Atypical Glandular Cells-not Otherwise Specified Research Articles

P16/Ki67 Dual Staining in Glandular Cell Abnormalities of the Uterine Cervix.

Very limited information exists about the role of p16/Ki67 dual staining on glandular cells in detecting glandular precancerous lesions and cervical adenocarcinoma. In this study, we investigated the diagnostic accuracy of p16/Ki67 dual staining for the detection of glandular and squamous lesions on the uterine cervix and for cancer of the upper reproductive tract. We performed a retrospective analysis of prospectively collected data on 96 patients with glandular cell abnormalities. We analyzed the diagnostic accuracy of p16/Ki67 dual staining for atypical glandular cells, not otherwise specified (AGC-NOS); atypical glandular cells, favor neoplastic (AGC-FN); adenocarcinoma in situ (AIS); and A-CA (cervical adenocarcinoma). A separate analysis for the detection of squamous precancerous lesions and squamous-cell carcinoma (CIN3+) and for cancer of the upper reproductive tract (EC/OC) was performed. Among patients who had normal histology or a low-grade lesion on final analysis, only 8.5% had positive dual staining. On the other hand, 85.7% of patients with AIS+ on final histology had positive dual staining. The respective specificities of p16/Ki67 dual staining on AGC-NOS for the detection of AIS+ (adenocarcinoma in situ or cervical adenocarcinoma), CIN3+ and EC/OC were 91.5%, 88.7% and 86.4%. High specificity values of p16/Ki67 dual staining on cervical smears labelled as AGC-NOS for the detection of CIN3+ and AIS+ suggest that this method might be a useful addition in cervical cancer screening.

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.
 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

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

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. 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. Of 87536 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. 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.

Cytomorphological patterns of cervical Papanicolaou smear abnormalities based on 2014 Bethesda System in North Karnataka region

Introduction: Cervical PAP smears are a cost effective, out-patient procedure to screen patients for cervical pathology. Objectives: To utilize cervical PAP smear examination in categorizing lesions according to the 2014 Bethesda System for cervical cytology, to analyse the spectrum of lesions andto evaluate its effectiveness as a screening procedure for detection of epithelial abnormalities in a teaching hospital in North Karnataka. Methods: A prospective one year study was carried on all conventional PAP smears received in the Department of Pathology, Navodaya Medical College, Raichur. Reporting was done in accordance with the 2014 Bethesda System for reporting cervical cytology. Correlation was done with the clinical findings. Results: A total of 578 cases were included in the study. The most common presenting complaint was abdominal pain (28.5%). The most frequent examination finding was white discharge per vaginum, WDPV (38.9%). 90.8% of PAP smears were categorized as ‘Negative for intraepithelial Lesion or Malignancy’. Specific infections were seen in 8.1%, squamous metaplasia in 15.5% and atrophic changes in 3.2%. Epithelial cell abnormalities comprised 9.2% of cases, of which Atypical Squamous Cells of Undetermined Significance (ASC-US) was 3.2%, Low grade Squamous Intraepithelial Lesion (LSIL) was 3.6%, High grade Squamous Intraepithelial Lesion (HSIL) was 1.9%, Squamous Cell Carcinoma (SCC) was 0.2% and Atypical Glandular Cells– Not Otherwise Specified (AGC-NOS) was 0.9%. Conclusion: The overall prevalence of epithelial cell abnormalities concurred with studies done in other parts of India and constituted9.2% of the total smears screened, LSIL being the most common lesion.

Cytologic parameters predicting neoplasia in Papanicolaou smears with atypical glandular cells and histologic follow-up: a single-institution experience

