Cervical cytology in endometrial cancer patients with Lynch syndrome: opportunities for early detection and limitations.

INTRODUCTION: Timely detection of endometrial carcinoma in Lynch syndrome patients ensures prompt treatment and appropriate cancer screening for the patient and impacted family members. While cervical cytology is utilized primarily in cervical cancer screening, endometrial glandular abnormalities can be identified as part of routine cervical cancer screening or during work-up for abnormal uterine bleeding. MATERIALS AND METHODS: We retrospectively evaluated cervical cytology samples from Lynch syndrome patients with endometrial carcinoma to determine how often atypical/malignant glandular cells were identified on prior/concurrent cytology. RESULTS: We identified 14 Lynch syndrome patients with cervical cytology available within a year of endometrial carcinoma diagnosis. The average patient age was 55 years (36-73). Cervical cytology preceded diagnostic biopsy in 57% and was concurrent in 43%. A glandular abnormality was identified on original diagnosis in 43% and ranged from atypical glandular cells (AGC), not otherwise specified to adenocarcinoma consistent with endometrial primary. In 4 cases, abnormal cervical cytology triggered the subsequent biopsy. Evaluation of 8 cases with accessible cytology slides revealed 2 previously unrecognized glandular abnormalities, leading to an abnormal rate of 63% among cases reviewed retrospectively and a final glandular abnormality detection rate of 57% based on either original or review diagnosis. CONCLUSIONS: In summary, abnormal glandular cells were commonly identified in endometrial cancer patients with Lynch syndrome and led to endometrial cancer work-up and diagnosis in a subset. These results suggest that cervical cytology may have utility in endometrial cancer screening in this population and indicate that awareness of the patient's familial cancer risk is important for maximizing sensitivity of this test. They also caution against primary human papillomavirus screening in the Lynch syndrome population, as this may result in missed opportunities for early endometrial carcinoma detection among these high-risk individuals.

The significance of extensive HPV genotyping for cervical high-grade neoplasia among women with atypical glandular cells.

OBJECTIVES: To examine the associated risk of cervical intraepithelial neoplasm grade 3+ (CIN3+) lesions in patients with AGC and extensive human papillomavirus (HPV) genotyping. METHODS: Cases with atypical glandular cell (AGC) interpretation on a Papanicolaou (Pap) test were identified along with associated extensive HPV genotyping and histologic follow-up results. RESULTS: Within this cohort of 469,694 Pap tests, 0.4% were diagnosed as AGCs. In total, 1267 cases had concurrent high-risk HPV (hrHPV) genotyping, and 40.3% were hrHPV positive. The percentage of AGC cases with cervical CIN3+ on histologic follow-up was 52.2% when hrHPV was positive, whereas it was 4.9% with a negative hrHPV result. The top 5 hrHPV genotypes associated with cervical CIN3+ in this cohort were HPV16, HPV18, HPV58, HPV52, and HPV33. Indeed, 92.8% of the hrHPV-associated CIN3+ lesions identified in this cohort were positive for at least one of these HPV genotypes. The sensitivity of detecting cervical CIN3+ lesions was 85.6% with the top 5 hrHPV genotypes (HPV16/18/58/52/33) and only increased to 89.0% when the additional 12 genotypes were included. CONCLUSIONS: In patients with an AGC Pap, the risk of having a cervical CIN3+ lesion is greatly increased by positivity for hrHPV types 16, 18, 58, 52, and/or 33. Incorporating comprehensive HPV genotyping into AGC cytology allows for refined risk stratification and more tailored management strategies.

Cytology-histology correlation of atypical glandular cells on cervical Papanicolaou tests: A study of 628 cases.

