Atypical squamous cells of undetermined significance: audit and the impact of potential litigation. Retrospective review of 682 cases

For quality assurance purposes, the frequency of 'abnormal' cytological diagnoses of the non-systematic National Cervical Cancer Screening Programme (NCCSP) was evaluated. In 1999, an unexpected high number of Class (Cl) III cases (i.e. atypical squamous cells of undetermined significance) was reported. The cytological and histological results were reviewed in order to detect a possible cause for this threefold increase. The abnormal Papanicolaou (PAP) smears examined by conventional methods from 1 January 1990 to 31 December 2002 were analysed. The smears of 682 cases diagnosed in 1999 with a Cl III category were reviewed in 2000 and correlated with the available histological diagnoses provided by the Central Department of Pathology. Of the 682 Cl III cases, 176 cases (26.1%) had no follow-up, 314 cases (46.0%) had repeat cytology and 192 cases (28.2%) an histological correlate corresponding to 90 (46.9%) benign lesions, 78 (40.6%) squamous intraepithelial lesions, two (1%) invasive cervical cancers (one squamous and one glandular). Twenty-two Cl III cases (11.5%) were histologically within normal limits. Retrospective smear review confirmed 330 Cl III diagnoses (48.3%), 127 cases (18.6%) were recategorized as Cl IIIG (i.e. atypical glandular cells of undetermined significance), 22 cases (3.2%) as Cl IIID (i.e. mild to moderate dysplasia) and six cases (0.9%) as Cl IVa (i.e. severe dysplasia and/or carcinoma in situ). A total of 197 original Cl III cases had to be reclassified in the Cl II category (28.9%), only two cases showing mild and moderate dysplasia on histology. Thus, 195 cases (28.6%) comprised cytological overdiagnoses. The Cl III category being, by definition, a delicate and often subjective diagnosis, all external influences such as pressure of litigation should be avoided to reduce cytological overdiagnoses as a result of an unnecessary 'fear-factor'.     

Proficiency testing in cytology laboratories in Ontario, Canada: a decade of experience. III. A precision study of consistency and reproducibility in cytology reporting

The Ontario Laboratory Proficiency Testing Program's testing model and the results of early surveys of cytology laboratories have been previously described. To test consistency and accuracy, the same slides from one survey were recirculated to the same laboratory in the next survey. There was no statistical difference in either the accuracy or consistency in reporting by the various categories of personnel. Analysis of the data by category of diagnosis showed the reporting of "no abnormal cells" and "benign atypia" to be slightly more accurate and "moderate dysplasia" and "severe dysplasia" to be slightly less accurate than the reporting in other categories. Consistency in reporting appeared to be slightly less accurate in severe dysplasia than in the other categories. The analysis, which includes the results from all licensed cytology laboratories in Ontario, provides evidence that, in the reporting of cervical cytologic material, it is feasible to differentiate among the various categories within the spectrum of squamous epithelial abnormalities with a general level of accuracy and consistency that, although satisfactory, is not yet ideal.     

Information, discrimination and divergence in cytology. III. Optimization of classification of Papanicolaou smears

The performance of a cytology laboratory can be objectively quantitated as the total discrimination, a defined quantity of information. The total discrimination is dependent on the number of categories used in gynecologic cytology and on the corresponding histologic states; over-classification results in a higher rate of misinformation and reduced total discrimination. Total divergence is another measure of the association between cytologic categories and histologic states; in contrast to the total discrimination, the total divergence does not require a one-to-one correspondence between the cytologic categories and the histologic states. Using data from the Gynecologic Cytology Laboratory of the University of Minnesota, the total discrimination was maximized when gynecologic cytology used three categories of diagnosis, consisting of (1) normal, atypical benign or reactive atypia, (2) cervical intraepithelial neoplasia (CIN) and (3) all malignancies. The use of four categories, (1) normal, atypical benign or reactive atypia, (2) mild or moderate dysplasia, (3) severe dysplasia or squamous carcinoma in situ and (4) all malignancies, was almost equally informative. Observations on the total divergences resulted in similar conclusions. These findings generally support the recommendation of the consensus workshop sponsored by the National Cancer Institute (the Bethesda System nomenclature) to group all degrees of CIN into two large categories.     

