What does a diagnosis of atypical glandular cells with High-grade Squamous Intraepithelial Lesions (HSIL) mean?

Understanding Atypical Glandular Cells with HSIL

A diagnosis of atypical glandular cells (AGC) with High-grade Squamous Intraepithelial Lesions (HSIL) represents a significant finding that requires immediate colposcopy due to the high risk of underlying cervical neoplasia, including both squamous and glandular lesions. 1, 2

What This Diagnosis Means

• AGC represents abnormal glandular cells that cannot be classified as clearly benign or malignant, occurring in only 0.2% of cervical cytology samples 1
• HSIL represents high-grade squamous abnormalities that encompass moderate and severe dysplasia (CIN II and III) 1
• The combination of these findings indicates abnormalities in both the glandular and squamous cell components of the cervix 3

Clinical Significance and Risk Assessment

• AGC can indicate significant underlying pathology in up to 38% of cases, including both squamous and glandular lesions 1
• When HSIL is detected on Pap smear, the risk of histologic HSIL and cancer is approximately 69% 1
• The combination of AGC with HSIL significantly increases the risk of having cervical intraepithelial neoplasia (CIN) 2 or worse compared to AGC alone 3
• Studies show that AGC associated with HSIL has a strong correlation with squamous neoplasia on histological examination 3

Required Management

• Immediate colposcopy with endocervical sampling is mandatory 1, 2
• HPV DNA testing should be performed as part of the initial evaluation 1
• Endometrial sampling is recommended for women 35 years and older or younger women with risk factors for endometrial cancer 1
• Reflex HPV testing or repeat cytology alone is unacceptable as initial management 1

Management Algorithm

1. Initial evaluation:

   • Colposcopy with endocervical sampling 1
   • HPV DNA testing 1
   • Endometrial sampling for women ≥35 years or with risk factors 1

2. If colposcopy identifies CIN 2,3:

   • Proceed with appropriate treatment based on the grade of lesion 2

3. If initial evaluation is negative or unsatisfactory:

   • A diagnostic excisional procedure (LEEP or cold knife conization) may be required 1, 2
   • This is particularly important with AGC-favor neoplasia or AIS 1

4. Follow-up after negative initial evaluation:

   • If HPV positive: Repeat cytology and HPV testing in 6 months 1
   • If HPV negative: Repeat cytology and HPV testing in 12 months 1
   • If both tests negative on reevaluation: Return to annual cytologic testing 1

Important Considerations

• The presence of AGC with HSIL represents a higher risk category than either finding alone 3
• CIN is the most common pathology found in women with AGC, especially those younger than 35 years 1
• Studies show that 35% of patients with AGC may have underlying HSIL on histological examination 4
• The combination of AGC with HSIL is strongly associated with squamous neoplasia but not necessarily with adenocarcinoma 3

Pitfalls to Avoid

• Do not rely solely on HPV testing or repeat cytology for initial management 1
• Do not underestimate the significance of this finding - even with negative HPV testing, the risk of significant disease remains high 2
• Avoid delaying colposcopy and endocervical sampling, as this combination of findings indicates high risk for underlying significant pathology 1, 2
• Remember that colposcopy alone can miss a significant number of lesions, particularly glandular lesions, which may require excisional procedures for definitive diagnosis 2