Intraobserver and interobserver variability in the diagnosis of epithelial abnormalities in cervical smears

In a study of variability in the diagnosis of epithelial abnormalities, cervical smears with abnormalities of different severity were rescreened twice by 19 observers with an interval of six months. The observers focused on grading atypicality of squamous, squamous metaplastic and endocervical columnar epithelial cells; their results were compared (1) for the two screenings to assess intraobserver variability and (2) to "review" (final) diagnoses to assess interobserver variability. When the same observer rescreened a smear, 83.3% of the diagnoses did not differ more than one grade between two screenings; however, average intraobserver variability differed considerably for individual observers. The intraobserver variability was only slightly (not significantly) influenced by the years of experience in cytopathology of the observers. Intraobserver variability proved to be an important factor in incorrect diagnoses: 49.1% of the smears with false-negative and 52.9% with false-positive diagnoses at the first rescreening were correctly assessed at the second rescreening. Of all diagnoses made at rescreening, 80.9% were in agreement with the review diagnosis. The interobserver variability also showed considerable differences between observers; however, there was a strong influence of the experience of the observer on the interobserver variability. Atypicality grading of endocervical columnar epithelium by the observers showed a low correlation with the review diagnoses. The relatively low accuracy in the evaluation of this kind of epithelial abnormality is likely to be attributable to the low incidence of abnormal changes of endocervical columnar epithelium. The results of this study point to intraobserver variability as the main cause of false diagnoses. When wrongly diagnosed, severe epithelial abnormalities are more often underestimated than completely overlooked. Apart from training in cytopathology, the establishment of laboratory protocols for multiple screening of even minor abnormalities seem to be the most effective means of reducing the number of false diagnoses.     

Evaluation of PAPNET-assisted cervical rescreening

Evaluation of PAPNET-assisted cervical rescreening
We have compared the results of targeted manual rescreening of 1211 randomly selected smears with the results of PAPNET-assisted rescreening of 1613 cervical smears, containing at least 6.3% low-grade squamous intraepithelial lesion (SIL). PAPNET diagnosis and the targeted rescreening diagnosis were compared with the initial report, issued on the corresponding smear. Reproducibility scores for inadequacy, presence of endocervical and endometrial cells, specific infections and squamous cell abnormalities were determined. The reproducibility scores for the diagnosis of inadequate smears and specific infections were lower with the PAPNET-assisted rescreening. The detection of squamous cell abnormalities was excellent for both methods (>0.95), with a higher detection rate for false-negative smears with the PAPNET testing system.     

Performance of 3 methods for quality control for gynecologic cytology diagnoses

OBJECTIVE: To evaluate performance and viability of internal quality control (QC) strategies in a public health laboratory of the state of S?o Paulo. STUDY DESIGN: A retrospective study was performed with 3 QC strategies to improve internal cytologic diagnoses: morphologic guided-list criteria (MGLC), 100% rapid-rescreening (100% RR) of negative slides ("turret" method) and 10% rescreening (10% R) of negative slides. Cases were examined at Adolfo Lutz Institute, S?o Paulo, Brazil, from 2002 to 2004. Histopathologic results, when available, were considered gold standard; cytologic consensus diagnosis was by 2 pathologists when histologic results were unavailable. RESULTS: MGLC selected 20.7% samples with cytologic atypias, 10% R selected 0.6% and RR selected 2.5%. Cytologic/histologic initial concordance was 57.4%, low-grade squamous intra-epithelial lesion false negative rate was 34.9% and high-grade squamous intraepithelial lesion false negative rate was 12.2%. After diagnosis, consensus concordance was 97.2%. CONCLUSION: The 100% RR and 10% R QC strategies detected more false negative cases in liquid-based cytology than in conventional Pap smears. The 100% RR strategy reduced the false negative results and allowed evaluation of individual staff performance. The 10% R strategy did not offer significant results. We concluded that association of MGLC and 100% RR strategies might improve cytologic diagnostic quality.     