Eliminating the diagnosis atypical squamous cells of undetermined significance: impact on the accuracy of the Papanicolaou test

OBJECTIVE: To assess eliminating the diagnosis "atypical squamous cells of undetermined significance" (ASCUS) from the Bethesda System for Reporting Cervical/Vaginal Cytological Diagnoses and analyze its impact on the sensitivity and positive predictive value of Pap smears. STUDY DESIGN: A total of 166 previously diagnosed ASCUS cases with follow-up biopsy results available were prospectively downgraded to within normal limits/benign cellular changes or upgraded to specific squamous intraepithelial lesions (SILs) or the malignant category. These review cytodiagnoses were compared with the histologic outcome. The impact on the sensitivity and positive predictive value of Pap smears was also assessed. RESULTS: Though there was a decrease in the sensitivity of the Pap smear from 100% to 76.3% for SIL overall and from 100% to 80% for high grade SIL (HSIL) alone, there was an improvement in the positive predictive value of diagnosing SIL from 46% to 85% and from 6% to 15% for HSIL alone. CONCLUSION: The ASCUS diagnosis can be minimized to a great extent, if not eliminated completely. The "ASCUS-favor reactive" group can be eliminated, while the diagnoses "ASCUS favor SIL" and "ASCUS-not otherwise specified" should be used sparingly.     

Morphologic scales and relative distances between lesions identified on Papanicolaou smears.

We fit a Gaussian-type curve to a nonmonotonic transform of initial arbitrarily given scales (pseudoscalar transform) of a two-way discrete classification table by maximizing the likelihood (entropy) and computing morphologic scales of clusters of objects identified by visual judgments. The scales give the relative distance between pairs of categories or states. Morphologic scales of histologic lesions (states) identified on Papanicolaou smears were computed from a confusion matrix consisting of 3,545 matched pairs of observations on Papanicolaou smears and colposcopically directed biopsies available from the Gynecologic Cytology Laboratory, University of Minnesota, between 1985 and 1987. The original (uncollapsed) confusion matrix consisted of eight cytologic categories and histologic states: normal plus atypical benign, reactive atypia (including condylomatous changes); mild, moderate and severe dysplasia; squamous carcinoma in situ; invasive squamous cell carcinoma; and other malignancies. The morphologic scales are expressed numerically, which reflects a degree of confusion between two diagnostic categories or states. Except for malignancies other than squamous cell carcinoma, morphologic scales of histologic states seen from cytology retained the order of clinical severity. We detected a high degree of confusion between severe dysplasia and carcinoma in situ. Malignancies other than squamous cell carcinoma fell between moderate and severe dysplasia. Such a transposition of the scales in this group containing adenocarcinoma was likely due to frequent association of adenocarcinoma with cervical intraepithelial neoplasia. Morphologic scales of cytologic categories seen from histology showed high degrees of confusion and transpositions between mild and moderate dysplasia and between severe dysplasia and carcinoma in situ.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytology of polychrome-stained equine synovial fluid smears. Comparison with clinical findings, histologic specimens, Wright-Giemsa-stained smears and outcome.