INTRODUCTION: The finding of atypical glandular cells (AGC) on Papanicolaou test is becoming more important as the incidence of squamous intraepithelial lesions decreases in recent decades. Therefore, the interpretation and follow-up of patients with AGC are particularly important. The aim of our study was to assess the histologic findings and clinical correlations in patients with AGC identified on Papanicolaou test. MATERIALS AND METHODS: A total of 714 patients with AGC identified on cervical Papanicolaou tests were studied for their clinicopathologic features, such as follow-up histology and patient age. We investigated the histologic follow-up results for each individual subcategories of AGC and their correlation with patients' age. RESULTS: Most of the glandular cell abnormalities (80.0%) in the study group were classified as "atypical glandular cells, not otherwise specified (NOS)". About 28.9% of patients' follow-up histology showed malignant or precancerous lesions. The mean age of patients with malignant or precancerous lesions was significantly higher than that of patients with benign or non-precancerous lesions. The malignant histologies included 52 cases of endometrial cancers and 31 cases of cervical carcinomas. The second most common subcategory was "atypical glandular cells, favor neoplastic" (5.0%), while "atypical endocervical cells, favor neoplastic" constituted about 2.7% of cases in our study. The average age of patients with "atypical glandular cells, favor neoplastic" was significantly higher than that of patients with "atypical endocervical cells, favor neoplastic". The follow-up histology of about 82.1% of "atypical glandular cells, favor neoplastic" showed endometrial (73.9%) or cervical malignancies (26.1%). The follow-up histology of about 70.6% of "atypical endocervical cells, favor neoplastic" showed endometrial (50.0%) or cervical cancers (50.0%). Other glandular abnormalities included 25 of 714 cases of "atypical endometrial cells" (3.5%) and 6 of 714 cases of "atypical endocervical cells" (0.8%). CONCLUSION: Based on our data, we have observed significantly more endometrial malignancies in both "atypical glandular cells, NOS" and "atypical glandular cells, favor neoplastic" subcategories and even some in "atypical endocervical cells, favor neoplastic" category. This predominance of endometrial malignancies is also associated with patients' age and tumor types.

Cytologic Parameters in Predicting the Outcome of Atypical Glandular Cells on Papanicolaou Smears: A Single-Institutional Experience.

Background: Atypical glandular cells (AGCs) diagnosis on Pap (Papanicolaou) smears are uncommon and may represent various benign and malignant lesions. Objective: This study aims to report the incidence of AGC on Pap smear, to study the relationship of AGC with malignancy, and to determine cytomorphological features that help in predicting malignancy. Materials and Methods: Retrospective analytical study conducted in the Department of Oncopathology at Tertiary Cancer and Research Institute. In this retrospective study, we included cases diagnosed with AGC between July 2017 to July 2022. All slides were reviewed and subclassified according to the Bethesda 2014 classification system (TBS). The predetermined cytomorphological features observed in the smears were recorded. The follow-up histopathological diagnoses of the cases were retrieved. The significant cytomorphological and clinicopathological findings for malignancy were determined. Results: Pearson χ2 test with SPSS software version 22 to compare cytologic features of cases with benign and malignant follow-up. The significant cytomorphological features observed in neoplastic cases were cells in 3-dimensional clusters, nuclear overlapping, reniform nucleus, irregular nuclear membrane, increased nuclear size, single macronucleoli, engulfed neutrophils, and prominently vacuolated cytoplasm. Conclusions: The diagnosis of AGC on cytology is associated with clinically significant lesions, and cytomorphologic parameters can be used to predict the benign and malignant outcome.

Analysis of atypical glandular cells in ThinPrep Pap smear and follow-up histopathology.

Background: Diagnosing atypical glandular cells (AGC) is a significant challenge in cytomorphology. Methods: A retrospective study was undertaken to assess the prevalence of AGC and the subsequent histological outcomes over 5 years at a single institution. Results: A total of 159,649 ThinPrep Pap tests, including 395 cases of AGC, were retrieved, of which 330 AGC cases had follow-up histopathology. Among these 330 cases, 43.9% were classified as AGC not otherwise specified, followed by AGC-endocervical cells at 33.3%. The most frequently observed histological findings at follow-up included CIN1 and benign mucosa with reactive changes, followed by high-grade squamous intraepithelial lesion and cervical squamous cell carcinoma. The overall 5-year insignificant AGC rate was 0.12%, and the overall 5-year significant AGC rate was 0.08%. Notably, 36.7% of AGC cases tested positive for high-risk human papillomavirus. Interestingly, the level of experience did not significantly impact the rates for significant or insignificant AGC diagnosis. However, senior cytopathologists had a higher AGC report rate compared to their junior peers. Conclusion: The AGC diagnostic rate at our institution falls within the range given by the College of American Pathologists. A significant number of cases had follow-up histologic results available, and the overall 5-year insignificant AGC rate was 0.12%.

