Cervical cytology: Evaluation of atypical and malignant glandular cells
- Annekathryn Goodman, MD
Annekathryn Goodman, MD
- Obstetrics, Gynecology, Reproductive Biology
- Harvard Medical School
- Division of Gynecologic Oncology
- Massachusetts General Hospital
- MGH Global Disaster Response
- Warner K Huh, MD
Warner K Huh, MD
- Margaret Cameron Spain Chair in Obstetrics/Gynecology
- Professor, Division of Gynecologic Oncology
- Senior Scientist, UAB Comprehensive Cancer Center
Cervical cytology became the standard screening test for cervical cancer and premalignant cervical lesions with the introduction of the Papanicolaou (Pap) smear in 1941 . Liquid-based, thin layer preparation (eg, ThinPrep, SurePath) of cervical cytology specimens was a subsequent modification in technique.
Atypical glandular cells on cervical cytology usually originate from the glandular epithelium of the endocervix or endometrium. Atypical glandular cells are found less commonly than abnormal squamous cells. Women with atypical glandular cells require further evaluation for premalignant conditions of the cervix, uterus, and rarely, ovary.
Evaluation of women with cervical cytology with atypical or malignant glandular cells is reviewed here. Cervical cancer screening strategies and techniques, interpretation of cervical cytology results, follow-up of other abnormal cytology results, and management of cervical neoplasia are discussed separately. (See "Screening for cervical cancer" and "Cervical cancer screening tests: Techniques for cervical cytology and human papillomavirus testing" and "Cervical and vaginal cytology: Interpretation of results (Pap test report)" and "Cervical cytology: Evaluation of atypical squamous cells (ASC-US and ASC-H)" and "Cervical cytology: Evaluation of low-grade squamous intraepithelial lesions (LSIL)" and "Cervical cytology: Evaluation of high-grade squamous intraepithelial lesions (HSIL)" and "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions".)
Terminology for reporting cervical cytology was standardized by the Bethesda System in 1988 . This system has been revised several times and the current system was developed in 2001 (table 1) [3,4]. The terminology used to classify atypical glandular cells is:
●Atypical glandular cells (AGC) – Endocervical, endometrial, or not otherwise specified (NOS) is noted as a subcategory. This replaces the previous term "atypical glandular cells of undetermined significance (AGUS)." This term should not be confused with terminology for squamous cell abnormalities, which includes atypical squamous cells of undetermined significance (ASC-US). (See "Cervical and vaginal cytology: Interpretation of results (Pap test report)", section on 'Intraepithelial cell abnormalities'.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Papanicolaou GN, Traut HF. The diagnostic value of vaginal smears in carcinoma of the uterus. Am J Obstet Gynecol 1941; 42:193.
- The 1988 Bethesda System for reporting cervical/vaginal cytological diagnoses. National Cancer Institute Workshop. JAMA 1989; 262:931.
- Broder S. From the National Institutes of Health. JAMA 1992; 267:1892.
- Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 2002; 287:2114.
- Marques JP, Costa LB, Pinto AP, et al. Atypical glandular cells and cervical cancer: systematic review. Rev Assoc Med Bras (1992) 2011; 57:234.
- Insinga RP, Glass AG, Rush BB. Diagnoses and outcomes in cervical cancer screening: a population-based study. Am J Obstet Gynecol 2004; 191:105.
- Sharpless KE, Schnatz PF, Mandavilli S, et al. Dysplasia associated with atypical glandular cells on cervical cytology. Obstet Gynecol 2005; 105:494.
- Veljovich DS, Stoler MH, Andersen WA, et al. Atypical glandular cells of undetermined significance: a five-year retrospective histopathologic study. Am J Obstet Gynecol 1998; 179:382.
- Geier CS, Wilson M, Creasman W. Clinical evaluation of atypical glandular cells of undetermined significance. Am J Obstet Gynecol 2001; 184:64.
- Eddy GL, Strumpf KB, Wojtowycz MA, et al. Biopsy findings in five hundred thirty-one patients with atypical glandular cells of uncertain significance as defined by the Bethesda system. Am J Obstet Gynecol 1997; 177:1188.
- Chhieng DC, Elgert P, Cohen JM, Cangiarella JF. Clinical significance of atypical glandular cells of undetermined significance in postmenopausal women. Cancer 2001; 93:1.
- DeSimone CP, Day ME, Tovar MM, et al. Rate of pathology from atypical glandular cell Pap tests classified by the Bethesda 2001 nomenclature. Obstet Gynecol 2006; 107:1285.
- Tam KF, Cheung AN, Liu KL, et al. A retrospective review on atypical glandular cells of undetermined significance (AGUS) using the Bethesda 2001 classification. Gynecol Oncol 2003; 91:603.
