Atypical glandular cells and the real significance in clinical practice: experience of a university hospital in the municipality of Niterói, RJ, Brazil

Authors

DOI:

https://doi.org/10.5327/DST-2177-8264-1479

Keywords:

Cervical cancer, cytology, screening, adenocarcinoma, HPV, colposcopy

Abstract

Introduction: Atypical glandular cells (AGC) are rare but clinically significant due to their association with cervical and endometrial lesions. Although human papillomavirus (HPV) is the main etiological agent of cervical lesions, not all AGC are HPV-related, particularly those of endometrial origin. Given the heterogeneity of associated findings, their characterization is essential to guide clinical management. Objective: To describe the distribution of AGC subcategories and evaluate subsequent diagnostic findings, comparing findings between AGC (not otherwise specified) NOS and AGC (favor neoplastic) FN in women evaluated at a Brazilian university hospital. Methods: This is an observational, retrospective, analytical study with a retrospective cohort design, based on the review of cytology reports with an AGC diagnosis and their subsequent diagnostic investigation. Associations between categorical variables were assessed using Fisher’s exact test, with a significance level of 5%. Results: Among 22,246 cytology samples, 161 showed AGC (0.72%). After exclusions, 126 cases were included: 85.7% AGC-NOS and 14.3% AGC-FN. Neoplasia at any site was identified in 22.2% of women and was more frequent in AGC-FN (55.6%) than in AGC-NOS (16.7%) (p=0.001). A statistically significant difference was observed in the distribution of cervical findings between groups (p=0.003), with a higher proportion of neoplastic lesions in AGC-FN. No significant difference was found for endometrial findings (p=0.400). Endocervical cytology was performed in 68 women, showing a significant association between the initial AGC classification and subsequent cytological findings (p=0.003), although 44.4% of AGC-FN cases had negative results. Conclusion: AGC represents a heterogeneous clinical entity, with a higher frequency of neoplastic findings in AGC-FN compared to AGC-NOS, particularly in the cervix. These findings reinforce the importance of a comprehensive diagnostic investigation, particularly in cases classified as AGC-FN. In settings without access to HPV molecular testing, clinical, colposcopic, and histopathological evaluation remains essential.

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References

Kumar N, Gupta R, Gupta S. Glandular cell abnormalities in cervical cytology: What has changed in this decade and what has not? Eur J Obstet Gynecol Reprod Biol. 2019;240:68-73. https://doi.org/10.1016/j.ejogrb.2019.06.006

Tao L, Zhou D, Luo M, Duan Z, Jia Y, Zheng A, et al. The relationship between atypical glandular cells and malignancy risk: a retrospective single-center study. Eur J Cancer Prev. 2025;35(1):21-8. https://doi.org/10.1097/cej.0000000000000969

Norman I, Yilmaz E, Hjerpe A, Hortlund M, Elfström KM, Dillner J. Atypical glandular cells and development of cervical cancer: Population‐based cohort study. Int J Cancer. 2022;151(11):2012-9. https://doi.org/10.1002/ijc.34242

Giannella L, Di Giuseppe J, Carpini GD, Grelloni C, Fichera M, Sartini G, et al. HPV-Negative Adenocarcinomas of the Uterine Cervix: From Molecular Characterization to Clinical Implications. Int J Mol Sci. 2022;23(23):15022. https://doi.org/10.3390/ijms232315022

Instituto Nacional de Câncer. Estimativa 2023: incidência de câncer no Brasil. Rio de Janeiro: Instituto Nacional de Câncer; 2023.

Nogueira-Rodrigues A, Ferreira CG, Bergmann A, De Aguiar SS, Thuler LCS. Comparison of adenocarcinoma (ACA) and squamous cell carcinoma (SCC) of the uterine cervix in a sub-optimally screened cohort: A population-based epidemiologic study of 51,842 women in Brazil. Gynecol Oncol. 2014;135(2):292-6. https://doi.org/10.1016/j.ygyno.2014.08.014

Da Silva BEB, De Lemos LMD, Moura AR, Ferrari YAC, Lima MS, Santos MDO, et al. Gynaecological cancer incidence and mortality trends in a Brazilian State with medium human development index: A 22-year analysis. Cancer Epidemiol. 2024;88:102493. https://doi.org/10.1016/j.canep.2023.102493

Instituto Nacional de Câncer. Diretrizes brasileiras para rastreamento do câncer do colo do útero. Rio de Janeiro: INCA; 2016.

World Health Organization. Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem. Geneva: World Health Organization; 2020.

Cartier R. Colposcopia Prática. São Paulo: Roca; 1994.

Prendiville W, Sankaranarayanan R. Colposcopy and treatment of cervical precancer. Lyon: International Agency for Research on Cancer, World Health Organization; 2017. (IARC technical publication; no. 45).