Studies investigating histologic follow-up of The 2001 Bethesda System diagnosis of atypical glandular cells (AGC) have focused on various screening methods, patient populations, and Papanicolaou preparations. Our aim was to report the histologic follow-up of AGC diagnoses from ThinPrep slides and evaluate specific cytologic features predicting benign or malignant follow-up results. A retrospective search identified liquid-based cervical cytology results interpreted as AGC. AGC diagnoses were stratified into four groups: atypical endometrial cells (AGC-EM); atypical endocervical cells (AGC-EC); AGC, favor neoplastic (AGC-FN); and AGC not otherwise specified (AGC-NOS). Evidence of disease was based on histologic follow-up (biopsy or resection specimen) with a diagnosis of cancer, complex endometrial hyperplasia, or high-grade squamous dysplasia. Available slides were blindly reviewed for specific cytologic features. Statistical analysis compared cytologic factors that would predict benign or malignant follow-up. We interpreted 264 samples as AGC from 2005 through 2009. Of the 246 (93.2%) with follow-up histologic material, 60 (24.4%) were AGC-EM; 36 (14.6%) were AGC-EC; 28 (11.4%) were AGC-FN; and 122 (49.6%) were AGC-NOS. Neoplasia was diagnosed in 80 (32.5%). Neoplastic cases showed significantly increased numbers of single cells, cells in 3-dimensional clusters, engulfed neutrophils, nuclear enlargement, increased nuclear-to-cytoplasmic ratio, irregular nuclear borders, reniform nuclei, loss of polarity, and macronucleoli. Cytologic parameters can be used to predict benign from neoplastic glandular lesions. Biopsy follow-up is necessary to correlate cytologic findings when AGC is diagnosed on a Papanicolaou smear.

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.

Comparison of the Histologic Results of Atypical Glandular Cells-Favor Neoplasia and Atypical Glandular Cells-Not Otherwise Specified

Objective: Cervical cancer screening programs are widely performed in all around the world. The interpretation of the Pap smear test is a big challenge in gynecology practice particularly when associated with atypical glandular cells. In this study, we performed a retrospective analysis of cytologic results associated with atypical glandular cells in our institution.Material and Method: We retrospectively reviewed Pap smear tests resulted as “atypical glandular cells”. A total of 122 women had screening tests reported as “atypical glandular cells” between 2003 and 2013 at the Ministry of Health, Etlik Maternity and Women’s Health Teaching Research. The cytology reported as “atypical glandular cells” were evaluated in two main groups: Atypical glandular cells-favor neoplasia (AGC-FN) and atypical glandular cells-not otherwise specified (AGC-NOS) compared by means of histologic results.Results: Thirty-two women have been reported as AGC-NOS on cytologic examination and 90 women were defined as AGC-FN. There was no significant difference between AGC-FN and AGC NOS groups in terms of age. In AGC-FN group, a total of 13 women (13/90) (14.4%) had malignant histological diagnosis. In AGC-NOS group only one woman (1/32) (3.1%) was diagnosed as malignant. All the malignant cases in this study are older than 35 years.Conclusion: The incidence of AGC is less than 1% in all Pap smear examinations. Two main factors were important in the outcome of the AGC. The first one is the subgroup. AGC-FN group has a higher risk of malignancy. The second important factor is the age of the patient. To be older than 35 years old seems to increase the risk of malignancy.

Evaluation of cervicovaginal smear results at postmenopausal period

&lt;p&gt;This study evaluates the statistical analysis of cervicovaginal smear results at postmenopausal period accompanied by literature. Cervicovaginal smear results of 894 postmenopausal women were evaluated retrospectively according to the 2001 Bethesda system (BS) in Adana Numune Training and Research Hospital of Obstetrics and Gynecology Clinic from 2007–2010. The study found, normal results on 287 patients (32.1%), benign findings on 556 patients (62.2%), abnormal epithelial cell changes on 48 patients (5.36%) and malignant changes on 3 patients (0.33%). The abnormal epithelial changes were observed to be atypical cells of undetermined significance (ASC-US) for 22 patients (2.46%), &lt;a href="http://medical-dictionary.thefreedictionary.com/high-grade+squamous+intraepithelial+lesion"&gt;low-grade squamous intraepithelial lesion&lt;/a&gt; (LSIL) for 11 patients (1.23%), &lt;a href="http://medical-dictionary.thefreedictionary.com/high-grade+squamous+intraepithelial+lesion"&gt;high-grade squamous intraepithelial lesion&lt;/a&gt; (HSIL) for 7 patients (0.78%), findings that cannot exclude a high-grade squamous intraepithelial lesion (ASC-H) for 6 patients (0.55%) and atypical glandular cells-not otherwise specified (AGC-NOS) for 2 patients (0.22%). Malignant results were 2 squamous cell carcinomas (SCC) (0.22%) and 1 adenocarcinoma (ACC) (0.11%). Cervical cancer screening programs should be expanded and Pap smear screening should be applied to all postmenopausal women. The longer time span involved from premalignant lesions to cancer improves our chance for the diagnosis and treatment. As the incidence of invasive cancer increases in menopausal period, gynecological smear examination and regular check-up are crucial. A high rate of abnormalities of epithelial cells was detected in this study.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;

