—  SLIDE SEMINAR #16  —

Diagnostic Cytopathology: Something for Everyone
Moderator: Dr. Celeste N. Powers

Case 7 - LBC (ThinPrep) increased sensitivity in the detection of glandular lesions

Dr. Terrence Colgan


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.


Case 7 - Slide 1
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So, how was the case signed out?
  • Satisfactory for evaluation
    • TZ present


  • 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?
    • i.e. using its high NPV


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.