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.

Cervical cytology profile by Papanicolaou smear in a rural setting in mid-Kerala

Background: With no systematic national screening programme, the rates of cervical epithelial cell abnormalities as reported by various studies range from 1.32% to 25% in India. Majority are epithelial squamous cell abnormalities that include atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL). Worldwide incidence of adenocarcinoma and its precursors have increased over past few decades. Objectives were to study the clinical and cervical cytological profile among women attending camps in rural areas of Thrissur district of Kerala.Methods: A cross sectional study was conducted in 214 women in the 25-65 years age group who attended cancer screening camps in rural areas of Thrissur district. Papanicolaou (Pap) smear was done using standard technique and reported using latest Bethesda classification. Pap smear results were considered as abnormal when the report was ASCUS, atypical glandular cells of undetermined significance, LSIL, high grade squamous intraepithelial lesion or invasive lesion.Results: Of all the smears, 41.6% were negative for intraepithelial lesion or malignancy. Inflammatory smears (nonspecific and specific infection associated) were seen in 57%. Glandular cell abnormality was found in 1.4% and these women were in 31-50 years age group. Among patients with glandular cell abnormality most common symptom was discharge per vaginum.Conclusions: The results of this study may be a pointer to an increase in glandular cytological abnormalities in our population and needs further large-scale studies to confirm. Current screening methods of Pap smear alone may not be adequate to pick up these lesions.

Adenocarcinoma cervical in situ: abordagem na atenção primária e secundária à saúde / Cervical adenocarcinoma in situ: approach in primary and secondary health care

O adenocarcinoma cervical in situ é uma doença rara, totalmente curável, diagnosticada predominantemente por meio de rastreamento cervicouterino seguido de biópsia guiada por colposcopia e/ou conização. O tratamento em pacientes que desejam preservar a fertilidade pode ser realizado num contexto ambulatorial; aquelas com paridade definida deverão ser abordadas em nível terciário.(AU)

Cervical adenocarcinoma in situ is a rare, fully curable disease diagnosed predominantly through cervical-uterine screening followed by colposcopy-guided biopsy and/or conization. Treatment in patients wishing to preserve fertility may be performed in an outpatient setting; those with defined parity should be approached at the tertiary level.(AU)

Adenocarcinoma cervical: diagnóstico na atenção primária e secundária à saúde / Cervical adenocarcinoma: diagnosis in primary and secondary health care

O adenocarcinoma cervical é uma patologia grave cuja incidência tem aumentado, principalmente em pacientes jovens. Um diagnóstico oportuno, na assistência primária e secundária à saúde, com métodos convencionais, melhora sobremaneira o prognóstico da paciente, a um custo tolerável para países em desenvolvimento.(AU)

The cervical adenocarcinoma is a serious pathology whose incident has increased mainly in young patients. One opportunistic diagnosis, in primary and secondary health care, with conventional methods, greatly improves the prognosis of the patients, at a cost tolerable to developing countries.(AU)

Application and clinical significance of human papilloma virus E6/E7 mRNA detection in cervical atypical glandular cells / 中国医师进修杂志

Objective To investigate the application and clinical significance of human papilloma virus (HPV) E6/E7 mRNA detection in cervical atypical glandular cells (AGC). Methods Four hundred and forty-five cervical AGC patients diagnosed by thin-layer liquid-based cytology in the Maternity Affiliated Hospital of Dalian Medical University from January 2014 to March 2018 were collected. Histological follow-up data and HPV E6/E7 mRNA detection results were analyzed, and histological differences in HPV E6/E7 mRNA positive and negative patients were compared. Results The histological result of 445 patients with cervical AGC showed that negative was in 306 cases (68.76%), and clinical significant lesion was in 129 cases (28.99%). In 445 patients with cervical AGC, HPV E6/E7 mRNA result was positive in 121 cases (27.19%), among whom the positive rate of HPV 16 and 18/45 type was 54.55% (66/121); HPV E6/E7 mRNA result was negative in 324 cases (72.81% ), including 13 non-cervical lesions. The negative rate of histological results in HPV E6/E7 mRNA negative patients was significantly higher than that in HPV E6/E7 mRNA positive patients: 91.05% (295/324) vs. 9.09% (11/121), and there was statistical difference (P＜0.01); the rates of adenocarcinoma in situ (AIS), high-grade squamous intraepithelial lesion (HSIL) and cervical adenocarcinoma of histological result in HPV E6/E7 mRNA positive patients were significantly higher than those in HPV E6/E7 mRNA negative patients: 40.50% (49/121) vs. 1.23% (4/324), 44.63% (54/121) vs. 1.23% (4/324), 3.31% (4/121) vs. 0.31% (1/324), and there were statistical differences (P＜0.01). The sensitivity of HPV E6/E7 mRNA in detecting clinical significant lesion of cervical AGC patients was 82.95% (107/129), the specificity was 95.57% (302/316), positive predictive value was 88.43% (107/121), and negative predictive value was 93.21% (302/324). Conclusions The histological result of cervical AGC shows that the amount of negative patients is significantly higher than clinical significant lesion. For cervical AGC patients with HPV E6/E7 mRNA negative results, conservative follow-up can be adopted after excluding extracervical lesions and fully assessing the risk of cervical lesions. However, the cervical AGC patients with HPV E6/E7 mRNA positive results need further examination to detect lesion and choose treatment earlier.