Interobserver and intraobserver variability in the cytologic diagnosis of normal and abnormal metaplastic squamous cells in pap smears

OBJECTIVE: Interoberver variability has important implications for patient care, diagnostic error and medical litigation. In the management of any cervical epithelial abnormality, its biologic significance as well as diagnostic reproducibility is very important. Interobserver variability has not been measured adequately for metaplastic squamous lesions. We analyzed interobserver and intraobserver variability and diagnostic accuracy in the diagnosis of dysplastic metaplastic cells. STUDY DESIGN: Sixty Pap smears from patients with abnormalities of metaplastic squamous cells of varying severity were selected from the files of Lankenau Hospital, Wynnewood, Pennsylvania, U.S.A., diagnosed between 1990 and 1996. These were reviewed by four observers with different levels of cytology experience. Each of the observers blindly and independently reviewed all Pap smears. Tabulated results were analyzed to determine interobserver and intraobserver variability and diagnostic accuracy. RESULTS: Statistically significant interobserver reproducibility was found between both inexperienced observers as well as between observers 1 (experienced) and 3 (inexperienced) and between observers 2 (experienced) and 4 (inexperienced). The observed degree of agreement between both experienced observers (1 and 2) reflected random rating rather than reproducibility. There was no difference in interobserver reproducibility in low vs. high grade lesions. Intraobserver reproducibility had no significant correlation with experience of the observer. The sensitivity ranged from 0.69 to 0.97 (mean, 0.79), while the specificity ranged from 0.09 to 0.46 (mean, 0.30). Mean diagnostic accuracy was better in benign and low grade squamous intraepithelial lesions in comparison to high grade squamous intraepithelial lesions. CONCLUSION: There was good interobserver agreement in classifying squamous metaplastic lesions. The agreement did not correlate with grade of dysplasia or experience of the cytopathologists. These findings should be considered in making treatment, quality assurance and legal decisions. A larger study is indicated to study interobserver and intraobserver variability and define cytologic criteria for lesions of metaplastic squamous cells.     

Intraobserver and interobserver variability in the quality assessment of cervical smears

Intraobserver and interobserver variability in assessing the quality of cervical smears, as measured by the presence or absence of endocervical columnar cells and squamous metaplastic cells, was evaluated. In total, 180 cervical smears representing the most important cytologic diagnoses were anonymously rescreened twice by 19 observers with an interval of six months. An absence of endocervical columnar cells was proven to correlate with a high percentage of false-negative diagnoses. Intraobserver agreement on the presence or absence of endocervical columnar cells was 85.7% between the two screenings. A predictive value of 57.7% was found for a negative scoring (absence of these cells) while the predictive value of a positive scoring (presence of endocervical cells) was 87.3%. Of the observer scorings, 83.9% concurred with the final diagnosis; there was no significant correlation between that concurrence and the number of years of experience in cytopathology of the observer. For squamous and squamous metaplastic cells in the cervical smear the predictive value of a negative scoring (absence) was only 20.6%. Compared to the final diagnosis, 69.5% of these scorings matched. A significant and relatively high correlation with the experience of the observer was found for the scoring for the presence of metaplastic cells. Even though the predictive values of these quality scorings were relatively low a significantly higher risk for false diagnoses was established when negative scorings were given. It is therefore advisable to have smears with negative scorings for endocervical columnar cells and squamous metaplastic cells always rescreened by another observer.     

Diagnostic accuracy of squamous cervical lesions studied in spatula-cytobrush smears

The cytologically positive cases found in 25,300 cervical smears of spatula samples and 6,168 smears prepared by combined spatula-Cytobrush sampling were analyzed. The diagnostic accuracy (the correlation between the cytologic and histologic diagnoses) was the same for both types of sampling. As to the histologic diagnosis, the rates of severe dysplasia, carcinoma in situ and squamous carcinoma in the spatula-Cytobrush group were more than twice as high as in the spatula group. In the spatula group, the majority of abnormal cells was of the mature type. In the spatula-Cytobrush group, the majority of smears contained a mixture of immature and mature abnormal cells. The more immature lesions, which are often located higher in the endocervical canal, seem to be better sampled by the Cytobrush. The results indicate that the Cytobrush reaches areas that a spatula cannot reach, resulting in a higher diagnostic efficiency.     

