) was 0.74 and after was 0.73. CONCLUSIONS: The number of high-grade lesions detected increased with the imager (p < 0.01). Technologist productivity increased by an average of 2.2 slides/hour.     

Proffered papers 14.00–15.00 Tuesday 16 September 2003

Background  ERCP-directed brush cytology is used to sample lesions of the pancreatic and biliary ducts and the ampulla of Vater. With conventional preparations, the sensitivity and specificity range from 44% to 63% and 80% to 98%, respectively, and increased N : C ratio, nuclear molding and loss of honeycombing are reliable features of malignancy. The performance and morphology of specimens prepared by ThinPrep, a liquid-based cytology technique is mostly unknown.
Methods  The laboratory information system was searched for all cases prepared by ThinPrep. Patient disease classification of benign or malignant was determined by linkage with the provincial cancer registry and was the gold standard against which sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. True positives and negatives were reviewed to identify predictive cytomorphologic features.
Results  Between 1996 and 2001, there were 149 ThinPrep specimens; 55 (37%) were reported as positive for malignancy and 94 (63%) as negative. Disease was classified as malignant in 86 (58%) patients and benign in 63 (42%). There were 42 false negative, 11 false positive, 52 true negative, and 44 true positive cytology results. Sensitivity was 51.2% (CI; 40.2 : 62.0), specificity 82.5% (CI; 70.5 : 90.6), and PPV and NPV 80.0% (CI; 66.6 : 89) and 55.3% (CI; 44.7 : 65.5), respectively. Cell groups with crowded, enlarged, irregular nuclei and nuclear features of vesicular chromatin and large, multiple irregular nucleoli correlated with malignant disease, while monolayered sheets of uniform columnar cells, regular nuclei and a finely granular chromatin correlated with benign disease.
Conclusions  The performance of ThinPrep brushings from this anatomic site equals conventional preparations. Cytomorphologic features of malignancy are more frequent and pronounced with ThinPrep.     

Thyroid fine needle aspiration: the morphological features on ThinPrep® slide preparations. Eighty cases with histological control

This study had several purposes: to define cytomorphological features of thyroid cells that might be modified by alcohol fixation; to optimize May-Grünwald–Giemsa (MGG) staining on ThinPrep^® (TP; Cytyc Inc., Bexborough, MA, USA) slides and to compare the diagnostic accuracy of slides prepared by a liquid-based method with those obtained by conventional technique. This study included 120 cases of ultrasound-guided fine needle aspiration (FNA) of the thyroid and 55 FNAs performed on surgically resected thyroid specimens. Histological control was available in 80 cases. In the first group of 120 FNAs, a split-sample technique was used for the TP. Three screenings were performed: first, an individual screening of the conventional smears (CS) and of the TP, a second screening to compare cells observed on the TP with the histological control and a third screening to assess the previously defined diagnostic criteria. Twenty-seven TP cases (22%) were considered unsatisfactory for diagnosis compared with 10 in CS (8%). The high rate of unsatisfactory cases with TP is likely to be due to the use of the split-sample technique. The sensitivity was 94% for CS and 81% for TP. The specificity was 67% and 60% for CS and TP, respectively. Two occult papillary carcinomas were missed by both methods. As for the MGG staining, the modified technique used for TP resulted in the same quality as the standard procedure. Conversely, TP did however induce uncommon morphological features. In this study, sensitivity and specificity levels are higher for CS than for TP; the difference may be explained by the fact that the methanol fixative used for TP induces some cytological alterations, especially in oncocytic tumours and lymphocytic thyroïditis.     

Proffered papers 14.00–15.00 Tuesday 16 September 2003 8 Ampullary,pancreatic and biliary duct exfoliative brush cytology prepared by the thinprep method: performance and morphology

Background ERCP‐directed brush cytology is used to sample lesions of the pancreatic and biliary ducts and the ampulla of Vater. With conventional preparations, the sensitivity and specificity range from 44% to 63% and 80% to 98%, respectively, and increased N : C ratio, nuclear molding and loss of honeycombing are reliable features of malignancy. The performance and morphology of specimens prepared by ThinPrep, a liquid‐based cytology technique is mostly unknown. Methods The laboratory information system was searched for all cases prepared by ThinPrep. Patient disease classification of benign or malignant was determined by linkage with the provincial cancer registry and was the gold standard against which sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. True positives and negatives were reviewed to identify predictive cytomorphologic features. Results Between 1996 and 2001, there were 149 ThinPrep specimens; 55 (37%) were reported as positive for malignancy and 94 (63%) as negative. Disease was classified as malignant in 86 (58%) patients and benign in 63 (42%). There were 42 false negative, 11 false positive, 52 true negative, and 44 true positive cytology results. Sensitivity was 51.2% (CI; 40.2 : 62.0), specificity 82.5% (CI; 70.5 : 90.6), and PPV and NPV 80.0% (CI; 66.6 : 89) and 55.3% (CI; 44.7 : 65.5), respectively. Cell groups with crowded, enlarged, irregular nuclei and nuclear features of vesicular chromatin and large, multiple irregular nucleoli correlated with malignant disease, while monolayered sheets of uniform columnar cells, regular nuclei and a finely granular chromatin correlated with benign disease. Conclusions The performance of ThinPrep brushings from this anatomic site equals conventional preparations. Cytomorphologic features of malignancy are more frequent and pronounced with ThinPrep.     

