Atypical Glandular Cells Cases Research Articles

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%.

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.

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. 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). 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). 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.

Clinical Diagnostic Value of Atypical Glandular Cells in Cervical Cytology: A Single Center Experience From China.

This study aimed to investigate the diagnostic value of atypical glandular cells (AGCs) by analyzing the prevalence and histopathology of AGCs according to cervical cytology. The authors retrospectively reviewed and analyzed the demographic characteristics and histopathological outcomes including pathological diagnosis, pathological site, and epithelial distribution of the AGC cases that were diagnosed by cervical cytology. A total of 387 AGC patients with follow-up records were included. Among them, the prevalence of AGC-not otherwise specified (NOS) and AGC-favor neoplastic (FN) was 73.39% (284/387) and 26.62% (103/387), respectively. The high-risk human papillomavirus (hr-HPV)-positive rate was higher in AGC-FN than in AGC-NOS ( p = .002). The difference in pathological severity was statistically significant between hr-HPV-positive and negative AGC patients ( p = .010). Hr-HPV-positive AGC mainly occurs in cervical diseases, whereas hr-HPV-negative AGC is mainly related to endometrial lesions. Precancerous or malignant lesions were found in 36.43% (141/387) of AGC cases and were more commonly seen in AGC-FN than AGC-NOS ( p < .001). The histopathological severity and the incidence of uterine disease were higher among AGC women aged 40 years and older than those younger than 40 years ( p < .05). The possibility of the abnormal origin of glandular epithelial was higher than that of squamous epithelial in AGC patients aged 40 years and older ( p = .0003). The management of AGC women by age triage is reasonable because the incidence of the glandular epithelial lesion and uterine disease increases in AGC patients 40 years or older. Standardized clinical diagnosis and regular follow-up are recommended for all AGC patients.

Clinicopathologic Significance of Atypical Glandular Cells in Cervical Cytology Smears: A five years Retrospective Study in a Tertiary Care Hospital

Introduction: Cervical cancer is the fourth most common cancer among women. Recently the incidence of cervicaladenocarcinoma has been increased significantly on the contrary to the decreasing incidence of cervical squamouscell carcinoma. Routine screening of cervical cancer by cervical smear cytology study to detect the pre-invasivelesions carries a significant role in reducing the incidence and mortality rate of cervical cancer.Objective: The aim of our study was to analyze the prevalence of Atypical Glandular Cells (AGCs) detected incervical smear screening, the follow up histopathological outcome and their clinical significance.Materials and Methods: This was a retrospective study done in College of Medicine and Sagore Dutta Hospital,Kolkata over a period of 5 years from June 2017 to June 2022. Patients detected with Atypical Glandular cells(AGCs) in cervical smears and having records of follow up histopathology reports were included in this study.The cases of AGCs in which the follow up histopathological reports were not available were excluded from thestudy.Result: The prevalence of atypical glandular cells were 0.57%. Out of the total 10,950 cervical smears examinedAGCs were found in 63 cases (0.57%). Out of 63 cases of AGCs subcategorization was done(according to TBS2015) which showed AGC not otherwise specified (AGC-NOS) in 46 cases (0.43%) and AGC Favoring Neoplasia(AGC-FN) were seen in 15 cases (0.13%). Both AGC -NOS and AGC-FN showed various pathology ranging fromreactive, metaplastic, benign to, in situ/Invasive carcinomas.Discussion: One of the major concern of AGC is that the cytological findings which characterize it have poorreproducibility between observers leading to interobserver variability. Due to the reported risk of premalignantand malignant lesions in AGCs it bear a great clinical significance and need for further histopathological correlation.&#x0D; Conclusion: Due to very low incidence of AGCs and the risk of malignancy associated with it multiple histologicalevaluation methods required for earlier diagnosis and management of the malignancies detected on histologicfollow up

Strategic Significance of Low Viral Load of Human Papillomavirus in Uterine Cervical Cytology Specimens.