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.     

Comparison of Cytobrush sampling, spatula sampling and combined Cytobrush-spatula sampling of the uterine cervix

Since the introduction of the Cytobrush for sampling the uterine cervix, some practitioners have ceased taking a concomitant cervical scraping using a spatula. To examine whether Cytobrush sampling alone is adequate for the diagnosis of cervical lesions, the Cytobrush and spatula samples in 444 smears (most with original diagnoses of at least mild dysplasia) were analyzed separately for the presence of diagnostic cells, endocervical cells and squamous cells. Of the 412 smears showing pathologic findings (mild to severe dysplasia or worse), diagnostic cells were present in 400 Cytobrush samples and in 369 spatula samples; the combination of both samples thus gave a 3% gain in correct diagnoses as compared to use of the Cytobrush samples alone. Another 18 smears would have been underdiagnosed based only on the Cytobrush samples. Endocervical cells were present in 95.3% of the Cytobrush samples and 83.8% of the spatula samples; squamous cells were present in 93.9% of the Cytobrush samples and 96.8% of the spatula samples. Analysis confirmed that it is important that the smear should contain both endocervical and squamous cells. A positive relationship between the absence of squamous cells in the Cytobrush sample and the probability of a false-negative assessment was suggested. It thus seems inadvisable to replace the combination sampling method by Cytobrush sampling alone, which may lead to a false-negative diagnosis.     

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.     

Endocervical atypical glandular cells of undetermined significance. I. Morphometric and cytologic characterization of cases that "cannot rule out adenocarcinoma in situ"

OBJECTIVE: To determine whether evaluating morphologic features through morphometry and cytology can lead to a more-satisfactory characterization of endocervical atypical glandular cells of undetermined significance (AGUS) cases that "cannot rule out adenocarcinoma in situ" (AIS). STUDY DESIGN: Fifty-seven endocervical AGUS cases showing incomplete criteria of AIS were morphometrically compared to five smears with normal endocervical columnar cells (ECC) and to five histologically confirmed endocervical adenocarcinoma cases. For each atypical nucleus, the area and shape were measured. Twenty-five cytologic criteria were used to review the AGUS and neoplastic smears. RESULTS: AGUS nuclei showed an intermediate value in terms of area and shape as compared to the values of normal and neoplastic nuclei. In particular, AGUS nuclear enlargement (136.626 micron 2) was about twice the area of normal nuclei and half the value of the area of neoplastic nuclei (P < .0000). AGUS nuclei also had the greatest variability in size and shape, indicating that anisonucleosis may be a morphologic discriminator of endocervical AGUS. The cytologic features useful in discriminating AGUS from neoplastic smears were: presence of normal ECCs, singly or in sheets (P < .001); absence of necrosis (P < .001); bare atypical cells (P < .001); papillary groups (P < .01); anisonucleosis (P < .05); irregular chromatin distribution (P < .05); and hyperchromasia (P < .01). CONCLUSION: Morphometry and cytology led to a better characterization of endocervical AGUS cases that "cannot rule out AIS."     

Analysis of cervical smears obtained within three years of the diagnosis of invasive cervical cancer

The cytologic histories of 376 women presenting with invasive carcinoma of the cervix were analyzed. In total, 202 (53.7%) of these women had had 355 smears taken during the three years preceding presentation. All 320 smears with an original cytologic diagnosis of less than cancer were reviewed. The original cytologic diagnosis was low in 95 (30.6%) of 310 adequate smears. Originally, 96 (30.9%) of the adequate smears were evaluated as negative; at review, only 55 (17.5%) of the adequate smears were evaluated as negative. Comparing the review diagnoses to the 355 total smears, the rates of negative smears were 13.5% (42 of 310) for squamous-cell carcinoma, 30.0% (12 of 40) for adenocarcinoma and 20.0% (1 of 5) for adenosquamous carcinoma (P less than .05). The cellular composition of the smear was significantly related to the cytologic detection of abnormalities: endocervical cylindrical and/or metaplastic cells were seen in only 45.5% of smears diagnosed as negative, but in 84.4% and 97.8% of smears diagnosed as atypia and cervical intraepithelial neoplasia, respectively P less than .00001). Smears without endocervical cells should be considered inadequate and should be repeated.     