Could nuclear matrix protein 22 (NMP22) play a role with urine cytology in screening for bladder cancer? – experience at Kuwait University

Objectives:  This prospective study was undertaken to evaluate nuclear matrix protein (NMP22) compared to urine cytology in the detection of bladder cancer and also to determine whether indexing suspicious cytology to NMP22 could enhance the clinical utility of cytology.
Methods:  Cytological findings of voided urine collected prior to a cystoscopic biopsy were correlated with urine NMP22 assay in 46 patients attending the urology clinic in Mubarak Al-Kabeer Hospital. The patients were clinically categorized into newly diagnosed cases of transitional cell carcinoma (TCC), recurrent TCC, TCC in remission and controls.
Results:  Using histological diagnosis as the gold standard the sensitivity and specificity of NMP22 were 78% and 43% respectively and of cases with malignant urine cytology were 30% and 87% respectively. If suspicious and malignant cytology were combined as positive results the sensitivity increased significantly to 87% while the specificity decreased but not significantly to 74%. Suspicious or malignant cytology enhanced by positive NMP22 gave a sensitivity of 70% and specificity of 87% neither of which was significantly different from cytology alone. There were three false positive cases on cytology and 13 false positive cases on NMP22 assay. There were three false negative cytology and five false negative NMP22 cases but only one was false negative for both, resulting in a high sensitivity (96%) but low specificity (30%) if either positive NMP22 or malignant or suspicious cytology was taken as a positive result.
Conclusion:  Combining NMP22 with malignant or suspicious cytological result improved sensitivity for the detection of bladder cancer but with a major decrease in specificity, suggesting a potential role in screening rather than diagnosis.     

Salivary gland fine needle aspiration using the ThinPrep technique: diagnostic accuracy, cytologic artifacts and pitfalls

OBJECTIVE: To retrospectively assess the diagnostic accuracy, cytologic features and pitfalls of ThinPrep (TP) (Cytyc Corporation, Marlborough, Massachusetts, U.S.A.) versus conventional (smear) preparation (CP) in salivary gland fine needle aspiration biopsies (FNABs) and second, to evaluate the reproducibility of the cytomorphologic criteria used in the evaluation of FNABs prepared by CP versus TP. STUDY DESIGN: All salivary gland fine needle aspiration biopsies (SGFNABs) between January 1996 and June 1999 were retrieved from the cytology files of the University of Michigan Hospital. Histologic correlation was identified when available. Two cytopathologists reevaluated the slides for artifacts, cellular preservation, background material, cellularity, and cytoplasmic and nuclear details. RESULTS: Seventy-four of the 134 (55%) cases identified had histologic follow-up. Fifty (68%) cases were processed by TP and 24 (32%) by CP. FNAB processed by TP and CP correctly identified malignancy in 14 and 9 cases, respectively. There were three (4%) false negative cases. These included two acinic cell carcinomas and one mucoepidermoid carcinoma. There were 37 true negative cases (24 TP and 13 CP) and one false positive case of cellular pleomorphic adenoma (cytologic interpretation, mucoepidermoid carcinoma). All discrepant cases were processed using the TP method. The overall specificity and sensitivity were 98% and 88%, respectively. However, specificity and sensitivity for TP-processed SGFNABs were 96% and 82% as compared to a 100% specificity and sensitivity for CP. Additionally, there were 10 (14%) nondiagnostic cases, 8 of which were processed by TP. Cytologic artifacts associated with TP included diminished/distorted extracellular and stromal elements, cellular shrinkage and tissue fragmentation CONCLUSION: The diagnostic accuracy of TP-processed SGFNABs approaches that of the CP. However, there are several artifacts that may lead to erroneous diagnoses. Additional studies, that depend on real-life clinical samples processed by TP are suggested to modify current diagnostic criteria.     