Atypical glandular cells and predictive features of malignancy in Pap smears: A retrospective monocentric study.

OBJECTIVE: The introduction of cytological screening with the Papanicolau smear significantly reduced cervical cancer mortality. However, Pap smear examination can be challenging, being based on the observer ability to decode different cytological and architectural features. This study aims to evaluate the malignancy rate of AGC (atypical glandular cells) category, investigating the relationships between cytological and histological diagnosis. METHODS: Eighty-nine patients, diagnosed as AGC at cytological evaluation and followed up with biopsy or surgical procedure at Policlinico Gemelli Hospital, Rome, Italy, were included in the study. The cytopathological architectural (feathering, rosette formation, overlapping, loss of polarity, papillary formation, three-dimensional formation) and nuclear (N/C ratio, nuclear enlargement and hyperchromasia, mitoses, nuclei irregularity, evident nucleoli) features of AGC were evaluated. Statistical analyses were performed to assess cyto-histological correlation and determine the relevance of architectural and nuclear features in the diagnosis of malignancy. RESULTS: Of the 89 AGC patients, 48 cases (53.93%) were diagnosed as AGC-NOS and 41 (46.07%) were diagnosed as AGC-FN, according to the Bethesda classification system. The follow-up biopsies or surgical resections revealed malignancy in 46 patients (51.69%). The rates of malignancy for AGC-NOS and AGC-FN were 35.41% and 70.73% respectively. Furthermore, analysing cytopathological features, we found that both architectural and nuclear criteria were statistically significant (p < 0.05). Only overlapping, nuclear irregularity and increased N/C ratio were not found to be statistically significant for detecting malignancy. CONCLUSIONS: Cytological diagnosis of glandular lesions remains a valid tool, when appropriate clinical correlation and expert evaluation are available.

Atypical glandular cells in Pap tests: cytology-histology correlation and risk assessment with human papillopmavirus (HPV) testing.

INTRODUCTION: Atypical glandular cells (AGC) represent less than 1% of Pap test cases and include a variety of lesions in both the cervix and endometrium. The study aimed to investigate the cytology-histology correlation in AGC patients and to evaluate the clinical utility of hrHPV testing in this diagnostic context. MATERIALS AND METHODS: We identified 491 atypical glandular cells (AGC) cases in our quality analysis (QA) database of 336,064 Pap tests interpreted between March 1, 2013 and July 12, 2016. Of these, 251 cases had follow-up biopsies with hrHPV tests in 148 cases. RESULTS: The most common histologic diagnosis associated with AGC was normal/benign or low-grade lesions, comprising 55% of cervical biopsies and 24% of endometrial biopsies. High-grade lesions were identified in 21% of follow-up biopsies. In patients with AGC cytology, a positive hrHPV test significantly increased the likelihood of cervical HSIL or above lesions on biopsy by 26.4 times (OR = 26.4, 95% CI: 5.8-119.4, P < 0.0001). A positive genotyping result for HPV 16 dramatically increased the likelihood of cervical HSIL or above lesions on biopsy (OR = 84, 95% CI: 12.0-590.5, P < 0.0001). The HPV test had a negative predictive value of 97% (CI: 85%-100%). CONCLUSIONS: Our study confirms that AGC is a significant diagnosis with an overall risk for high-grade cervical or endometrial lesions as high as 21%. hrHPV testing with genotyping is an effective tool for identifying high-risk individuals within the AGC population, with excellent positive and negative predictive values. This approach is valuable for clinical risk stratification and differential diagnosis in patients with AGC cytology.

Correlation of immediate prevalence of cervical precancers and cancers with HPV genotype and age in women with atypical glandular cells cytology: A retrospective analysis of 369 cases.