Polychrome-stained equine synovial fluid specimens from 34 normal joints and 129 joints with clinical abnormalities were examined cytologically. The smears from joints with abnormalities were categorized as within normal limits (4.7%), slight abnormality (27.9%), proliferative synovitis (21.7%), neutrophilic pattern (20.2%), elongated cell pattern (10.1%), other moderate to marked abnormality (11.6%) and unsatisfactory (3.9%). Cytologic abnormalities that were not restricted to a single category included spindle cells, crystals, stellate cells and cartilage fragments. Multinucleate cells and mononucleate cells with dense cytoplasm and a delicate periphery were seen in smears from cases with clinical diagnoses of osteochondrosis or fracture; interpretation of these cells as osteoclasts and their mononucleate precursors was supported by positive staining with tartrate-resistant acid phosphatase. Smears within the same cytologic category were not found to correspond with a single clinical diagnosis. The identification of several cytologic patterns in cases with the same clinical diagnosis suggests that multiple stages of disease were sampled. Except in cases with the cytologic neutrophilic pattern, there was not a consistent relationship between the histologic features in synovial biopsy specimens and the cytologic findings; the morphologic variation within synovial membrane sections and between sections from different locations was sometimes marked. When compared with air-dried, Wright-Giemsa-stained smears, the polychrome-stained smears were more sensitive in the detection of cytologic abnormalities and were less often falsely negative or unsatisfactory. Following surgery, cases with clinical diagnoses of osteochondrosis (29 cases) and fracture (25 cases) were analyzed according to clinical outcome and cytologic category. While 80% of the horses with proliferative synovitis in cytologic specimens were sound, only 67% of those with the elongated cell pattern, 50% of those with slight abnormality and 33% of those with other moderate to marked abnormality were sound. A statistically significant relationship (P less than .02) was found in cases with a diagnosis of osteochondrosis: animals with a proliferative synovitis pattern were almost three times as likely to be sound as compared to those with slight abnormality. These findings indicate that polychrome-stained equine synovial fluid smears (1) provide information that is different from that found in corresponding histologic sections and (2) are superior to air-dried, Wright-Giemsa-stained smears for cytologic examination. The polychrome-stained equine synovial fluid smears were found to provide information supportive of clinical, radiographic and prognostic data.     

Karyometric image analysis for intraepithelial and invasive cervical lesions

OBJECTIVE: To derive an objective, numeric measure for the progression of intraepithelial and invasive squamous cell cervical lesions. STUDY DESIGN: Thin-layer cervical cytology preparations from colposcopically confirmed normal cervix, low grade squamous intraepithelial lesions, high grade squamous intraepithelial lesions and carcinoma were identified from a cross-sectional study. Fifty-nine cases representing 4 diagnostic categories were selected, and 2,375 nuclei from epithelial cells representative of the diagnostic category were randomly selected for imaging and measurement from these cases. Additionally, 1,378 visually normal appearing intermediate cells from low and high grade squamous intraepithelial lesions, as well as from carcinoma cases, were identified for analysis. The nuclei were quantitatively characterized, and discriminant analyses were performed to derive a progression curve from normal cytology to carcinoma. RESULTS: The lesion signatures show a clear increase in nuclear abnormality with increasing progression. A progression curve was derived based on mean discriminant function scores for each diagnostic category and on the mean nuclear abnormality values for the nuclei in each category, as expressed by their deviation in feature values from normal reference nuclei. CONCLUSION: A numeric assessment of lesion progression for cervical precancerous and cancerous lesions based on karyometric measurements is possible and may provide an objective, precise characterization of each lesion as well as a basis for improved performance in automated cytology-based cervical cancer screening.     

Pulmonary fine needle aspiration biopsy. Assessing the negative diagnosis.

OBJECTIVE: To assess the significance of the "negative for malignancy" category when applied to pulmonary transthoracic fine needle aspiration biopsy (FNAB). STUDY DESIGN: Transthoracic lung FNABs diagnosed as "negative for malignancy" were identified from the files of Barnes-Jewish Hospital's South and North Campus over a period of five and nine years, respectively. Histologic correlation and clinical follow-up were obtained. RESULTS: Of the 1,181 lung FNABs performed during the study period, 108 cases (9%) had a negative cytologic diagnosis. Histologic correlation was available in 46 cases (43%), of which 23 cases had benign histologic findings, and 19 cases were malignant. Thirty-five of the 62 cases without histologic correlation had clinical follow-up consistent with a benign process. CONCLUSION: Based on the histologic correlation and clinical data available, the negative predictive value was 77%. Inadequate sampling was responsible for all false negative cytologic diagnoses in this series.     