Comparison of manual and automated methods of liquid-based cytology. A morphologic study

OBJECTIVE: To evaluate the morphologic characteristics of gynecologic samples prepared by 3 different methods of liquid-based cytology. STUDY DESIGN: Cytologic samples from representative cases of each diagnostic category of squamous epithelial lesion, prepared by automated and manual liquid-based systems, were analyzed by 3 laboratories in the United States, Portugal and Brazil. The systems included: ThinPrep (automated, U.S. Food and Drug Administration approved; Cytyc Corp., Boxborough, Massachusetts, U.S.A.), Autocyte PREP (South American system, manual; TriPath Imaging, Inc., Burlington, North Carolina, U.S.A.) and DNACITOLIQ (manual; Digene Brazil, S?o Paulo, Brazil). A panel of 16 morphologic parameters was evaluated: cellularity, clean background, uniform distribution, artifacts, cellular overlapping, architectural and cytoplasmic distortion, cytoplasmic vacuolization, cellular elongation, imprecise cytoplasmic borders, folded cytoplasmic borders, nuclear hyperchromasia, coarse chromatin, prominent nucleolus, irregular nuclear borders, atypical mitosis and inflammatory infiltrate. Negative, atypical squamous cells of undetermined significance, low grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL) cases were included. Cases without biopsies were confirmed by consensus. RESULTS: Cellularity was adequate in all samples. Clean background was observed in the vast majority of samples with all liquid-based systems. Uniform distribution was frequently found in ThinPrep and Autocyte PREP samples but not in DNACITOLIQ. Artifacts were not present in DNACITOLIQ samples, rare in ThinPrep and observed in 8 (34.7%) Autocyte PREP. Cellular overlapping was observed in all 3 system samples: 11 (31.42%) cases in ThinPrep, 16 (69.56%) in Autocyte PREP and 17 (68%) in DNACITOLIQ System. Architectural and cytoplasmic distortion were present in 3 cases of HSIL (13%) and cytoplasmic vacuolization in 2 cases of LSIL and 1 HSIL of Autocyte PREP. Cellular elongation was found in 13 (56.5%) Autocyte PREP and in 5 (20%) DNACITOLIQ samples. Inflammatory infiltrate was found in all 3 system samples but with more frequency in the Autocyte PREP (69.56%) and DNACITOLIQ System (72%). CONCLUSION: This study clearly indicated that in spite of the different methodologies, the 3 methods adequately preserved cellular structure for morphologic evaluation. The choice of method will depend on price, availability and procedures involved.     

Experience with a thin-layer,liquid-based cervical cytologic screening method

OBJECTIVE: To assess the utility of a thin-layer cytology system for cervicovaginal screening in clinical practice. STUDY DESIGN: Twenty-five hundred cervicovaginal split samples were processed with the traditional direct smearing method and with the ThinPrep Pap Test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) method and evaluated according to the Bethesda system, focusing mainly on the cytomorphologic features. RESULTS: The ThinPrep Pap Test yielded improved specimen adequacy and an increased detection rate of squamous abnormalities, which resulted in a decrease in the ASCUS/SIL ratio. Moreover, the thin-layer system provided adequate material for concomitant HPV testing, mainly in the LSIL and the ASCUS favor SIL cases, with satisfactory results, as well as for cell block preparations in a few selected cases that presented diagnostic difficulties. Furthermore, the morphologic features of the LSIL cases were virtually identical on both preparations, while in the HSIL cases, distinct features were noted on ThinPrep. CONCLUSION: The ThinPrep Pap Test is significantly more effective than the conventional smear in clinical practice. However, training and experience are necessary to take full advantage of this promising new technology.     

Application of ThinPrep Bronchial Brushing Cytology in the Early Diagnosis of Lung Cancer: A Retrospective Study

The majority of lung cancer patients are diagnosed at advanced stages of disease. This study evaluated the diagnostic value of ThinPrep (TP) bronchial brushing cytology in lung cancer. A total of 595 patients with suspicious lung cancer were enrolled in this study. The bronchial brushing samples were prepared by TP. The data were then compared to histology of lung tissue samples. Histologically, 479 of these 595 patients were diagnosed with lung cancer, including 223 cases of lung squamous cell carcinoma (SCC), 77 cases of lung adenocarcinoma (ADC), and 152 cases of small cell lung carcinoma (SCLC). The TP cytology revealed a total of 460 cases of lung cancer (including 232 SCCs, 91 ADCs, and 108 SCLCs). The TP cytological technique had 87.06% sensitivity and 62.93% specificity in the diagnosis of lung cancer. Specifically, TP cytology confirmed 195 of 223 SCCs, 47 of 77 ADCs, and 94 of 152 SCLCs. The TP cytology showed 87.44% sensitivity and 90.05% specificity for the diagnosis of SCC, with a Matthew''s correlation coefficient (MCC) of 0.820; while the sensitivity was reduced to 61.04% and the specificity was 90.93% for the diagnosis of ADC, with a MCC of 0.464. For the diagnosis of SCLC, the sensitivity was 61.84% and the specificity was 96.84%, with a MCC of 0.648. Thus, this study demonstrated the usefulness of TP bronchial brushing cytology in the early diagnosis of lung cancer, especially the early stage of lung SCC. A prospective clinical trial will verify these data before being translated into the clinic.