BACKGROUND: This study aims to assess the immediate risk of cervical precancers and cancers in women with atypical glandular cells (AGC) cytology, based on high-risk human papillomavirus (hrHPV) genotypes and age. METHODS: A retrospective analysis was conducted on 369 cases of AGC with immediate follow-up biopsy results, including 299 AGC-not otherwise specified (NOS) and 70 AGC-favor neoplastic (FN). RESULTS: Among the 369 AGC cases, 127 tested positive for hrHPV (34.4%). The predominant high-risk type was other 11 genotypes (44.1%), followed by 16+ (29.1%), 18/45+ (26.0%), and 16 and 18/45 double-positive (0.79%). Precancers and cancers were detected in 30.4% (112 of 369) and 9.8% (36 of 369) of cases, respectively. The HPV-18/45+ group had notably higher adenocarcinoma in situ and adenocarcinoma (AIS+) prevalence compared to other 11 genotype groups (p < .0001 and p = .001, respectively). The HPV-16+ group showed significantly higher high-grade cervical squamous epithelial lesion and squamous cell carcinoma prevalence than other 11 genotype groups (p < .0001 and p = .017, respectively). Using 40-year cutoff, older women had significantly higher prevalence of abnormal glandular lesion+ lesions (17.6% vs. 7.6%, p = .005) and adenocarcinoma (AC) (12.4% vs. 2.5%, p = .001). Using 50-year cutoff, older women had higher prevalence of squamous cell carcinoma (SCC) (3.3% vs. 0.4%, p = .042) and AC (15.2% vs. 5.8%, p = .005). Subgroup analysis revealed that AGC-FN women showed more severe cervical pathology than AGC-NOS women (p < .001). CONCLUSIONS: AGC women have a significantly increased risk of cervical precancerous lesions and cancer. HPV genotyping and patient age factors need to be taken into consideration in the clinical management process of AGC patients.

Diagnostic utility of ThinPrep Imaging System® for detecting atypical glandular cells in cervical smear samples.

INTRODUCTION: The ThinPrep Imaging System® (TIS) is an automated system that has now been used for over 20 years in the primary screening of ThinPrep liquid-based cervical samples. Although there are a lot of publications about the diagnostic utility of this method in squamous cell lesions, which has advantages such as time-saving and standardization, there are only a few publications on this issue in glandular cell lesions in the literature. We aimed in this study to investigate the diagnostic utility of the system in the detection of premalignant and malignant glandular lesions in cervical smears. MATERIAL AND METHOD: Our study was conducted retrospectively, and a total of 126 cervical smear samples between 2010 and 2022 that have histological confirmation of endometrial adenocarcinoma (EAC), endocervical adenocarcinoma (ECAC), or adenocarcinoma in situ (AIS), were included. These samples were re-evaluated by manual and TIS by two experienced pathologists, and the results were compared in terms of sensitivity. RESULTS: We found out that 70 of the 126 smear samples have atypical glandular cells. We detect 48 cases (48/70) (sensitivity 68.5%) in manual examination, however TIS successfully determined 66 cases (66/70) (sensitivity 94.3%). In 4 cases (5.7%) TIS could not detect the atypical cells within the 22 areas. CONCLUSION: TIS is quite an effective method with a high sensitivity for detecting atypical glandular cells in cervical smears, like detecting squamous cell anomalies. Imposing this system in our laboratory and using them appropriately, save us time and help to ensure standardization. Additionally, it may be a good way to adopt artificial intelligence and digital pathology in today's world.

Clinicopathological features of atypical glandular cells, not otherwise specified, on cervicovaginal pap smears.

OBJECTIVE: The Papanicolaou (Pap) smear test is a standard screening test that detects cervical lesions and cancers. In this multicentric study, we performed a retrospective analysis of cytological results associated with atypical glandular cells, not otherwise specified (AGC-NOS). METHODS: We retrospectively reviewed Pap smear tests that resulted as AGC-NOS. A total of 254 women who underwent colposcopy due to a Pap smear result of AGC-NOS were included the study between 2003 and 2021. The ages, Pap smear results, HPV results if any, colposcopic biopsy results, endocervical and endometrial pathology results, and management of these patients were analysed. RESULTS: Two hundred fifty-four patients with AGC-NOS Pap smear results were included in the study. A total of 70 (27.6%) patients had cervical and endometrial premalignant or malignant lesions. Malignancy was observed in 17 (6.7%) patients (endometrium, n = 11 [4.3%]; cervix, n = 6 [2.4%]). Isolated premalignant or malignant lesions of the cervix and endometrium were detected in 57 (22.4%) and 12 (4.7%) patients, respectively. CONCLUSIONS: Patients diagnosed with AGC-NOS should undergo a careful evaluation with all clinicopathological features. Because cancer of the cervix and endometrium is not rare in patients diagnosed with AGC-NOS, colposcopic examination with endocervical sampling should be a priority based on a cervicovaginal smear. Endometrial sampling is also required according to the patient's clinic, age, and examination characteristics.

