The Founding Pioneer Cytotechnologists: The Women Who Assisted George N. Papanicolaou, MD, PhD, Develop the Pap Test for Cervical Cancer Prevention.

BACKGROUND: The earliest cytotechnologists are largely unknown. SUMMARY: In 1943, the book "Diagnosis of Uterine Cancer by the Vaginal Smear" by Papanicolaou and Traut recognized several women who have largely faded from memory. While Mary Papanicolaou and Charlotte Street are familiar names, others like Alberta Kuder and Huldah Boerker, who inadvertently laid the groundwork for the field of cytotechnology, remain obscure. There were also women like Christine Rassias and Adele Reboul who did not receive recognition. Notably, Mrs. Lady Mary G. Papanicolaou, despite her significant contributions both in the lab and at home since 1914, was not acknowledged in her husband's work until the publication of his Atlas in 1954. KEY MESSAGE: These women set the benchmark for future cytotechnologists, unknowingly shaping the profession as we know it today.

Reporting of Benign Endometrial Cells in Papanicolaou Tests.

OBJECTIVES: The 2014 Bethesda System (TBS 2014) guidelines for reporting cervical cytology revised the age for reporting benign endometrial cells (BECs) from 40 years or older to age 45 years or older. We evaluated this change and further investigated if extending the reporting age to 50 years or older may be acceptable. METHODS: We reviewed cases with BECs reported on Papanicolaou tests in women age 40 years or older and 45 years or older before and after implementation of TBS 2014. Follow-up endometrial biopsy/curettage results were categorized as benign, endometrial hyperplasia with or without atypia, or malignant. Hyperplasia and malignant follow-up were considered clinically significant. Clinical data were documented. Results were compared for women age 40 to 44, 45 to 49, and 50 years or older. RESULTS: Follow-up in 15 (100%) women age 40 to 44 years was benign. In women age 45 to 49 years, 61 (96.8%) had benign follow-up, one (1.6%) had atypical hyperplasia, and one (1.6%) had malignant follow-up. In women age 50 years or older, 57 (86.5%) had benign follow-up, four (6%) had malignant follow-up, and seven (7.5%) had atypical or nonatypical hyperplasia. There was a significant difference in follow-up between the age groups of 40 to 49 and 50 or older (P = .023). CONCLUSIONS: We conclude that the TBS 2014 revision was justified. Our data suggest that age 50 years or older rather than age 45 years or older may be an acceptable cutoff for reporting BECs.

Cytomegalovirus (CMV) in cervical cancer screening tests: A series of 8 cases and review of the literature.

OBJECTIVE: Cytomegalovirus (CMV) is a ubiquitous infection typically affecting over 50% of the US population by age 40. We report 8 cases of CMV infections detected in cervical cancer screening tests, the largest series of cases thus far reported in gynecologic cytology specimens. METHODS: A retrospective review of our pathology archival computer database was performed from January 1, 1994 through December 31, 2016 for CMV infections reported in cervical cytology specimens. The slides were retrieved for review if available. RESULTS: The eight patients ranged in age from 21-46 years, with a median age of 27 years and average age of 29.5 years. Two patients were significantly immunocompromised with one patient having AIDS and one patient diagnosed with autoimmune disease. The remaining six patients are considered immunocompetent. Cases were identified most often in the fall and winter months (6 of 8 cases). Seven cases were found using Surepath Pap (SP) liquid-based processing and one case was reported in a classic Papanicolaou smear (CPS). CONCLUSION: There was no correlation of cytologic presentation of CMV with a distinct cytohormonal pattern or inflammatory constituents. Rare diagnostic cells with changes of CMV infection were seen in 75% of the cases. The presence of CMV did not usually result in adverse patient outcome, except where CMV was one of the multiple opportunistic infections detected in the patient with AIDS.

Atypical repair on Pap smears: clinicopathologic correlates in 647 cases.

The Bethesda system separates atypical reparative changes (ARC) from "typical" repair and places it into the atypical squamous cells of undetermined significance (ASC-US) category. The cytologic diagnosis of ARC represents both diagnostic and management challenges because its clinical significance is controversial and has not been fully investigated. On the basis of scant literature on follow-up of women with ARC on Papanicolaou (Pap) test, we reviewed data from our patient population, which consists of a mixture of low- and high-risk women. Six hundred forty-seven patients with ARC on their Pap tests were identified in a 7-yr period. Of this, 189 (29%) women were lost to follow-up. Of the 458 women with follow-up, 31% had cervical biopsies and 69% were followed by repeated Pap tests. The age ranged from 16 to 86 (mean 47 yr). The incidence of squamous intraepithelial lesion was 5.2% (5% low-grade and 0.2% high-grade). Most women (62%) with ARC on Pap test had a benign condition on follow-up. For some women, the immediate cause was not known and the Pap abnormality resolved spontaneously. Our study questions the validity of reporting ARC within the ASC-US category.

Interobserver variability in assessing adequacy of the squamous component in conventional cervicovaginal smears.

We compared the interobserver reproducibility of estimating the adequacy of the squamous component of conventional Papanicolaou (Pap) smears using traditional and newly proposed criteria. Forty conventional Pap smears with varying degrees of squamous cellularity were reviewed by 13 observers who evaluated adequacy (satisfactory vs unsatisfactory) based on the traditional criterion of estimating 10% slide coverage. After being introduced to the new criterion and the reference images, the observers reevaluated adequacy on the same set of smears, using the new criterion and the reference images. With the original criterion of 10% slide coverage, 15 smears had a unanimous designation; the overall kappa value was 0.49 (P < .001). With the newly proposed adequacy criterion and reference images, 17 smears had a unanimous designation; the overall kappa value was 0.60 (P < .001). The difference in the kappa correlation coefficients was statistically significant (P = .007). While traditional and newly proposed criteria resulted in fair interobserver agreement, it seemed that the newly proposed criterion, along with the use of reference images, for evaluating adequacy of the squamous component of conventional Pap smears results in better interobserver reproducibility.