Importância clínica e correlação histológica das células glandulares atípicas detectadas no exame colpocitológico / Clinical implications and histological correlation of atypical glandular cells found in cervicovaginal smears

Introduction: Atypical glandular cells (AGC) are carriers of insufficient nuclear abnormalities for the diagnosis of adenocarcinoma, but exceed the criteria for classification as reactive glandular cells. This is an uncommon diagnosis, which may be associated with neoplastic lesions. Objective: To evaluate the clinical significance of primary cytological diagnosis of AGC through correlation with results of subsequent cyto-histologic examination. Materials and methods: 10 years retrospective study based on cervical cytologic results indicating AGC, classified as "possibly non-neoplastic" or "cannot exclude high-grade intraepithelial lesion". It was performed cyto-histopathological correlation in cases that were submitted to subsequent histopathological examination up to two years after cervical cytology analysis. Results: AGC were reported in 380 (0.06%) exams, providing 160 cases with subsequent biopsy. 85 (53.1%) of these, presented benign changes and 75 (46.9%) neoplastic lesions. From 114 "possibly non-neoplastic" cytological results, 71 (62.3%) had benign histological changes, and 43 (37.7%) neoplastic lesions, corresponding to a negative predictive value (NPV) of 62.3%. In contrast, among the 46 AGC "cannot exclude high-grade intraepithelial lesion" results, 14 (30.4%) presented benign changes and 32 (69.6%) neoplastic lesions (positive predictive value [PPV] = 69.6%). Discussion: The high rate of cancer associated with the diagnosis of AGC reassures the importance of recognizing these atypical cells in pap smears. The classification of "possibly non-neoplastic" and "cannot exclude high-grade intraepithelial lesion" may suggest the origin of cytological changes. Conclusion: Our results reinforce the importance of adequate follow-up of patients with AGC diagnosis on cervical cytology...

Introdução: Células glandulares atípicas (CGA) são portadoras de alterações nucleares insuficientes para o diagnóstico de adenocarcinoma, mas excedem os critérios para classificação como células glandulares reacionais. Trata-se de um diagnóstico incomum, porém pode relacionar-se com lesões neoplásicas. Objetivo: Avaliar o significado clínico do diagnóstico citológico primário indicando CGA por meio da correlação com os resultados de exames histológicos subsequentes. Materiais e métodos: Estudo retrospectivo de 10 anos com base em resultados colpocitológicos indicando CGA, classificados como "possivelmente não neoplásicas" ou "não se pode afastar lesão intraepitelial de alto grau". Realizou-se a correlação cito-histopatológica nos casos que foram submetidos ao exame histopatológico até dois anos após a análise colpocitológica. Resultados: CGA foram relatadas em 380 (0,06%) exames, dispondo-se de 160 casos com biópsia subsequente. Destes, 85 (53,1%) apresentavam alterações benignas e 75 (46,9%), lesões neoplásicas. Dos 114 resultados citológicos "possivelmente não neoplásicas", 71 (62,3%) apresentavam alterações histológicas benignas e 43 (37,7%), neoplásicas, correspondendo a um valor preditivo negativo (VPN) equivalente a 62,3%. Contrariamente, entre os 46 resultados de CGA "não se pode afastar lesão intraepitelial de alto grau", 14 (30,4%) apresentavam alterações benignas e 32 (69,6%), neoplásicas (valor preditivo positivo [VPP] = 69,6%). Discussão: As altas taxas de neoplasias associadas ao diagnóstico de CGA reafirmam a importância do reconhecimento dessas atipias. A classificação em "possivelmente não neoplásicas" e "não se pode afastar lesão intrapitelial de alto grau" pode sugerir a origem das alterações citológicas. Conclusão: nossos resultados reforçam a importância do segmento das pacientes com diagnóstico de CGA no exame colpocitológico...