- Zhao C, Florea A, Onisko A, Austin RM. Histologic follow-up results in 662 patients with Pap test findings of atypical glandular cells: results from a large academic womens hospital laboratory employing sensitive screening methods. Gynecol Oncol 2009; 114:383.
- Scheiden R, Wagener C, Knolle U, et al. Atypical glandular cells in conventional cervical smears: incidence and follow-up. BMC Cancer 2004; 4:37.
- Hammoud MM, Haefner HK, Michael CW, Ansbacher R. Atypical glandular cells of undetermined significance. Histologic findings and proposed management. J Reprod Med 2002; 47:266.
- Schnatz PF, Guile M, O'Sullivan DM, Sorosky JI. Clinical significance of atypical glandular cells on cervical cytology. Obstet Gynecol 2006; 107:701.
- Wang J, Andrae B, Sundström K, et al. Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study. BMJ 2016; 352:i276.
- Ruba S, Schoolland M, Allpress S, Sterrett G. Adenocarcinoma in situ of the uterine cervix: screening and diagnostic errors in Papanicolaou smears. Cancer 2004; 102:280.
- Kim TJ, Kim HS, Park CT, et al. Clinical evaluation of follow-up methods and results of atypical glandular cells of undetermined significance (AGUS) detected on cervicovaginal Pap smears. Gynecol Oncol 1999; 73:292.
- Zhao C, Florea A, Austin RM. Clinical utility of adjunctive high-risk human papillomavirus DNA testing in women with Papanicolaou test findings of atypical glandular cells. Arch Pathol Lab Med 2010; 134:103.
- Cheng RF, Hernandez E, Anderson LL, et al. Clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance. J Reprod Med 1999; 44:922.
- Schnatz PF, Pattison K, O'Sullivan DM. The association of breast disease and atypical glandular cells on cervical cytology. Menopause 2011; 18:67.
- Cheng WF, Chen YL, You SL, et al. Risk of gynaecological malignancies in cytologically atypical glandular cells: follow-up study of a nationwide screening population. BJOG 2011; 118:34.
- Saad RS, Takei H, Liu YL, et al. Clinical significance of a cytologic diagnosis of atypical glandular cells, favor endometrial origin, in Pap smears. Acta Cytol 2006; 50:48.
- Zhao C, Austin RM, Pan J, et al. Clinical significance of atypical glandular cells in conventional pap smears in a large, high-risk U.S. west coast minority population. Acta Cytol 2009; 53:153.
- Wright TC Jr, Cox JT, Massad LS, et al. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA 2002; 287:2120.
- Derchain SF, Rabelo-Santos SH, Sarian LO, et al. Human papillomavirus DNA detection and histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in their Pap smears. Gynecol Oncol 2004; 95:618.
- Castle PE, Fetterman B, Poitras N, et al. Relationship of atypical glandular cell cytology, age, and human papillomavirus detection to cervical and endometrial cancer risks. Obstet Gynecol 2010; 115:243.
- Irvin W, Evans SR, Andersen W, et al. The utility of HPV DNA triage in the management of cytological AGC. Am J Obstet Gynecol 2005; 193:559.
- Zeferino LC, Rabelo-Santos SH, Villa LL, et al. Value of HPV-DNA test in women with cytological diagnosis of atypical glandular cells (AGC). Eur J Obstet Gynecol Reprod Biol 2011; 159:160.
- Koonings PP, Price JH. Evaluation of atypical glandular cells of undetermined significance: is age important? Am J Obstet Gynecol 2001; 184:1457.
- Tam KF, Cheung AN, Szeto E, Ngan HY. Atypical glandular cells diagnosed during pregnancy and the postpartum period: a retrospective analysis. Eur J Obstet Gynecol Reprod Biol 2011; 155:213.
- Chhieng DC, Elgert P, Cangiarella JF, Cohen JM. Significance of AGUS Pap smears in pregnant and postpartum women. Acta Cytol 2001; 45:294.
- Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2013; 17:S1.
- Krane JF, Lee KR, Sun D, et al. Atypical glandular cells of undetermined significance. Outcome predictions based on human papillomavirus testing. Am J Clin Pathol 2004; 121:87.
- http://www.asccp.org/ (Accessed on March 22, 2012).
- RISK OF PREMALIGNANT OR MALIGNANT DISEASE
- Histology and site of lesion
- Modifying factors
- - AGC subcategory
- - Coexisting squamous cytologic abnormality
- - Human papillomavirus infection
- - Age
- - Other factors
- INITIAL EVALUATION
- All AGC categories (except endometrial)
- NEGATIVE OR LOW-GRADE FINDINGS ON INITIAL EVALUATION
- AGC-NOS or endocervical
- - Persistent abnormal cytology
- AGC favor neoplasia, AIS, adenocarcinoma
- EVALUATION FOR OVARIAN CANCER OR OTHER MALIGNANCIES
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS