Cervical Glandular and Endocervical Lesions

Glandular abnormalities of the cervix — atypical glandular cells (AGC) and endocervical adenocarcinoma in situ — are a distinct and diagnostically challenging category of cervical cytology. They are less common than squamous lesions, harder to interpret reliably, and carry a meaningful risk of underlying high-grade glandular or squamous disease, making their recognition important in cervical cytopathology.

Definition

Cervical glandular lesions are cytologic abnormalities of endocervical (or endometrial) glandular cells, ranging from atypical glandular cells of uncertain significance through endocervical adenocarcinoma in situ to invasive adenocarcinoma, reported within the glandular section of the Bethesda System.

Scope

This topic covers the cytologic recognition of glandular abnormalities, the Bethesda glandular categories (AGC and its subtypes, endocervical adenocarcinoma in situ, adenocarcinoma), their relationship to HPV-associated endocervical neoplasia, and the diagnostic difficulties that distinguish them from squamous lesions. It is a reference description of the cytologic entity, not individualised clinical management.

Core questions

• How are glandular abnormalities recognised and distinguished from squamous lesions on cytology?
• What do the Bethesda glandular categories (AGC, AIS) signify in terms of underlying risk?
• How does HPV relate to endocervical adenocarcinoma and its precursors?
• Why are glandular lesions less reproducibly detected by cytology and screening?

Key concepts

• Atypical glandular cells (AGC) and subclassification
• Endocervical adenocarcinoma in situ (AIS)
• Endocervical versus endometrial cell origin
• HPV-associated (usual-type) endocervical adenocarcinoma
• Crowded sheets, rosettes, and feathering as cytologic clues
• Lower reproducibility and detection of glandular disease
• Risk of concurrent squamous lesions with AGC

Mechanisms

Most usual-type endocervical adenocarcinomas and their precursor, adenocarcinoma in situ, are associated with high-risk HPV, paralleling the squamous pathway but arising in glandular epithelium of the endocervical canal. Cytologically, glandular neoplasia produces crowded three-dimensional cell groups with nuclear stratification, feathering, rosettes, and mitoses; these features overlap with benign reactive changes and are harder to sample and interpret than squamous lesions, which contributes to lower sensitivity for glandular disease (solomon-2002, schiffman-2007).

Clinical relevance

Because a glandular result such as AGC carries a substantial risk of underlying high-grade glandular or squamous disease and because the endocervical canal is less accessible to sampling, glandular abnormalities are an important diagnostic category in cervical cytopathology. This entry describes the entity and its interpretive challenges for reference; it does not specify evaluation, follow-up, or treatment for any individual.

Epidemiology

Glandular lesions are considerably less common than squamous lesions in cervical cytology, and cervical adenocarcinoma represents a minority of cervical cancers. Its relative proportion has tended to rise in settings where squamous disease has been reduced by screening, reflecting in part the lower sensitivity of cytology-based screening for glandular disease (schiffman-2007).

History

Glandular abnormalities were given a defined place in cervical reporting with the Bethesda System, which separated atypical glandular cells from squamous categories and, in its 2001 and 2014 revisions, refined the AGC subcategories and the recognition of endocervical adenocarcinoma in situ. The recognition that most endocervical adenocarcinomas are HPV-associated further integrated glandular disease into the HPV model of cervical neoplasia (solomon-2002, nayar-wilbur-2015).

Debates

Limited sensitivity of cytology for glandular disease

Cytology and even HPV testing detect endocervical glandular lesions less reliably than squamous lesions because of sampling difficulty and morphologic overlap with benign change, raising ongoing questions about how best to detect and manage glandular abnormalities within screening.

Key figures

• Diane Solomon
• Ritu Nayar
• David Wilbur
• Robert Kurman
• L. Stewart Massad

Seminal works

• solomon-2002
• nayar-wilbur-2015

Frequently asked questions

Why are glandular lesions considered harder to diagnose than squamous lesions?

Glandular abnormalities arise in the endocervical canal, which is less accessible to sampling, and their cytologic features overlap with benign reactive changes. As a result they are detected less reliably and are reported with more diagnostic caution than squamous lesions.

Is cervical adenocarcinoma also caused by HPV?

Most usual-type endocervical adenocarcinomas and their precursor, adenocarcinoma in situ, are associated with high-risk HPV, similar to squamous cervical cancer, although a minority of glandular cancers are HPV-independent and follow a different pathway.