Bethesda 2001. Impact on the reporting of gynecologic cytology

OBJECTIVE: To examine the impact of implementing Bethesda 2001 in one laboratory. STUDY DESIGN: A computer search identified all cervicovaginal specimens evaluated between July 2001 and June 2002. Bethesda 2001 was implemented on January 1, 2002. The rates of specimen adequacy and the frequency of each diagnostic category 6 months before and 6 months after the implementation of Bethesda 2001 were compared. RESULTS: A total of 21,332 cervicovaginal specimens were evaluated during the study period. During the first 6 months, 10,695 specimens were examined; 40% were liquid-based preparations. During the next 6 months, 10,367 specimens were examined; 60% were liquid-based preparations. Prior to the implementation of Bethesda 2001, the percentages of each category were as follows: 74.99% within normal limits, 7.10% reactive/reparative cellular changes (R/R), 10.29% atypical squamous cells (ASC), 0.24% atypical glandular cells (AGC), 3.45% low grade squamous intraepithelial lesion (LSIL), 3.44% high grade squamous intraepithelial lesion (HSIL) and 0.73% unsatisfactory. In addition, 19.00% were classified as "satisfactory but limited by" (SBLB). Following the implementation of Bethesda 2001, the percentages of each category were as follows: 80.09% negative for intraepithelial lesion and malignancy including 6.94% with the qualifier R/R, 10.32% ASC, 0.27% AGC, 4.54% LSIL, 3.44% HSIL and 0.81% unsatisfactory. In addition, 17.40% were satisfactory with a quality indicator (SAT with QI). The incidence of reporting benign endometrial cells in patients over age 40 was the same for both periods. There was a significant decrease in the percentage of specimens classified as SAT with QI when compared to that of specimens classified as SBLB. A statistically significant increase in the percentage of specimens was noted in the category LSIL (P < or = .001) and satisfactory (.005) after implementing Bethesda 2001. No significant changes were noted in other categories. CONCLUSION: Our laboratory experienced some changes in the laboratory statistics of reporting gynecologic cytology after the implementation of Bethesda 2001. Continuous monitoring of reporting trends is indicated to clearly understand the impact of Bethesda 2001 on laboratory statistics.     

Fine needle aspiration cytology of breast fibroadenoma. A cytohistologic correlation study of 405 cases.

OBJECTIVE: To evaluate the cytohistologic correlation of breast fibroadenoma (FA) in order to assess the value of cytology in the conservative management of this lesion. STUDY DESIGN: A retrospective analysis of all aspirates diagnosed as FA or fibroadenomatous lesion (n = 1,549) for which a histologic follow-up study was available (n = 362). Forty-three aspirates, including 14 nonrepresentative smears, from histologically proven FAs with a different cytologic report were also included in the study. RESULTS: Cytohistologic agreement was present in 287 of the 362 cytodiagnoses. Lack of correlation was observed in 75 cases. Most diagnostic errors accumulated in the older patient group. The sensitivity of the cytologic diagnosis of FA was 86.9% (90.8% excluding nonrepresentative cases), with a positive predictive value of 79.3%. In 43 cases a histologic diagnosis of FA was given after previous erroneous (n = 29) or nonrepresentative cytodiagnoses (n = 14). The specificity of the cytologic diagnosis of FA reached 93.8%, with a negative predictive value of 96.3% (97.5% excluding nonrepresentative cases). Regarding malignancy, five tumors were diagnosed as FA and were malignant. No false positive diagnoses of malignancy were given, but nine aspirates were included in the category "suspicious for carcinoma." CONCLUSION: FA of the breast remains a diagnostic challenge for the cytopathologist. A considerable amount of benign breast lesions can mimic FA on cytology, and such diagnostic categories as "fibroadenomatous lesion" or "consistent with FA" are associated with low diagnostic accuracy. While the cytologic requisites for entering a program of conservative management of FA are established, it seems that strict diagnostic criteria should be applied even at the expense of diminishing sensitivity.     

ASCUS, mature metaplastic type. Cytologic diagnosis and follow-up

OBJECTIVE: To study the cytologic criteria for follow-up of mature metaplastic cells within the atypical squamous cells of undetermined significance (ASCUS) category. STUDY DESIGN: Squamous epithelial abnormalities between January 1994 and June 1997 at our institution totaled 2,632 and included squamous carcinoma (1), high grade squamous intraepithelial lesions (278), low grade squamous intraepithelial lesions (875) and ASCUS (1,478). From the ASCUS group, 134 (9.06%) were metaplastic; 89 were selected for review. Criteria for case selection were follow-up with tissue biopsy or at least two Pap smears and no previous epithelial abnormality. Patients ranged from 27 to 70 years of age. Parameters tabulated included number of abnormal cells per slide, their architecture, cell size, shape, cytoplasmic hue and texture, nuclear size and contour, chromatin pattern and nucleoli. Additionally, specimens were reviewed for hormonal status and inflammation. The findings were correlated with follow-up data. RESULTS: Cells generally appeared single or in loose, monolayered sheets of three to seven cells per group. The cells were well demarcated, polygonal or oval and ranged from 11 to 30 microns with cyanophilic or eosinophilic thickened cytoplasm. The round to oval nuclei with slight irregularity showed a minimally increased nuclear/cytoplasmic ratio with stippled chromatin. Upon review, 69 smears were confirmed as ASCUS-M. Follow-up revealed 42 with benign findings, 9 with persistent ASCUS/ASCUS-M and 18 with low grade squamous intraepithelial lesions. CONCLUSION: In mature metaplastic cells with minimal atypia in patients with no previous or concurrent dysplasia, the follow-up details were similar to those described for ASCUS-superficial/immediate squamous cells. These patients could be followed conservatively.     

The use of the 'borderline' category in the reporting of cervical cytopathology in the UK: results of a survey conducted under the aegis of the British Society for Clinical Cytology

Objective: To determine how the ‘borderline’ category was used by cytopathologists in the UK when reporting cervical smears. Methods: A questionnaire was sent by email to members of the British Society for Clinical Cytology. Results: There is wide variation in the use of the ‘borderline’ category in the UK but the majority of respondents (77.6%) used it when reporting smears that were either on the borderline between negative and low grade squamous dyskaryosis (‘borderline ?low grade’), or on the borderline between negative and high grade squamous dyskaryosis (‘borderline ?high grade’), or on the borderline between negative and glandular dyskaryosis ‘borderline ?glandular dyskaryosis’). A significant minority (15.7%), however, did not use ‘borderline’ when reporting smears that showed an abnormality that was possibly high grade squamous dyskaryosis. A majority (79.1%) of respondents thought that it would be useful to have separate reporting categories for ‘borderline ?low grade’ and ‘borderline ?high grade’. Conclusions: There is diversity in the use of the category ‘borderline’ in the UK. The proposed revised BSCC terminology with separate categories for borderline ?low grade, borderline ?high grades and borderline ? glandular dyskaryosis reflects the opinion of the majority of respondents to the questionnaire.     

Glandular and squamous atypia and intraepithelial lesions in atrophic cervicovaginal smears. One institution's experience