Factors predicting pathologic significance among women with atypical glandular cells on liquid-based cytology

ObjectiveTo determine incidence, originating organ, and factors predicting significant histopathology (premalignant and malignant lesions) among women with atypical glandular cells (AGCs) on liquid-based cytology (LBC). MethodsIn a retrospective study at Siriraj Hospital, Bangkok, Thailand, clinical and histologic data were reviewed for women with AGCs who underwent appropriate examinations from January 2007 to December 2010. ResultsThere were 284 women with AGC cytology (mean age, 51.2years). The incidence of significant pathology and invasive cancer was 43.3% and 34.5%, respectively. The most common malignant organ was the uterus (64/123, 52%). Predictors of serious pathology were AGC favor neoplasia (AGC-FN) endocervical (odds ratio [OR], 5.64; 95% confidence interval [CI], 1.62–19.57), AGC-FN endometrial (OR, 4.11; 95% CI, 1.27–13.32), AGC-FN glandular (OR, 8.23; 95% CI, 2.02–33.49) subtypes, and bleeding (OR, 2.88; 95% CI, 1.47–5.65). Combining patient age and AGC subtype, there were no serious cervical lesions among women aged 50years or younger with AGC-FN glandular subtype, or serious non-cervical neoplasia among women aged 50years or younger with AGC not otherwise specified (AGC-NOS) or AGC-FN endocervical subtypes. ConclusionAGC subcategories defined from LBC, alone or combined with patient age, might be predictors of significant histopathology, cancer incidence, and originating organ.

Value of HPV-DNA test in women with cytological diagnosis of atypical glandular cells (AGC)

ObjectiveThis study analyzed whether HPV (human papillomavirus) testing contributes towards defining histological abnormalities in women with atypical glandular cells (AGC) diagnosed at cervical cytology. Study designOne hundred and eight women with conventional cervical cancer screening smears suggestive of AGC not otherwise specified (AGC-NOS) and favor neoplastic (AGC-FN) were consecutively enrolled. All women underwent colposcopic examinations and biopsy was performed according to the cytopathologic and/or colposcopic abnormalities present. All specimens were tested for high risk HPV genotypes by Roche's polymerase chain reaction reverse line blot assay. The chi-square test was used to evaluate the association between HPV findings and a diagnosis of high-grade pre-invasive or invasive disease (CIN 2 or worse) taking negative tests or CIN 1 as a reference. Odds ratios (OR) with their respective 95% confidence intervals (95%CI) were used to evaluate the magnitude of the association between HPV testing and CIN 2 or worse. Sensitivity, specificity and their respective 95% confidence intervals (95%CI), positive predictive values (PPV) and negative predictive values (NPV) were also calculated. ResultsFinal diagnosis revealed a negative outcome in 80 cases (74%), cervical epithelial neoplasia 1 (CIN 1) in 13 cases (12%), CIN 2 or worse in 12 cases (11%) and glandular neoplasia in 3 (3%) cases. The overall detection rate of HPV was 21% (23/108). Neoplasia was significantly associated with positive HPV-DNA in women with AGC-NOS (OR=15.21; 95%CI: 2.64–87.50); however, there was no significant association between a histological diagnosis of neoplasia and HPV positivity in women with AGC-FN (OR=3.00; 95%CI: 0.36–24.92). The sensitivity, specificity, positive predictive value and negative predictive value of HPV-DNA testing for the detection of CIN 2 or worse in women with AGC-NOS were 71%, 86%, 29% and 97%, respectively. In women with AGC-FN, these values were 50%, 75%, 66% and 60%, respectively. ConclusionsHPV testing at the time of colposcopy for patients with AGC in whom no colposcopic abnormality is found may be a powerful ancillary tool for identifying women at a high risk of underlying significant cervical lesions.