Role of High-Risk HPV Testing in Papanicolaou Tests With Atypical Glandular Cells With and Without Concurrent Squamous Cell Abnormalities.

OBJECTIVES: Data on Papanicolaou (Pap) tests with atypical glandular cells (AGCs) with concurrent squamous cell abnormalities (AGC + Sq) are limited. We evaluated histologic outcomes and the role of high-risk human papillomavirus (HR-HPV) testing in this setting compared with AGCs without concurrent squamous cell abnormalities (AGC-alone). METHODS: This study used a retrospective cohort of patients with Pap test diagnoses of AGC + Sq and AGC-alone between October 2013 and August 2021. RESULTS: We included 287 Pap tests from 278 patients. The HR-HPV test was positive in 55% of AGC + Sq cases and 14% of AGC-alone cases (P < .0001). Most AGC + Sq cases displayed squamous lesions (41.5%) or were benign (41.5%) on histology, whereas AGC-alone cases were predominantly benign (72%) or extracervical neoplasms (18%). AGC + Sq cases showed higher rates of significant histologic lesions (P = .0001), which were associated with positive HR-HPV status (P = .0012). In AGC-alone cases, HR-HPV status was associated with significant histology only in patients 50 years of age or younger. In both groups, 20% or more of HR-HPV-negative patients harbored significant lesions. CONCLUSIONS: AGC + Sq represents a distinct group of patients. HR-HPV testing and patient age provide useful information in the evaluation of AGC, but triage based on HR-HPV testing is not recommended because of the potential for missing significant lesions.

Atypical glandular cells and development of cervical cancer: Population-based cohort study.

The effect of cervical screening on cervical adenocarcinoma has been variable, possibly because the risk associated with the precursor atypical glandular cells (AGC) is not well known. A cohort of all 885 women in the capital region of Sweden with AGC, a concomitant human papillomavirus (HPV) analysis, and a histopathology was followed until 2019. Cumulative incidence proportions of cervical intraepithelial lesion grade 3 or worse (CIN3+) by HPV type was determined by 1-Kaplan-Meier estimates. Hazard ratios (HR) for CIN3+ or for invasive cancer were estimated with Cox regression. After 2 years of follow-up, the cumulative incidence proportions of CIN3+ were 80% (95% confidence interval [CI]: 74-86%), 58% (95% CI: 50-60%) and 10% (95% CI: 5-18%) among HPV16/18 positive, "other HPV" positive and HPV-negative women, respectively. Among the 300 women with HPV16/18 positive AGC, 217 developed CIN3+ of which 35 were invasive cervical cancer. The 2-year cumulative invasive cancer risk for HPV16/18 positive AGC was 17% (95% CI: 12-24%). Primary HPV-screening had a similar yield of CIN3+ as cytology screening, albeit HPV-negative AGC is by design not detected by HPV screening. Among 241 women with HPV-negative AGC, 11 developed CIN3+ mostly after clinically indicated samples. We found no significant risk differences depending on age or sampling indication. The low CIN3+ risk after HPV-negative AGC implies safety of primary HPV screening. The high risk of invasive cervical cancer after HPV16/18 positive AGC implies that management of this finding is a priority in cervical screening.

Atypical glandular cells (AGC): Cytology of glandular lesions of the uterine cervix.

The Pap smear is a well-known screening tool for squamous lesions of the uterine cervix. However, its screening role in glandular lesions is less effective. The incidence of squamous cell carcinoma of the cervix has dramatically decreased with the advent of Pap smear and recent understanding related to HPV carcinogenesis of cervical cancers including the advent of HPV vaccines. However, in recent years, the incidence of glandular abnormalities, diagnosed on Pap smears, has increased with greater sensitivity and precision. The incidence of atypical glandular cells (AGC) is approximately 0.18-0.74% of all cervical smears with a reported prevalence of 2.5% among all Pap smears. A high degree of suspicion, good clinical history, and the presence of diagnostic cytomorphological findings are essential for the proper interpretation of glandular cell abnormalities. A methodical approach to evaluate Pap smear greatly helps interpretation and avoids the diagnostic pitfalls. The Bethesda System for reporting cervical cytology has categorized glandular cell abnormalities into various categories as follows: Endocervical adenocarcinoma in situ (AIS)Atypical glandular cells (AGCs) Endocervical cells: a1 NOS or specify in comments; a2 Favor neoplasticEndometrial cells: NOS or specify in comments Adenocarcinoma (AdCa) EndocervicalEndometrialExtrauterineNOS Subtle differences in quantitative and qualitative cytologic features are essential for distinguishing one category from another. In this chapter, we highlight an organized approach for the interpretation of glandular abnormalities in Pap smear for our readers. This is an overview of the Bethesda categories, the reason for classification, and differential diagnosis with key characteristic features. An approach to the methodical evaluation of hyperchromatic crowded groups is discussed with key cytomorphologic differences. An algorithmic approach is suggested to facilitate the interpretation of various AGC categories.

Preventing Uterine Cervix Cancer: The Clinical Meaning of Atypical Glandular Cells / Prevenção do câncer do colo uterino: Significado clínico das células glandulares atípicas

Abstract Objective To determine the prevalence of the atypical glandular cells (AGCs) cytology and to analyze its clinical significance in different age ranges. Methods Retrospective observational study using computerized data from the Brazilian National Cancer Institute, including women screened between January 2002 and December 2008. The women included were those with an AGC result who were properly followed-up with colposcopy and a second cytology. Results A total of 132,147 cytopathological exams were performed during the study period. Five-hundred and thirty-three (0.4%) women with AGC cytology were identified and, of these, 69.41% (370/533) were properly referred for colposcopy and a new cytology. Most of the women (79.2%) with a 1st or 2nd AGC cytology were between the ages of 25 and 54 years. The 2nd cytology demonstrated 67.6% (250/370) of normality, 24.5% (91/370) of squamous atypia, and 6.2% (23/370) of AGC, 0.8% (3/370) adenocarcinoma in situ and 0.8% (3/370) adenocarcinoma invasor. On biopsy of the women with a second AGC cytology, 43.4% (10/23) had normal histology, 43.4% (10/23) had squamous lesions, 8.7% (2/23) had invasive adenocarcinoma, and 1.2% (1/23) had an inconclusive report. All of the women with high-grade squamous intraepithelial lesion (HSIL) or invasive adenocarcinoma (respectively 5 and 2 patients), after a 2nd AGC cytology were 25 years old or older. Conclusion The prevalence of the AGC cytology was low in the studied population. Most of the AGC cytology cases occurred in adult women between the ages of 25 and 54. Although most of the patients had normal histology after follow-up, several of them presented with squamous intraepithelial lesions or invasive adenocarcinoma.

Resumo Objetivo Determinar a prevalência de citologia com laudo de células glandulares atípicas (AGCs, na sigla em inglês) e analisar a significância clínica nas diferentes faixas etárias Métodos Estudo observacional retrospectivo, usando os dados arquivados no sistema do Instituto Nacional de Câncer no Brasil, que incluiu mulheres rastreadas entre janeiro de 2002 a dezembro de 2008. As mulheres incluídas tinham citologia com resultado de AGCs, que foram acompanhadas com colposcopia e nova citologia Resultados Um total de132,147 exames citopatológicos foram incluídos durante o período de estudo. Quinhentas e trinta e três mulheres com citologia de AGC foram identificadas e destas, 69.41% (370) foram encaminhadas para colposcopia e nova citologia. A prevalência de citologia de AGC na população estudada foi 0.4%. A maioria das mulheres (79.22%) com resultado citológico de AGC tinham idade entre 25 e 54 anos. A segunda citologia demonstrou 67.56% (250/370) de normalidade, 24.5% (91/370) de atipias escamosas, e 6.2% (23/370) de AGC. Na biopsia das mulheres com a 2ª citologia de AGC, 43.4% (10/23) tinham histologia normal, 43.4% (10/23) tinha lesões escamosas, 8.7% (2/23) tinha adenocarcinoma invasor e 1.2% (1/23) tinha laudo inconclusivo. Todas as mulheres com lesões intraepiteliais escamosas de alto grau (HSIL, na sigla em inglês) ou adenocarcinoma invasor (respectivamente 5 e 2pacientes), após a 2ª citologia com AGC, tinham 25 anos de idade ou mais. Conclusão A prevalência de citologia com AGC foi baixa na população estudada. Muitos casos de citologia com AGC apareceram em mulheres adultas, entre 25 e 54 anos de idade. Embora a maioria das pacientes tiveram histologia normal após seguimento, várias apresentaram lesões intraepiteliais escamosas ou glandulares invasoras.