Brasil. Ministério da Saúde. Ministério da Saúde oferta tecnologia inovadora 100% nacional para detectar câncer do colo do útero no SUS [Internet]. Ministério da Saúde; 2025 [cited on 2025 sept. 4]. Available from: https://www.gov.br/saude/pt-br/assuntos/noticias/2025/agosto/ministerio-da-saude-oferta-tecnologia-inovadora-100-nacional-para-detectar-cancer-do-colo-do-utero-no-sus

Ministério da Saúde. Diretrizes Brasileiras para o Rastreamento do Câncer do Colo do Útero: Parte I - Rastreamento organizado utilizando testes moleculares para detecção de DNA-HPV oncogênico. Brasília: Ministério da Saúde; 2025. Relatório de Recomendação n.: 977.

Goetz LH, Evans HL, Armylagos D, Zhou H, Mody DR, Schwartz MR, et al. Atypical glandular cells in Pap tests: cytology-histology correlation and risk assessment with human papillopmavirus (HPV) testing. J Am Soc Cytopathol. 2024;13(3):227-32. https://doi.org/10.1016/j.jasc.2024.01.004

Sociedade Brasileira de Citopatologia. Atualização da Nomenclatura Brasileira para Laudos Citopatológicos do Colo Uterino e Áreas Ano-genitais [Internet]. Rio de Janeiro: SBC; 2020 [cited on 2025 Jul 15]. Available from: https://www.sbp.org.br/e-book-sociedade-brasileira-de-citopatologia-sbc/

Nayar R, Wilbur DC. The Bethesda System for Reporting Cervical Cytology: Definitions, Criteria, and Explanatory Notes. 3rd ed. Cham: Springer; 2015. 321 p.

Kim M-K, Lee YK, Hong SR, Lim KT. Clinicopathological significance of atypical glandular cells on cervicovaginal Pap smears. Diagn Cytopathol. 2017;45(10):867-72. https://doi.org/10.1002/dc.23777

Cianfrini F, d’Amati A, Arciuolo D, Travaglino A, D’Alessandris N, Scaglione G, et al. Atypical glandular cells and predictive features of malignancy in Pap smears: A retrospective monocentric study. Cytopathology. 2024;35(4):473-80. https://doi.org/10.1111/cyt.13383

Hassan D, Findley J, Braun A, Cheng L, Yan L. Cytology-histology correlation of atypical glandular cells on cervical Papanicolaou tests: A study of 628 cases. J Am Soc Cytopathol. 2024;13(5):377-85. https://doi.org/10.1016/j.jasc.2024.05.002

Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F, et al. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis. 2020;24(2):102-31. https://doi.org/10.1097/lgt.0000000000000525

Cancer Council Australia. National Cervical Screening Program Guidelines [Clinical Practice Guideline] [Internet]. Australian Government Department of Health and Aged Care; 2022 [cited on 2025 jun. 25]. p. 312. Available from: https://www.cancer.org.au/clinical-guidelines/cervical-cancer/cervical-cancer-screening

Almeida G, Sainz JE, Fonseca R, Chaves N, Silva KS, Nunes J, et al. Preventing Uterine Cervix Cancer: The Clinical Meaning of Atypical Glandular Cells. Rev Bras Ginecol Obstet. 2022;44(5):483-8. https://doi.org/10.1055/s-0042-1742318

Federação Brasileira das Associações de Ginecologia e Obstetrícia (FEBRASGO). Lesões glandulares do colo uterino. In: Manual de Orientação em Trato Genital Inferior e Colposcopia. São Paulo: FEBRASGO; 2010. p. 165-72.

Jones TE, Zeng X, Matsko J, Harinath L, Elishaev E, Bhargava R, et al. The clinical significance of atypical glandular cells in Papanicolaou tests: changes in diagnostic patterns over 15 years at a single institution. J Am Soc Cytopathol. 2025;14(6):434-43. https://doi.org/10.1016/j.jasc.2025.05.003

Willows K, Selk A, Auclair M-H, Jim B, Jumah N, Nation J, et al. Canadian Colposcopy Guideline: A Risk-Based Approach to Management and Surveillance of Cervical Dysplasia. Curr Oncol. 2023;30(6):5738-68. https://doi.org/10.3390/curroncol30060431

Kawano K, Yamaguchi T, Nasu H, Nishio S, Ushijima K. Subcategorization of atypical glandular cells is useful to identify lesion site. Diagn Cytopathol. 2020;48(12):1224-9. https://doi.org/10.1002/dc.24549

Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344-9. https://doi.org/10.1016/j.jclinepi.2007.11.008

Pirog EC. Cervical Adenocarcinoma: Diagnosis of Human Papillomavirus–Positive and Human Papillomavirus–Negative Tumors. Arch Pathol Lab Med. 2017;141(12):1653-67. https://doi.org/10.5858/arpa.2016-0356-ra

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2026-08-04

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1.
Duvivier KM, Moraes JR de, Fialho SCAV, Martins CA de O, Giordano CBP, Campos BM da S, et al. Atypical glandular cells and the real significance in clinical practice: experience of a university hospital in the municipality of Niterói, RJ, Brazil. DST [Internet]. 2026 Aug. 4 [cited 2026 Aug. 4];38. Available from: https://bdst.emnuvens.com.br/revista/article/view/1479

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