Practice guidelines for the early detection of cervical cancer in Korea: Korean Society of Gynecologic Oncology and the Korean Society for Cytopathology 2012 edition / 부인종양

The consensus guideline development committee of Korean Society of Gynecologic Oncology was reconvened in March 2012. The committee consisted of 36 experts representing 12 university hospitals and professional organizations. The objective of this committee was to develop standardized guidelines for cervical cancer screening tests for Korean women and to distribute these guidelines to every clinician, eventually improving the quality of medical care. Since the establishment of the consensus guideline development committee, evidence-based guidelines have either been developed de novo considering specific Korean situations or by adaptation of preexisting consensus guidelines from other countries. Recommendations for cervical cancer screening tests, management of atypical squamous and glandular cells, and management of low-grade and high-grade squamous intraepithelial lesions were developed. Additionally, recommendations for human papillomavirus DNA testing and recommendations for adolescent and pregnant women with abnormal cervical screening test results were also included.

Histologic Correlation of Atypical Glandular Cells in Cervical Smears

BACKGROUND: The study evaluated the histologic correlation and clinical significance of atypical glandular cells (AGC) detected either on conventional smears (CS) or liquid-based cytology (LBC). METHODS: Two hundred and seventy-seven (0.11%) of 261,925 cervical smears were interpreted as AGC by the Bethesda system 2001 from January 2006 to December 2008. Cytohistological correlation was performed on 192 cases. RESULTS: The prevalence of AGC was 0.07% and 0.13% for CS and LBC smears, respectively. Distribution of AGC subcategories were as follows: atypical endometrial cells 53.8%, atypical endocervical cells 22.7%, atypical glandular cells 19.5%, atypical endocervical cells favoring neoplasia 2.2%, and atypical glandular cells favoring neoplasia 1.8%. Fifty-nine (27.4%) of 192 patients were confirmed as having clinically significant lesions comprising endometrial adenocarcinoma (12.5%), endometrial hyperplasia (6.0%), cervical adenocarcinoma (2.3%), high-grade squamous intraepithelial lesion (HSIL) (1.9%), low-grade SIL (1.9%), adenocarcinoma in situ (1.4%), or ovarian metastasis (1.4%). Conclusion: Compared with CS, LBC was presently associated with a higher prevalence of AGC. Histologic follow-up showed a very low HSIL rate compared to other studies. Endometrial adenocarcinoma was the most common malignant lesion detected because of increasing prevalence of endometrial adenocarcinoma, concentration on endometrial cytology, and introduction of LBC.

Diagnostic role of HPV DNA chip test in patient with atypical glandular cell cytology / 대한산부인과학회지

OBJECTIVE: This study was aimed to identify the diagnostic role of HPV DNA chip test that may predict high grade lesions in gladular cell abnormalities on cervical cytology. METHODS: This study was performed in 88 patients, who were reported for atypical glandular cells on liquid-based cytologic test and was done subsequent cervical biopsies in Chonnam National University Hospital, between January 2003 and June 2007. HPV DNA chip test was performed on residual material of previous liquid-based cytologic test. And it was compared with pathologic results. RESULTS: Of the 88 patients with atypical glandular cells, the distribution was as follows: 60 patients were reported as atypical glandular cells, not otherwise specified (AGC, NOS), 28 patients were reported as atypical glandular cells, favor neoplastics (AGC, favor neoplastics). Of the 88 patients with an AGC result, pathologic results were as follows: 47 patients (53.4%) had a clinically significant high grade lesions. Of this high grade lesions, 5 cases of high grade squamous intraepithelial lesion, CIN 2 & CIN 3 (83.4%, 5/6), 2 cases of SCC (66.7%, 2/3), 4 cases of AIS (80.0%, 4/5), and 11 cases of endocervical adenocarcinoma (69%, 11/16) were positive on HPV DNA chip test. The sensitivity of human papilloma virus positivity to predict the presence of high grade lesion in cervix was 73.3%, specificity 85.3%, positive predictive value 78.5%, and negative predictive value 81.3%. There were 16 patients with endometrial cancer. Only 3 patients were HPV DNA chip positive. CONCLUSION: HPV DNA detection was strongly associated with high grade lesions in women with atypical glandular cells on cervical pap smear. These results suggest that although there is no high grade lesion in patients with HPV positive AGC-NOS at initial work-up, meticulous search like cone biopsy should be done to find high grade lesion. If the women with a diagnosis of AGC on pap smear are over 35 years of age and has abnormal utero-vaginal bleeding, this patients needed to be evaluated with endometrial biopsy.