Infection with high-risk (HR) Human Papillomavirus (HPV) is associated with the development of precancerous lesions or invasive carcinoma of the uterine cervix. Thus, the high viral load (VL) of HR-HPV DNA currently serves as a representative quantitative marker for cervical cancer. However, the clinical significance of low HPV DNA VL remains undetermined. This study aimed to evaluate the clinical association between the low HPV DNA VL and cytology/histologic diagnosis of cervical samples. We searched the electronic medical databases for the resultant analyses of HPV genotyping among patients who underwent treatment for any cervical lesion or who had undergone gynecological examinations with any positive HPV results according to the national cancer screening service between 2015 and 2016. HPV testing with genotyping and semi-quantitative VL measurement was conducted using an AnyplexTM II H28 Detection assay (H28 assay, Seegene, Seoul, Republic of Korea). The H28 assay is a multiplex semi-quantitative real-time PCR test using the tagging of oligonucleotide cleavage and extension (TOCE) technology. The VL was semi-quantified as high (3+; positive signal before 31 PCR cycles), intermediate (2+; positive between 31 and 39 PCR cycles), or low (1+; positive after 40 PCR cycles). Out of 5940 HPV VL analyses, 356 assays (5.99%) were reported as low VL (1+) of HPV DNA. Matched cytology diagnoses were mostly negative findings (n = 347, 97.5%), except for seven cases of atypical squamous cells of undetermined significance (1.9%) and two cases of atypical glandular cells (0.6%). During the follow-up periods, abnormal cytologic diagnoses were identified, including one case of high-grade squamous intraepithelial lesion (HSIL) and two low-grade squamous intraepithelial lesions (LSILs). The matched, confirmative histologic diagnosis of HSIL cytology was compatible with chronic inflammation, wherein the two LSILs had regular check-ups. None revealed clinically concerned outcomes associated with HPV-related squamous lesions. The cytology was most likely negative for malignancy when the VL of HPV DNA was low (1+). Additional strategic monitoring and management may thus be unnecessary.

Cyto-histo correlation of conventional Pap smear with cervical biopsy in diagnosis of precancerous and cancerous lesions of cervix

Introduction: Carcinoma of uterine cervix is the third most common cancer among women worldwide and it contributes significantly to cancer related morbidity and mortality. The incidence of cervical carcinoma is incredibly high in developing countries (almost 80%) due to lack of proper knowledge. The extensive use of cervical screening with Pap smears has considerably increased the detection of precancerous and cancerous lesions of uterine cervix. Aims: To evaluate cyto-histo correlation of precancerous and cancerous lesions of uterine cervix and to calculate the sensitivity and specificity of Pap smear in diagnosing invasive malignancy. Materials and Methods: This was a retrospective observational study conducted in the Department of Pathology, Chirayu Medical College & Hospital, Bhopal from January 2013 to April 2018. All the cases reported in Pap smear as cervical intraepithelial lesions and invasive malignancies were retrieved. We also retrieved the same cases, if they had undegone cervical biopsy for correlation. Result: During the study period total 303 cases which were positive for intraepithelial lesions and malignancies were retrieved. Out of these 303 cases we excluded 23 cases because in these cases cervical biopsy had not been done. So in the final analysis 280 cases were included. Of the 280 Pap smears, maximum cases (33.92%) were reported as low grade squamous intraepithelial lesion (LSIL), followed by high grade squamous intraepithelial lesion (HSIL) (24.28%), atypical squamous cells of undetermined significance (ASCUS) (19.64%), atypical squamous cells – cannot rule out HSIL (ASC-H) (10%). We had 23 cases of invasive malignancy which includes 21 cases of squamous cell carcinoma (SCC) and 2 cases of adenocarcinoma. There were 11 cases of atypical glandular cells of undetermined significance (AGUS). We found that total numbers of concordant cases were 68.57% (192/280) and discordant cases were 31.43% (88/280). We also found that sensitivity and specif

Subcategorization of atypical glandular cells is useful to identify lesion site.