Inter- and intraobserver reproducibility of thyroid fine needle aspiration cytology: an analysis of discrepant cases

OBJECTIVE: To determine the inter- and intraobserver reproducibility and analyse the discrepant cases of fine needle aspiration cytology (FNAC) of the thyroid. METHODS: Cases of thyroid FNAC with a corresponding histological diagnosis were reviewed regarding the original cytological diagnoses by two observers. The final cytological diagnoses (FCD) included both concordant and consensus diagnoses. The inter- and intraobserver reproducibility and efficacy of thyroid FNAC were calculated based on the FCD. RESULTS: A total of 97 FNAC cases with corresponding histopathological specimens were analysed. Although inter- and intraobserver disagreement in the cytological diagnoses occurred in about one-quarter of the cases analysed (24.7% and 23.7%, respectively), a substantial level of diagnostic interobserver (kappa = 0.71) and intraobserver (kappa = 0.66) reproducibility was observed. The efficacy of the method was 94.4%. Disagreement in the diagnosis was detected in 24 cases (24.7%), most of them (41.7%) for follicular lesions. Discordant cytological diagnoses between the two observers were represented by six (16.2%) of the 37 cases with an FCD of colloid nodule, five (41.7%) of the 12 cases of cellular follicular lesion, all three cases of follicular neoplasm, in two (6.3%) of the 32 cases of PTC, one (16.7%) of six cases of follicular neoplasm with a predominance of Hürthle cells and in one case of poorly differentiated neoplasia. Similarly, major disagreement in intraobserver cytological diagnoses was observed for the diagnosis of follicular lesions: 18 (78.3%) of a total of 23 discordant cases. CONCLUSION: As discrepancies in the cytopathological diagnosis can have repercussions in the management of patients, all cases with a cytological diagnosis of follicular lesions/neoplams should be reviewed in multidisciplinary meetings thus minimizing interobserver variability.     

Retrospective evaluation of gynecologic cytodiagnosis. II. Interlaboratory reproducibility as shown in rescreening large consecutive samples of reported cases

Two laboratories exchanged and rescreened a large sample of cases with cervicovaginal smears they had consecutively accessioned to examine the reproducibility of gynecologic cytodiagnosis under optimum conditions. At least a "working agreement" (diagnoses within +/- 1 category on a ten-category scale) was achieved in diagnoses of normal, benign reaction and squamous abnormality (from minimal dysplasia though invasive cancer) in 18,859 cases (96.8%), of endometrial abnormality in 21 cases (42%) and of "unsatisfactory" in 99 cases (20.7%). Larger differences occurred in greater than or equal to 30% of cases except in the categories of "normal" and "benign reaction," reaching a maximum of 82% for moderate dysplasia. Reexamining 382 cases decreased disagreement by category to the 20% to 65% range only in the five categories of dysplasia plus carcinoma in situ. Agreement was not predicated on the presence of endocervical cells or squamous metaplasia; the basis for "unsatisfactory" calls was not uniform. Comparison of the laboratories' diagnoses with referee diagnoses or, on 178 cases, with tissue diagnoses also demonstrated differences in diagnostic criteria.     