False-negative Papanicolaou tests in women with biopsy-proven invasive endocervical adenocarcinoma/adenocarcinoma in situ: a retrospective analysis with assessment of interobserver agreement.

INTRODUCTION: The objectives of our study were to identify factors contributing to false-negative Papanicolaou (Pap) tests in patients with endocervical adenocarcinoma (EA) or adenocarcinoma in situ (AIS), and to analyze the impact of educational instruction on interobserver agreement in these cases. MATERIALS AND METHODS: False-negative Pap tests from patients with EA/AIS were reviewed by a consensus group and by 12 individual reviewers in 2 rounds, with an educational session on glandular neoplasia in Pap tests conducted between the 2 rounds. RESULTS: Of 79 Pap tests from patients with EA/AIS, 57 (72.2%) were diagnosed as abnormal and 22 (27.8%) as negative. Of the 22 false-negative cases, 10 remained negative on consensus review, with false-negative diagnoses attributed to sampling variance. The other 12 cases were upgraded to epithelial abnormalities (including 8 to glandular lesions). The false-negative diagnoses were attributed to screening variance in 2 cases and interpretive variance in 10 cases. On individual review, abnormal cells were misinterpreted as reactive glandular cells or endometrial cells in 7 of 8 and 5 of 8 cases upgraded to glandular abnormalities, respectively. With education, the proportion of individual reviewers demonstrating at least moderate agreement with the consensus diagnosis (Cohen's kappa >0.4) increased from 33% (4 of 12) to 75% (9 of 12). CONCLUSIONS: Sampling and interpretive variance each accounted for nearly one-half of the false-negative Pap tests, with underclassification as reactive glandular or endometrial cells the main source of the interpretive variances. Educational instruction significantly decreased the interpretive variance and interobserver variability in the diagnosis of glandular abnormalities.

Endometrial adenocarcinoma presenting in a voided urine cytology specimen: Case report.

Though the primary diagnostic utility of urine cytology is in the detection of high grade urothelial carcinoma, malignancies other than those of urinary tract origin may also be present. Direct invasion of the bladder by an adjacent neoplasm, metastasis from a distant primary, or inadvertent contamination during specimen collection may all result in nonurothelial tumor cells being present in a urine cytology specimen. Here, we report a case of endometrial adenocarcinoma that was first identified in a voided urine specimen collected for the routine evaluation of hematuria. The presence of cohesive clusters with apparent glandular differentiation raised the possibility of a nonurothelial neoplasm and prompted an additional workup. Immunohistochemical stains performed on cell block material demonstrated that the glandular cells were positive for PAX8 and negative for GATA3, suggestive of gynecologic origin. A subsequent endometrial curettage and hysterectomy revealed endometrial adenocarcinoma. When faced with papillary groups in a voided urine specimen, the cytopathologist must remember to consider a broad differential diagnosis to include malignancies outside of the urinary tract. It was our awareness of valuable clinical information and keen cytologic assessment which allowed for an accurate diagnosis in the setting of this unexpected finding.

Cytomorphologic clues for the diagnosis of fallopian tube prolapse in liquid-based vault samples with review of the literature.

INTRODUCTION: Fallopian tube prolapse (FTP) is a rare complication of hysterectomy. The cytological features of the prolapsed fallopian tube in vault smears have been occasionally described in the literature. MATERIALS AND METHODS: This was a retrospective study conducted to identify and describe the characteristic cytologic features of histopathologically confirmed cases of FTP in SurePath™ liquid-based preparations. Additionally, the literature documenting cytologic features of the prolapsed fallopian tube in vault smears was also reviewed. RESULTS: A total of four corresponding vault cytology samples of FTP cases, reported on histopathology, were available. On cytologic examination, these cases demonstrated strips and papillaroid clusters of columnar-shaped cells with mild nuclear enlargement, round to elongated nuclei, fine chromatin, inconspicuous nucleoli, and a moderate amount of wispy cytoplasm. Admixed inflammatory cells were also noted. Some of these cells demonstrated the presence of cilia and terminal bar toward the apical surface, indicative of tubal epithelium. The presence of three-dimensional papillaroid clusters lined by columnar cells as well as strips of similar cells with cilia and terminal bars at the apical surface and fine nuclear chromatin were the most consistent cytologic features in these cases. CONCLUSION: We conclude that a high index of clinical suspicion in post-hysterectomy cases with knowledge of the characteristic cytologic features can help in suggesting a diagnosis of tubal prolapse in vault samples.