In the subcategorization of atypical glandular cells (AGCs), origin of cells should be mentioned to estimate lesion sites for diagnosis. However, cases without subcategorization are often encountered due to limited reproducibility. We evaluated whether the subcategorization of AGC based on the Bethesda terminology can estimate lesion sites. We retrospectively investigated cases whose cervical smears were interpreted as AGC and underwent pathological assessment at our institution between June 2009 and September 2017. AGC was subcategorized based on the Bethesda System. Not-otherwise-specified (NOS) was subcategorized into endocervical cells (NOS-EC), endometrial cells (NOS-EM), or glandular cells (NOS-G). Favor neoplastic (FN) was subcategorized into endocervical cells (FN-EC) or glandular cells (FN-G). FN-G was further subcategorized into endometrial cells (FN-EM) or unknown origin (FN-UO). Clinicopathological data were retrieved from the medical records. Of 88 AGC cases, there were 30 NOS-EC (34.1%), 2 NOS-EM (2.3%), 25 FN-EC (28.4%), 22 FN-EM (25.0%), and 9 FN-UO (10.2%). A significantly higher proportion of neoplastic lesions occurred in FN than in NOS (P <.001). The concordance of AGC subclass and lesion site was 88.0%, 70.7%, and 77.3% in FN-EC, FN-G, and FN-EM, respectively. The concordance of FN-EM and lesion site increased to 88.9% in patients aged >50 years. Of nine cases of FN-UO, six experienced nonendometrioid endometrial cancer and extrauterine malignancy. Subcategorization of NOS and FN would be useful in estimating neoplastic lesions. Further subcategorization into FN-EC, FN-EM, and FN-UO would similarly be beneficial in estimating the lesion site, especially for small endometrial and extrauterine lesions.

Cytohistological correlation in patients with atypical glandular cells on Papanicolaou test in a Chilean population.

The standard screening test for detecting cervical lesions and cancers is a Papanicolaou (Pap) smear. While squamous cell abnormalities remain the most common positive Pap test result, cytologic findings of glandular cell abnormalities have become more frequent in recent decades. The 2014 Bethesda System for reporting cervical cytology includes the classification "atypical glandular cells" (AGC). AGC have morphological abnormalities that fall outside the range of reactive changes, but are insufficient for a diagnosis of invasive adenocarcinoma. In several histologic follow-up studies, most AGC cases were found to represent a benign condition. In the current study, we evaluate the significance of AGC cytology findings by analyzing the histologic follow-up results of a large number of patients with AGC. Most patients with AGC in this study were found to have a significant lesion on follow-up (63.9%), with negative histologic results in only 36.1% of patients. Among patients with significant lesions, the most common result was low-grade squamous intraepithelial lesion (26.6%), followed by high-grade squamous intraepithelial lesion (23.2%). This provides further evidence to support the Chilean Clinical Guidelines for Cervical Cancer, which recommends diagnostic follow-up studies in all women with AGC to minimize the chance of undetected serious cervical disease.

Clinicopathological Characteristics of Atypical Glandular Cells Determined by Cervical Cytology in Japan: Survey of Gynecologic Oncology Data from the Obstetrical Gynecological Society of Kinki District, Japan

Background: The purpose of this study was to clarify the clinicopathological characteristics of, and the clinical approach used to identify, atypical glandular cells (AGCs) in Japan based on cervical cytology screening. Objectives: This study included 1,254 patients with AGCs who underwent cervical cytology. Method: Data from patients with AGCs were used to examine the practical management of AGCs and the histological results. Results: The incidence of AGCs was 0.20% (1,254/614,791). The 1,254 AGC cases included 859 endocervical cells not otherwise specified (NOS), 3 glandular cells NOS, 91 endocervical cells favor neoplasia (FN), and 301 atypical endometrial cells (AEMCs). Among the 1,254 AGC patients, the histological diagnosis was benign in 666 (53.1%), cervical intraepithelial neoplasia (CIN) 1 in 60 (4.8%), CIN2 in 31 (2.5%), CIN3 in 52 (4.1%), squamous cell carcinoma in 19 (1.5%), adenocarcinoma in situ in 39 (3.1%), cervical adenocarcinoma in 106 (8.5%), endometrial carcinoma in 209 (16.7%), ovarian cancer in 26 (2.1%), other malignancy in 4 (0.3%), and other under follow-up in 42 (3.3%). When the 1,254 AGC patients were divided into three medical intervention degrees according to histology, AGC-NOS, AGC-FN, and AEMC required no medical intervention in 78.7, 13.2, and 25.9% (678, 12, and 78) of the patients, cervical cone resection in 13.0, 9.9, and 0.3% (112, 9, and 1) of the patients, and radical laparotomy for invasive cancer in 8.3, 76.9, and 73.8% (72, 70, and 222) of the patients, respectively. Conclusions: Our histological results supported the medical interventions applied for AGC diagnosis and treatment. AGC cases require careful histological evaluation.

