Moderator: Dr. Celeste N. Powers
LBC (ThinPrep) increased sensitivity in the detection of glandular lesions

Dr. Terrence Colgan
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Clinical History
Pap test. A 44-year old woman was referred for colposcopy and management of an abnormal Pap smear.
The patient subsequently underwent a loop electro-excisional procedure (LEEP). Four months later she
returned for a follow-up visit and this ThinPrep was taken.

 Slide 1
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So, how was the case signed out?
- Satisfactory for evaluation

- Atypical glandular cells of undetermined significance not otherwise specified.

LBC (ThinPrep) increased sensitivity in the detection of glandular lesions
- "The ThinPrep Pap test was more sensitive in
detecting endometrial adenocarcinomas (65.2% vs. 38.6%; P=0.01), and there was a trend for a higher
sensitivity in detecting cervical adenocarcinomas (87.1% vs. 55.5%; P=0.108)
- Schorge et al. Cancer (Cytopath) 2002; 96: 338
– 43.

- "The predictive value of AGUS for a positive follow-up result was
22% in the TP group and 15% in the CP group."… i.e ↑'d specificity
- Hecht et al. Cancer (Cytopath) 2002; 96: 1 –

LBC (ThinPrep) increased sensitivity in the detection of glandular lesions
Sept. 2005, US/FDA accepted PMA Supplement
- Improved ability of ThinPrep to detect
glandular disease as compared to the conventional smear

- More frequent biopsy
confirmation of abnormal glandular findings

- Therefore, glandular abnormalities
on a ThinPrep merits increased attention

ASCCP 2001 AGC Management Guidelines*
For all AGC, except atypical endometrial cells:
- Colposcopy with endocervical sampling,

- And endometrial sampling if the woman is > 35 years or abnormal bleeding.
- re-affirmed in Apr'06 ASCCP posting

HPV testing: a role in the management of AGC? [1]
- HPV testing has a high sensitivity for both
AIS and CIN, with

- A Positive Predictive Value (PPV) of 40 - 61%, probably
better than repeat cytology

- Could avoid colposcopic referral
BUT….

HPV testing: a role in the management of AGC? [2]
- The risk of HSIL & Cancer is much higher
in AGC than ASC

- Women with AIS (&AGC favour neoplasia?) on cyto' should
proceed to colposcopy regardless

- In the > 35 year old, endometrial sampling
for non-HPV related disease is recommended

- Some adenoca are not HPV related

- Rare adenoca's have L1/L2 deletion & are not detected by current assays

Does HPV Testing have a role in the management of AGC? [3]
- Is the role of HPV testing as an adjunctive
test only?

- For example as an exit criterion after colposcopy and endocervical
sampling +/- endometrial sampling?

Case presented with a SIL lesion: unusual?

Index Pap test history & presenting symptoms of biopsy proven AIS patients (n=100)
- Symptoms (known in 87 cases)
- None in 82%

- Bleeding,
discharge, other in 18%

- Index Pap Test (known in 83 cases)
- AGC or AIS in 54%

- HSIL
in 64%

- Both AGC and HSIL in 17%

- Hwang et al. J
Lower Genital Tr Dis 2004; 8: 125 – 31.

Take home message – Case 7
- AGC remains an important cytodiagnosis

- LBC (ThinPrep) is more sensitive in the detection of glandular abnormalities than
conventional smears

- The index Pap test for biopsy proven AIS is frequently
SIL

- The management of women with AGC on Pap test continues to evolve BUT for all
AGC, except atypical endometrial cells - colposcopy with endocervical sampling

References:
- Cox JT. The Clinician's View – Role of HPV testing in the ASCCP Guidelines for the management of abnormal cervical cytology and cervical cancer precursors. Arch Pathol Lab Med 2003; 127: 950 – 958.

- Hecht JL, Sheets EE, Lee KR. Atypical glandular cells of undetermined significance in conventional cervical/vaginal smears and Thin-layer preparations. Cancer (Cytopathol) 2002; 96: 1 – 4.

- Hwang D, Lickrish GM, Chapman W, Colgan TJ. Long-term surveillance is required for all women treated for cervical adenocarcinoma-in-situ. J Lower Genital Tr Dis 2004; 8: 125 – 31.

- Irwin W, Evans S, Anderson W et al. The utility of HPV DNA triage in the management of cytological AGC. Am J Obstet Gynecol 2005; 193: 559 – 65.

- 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 – 92.

- Pirog EC, Kleter B, Olgac S et al. Prevalence of HPV DNA in different histological subtypes of cervical adenocarcinoma. Am J Pathol 2000; 157: 1055 – 62.

- Saqi A, Gupta PK, Erroll M et al. High-risk HPV DNA testing: a marker for atypical glandular cells. Diagn Cytopathol 2006; 34: 235 – 9.

- Schorge JO, Saboorian MH, Hynan L, Ashfaq R. ThinPrep detection of cervical and endometrial adenocarcinoma. Cancer (Cytopathol) 2002; 96: 338 – 343.

- Wright TC, Cox JT, Massad LS, et al. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA 2002; 287: 2120 – 9.
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