The Clinical Significance and Utility of HPV-DNA Testing in Korean Women with Atypical Glandular Cells in Cervical Pap Tests: An Analysis of 311 Cases at a Single Institution.

The aim of this study is to analyze the correlation between clinically significant histologic results and HPV in women with AGC in pap test. Of the 311 women confirmed as AGC, 111 women (35.7%) was identified as positive for HPV. In the AGC analysis, cervical lesions were significantly more common in HPV positive group compared to HPV negative group (61.2 vs. 10.5%, p < 0.001). In contrast, endometrial lesions were not associated with HPV infection (8.1 vs. 4.5%, p = 0.12). The HPV-DNA testing in women with AGC may be a useful tool for predicting clinically significant cervical lesions.

Atypical glandular cells in Papanicolaou test: Which is more important in the detection of malignancy, architectural or nuclear features?

OBJECTIVE: Atypical glandular cells (AGCs) in Pap (Papanicolaou) smears are uncommon but may represent various benign and malignant lesions. The aim of this study was to evaluate the AGC incidence in Pap smears, analyse the relationship between AGC and malignancy, and reveal the importance of architectural and nuclear features observed cytologically in malignancies. METHODS: Patients diagnosed with AGC on the basis of cervicovaginal cytology between May 2011 and July 2018 were included in this study. All slides were retrospectively reviewed and subclassified according to the Bethesda 2001 classification system. The cytomorphological features observed in the smears were recorded. Cytohistological correlations were evaluated, and the significant clinicopathological findings for malignancy were determined. RESULTS: Of 87 536 Pap smears, 195 (0.22%) had AGC results and 156 had tissue follow-up. Among the 156 smears with AGC, 80 (51.3%) were diagnosed as AGC-NOS (atypical glandular cells, not otherwise specified) and 76 (48.7%) as AGC-FN (atypical glandular cells, favour neoplastic). Follow-up biopsies revealed benign pathologies in 49 cases (31.4%) and malignant pathologies in 107 (68.6%). The rate of malignancy observed in AGC-FN cases (89.5%) was higher than the rate of malignancy in AGC-NOS cases (48.8%). Among the cytomorphological features, nuclear irregularity, presence of macronucleoli, feathering, loss of polarity, papillary pattern, and three-dimensional formation were found to be significant indicators of malignancy. CONCLUSION: As AGC in Pap smear was associated with a clinically significant diagnosis in 68.6% of the cases in our study, we suggest that all patients with AGC should undergo further clinical assessment.

How useful are cervical Pap smears in detecting endometrial carcinomas? A tertiary cancer center experience.

OBJECTIVE: To determine the role of routine cervical Pap smears in detecting endometrial carcinomas. METHOD: A retrospective study was carried out from the histopathology archives for cases diagnosed as endometrial carcinomas with Pap smears within 6 months before histological diagnosis. The demographic details, reports of Pap smears and other tumor parameters on histopathology were noted. RESULTS: We identified 380 of 482 cases of endometrial carcinoma with a documented Pap smear within 6 months before histopathogical diagnosis. Out of 380 cases, 187 cases (49.2%) had shown abnormalities on Pap smear of which 80 cases (42%) were diagnosed as atypical glandular cells and 78 cases (41.7%) were diagnosed as adenocarcinoma. The presence of glandular abnormality on Pap smear significantly correlated with the tumor type, myometrial invasion and cervical involvement on histopathology (P < .05). Cases which had higher FIGO staging also had a higher detection rate on Pap smear (P < .05). CONCLUSION: The Pap smear may help in detection of endometrial carcinoma especially in cases with type 2 endometrial carinomas, tumor with cervical involvement and/or advanced FIGO stage.