Population-based primary HPV mRNA cervical screening compared with cytology screening

Primary HPV screening for cervical cancer by HPV mRNA testing (Aptima) was implemented in January 2017, for women ≥30 through 70 years, in the Region of Skåne, Sweden. HPV positive samples underwent cytology assessment, and women with any degree of abnormal cytology were referred for colposcopy. The aim was to audit the primary HPV screening program, by comparing the cytology results to those of corresponding women (aged ≥30 through 65 years) screened with conventional cytology during 2016. Overall, HPV was detected among 7.0% (4433/63,055) of the women ≥30–70 years in the primary HPV screening program. Among a co-tested (cytology and HPV) subgroup aged 40–42 years (N = 5039), HPV was detected in 100% (28/28) of high-grade squamous intraepithelial lesions (HSIL) and atypical squamous cells of undetermined significance (ASCUS) where HSIL could not be excluded (ASCH) (9/9), and in 80% (4/5) of cases of atypical glandular cells (AGC). Among women ≥30–65 years, the proportion ASCUS or worse (ASCUS+) was similar with cytology (3.52% [2016]) and primary HPV screening (3.70% [2017]). Only the proportion of ASC-H changed by the use of primary HPV screening, from 0.13% (2016) to 0.23% (2017) (p < 0.001). The colposcopy referral rate increased by 54% (3.70 vs 2.41%), when primary HPV screening was introduced. In conclusion, the implemented primary HPV screening approach demonstrated similar prevalence of ASCUS+ cytology as conventional screening. In addition, primary HPV screening decreased cytology assessments by 86% in our screening population of women 30 through 70 years taken into account the co-tested women.

Atypical Glandular Cells: Interobserver Variability according to Clinical Management

Objective: The 2014 Bethesda System diagnostic criteria for atypical glandular cells (AGC) aids in classification of atypical cells in cervical cytology. There is limited literature regarding reproducibility and interobserver variability in the application of the 2014 AGC criteria. Our aim is to assess the interobserver variability of AGC with a focus on how diagnostic categories link with guideline-driven management. Study Design: Three observers re-reviewed 51 previously diagnosed AGC Papanicolaou tests. The diagnoses were categorized as follows: (1) according to guideline-specified management, and (2) as glandular vs. squamous lesions. The κ statistic was used to evaluate interobserver agreement. Results: The interobserver variability per guideline management by weighted 2-observer κ ranged from 0.009 to 0.530, with half of the interobserver pairings meeting the threshold for at least fair-moderate agreement. For categorization as glandular, squamous, or both, unweighted κ yielded at best fair interobserver agreement (κ = 0.250) in 1 pairing, with low κ scores in the remainder of reviewer pairs (range 0.015–0.152). Conclusions: There is significant interobserver variability in the diagnosis of AGC. The AGC cases when divided by clinical management had fair-moderate interobserver agreement, suggesting that diagnostic variability likely has a real effect on patient care. This diagnostic uncertainty should be understood by cytologists and clinicians.

Clinicopathological significance of atypical glandular cells on cervicovaginal Pap smears