OBJECTIVE: To review the cytologic features and follow-up histologic findings in atrophic cervicovaginal smears with the diagnoses of glandular or squamous atypia or intraepithelial lesion. STUDY DESIGN: A total of 228 cases were included in the study. The selection criteria included: age > 48 years and a diagnosis of either atypical glandular cells (AGC) (51 cases), cellular changes suggestive of human papillomavirus (HPV) infection (S/O HPV, 97 cases), low grade squamous intraepithelial lesion (LSIL) (60 cases) or high grade squamous intraepithelial lesion (HSIL) (20 cases). Follow-up biopsy information was available for 103 cases (45%). RESULTS: From the AGC group, 35 (69%) cases had tissue studies; 14 (40%) cases showed glandular lesions; 5 (14%) showed squamous intraepithelial lesion (SIL) and atypical cells. Follow-up information was available for 32 (33%) cases classified as S/O HPV; significant lesions (glandular/squamous) were found in 11 (34%). In the LSIL category, 22 (37%) cases had follow-up; 16 (73%) showed SIL. In the HSIL category, 14 cases (70%) underwent biopsy, and all showed SIL (four LSIL and nine HSIL) or squamous cell carcinoma. CONCLUSION: Even though atrophy-related epithelial changes often pose diagnostic difficulties in the interpretation of postmenopausal smears, application of reproducible and established cytologic criteria in diagnosing SIL and/or glandular lesions can improve diagnostic accuracy and result in selection of patients for follow-up tissue studies.     

Prediction of cervical neoplasia diagnosis groups. Discriminant analysis on digitized cell images

The purpose of this study was to develop discriminant analysis models for predicting cervical dysplasia/neoplasia case diagnoses using cytometric features derived from the digital image analysis of cell monolayers. The data base consisted of 925 cells from 27 cases diagnosed either as moderate dysplasia (n = 10), severe dysplasia (n = 5), carcinoma in situ (n = 8) or invasive carcinoma (n = 4) on both tissue biopsy and monolayer preparations. Cell features examined were cell diameter, nuclear diameter, nuclear mean optical density (OD), nuclear integrated OD (IOD), nuclear OD standard deviation, normalized IOD, nuclear texture and nuclear-cytoplasmic ratio. Features derived from cells visually classified as moderate dysplasia correctly predicted the case diagnosis of moderate dysplasia versus more severe disease for 85% of the cells. Prediction models using summary measures (mean and variance) derived from all visually classified abnormal cells within each case correctly separated all cases into their respective diagnostic categories. These findings suggest that dysplastic cells in a cytologic sample have features that collectively reflect the tissue diagnosis, regardless of the visual differences among the cells. Such information has potential use for diagnosis and possibly for prognosis.     

Diagnostic value of nucleolar organizer regions (AgNORs) in brush biopsies of suspicious lesions of the oral cavity.

OBJECTIVE: The aim of this retrospective study was to report on the diagnostic accuracy of AgNOR-analysis as an adjunctive diagnostic tool of conventional oral exfoliative cytology taken from suspicious lesions in our clinic. STUDY DESIGN: Cytological diagnoses obtained from brush biopsies of macroscopically suspicious lesions of the oral mucosa from 75 patients (final diagnoses: 53 histologically proven squamous cell carcinomas, 11 leukoplakias and other inflammatory oral lesions) and from 11 patients with normal mucosa as a negative control group were compared with histological and/or clinical follow-ups. Five smears were doubtful and seven suspicious for tumor cells in the cytologic report. Number of AgNOR's were counted in 100 squamous epithelial cell-nuclei per slide after silver-restaining. RESULTS: Sensitivity of our cytological diagnosis alone on oral smears for the detection of squamous carcinomas was 92.5%, specificity 100%, positive predictive value was 100% and negative 84.6%. The best cut-off value of the mean number of AgNOR dots per nucleus distinguishing benign from malignant cells was 4.8. The percentage of nuclei with more than three AgNORs had a cut-off level of 70%. Applying these methods to twelve doubtful or suspicious cytological diagnoses we were able to correctly establish the diagnosis of malignancy in ten cases of histologically proven cancers and to reveal benignity in two histologically proven cases. Thus we achieved a positive and negative predictive value of 100% each. CONCLUSIONS: Smears from brushings of visible oral lesions, if clinically considered as suspicious for cancer, are an easily practicable, non-invasive, painless, safe and accurate screening method for detection of oral cancerous lesions. We conclude that AgNOR-analysis may be a useful adjunct to other methods in routine cytological diagnosis of oral cancer that can help to solve cytologically suspicious or doubtful cases.     