ProExC Triage of Atypical Glandular Cells on Liquid-Based Cervical Cytology Specimens

Morphologic distinction between atypical glandular cells not otherwise specified (AGC-NOS) and AGC-favor neoplasia (AGC-FN) can be difficult. Distinction between these entities is important as the American Society for Colposcopy and Cervical Pathology 2006 consensus guidelines state that management of AGC-NOS differs from that of AGC-FN. The objective of this study was to determine the potential role of ProExC immunocytochemical triage of AGC-NOS. Cytopathology records from a pathology practice were reviewed from January 2006 to December 2009 to identify AGC-NOS liquid-based Pap smears with subsequent biopsy correlation. Archival slides were examined, and ProExC immunocytochemistry was performed. The AGC groups were assessed for nuclear staining, and results were correlated with subsequent biopsy findings. Twenty-eight AGC-NOS cases with biopsy correlation were identified: 13 with subsequent high-grade neoplastic or malignant (positive) diagnoses and 15 with benign diagnoses. Of 13 AGC-NOS cases with positive diagnosis, 10 were ProExC-positive and 3 were ProExC-negative (metastatic tumors from distant sites). Of 15 AGC cases with benign follow-up, 13 were ProExC-negative and 2 were ProExC-positive (sensitivity, 77%; specificity, 87%). For patients with cervical intraepithelial neoplasia or carcinoma originating from the female genital tract, 100% (10/10) were ProExC-positive (sensitivity, 100%; specificity, 87%). Results suggest that ProExC-positive AGC-NOS may be classified as AGC-FN. Although positive immunocytochemical staining for ProExC requires management similar to AGC-FN, negative staining does not rule out malignancy such as metastatic tumor. Management for ProExC-negative AGC-NOS cases should proceed according to the current guidelines for AGC-NOS.

Atypical glandular cells in conventional cervical smears: incidence and follow-up.

BackgroundAtypical glandular cells on cervical smears are often associated with clinically significant uterine lesions. The frequency and accuracy of AGC-NOS (i.e. atypical glandular cells, not otherwise specified) diagnoses, regardless of the gland cell type or the degree of suspicion, and their outcome were investigated.MethodsFrom January 1, 1990 to December 31, 1999 a total of 261 patients had an AGC-NOS diagnosis made by conventional cervical Papanicolaou smear interpretation representing 0.05% of all Pap-smears analyzed at the national level. 191 (73.2%) patients had a subsequent histological examination, 8 samples were not representative by origin and were excluded.ResultsOut of 183 AGC-NOS diagnosed, 56.3% (103/183) were associated with tissue-proven precancerous and/or cancerous lesions, 44% being of endocervical and 56% of endometrial origin. 75% of all AGC-patients were asymptomatic. 66.7% (6/9) of the patients with subsequent invasive endocervical adenocarcinoma (AC) and 56% (28/50) of those patients with invasive endometrial AC were without clinical symptoms. 3 patients out of 9 with an invasive endocervical AC were 35 years of age or less. 10.1% and 12.3% of all 'new' tissue-proven invasive endocervical or endometrial AC respectively recorded by the national Morphologic Tumour Registry (MTR) were first identified by a cytological AGC-NOS diagnosis.ConclusionOur findings emphasize the importance of the cytological AGC-category even in the absence of a precise origin or cell type specification. 56% of the AGC-diagnoses being associated with significant cancerous or precancerous conditions, a complete and careful evaluation is required.

Prevalence and typing of HPV DNA by hybrid capture II in women with ASCUS, ASC-H, LSIL, and AGC on ThinPrep Pap tests.

Testing for human papillomavirus (HPV) DNA is now a viable option for the management of women with atypical squamous cells of undetermined significance (ASCUS). The utility of reflexive HPV DNA testing for women with a cytologic diagnosis of atypical glandular cells-not otherwise specified (AGC-NOS), ASCUS subtypes, and low-grade squamous intraepithelial lesion (LSIL) has not been well established. In the present investigation, reflex Hybrid Capture II HPV DNA testing results were evaluated for HPV prevalence and type in 371 women with abnormal cytologic diagnoses of ASCUS-not otherwise specified (ASCUS-NOS), ASCUS-suspicious for low-grade squamous intraepithelial lesion (ASCUS-L), atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H), AGC-NOS, and LSIL on ThinPrep Pap tests. Positive high-risk HPV DNA was identified in 53.6% of the study samples, including ASCUS-NOS 40.2% ASCUS-L 71.4%, ASC-H 37.5%, LSIL 88.6%, and AGC-NOS 0%. We conclude that reflex HPV DNA testing appears to not be useful for colposcopy triage for cytologic diagnoses of LSIL or AGC-NOS.