To evaluate the histologic correlation and clinical significance of atypical glandular cells (AGC) detected on Pap tests. Pap tests interpreted as AGC were retrieved from an institutional cytopathology database. The AGC subcategories according to the Bethesda system 2001 include atypical glandular cells, not otherwise specified (AGC-NOS), atypical endometrial cells (AEM), and atypical endocervical cells (AEC). Clinicopathologic variables were collected from medical records retrospectively, and histologic follow-up diagnoses were correlated with AGC subcategories. From January 2009 to December 2014, 741 (0.17%) of 435778 cervical smears were interpreted as AGC. Of 713 cases included in the study analysis, the distribution of AGC subcategories was as follows: AGC 15.3%, AEM 59.6%, and AEC 25.1%. Of 508 cases with histologic follow-up results, 33.9% of cases were diagnosed to have clinically significant lesions, which include cervical squamous or glandular neoplasia (1.4% and 10.0%), endometrial neoplasia (21.5%), and other metastatic carcinoma (1.0%). Endometrial neoplasia was the most common significant pathology in women aged ≥40 years (28.4%), whereas cervical glandular neoplasia was the most commonly diagnosed lesion in women aged <40 years (14.5%, P < 0.001). When considering past histories which could affect the Pap results, IUD use (10.3%) and pregnancy (7.3%) were most frequently documented. Although IUD users showed low prevalence of significant pathology (2.6%), AGC cases related with pregnancy preceded significant pathologic lesions in 14.3%. The relatively high incidence of significant neoplasia linked to AGC emphasizes the importance of adherence to the AGC management guidelines which recommend early and intensive investigation using multiple testing modalities.

Significance of high-risk HPV detection in women with atypical glandular cells on Pap testing: Analysis of 1857 cases from an academic institution.

The role of high-risk human papillomavirus (hrHPV) testing in women with various types of atypical glandular cells (AGC) on Papanicolaou (Pap) test is undetermined. Herein, the authors retrospectively searched their pathology database for cases of AGC with concurrent hrHPV testing and histological follow-up results within 1 year between January 2008 and December 2013. Among 3709 AGC cases occurring during the study period, 2287 had concurrent Hybrid Capture 2 HPV testing results. The overall rate of hrHPV positivity (hrHPV+) was 27.7%. Of these 2287 cases, 1857 cases (81.2%) had histological follow-up results within 1 year, including 529 hrHPV + cases and 1328 hrHPV-negative (hrHPV-) cases. Among the hrHPV + cases, 16.8% had cervical intraepithelial neoplasia 2/3 (CIN2/3), 5.7% had cervical adenocarcinoma in situ (AIS)/adenocarcinoma (ADC), and 1.1% had an endometrial carcinoma. Among the hrHPV- cases, 0.6% had CIN2/3, 0.2% had AIS/ADC, and 3.8% had an endometrial carcinoma. The rate of high-grade cervical lesions (CIN2/3, AIS, or ADC) was significantly higher in women who were hrHPV + compared with hrHPV- women for all age groups. Endometrial carcinoma was most commonly present in women aged ≥50 years. To the authors' knowledge, the current study is the largest follow-up study published to date regarding women with AGC cytology and HPV testing. The study data indicate that hrHPV testing is useful for predicting the risk of high-grade cervical neoplasia in women with AGC, but has no significant value in evaluating the risk of endometrial carcinoma. The combination of cytology, hrHPV testing, and patient age can significantly aid in the appropriate management of these individuals. Cancer Cytopathol 2017;125:205-211. © 2016 American Cancer Society.

Management of "Atypical Endocervical Cells" Compared to "Atypical Glandular Cells".

To assess adherence to management guidelines based on the terminology used to describe atypical glandular cells (AGC) on cytology reports. We analyzed AGC pathology reports from Hartford Hospital, 2004-2007, and identified cases of AGC with the terminology atypical glandular cells or atypical endocervical cells (AEC). We calculated rates of clinical evaluations based on the terminology used to describe the AGC. Statistical analysis was performed using the χ test. Seventy-eight reports contained the terminology AEC and 97 reports contained the terminology AGC. The rate of histologic sampling in women with AEC was lower than in women with AGC (52.6% vs 83.5%; p < .01). Similarly, the rate of comprehensive evaluations was lower (33.3% vs 71.1%; p < .01). Fewer endocervical curettages (47.4% vs 77.3%; p < .01) and fewer endometrial biopsies in women 35 years or older were performed (26.9% vs 69.1%; p < .01) in women with AEC than in women with AGC. Women with AGC reports containing the term AEC were managed less optimally than those with AGC. These results suggest that the terminology used to describe the finding of atypical glandular cells may influence the clinical evaluation. Clinicians may not recognize AEC as AGCs. Ours results suggest that the terminology atypical endocervical cells should be avoided or accompanied by the terminology atypical glandular cells.

