Following the publication of the revised Bethesda System terminology for reporting cervical cytology results and the revised guidelines for cervical cancer screening in 2001, the American Society for Colposcopy and Cervical Pathology (ASCCP) convened a consensus forum for the development of evidence-based guidelines for management of women with abnormal cervical cytology, cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS). The first management guidelines were published in 2002 with revisions published in 2007 and most recently in 2013 [1].

The following describes the management guidelines for cytology interpretations of glandular lesions identified in cervical cytology samples.

The interpretation of atypical glandular cells (AGC) on cervical cytology is not common and the cytologic criteria have been found to be poorly reproducible. The spectrum of underlying pathology leading to the interpretation of AGC can vary from benign reparative processes, metaplasia, endocervical polyps, and changes secondary to intrauterine devices to adenocarcinomas of the cervix, endometrium, fallopian tubes, ovaries, and more distant sites as detailed in earlier chapters of this monograph. The AGC interpretation can be qualified by “favor neoplasia” which is associated with a higher risk of serious pathology. Although the cytologic criteria for the recognition of AIS have been refined over the years, an interpretation of AIS is uncommonly made on cytology samples in comparison to the more common AGC categorization. The risk of neoplasia or preneoplasia following the interpretation of AGC has been reported to be 29 % [2]. The most common underlying pathology in patients with AGC cytology is squamous dysplasia including LSIL. Squamous dysplasia is found in association with AIS in about 50 % of women diagnosed with AIS. The risk of pathology is increased when concurrent ASC-US is present. The risk of CIN2+ is increased in younger women while the risk of underlying carcinoma is higher in older women [3]. Except for young women with a genetic predisposition, the risk of endometrial adenocarcinoma is especially high in older women. A large study from California found the risk of CIN3+ was 9 % following a cytologic interpretation of AGC and the risk of carcinoma was 3 % [4]. Although endocervical adenocarcinoma and AIS are associated with HPV in the majority of cases, adenocarcinoma or hyperplasia of the endometrium is not, so testing for HPV will not help triage women who need additional investigation. But a negative HPV test can suggest an endometrial origin rather than endocervical lesion [5]. Other potential cytologic clues of underlying endometrial disease are the presence of benign-appearing endometrial glandular cells or stromal cells in women over 40 years of age, especially those who have exited their reproductive years.

Management of all subcategories of AGC should always prompt colposcopy with endocervical sampling (Table 8.1). HPV testing is not recommended because colposcopy is advised regardless of HPV status; however, if an HPV test is obtained it can be used in the downstream management of the patient following the initial work-up. Likewise, repeat cervical cytology should not be considered as the primary follow-up of these diagnoses. In women aged 35 and older or in younger women with risk factors for endometrial adenocarcinoma, sampling of the endometrium should be performed along with colposcopy and sampling of the endocervical canal. Risk factors for endometrial adenocarcinoma in younger women include abnormal vaginal bleeding and chronic anovulation.

In the setting of atypical endometrial cells, sampling of the endometrium and endocervical canal should be performed but colposcopy may be deferred until the results of endometrial and endocervical samples are finalized. If no pathology is identified, colposcopy should then be performed, because of the possibility of endometrioid neoplastic lesions of the cervix as have been previously described.

In the setting of AGC—not otherwise specified, in which there is no evidence of CIN2+ identified on biopsy, the guidelines recommend follow-up co-testing with cytology and HPV at 12 and 24 months (Table 8.2). If the additional tests are negative, the patient should return for repeat co-testing in 3 years. If abnormal results are found on any of the tests, the patient should be evaluated with colposcopy.