Interpreting microbiopsies in cervical smears. A cytohistologic approach

OBJECTIVE: To assess interobserver variation in the diagnosis of thick tissue specimens (microbiopsies) in cytology smears and histologic sections taken from them, to evaluate the applicability of MIB-1 in histologic sections from microbiopsies and to evaluate whether processing microbiopsies in inconclusive smears has additional diagnostic value. STUDY DESIGN: Cytologic smears were selected in which there were diagnostic disagreements between pathologists and cytologists and microbiopsies were present. Interobserver variation among three pathologists and three cytologists in the diagnosis of these microbiopsies was investigated. The smears were processed for histologic sections, and interobserver variation between pathologist diagnoses were analyzed. An additional histologic slide stained for MIB-1 was used for consensus diagnosis. The consensus diagnosis was compared with available follow-up and its sensitivity and specificity determined. The value of applying the microbiopsy technique in slides diagnosed as inadequate or atypical squamous cells of undetermined significance (ASCUS) was analysed. RESULTS: From a series of 62,334 cervical smears, 49 with microbiopsies were selected. It was possible to derive histologic slides from 38 cases. Interobserver variability in the diagnosis of microbiopsies and histologic sections from them was moderate--kappa = .44 (SE = .06) and kappa = .44 (SE = .09), respectively. In the consensus meeting for all cases, a conclusive diagnosis was reached. The Pearson correlation coefficient between the consensus diagnosis and MIB-1 staining was r = .62. The sensitivity of the consensus diagnosis for the follow-up diagnosis was 71% and the specificity 60%. Diagnosis on approximately 50% of slides diagnosed as inadequate or ASCUS could be made. CONCLUSION: The histotechnical workup of microbiopsies is not difficult; however, their diagnosis can be a problem. Adequate diagnostic criteria are not available. Aided by MIB-1 staining, histologic sections from microbiopsies can be diagnosed, and the diagnoses correlated with follow-up in most cases. Processing of microbiopsies in smears with an inconclusive cytologic diagnosis or a diagnosis of ASCUS allowed correct diagnosis in 50% of cases in this study.     

Quality assurance in cervical smears: 100% rapid rescreening vs. 10% random rescreening

OBJECTIVE: To compare 100% rapid rescreening of cervical smears with 10% random rescreening as a method of quality assurance. STUDY DESIGN: A total of 5215 smears, randomly selected from smears reported as negative by cytotechnologists during routine screening, underwent 100% rapid rescreening by senior cytotechnologists. Ten percent of these smears, selected at random, were rescreened by other senior cytotechnologists. The gold standard was defined by cytopathologists, who rescreened all 5215 smears. After excluding unsatisfactory smears detected by cytopathologists, 4271 were included in the analysis. RESULTS: The 100% rapid rescreening method identified 69.9%, 95.7% and 100%, respectively, of atypical squamous cells of undetermined significance, low grade squamous intraepithelial lesion and high grade squamous intraepithelial lesion cases reported by the cytopathologists. The 100% rapid rescreening method showed a sensitivity of 73.5% and specificity of 98.6%. The 10% rescreening method showed sensitivity of 40.9% and specificity of 98.8%. CONCLUSION: One hundred percent rapid rescreening is an efficient method of internal quality assurance in cervical smear diagnosis. It can reduce the false negative rate and therefore can provide greater certainty to women who have received negative results. Well-trained cytotechnologists are able to identify abnormal smears in 1-minute rapid rescreening.     

Vaginal intraepithelial neoplasia and the Pap smear

OBJECTIVE: To assess the sensitivity of the vaginal smear cytologic examination in detecting vaginal intraepithelial neoplasia (VAIN) and to evaluate the cytologic findings of cases of VAIN. STUDY DESIGN: Cases with a histologic diagnosis of VAIN were identified from the Barnes-Jewish Hospital South and North Campus over a period of five and nine years, respectively. Only posthysterectomy patients with a tissue biopsy diagnosis of VAIN and with a vaginal smear obtained within three months of the biopsy were included in the study. Pertinent clinical information was obtained by reviewing the medical records. Two pathologists reviewed the pathologic samples. RESULTS: Thirty-five vaginal smears from 31 posthysterectomy patients were included in the study. The mean age was 57 years (range, 29-84). The cytologic diagnoses of smears from patients with VAIN included: high grade squamous intraepithelial lesion (19 cases), low grade squamous intraepithelial lesion (10 cases), atypical squamous cells of uncertain significance (5 cases) and negative for malignancy (1 case). CONCLUSION: The sensitivity of the vaginal smear cytologic examination in detecting VAIN is 83%. Obscuring inflammation contributed to false negative diagnoses in two cases.     