Interpretation and management of AGC cytology

Background Cervical cytology has continually evolved. Nowadays, the category of atypical glandular cells (AGC) is less frequent than atypical squamous cells (ASC), associating poorlyreproducible inter-observer interpretation. Cellular characters sometimes surpass benign reparatory processes or associate high-grade squamous precursor lesions, glandular neoplasia, including cervical adenocarcinoma, endometrial neoplasm and even extrauterine adenocarcinomas. Therefore, AGC needs special attention and aggressive diagnostic procedures. Nevertheless, the most common viral infection of the reproductive tract, the human-papillomavirus (HPV) infection, shouldn’t be underestimated, as about 30% of AGC cases are HPV-positive. The presence of HPV in AGC patients identifies a group at higher-risk for developing cervical neoplasia. Studies show that 70% of AGCHPV-negative patients have no evidence of cervical cancer, and 76% of AGC-HPV-positive results may present glandular or squamous neoplasia.

Diagnostic Value of Complementary Cell Block Preparation From Residual SurePath™ Pap Material for Atypical Glandular Cells

Intoduction: Within the Bethesda Reporting System, the category of Atypical Glandular Cells (AGC) is an infrequent and diagnostically challenging interpretation, which is predictive of significant lesions in 10-40% of subsequent biopsies. Prior studies have attempted to enhance the diagnostic accuracy of AGC by creating complementary cell blocks (CB), from residual material of conventional or ThinPrep Pap specimens. These studies ranged from 22 to 71 cases, and showed resultant positivity rates of 65-75%. In our study, we sought to determine the efficacy of CB preparations from residual SurePath Pap material of our AGC cases. Materials and Methods: From February 2012 to April 2013, CBs were prepared from residual SurePath material of 57 AGC cases submitted to 2 departmental cytopathologists. During this study period, a total of 100,943 Pap tests were evaluated in our laboratory, with a resultant AGC rate of 0.03%. Results: Fifteen (27%) of our AGC CB preparations histologically demonstrated precancerous or malignant cells (Table 1, Figures 1-3). Five (9%) of the CBs revealed only scant atypical glandular cells, precluding definitive diagnosis. Two (40%) of these cases were confirmed on subsequent biopsy to be endometrial cancers. Of the remaining 37 (65%) negative CBs, 16 (43%) had surgical follow-up. Thirteen (81%) of these biopsies were positive, including 11 (85%) endometrial and 2 (15%) endocervical cancers. Thus, the overall sensitivity of our CB preparations from residual SurePath samples was 50%. Sensitivities for endocervical and endometrial cancers were 67% and 28%, respectively.

Can we improve the positive predictive value of atypical glandular cells not otherwise specified?

The category of atypical glandular cells (AGC) in gynecologic cytopathology presents many well-documented diagnostic challenges, the most significant related to high interobserver variability, low specificity, and low positive predictive value. The current Bethesda System provides criteria for specific glandular categories including atypical endocervical cells not otherwise specified (AEC-NOS), AEC favor neoplastic, and atypical endometrial cells. The Bethesda System does, however, acknowledge that in some cases AGC cannot be categorized based upon cell of origin, in which case the generic term "atypical glandular cells" (AGC) may be used. We sought to determine whether further refinement of the current Bethesda System criteria for AEC-NOS might increase the positive predictive value of the general category of AGC. Fifty-three cases of AGC with documented histologic follow-up at the University of Illinois Hospital were reviewed. The cases were graded on each of the eight specific cytologic criteria recommended by the current Bethesda System for AEC-NOS using a study-developed three-tier grading system. Multiple regression analysis showed that four of the cytologic criteria in combination--nuclear enlargement, nuclear pleomorphism, increased nuclear-to-cytoplasmic (N/C) ratio, and cells occurring in sheets and strips with cell crowding and nuclear overlap--discriminated positive histologic outcome slightly better than any single criterion alone. In addition, simple logistic regression analysis showed nuclear enlargement to have a marginal independent association with positive histologic outcome (P = 0.0566). No other criterion was independently associated with outcome. Ancillary methods seem indicated to increase the positive predictive value of AGC at this time.