Risk factors of High Grade Lesions in Glandular Cell Abnormalities on Cervical Cytology / 대한산부인과학회지

OBJECTIVE: To identify the risk factors that may predict high grade lesions in glandular cell abnormalities on cervical cytology. METHODS: This study was performed from January 2002 to December 2005 and included 87 cases of glandular cell abnormalities on Pap smear. Among them, 65 (74.7%) cases were atypical glandular cells (AGC) and 22 (25.3%) cases were AGC, favor neoplastic. The histologic diagnoses were classified as low grade lesions [normal, cervical intraepithelial neoplasia (CIN) I, and simple hyperplasia without atypia] and high grade lesions [CIN II/III, adenocarcinoma in situ (AIS), and invasive cancer]. RESULTS: Fifty-three (60.9%) cases had negative biopsies or cervicitis. Twenty-five cases had cervical lesions including one CIN I, ten CIN II/III, two AIS, twelve invasive cancers. There were 7 endometrial lesions: 5 adenocarcinomas and 2 malignant mixed mullerian tumors. Two patients had one tubal cancer and one CIN II with simple hyperplasia without atypia. High-risk human papillomavirus (HPV) positive and AGC, favor neoplastic cases were significantly associated with high grade lesions (OR 15.4, CI 2.2-109.7; OR 7.0, CI 1.1-42.8). In the cervix, only high-risk HPV positive were significantly associated with high grade lesions (OR 64.6, CI 4.5-930.8). In the endometrium, age, menopausal status, and cytologic classification were significantly associated with low grade lesions or high grade lesions (p<0.05). CONCLUSION: High-risk HPV DNA detection was strongly associated with high grade lesions in women with glandular cell abnormalites on their Pap smear. These results suggest that HPV testing may be useful as a triage of the management in women with glandular cell abnormalities.

Cytologic and histologic correlation of atypical glandular cells of undetermined significance

To determine the cytologic and histologic correlation of atypical glandular cells of undetermined significance (AGUS) in Papanicolaou smears, a cytology file from January 1998 to May 1999 was reviewed. Surgical pathology files were searched to determine which patients received subsequent biopsies. One hundred thirty-two patients with AGUS were identified. Corresponding biopsies were available for 82 of these cases. AGUS has been sub-classified into 3 subtypes: 1) AGUS, favor reactive; 2) AGUS, not otherwise specified; and 3) AGUS, favor neoplasia. The pathologic findings for the respective Papanicolaou smears with the diagnosis of each subtype of AGUS through the follow-up period were as follows: benign lesions in 56.1%, 0%, and 1.2%; squamous intraepithelial lesions 2.4%, 0%, and 1.2%; glandular intraepithelial lesions 0%, 0%, and 17.1%; endometrial simple hyperplasia 1.2%, 0%, and 0%; and carcinoma 0%, 9.8%, and 11%, respectively. In conclusion, AGUS, on cervical cytologic screening, was correlated with significant pathologic findings in 41.5% of the patients (37.8% with preinvasive or invasive glandular lesions and 9.6% with combined squamous intraepithelial lesions). It is thought that intensive follow-up studies, including colposcopy, cervical biopsy, and curettage, should be recommended for complete evaluation of AGUS.

Atypical Glandular Cells of Undetermind Significances (AGUS) ; Histopathologic Results and the Significance of the HPV DNA Detection / 대한산부인과학회잡지

OBJECTIVES: AGUS often reflects an immediate cervical cancer precursor such as a HSIL mimicking an endocervical glandular lesion. In this study, we attempted to assess the clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance (AGUS) and determine the usefulness of the human papillomavirus (HPV) DNA testing as the triage strategies in evaluating AGUS. METHODS: Between 1994 and 1998, 67,730 Papanicolaou smears were evaluated at Kangnam and Uijongbu St Mary's Hospital. There were 87 (0.13%) cases of AGUS smears during that time. Colposcopy was performed on all women, and HPV DNA testing was performed on 11 persons. RESULTS: Mean age of these patients was 45.8 years. Histologic diagnosis of AGUS were kolocytosis and CIN-I in 6 (6.9%), CIS in one, endometrial hyperplasia in 2 (2.3%), endometrial adenocarcinoma in 7 (8.0%), cervical adenocarcinoma in 14 (16.1%) and cervical squamous cell carcinoma in 2 (2.3%) cases. Endometriosis was 8.9% under 46 years old and none in over 46. CIN was 8.9% and 7.2%, respectively. Cervical adenocarcinoma was 6.7% under 46 and 19.1% over 46. Endometrial cancer was 4.4% and 11.9%, respectively. The risk of cervical cancer and endometrial cancer was high in the AGUS with