Negative predictive value of pulmonary fine needle aspiration cytology.

Percutaneous fine needle aspiration (FNA) for cytologic examination is an accepted and reliable technique for diagnosing neoplasia. It is less useful, however, in excluding that diagnosis. We performed a retrospective analysis of a consecutive series of pulmonary FNA specimens at Memorial Sloan-Kettering Cancer Center to determine the negative predictive value (NPV) of this technique in the setting of a large cancer hospital. Fifty-seven cases were studied. Six cases (10.5%) were initially diagnosed as negative but acellular and were not further analyzed, and another 6 were lost to follow-up; 24 cases (42.1%) were subsequently confirmed negative by tissue or clinical follow-up, and 21 of the cases (36.8%) were proven positive for malignancy by repeat aspiration, tissue diagnosis or clinical means. Of these 21 cases, 1 was misdiagnosed as negative, and review demonstrated malignant cells on the slide; 3 of the 21 cases should have been initially rejected as unsatisfactory, and 18 of the 21 contained material sufficient for a cytologic diagnosis but not representative of the lesion. On follow-up the false-negative cases showed primary adenocarcinoma, epidermoid carcinoma, lymphoma, metastatic breast carcinoma and metastatic sarcoma. Specific benign diagnoses were made on the initial cytologic preparation in three cases. No benign tumors were found. The NPV in our series was 53.3%, comparable to values in previous reports. The single largest factor contributing to false-negative diagnoses is sampling error, and we recommend repeat aspiration when no specific benign diagnosis is made. In addition, we suggest that the diagnoses of negative for malignant cells and insufficient for diagnosis or acellular be considered separate categories.     

Interobserver variability in cytologic subclassification of squamous intraepithelial lesions--the Bethesda System vs. World Health Organization classification

The aim of the study was to compare interobserver variability for The Bethesda System (TBS) and World Health Organization (WHO) classification of cervical squamous intraepithelial lesions. A total of 1,000 conventional Papanicolaou smears (156 positive and 884 negative) were examined "blindly" by three cytologists and one cytotechnician. The degree of observer agreement was expressed by kappa statistics using a program for the calculation of interobserver variation and association "Agree" (Svanholm and Jergensen, 1989). Kappa (kappa) was determined for each cytologic diagnosis within a particular classification and total for either classification. The association with and separation from other diagnoses was determined for each cytologic diagnosis in the form of conditional probability (P(j)). In WHO classification, the diagnoses of dysplasia media and dysplasia gravis showed poor reproducibility (kappa = 0.114 and kappa = 0.259, respectively), the diagnosis of dysplasia levis good reproducibility (kappa = 0.639), and the diagnosis of carcinoma in situ excellent reproducibility (kappa = 0.762). WHO classification yielded pool kappa of 0.741. In TBS classification, the diagnosis of LSIL showed good, and HSIL excellent reproducibility (kappa = 0.542 and kappa = 0.763, respectively). TBS classification yielded pool kappa of 0.699. Dysplasia media (P(j) = 0.121) and dysplasia gravis (P(j) = 0.274) were found to be morphologically poorly defined, and carcinoma in situ (P(j) = 0.777) and dysplasia levis (P(j) = 0.651) well defined diagnoses. LSIL was morphologically moderately defined (P(j) = 0.587) and HSIL well defined (P(j) = 0.789) diagnosis. Accordingly, TBS does not substantially improve diagnostic reproducibility of the cytologic diagnoses of squamous intraepithelial lesions, while providing considerably less information to the clinician than the four-grade dysplasia/CIS terminology, thus eliminating the opportunity of choosing a different procedure for the diagnosis of dysplasia media, which is of utmost importance in the population of young nulliparae.     