Adherence to practice guidelines for atypical glandular cells on cervical cytology

Atypical glandular cells (AGC) on cervical cytology are high-risk, requiring an extensive evaluation. Compliance with practice guidelines for AGC, however, has been low. Some AGC cytology reports contain cytopathologist recommendations for evaluation. This study determines whether evaluation rates for AGC have improved over time, and whether cytopathologists' recommendations correlate with the types of evaluation women receive. Evaluation rates from 284 women with AGC (2004-2007) were compared with findings from 1998-2001. Rates of evaluations were compared based on cytology report recommendations. A total of 76.1% of the AGC cases had histologic sampling, and 58.8% had a comprehensive evaluation. These rates are higher than those from 1998-2001 (63.5% and 35.8%, respectively; P<.01). Rates of evaluations of women with AGC "favor neoplasia" did not increase between the 2 time periods. Between 2004-2005 and 2006-2007, rates of comprehensive initial evaluations and endometrial sampling in women ≥35 years of age did not increase. Of the AGC reports that did contain cytopathologist recommendations, 28% were consistent with practice guidelines, 26% recommended an incomplete histologic evaluation, and 46% recommended repeat cytology. Women whose AGC report recommended a comprehensive evaluation or any histologic evaluation were more likely to have a comprehensive work-up (79%) than those whose reports did not contain recommendations (55%, P <0.01) or recommended repeat cytology (51%, P<0.02). Adherence to practice guidelines for the evaluation of women with AGC has improved but continues to be suboptimal. Our findings suggest that continuing education and including practice guidelines on AGC cytology reports may improve compliance.

Type-Specific Human Papillomavirus DNA Detected in Atypical Glandular Cell Pap Tests

Objectives: To evaluate the presence of type-specific human papillomavirus (HPV) DNA in atypical glandular cells (AGCs) from cervical liquid-based cytology and to report the relationship between HPV types and cervical histological abnormalities. Study Design: We used a nested multiplex polymerase chain reaction assay to test AGC Papanicolaou (Pap) tests for the presence of 14 high-risk (HR) HPV types. Results: HR HPV types were detected in 33 of 161 AGC Pap tests (20.3%). Types 16 and/or 18 were detected in 13 samples (8%). Eight other HPV types were detected in 1–4 samples each. HPV-associated disease was diagnosed in 8 AGC cases (8%) with available histology results. The sensitivity and specificity of the HR HPV test were 87.5 and 90%, respectively, and the negative predictive value (NPV) was 99%. For a test that can isolate HPV types 16 and 18, the sensitivity and specificity were 62.5 and 100%, respectively, the positive predictive value (PPV) was 100% and the NPV was 97%. Conclusion: HPV 16 and 18 were the most common types detected in AGC Paps. We found high specificity, PPV and NPV with a test that can isolate these 2 HPV types. These results indicate a possible role for type-specific HPV testing in the management of AGC Pap tests.

Atypical Glandular Cells on Cervical Cytology and Breast Disease

To determine whether metastatic mammary carcinoma can be detected on cervical cytology in patients with atypical glandular cells (AGCs). This blinded study of AGC cases with a matched control group was approved by Hartford Hospital institutional review board. Between January 2002 and November 2008, inclusive, all Pap tests in our database with AGC were identified. The AGC cases from patients with breast disease, compared with the control group of AGC patients without breast disease, were reanalyzed independently by 2 pathologists. Among the 40 women who had an AGC Pap test with breast disease, 21 cases were available for review (16 with invasive and 5 with in situ breast lesions). Seventeen cases of AGC in patients without breast disease served as the control group. The 2 pathologists agreed with the original Pap finding (AGC) in 84.2% to 89.5% of cases. There were no cases, either among those with breast disease or those without, where cells consistent with breast disease were seen, nor were "tamoxifen cells" identified, on Pap testing. Studies have found that an association exists between patients with AGCs on cervical cytology and extrauterine malignancies, including breast disease. The results of this analysis would suggest that, at least for breast disease, the higher association of cancer or precancerous lesions in those with AGC is not related to the direct extension of disease or metastasis. Further research will be needed to help delineate the potential etiology of this association.