Identification of Campylobacter pylori in gastric biopsy smears

The use of gastric biopsy imprint smears to diagnose Campylobacter pylori was compared with the use of tissue sections and cultures. Multiple gastric biopsies were taken from the mucosa of 42 patients during endoscopy. Imprint smears were prepared from the samples used to make tissue sections; other samples were used for microbiologic culture. There was a good concordance (93%) between the morphologic diagnosis of C pylori in the air-dried, Giemsa-stained smears and the tissue sections; the cytologic preparations were clearly positive in six cases (14%) whose sections contained low numbers of the organisms. There was a concordance of 83% between the combined morphologic techniques and the bacteriologic culture. Six positive cases were detected only by the morphologic techniques while one positive case was detected only by bacteriologic culture. C pylori was identified in one or more preparations of the antral biopsy specimens in 23 (55%) of the 42 cases, including 23 (74%) of the 31 cases with a final diagnosis of gastritis or ulcer. These results show the usefulness of the cytologic study of gastric biopsy smears in diagnosing C pylori infections.     

The detection of endocervical gland involvement by high grade squamous intraepithelial lesions in smears prepared from endocervical brush specimens

The cytologic features of squamous cell carcinoma in situ with endocervical gland involvement have been described in cervical smears. We evaluated the presence of two types of cellular fragments in 43 cervical smears of high grade squamous intraepithelial lesions (HGSIL) to assess their ability to predict glandular involvement by HGSIL in subsequent cone biopsies. an endocervical brush was used to obtain all endocervical specimens. of 16 cases without glandular involvement, fragments were present in 13 smears. of 27 cases with glandular involvement, fragments were absent in 11 smears. No statistical association was identified between the presence of abnormal cellular fragments on cervical smears of HGSIL and endocervical gland involvement on cone biopsies.     

Decisive role of intermediate filament typing of tumor cells in the differential diagnosis of difficult fine needle aspirates

Thirty-six diagnostically difficult fine needle aspirates from enlarged lymph nodes and malignant soft tissue tumors, containing tumor cells with scanty or no obvious light microscopic features indicative of their differentiation, were assessed by a panel of six cytopathologists. Their diagnoses were recorded and then compared with the definitive diagnosis established by combining the cytologic findings with the results of intermediate filament typing of tumor cells in the smears using monoclonal antibodies specific for each filament type. The results show that use of these antibodies can markedly improve the accuracy of the cytologic diagnosis of tumor type as well as revise or prevent erroneous cytologic diagnoses in difficult cases. This pertains especially to the differential diagnoses of carcinoma versus malignant lymphoma, carcinoma versus malignant melanoma, carcinoma versus sarcoma and squamous carcinoma versus carcinoma of simple epithelia. Intermediate filament typing of tumor cells in aspirates as an objective histogenetic criterium makes the differential diagnosis of the difficult aspirates much more reliable and reproducible, provided that appropriate questions are asked, monoclonal antibodies with well-defined specificities are used and the antigenicity of the intermediate filaments in smears is preserved.     

Cellular composition of cervical smears in relation to the day of the menstrual cycle and the method of contraception

The influence of the day of the menstrual cycle and the method of contraception on the cellular composition of cervical smears was investigated. The percentage of unsatisfactory smears during the first four days of the cycle was understandably very high, leaving only 80% of the smears of sufficient quality for cytologic diagnosis. The percentage of smears of insufficient quality during the remainder of the cycle was significantly higher in women using oral hormonal contraceptives. The percentages of smears containing endocervical columnar cells, a criterion for judging smears to be of high quality, differed significantly among women using different modes of contraception. The highest percentage of smears without endocervical columnar cells was found in women using oral contraceptives; during the first half of the cycle in these women, smears were of higher quality than during the second half of the cycle. In women not practicing contraception or using nonhormonal methods of contraception, the differences in cellular composition during the cycle, though significant, were too small to be of practical importance. Women using oral contraceptives thus have an increased risk for a potential false-negative diagnosis because of the higher percentage of smears of unreliable quality taken in these women. In women using oral hormonal contraceptives, smears should be taken during the first half of the cycle because of the higher percentage of smears of high quality in that period.