Contribution of exfoliative cytology to the diagnosis of laryngeal lesions

OBJECTIVE: To estimate the diagnostic accuracy and reliability of exfoliative laryngeal cytology. STUDY DESIGN: Over three years (1996-1999) cytologic smears were obtained from clinically suspicious laryngeal lesions during laryngoscopy in a total of 31 selected patients (28 males and 3 females with an age range from 28-90 years). The cytologic diagnoses were analyzed and correlated with the histologic and final clinical diagnoses in 17 and 14 cases, respectively. Cytologic identification of the exact histologic type of the lesion was evaluated in 17 patients from whom both cytologic smears and biopsy material were obtained. RESULTS: The overall specificity was 100%, with no false positive diagnoses. The overall sensitivity was 93.3%, with one false negative cytologic diagnosis, in a case of non-Hodgkin's lymphoma. Cytohistologic correlation showed complete agreement between cytologic and histologic diagnoses in five of six benign lesions, in four cases of dysplasia and in six cases of squamous cell carcinoma. The overall diagnostic accuracy of cytology was 96.7% CONCLUSION: Exfoliative cytology by the smear technique is a reliable and accurate method in clinically suspected laryngeal lesions. Moreover, exfoliative cytology may be applied as the only alternative diagnostic method, especially in elderly patients with coexistent cardiorespiratory problems, when biopsy is not advisable or indicated.     

Diverse glandular pathologies coexist with high-grade squamous intraepithelial lesion in cyto-histological review of atypical glandular cells on ThinPrep specimens

Objective: To identify in cytology, high‐grade squamous intraepithelial lesions with endocervical glandular extension in cases previously diagnosed as atypical glandular cells (AGC), analyse possible reasons for the diagnostic pitfall and document the frequency of glandular pathology coexisting with high‐grade cervical intraepithelial lesion in histology. Methods: Thirty‐nine ThinPrep® cervical smear (Pap) tests reported as AGC of undetermined significance and showing high‐grade lesions on histology [cervical intraepithelial neoplasia (CIN) 2 or 3, endometrial or extrauterine adenocarcinoma] were reviewed retrospectively to identify the cases of high‐grade squamous intraepithelial lesion with endocervical glandular extension, using the Bethesda 2001 system. Cyto‐histological correlation was performed. Results: A high frequency of diverse glandular pathologies coexisted with high‐grade cervical intraepithelial lesions on histology. This included endocervical glandular extension in 63%, benign glandular pathology in 33% and pre‐neoplastic or malignant glandular pathology (endocervical glandular dysplasia, adenocarcinoma in situ and metastatic breast carcinoma) in 17% cases. On cytology, the sensitivity was 40%, specificity was 80% and positive predictive value was 86% for endocervical gland extension in high‐grade squamous intraepithelial lesions. Conclusions: Special efforts to recognize endocervical glandular extension in high‐grade squamous intraepithelial lesions and glandular neoplasia coexisting with squamous intraepithelial lesions from the heterogeneous category of AGC can contribute to increasing the diagnostic accuracy. The identification of endocervical glandular extension on cervical cytology would alert the gynaecologist to perform a thorough assessment of the endocervix during colposcopy. This could also help to decide on the need to perform deeper conization rather than loop electrosurgical excision procedure to ensure negative margins when colposcopic biopsy shows CIN 2 or 3.     

Proficiency testing in cytology laboratories in Ontario, Canada: a decade of experience. II. Results of initial surveys

The results of the initial surveys in the cytology proficiency testing of the medical laboratories in the Province of Ontario, Canada, showed a high correlation between the opinions of the testing committee and the participants in the categories of "no abnormal cells," "metaplasia" and forms of "benign atypia." The proportion of times that slides were tested in the categories of dysplasia and malignancy in the surveys increased from 38% by the end of survey 3 to 46% by the end of survey 5. A progressive improvement in the diagnostic accuracy was demonstrated in the categories of malignancy and severe dysplasia while results were more variable in the categories of moderate and mild dysplasia. Several educational activities were initiated following survey 3, including development and circulation of demonstration sets of marked glass slides for repeated circulation to participants as well as copies of a slide/tape presentation describing the program and specific case material.