ASCCP patient management guidelines: Pap test specimen adequacy and quality indicators.

Our objective was to provide management guidelines according to Papanicolaou (Pap) test specimen adequacy based on literature review and expert opinion. A task force named by the American Society for Colposcopy and Cervical Pathology (ASCCP) conducted a literature review and discussed appropriate management. The Steering Committee of the ASCCP and other experts reviewed the guidelines. The guidelines recommend a repeated Pap test in 12 months for most women undergoing routine annual/biennial screening if the current Pap test is negative but either lacks an endocervical/ transformation zone component or is partially obscured. Indications for considering an earlier repeat are also provided. The preferred managementfor unsatisfactory Pap tests is a repeated Pap test within a short interval of 2 to 4 months. The management guidelines will help promote optimal and uniform follow-up of women according to Pap test specimen adequacy.

False-positive squamous cell carcinoma in cervical smears: cytologic-histologic correlation in 19 cases.

Cytologic features of squamous intraepithelial lesions (SIL) can mimic those of invasive squamous-cell carcinoma. We compare and correlate the cytological findings of 19 false-positive squamous-cell carcinomas with follow-up cone biopsies or hysterectomy specimens to define which type of dysplasia is more prone to diagnostic errors on cervical Papanicolaou (Pap) smears. Out of 128 patients diagnosed with invasive squamous-cell carcinoma from 1994-2000, 19 (14.8%) with follow-up cone biopsies or hysterectomy specimens were false-positive cases, showing only cervical intraepithelial neoplasia (CIN). We reviewed tissue sections from these 19 cases of CIN for cytologic features of squamous-cell carcinoma, such as markedly pleomorphic and/or dysplastic squamous cells, necrosis, and nucleoli. Twelve of 19 patients (63%) were menopausal. The mean age was 50.5 yr. On review of cervical smears, 18 cases qualified for the cytologic diagnosis of squamous-cell carcinoma, keratinizing type, and one case qualified for squamous-cell carcinoma, nonkeratinizing type. Pleomorphic and/or keratinizing dysplasia was found in 15 out of 19 patients (79%), necrosis within superficial endocervical glands in 9 out of 19 patients (47%), and conspicuous nucleoli in 12 out of 19 patients (63%). One or more of these changes were seen in all but 2 patients (89%). Endocervical gland involvement was present and extensive in 18 of the 19 cases (94%). The mean age was older than expected for SIL (50.5 vs. a reported 40), and matched the mean age found in patients with invasive squamous-cell carcinoma. Pleomorphic and/or keratinizing dysplasia involving endocervical glands may exhibit the cytologic features of squamous-cell carcinoma on cervical Pap smears.

Interobserver variability: comparison between liquid-based and conventional preparations in gynecologic cytology.

BACKGROUND: Studies have shown that the ThinPrep Papanicolaou test (TP) increases the detection of epithelial cell abnormalities compared with the conventional preparation. Little is known about the interobserver variability of reporting gynecologic cytology results using the TP preparation and its comparison with results obtained using the conventional method. METHODS: To compare the interobserver variability between the TP method and the conventional method for reporting the diagnoses of gynecologic cytology, 20 pairs of conventional and TP slides (total, 40 slides) that were prepared from split samples were evaluated blindly by 19 cytotechnologists from three different laboratories. Each reviewer was asked to categorize each slide into the following five categories: within normal limits, benign cellular changes, atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL). For both conventional and TP preparations, interobserver variability was analyzed using Spearman rank correlation coefficients. The mean correlation coefficients (weak, 0.0-0.4; fair, 0.4-0.7; and strong, 0.7-1.0) between the TP method and the conventional method were then compared. RESULTS: The overall interobserver agreement as well as interobserver agreement within each laboratory was good for both TP and conventional preparations. Based on the set of conventional cervical smears, only one slide that was diagnosed as HSIL had unanimous agreement; whereas, based on the set of TP slides, three slides, including two diagnosed as HSIL and one diagnosed as LSIL, had a unanimous diagnosis. The difference in the interobserver agreement between TP and conventional methods, based on comparing their mean +/- standard deviation correlation coefficients (TP method, 0.84 +/- 0.081; conventional method, 0.82 +/- 0.105; P < 0.001), was statistically significant. CONCLUSIONS: Interobserver agreement in reporting gynecologic cytology using the TP method is good, particularly for squamous intraepithelial lesions, and appears to be superior to the conventional method.

ASCCP Patient Management Guidelines: Pap Test Specimen Adequacy and Quality Indicators.

OBJECTIVES: To provide management guidelines according to Pap test specimen adequacy based on literature review and expert opinion. METHODS: A task force named by the American Society for Colposcopy and Cervical Pathology conducted a literature review and discussed appropriate management. The steering committee of the American Society for Colposcopy and Cervical Pathology and other experts reviewed the guidelines. RESULTS: The guidelines recommend a repeat Pap test in 12 months for most women who are undergoing routine annual/biennial screening if the current Pap test is negative but either lacks an endocervical/transformation zone component or is partially obscured. Indications for considering an earlier repeat are also provided. The preferred management for unsatisfactory Pap tests is a repeat Pap test within a short interval of 2 to 4 months. CONCLUSIONS: The management guidelines will help promote optimal and uniform follow-up of women's Pap tests, according to Pap test specimen adequacy.