Squamocolumnar Junction-Specific Markers Define Biologically and Clinically Distinct Subsets of Low-Grade Cervical Intraepithelial Neoplasia
Michael Herfs, Brooke Howitt, Carlos Parra Herran, Marisa R Nucci, Sarah Feldman, Frank D Mckeon, Wa Xian, Christopher P Crum. Brigham and Women's Hospital, Boston, MA; University of Liege, Liege, Belgium; A-STAR, Singapore, Singapore
Background: A fundamental dilemma in the management of early cervical neoplasia is the pathologic distinction of low (LSIL) from high (HSIL) grade squamous intraepithelial lesions. In a recent report, a putative cell of origin in the squamocolumnar (SC) junction was identified; SC junction-specific biomarkers were expressed in high frequency in HSIL, whereas LSILs included both SC junction positive and negative (metaplastic) subsets. In this study, we compared the characteristics of SC junction positive and negative LSILs.
Design: 203 cases of SIL were independently reviewed by two experienced pathologists and classified as LSIL or HSIL using published criteria. Concordant LSILs (agreement by both observers) were subdivided into SC junction positive and negative using SC junction-specific antibodies. Agreement with the original diagnosis (pathology report), HPV type, p16 staining pattern and outcome were compared.
Results: 71 and 37 SC junction (-) and SC junction (+) LSILs were identified. Respectively, 0 (0%) and 17 (46%) were originally classified as HSIL, 42 (59.2%) and 35 (94.5%) displayed a diffuse basal or full-thickness p16ink4 staining suggesting an infection with a high-risk HPVs. This was confirmed by PCR amplification with HPV type-specific primers. Of 48 and 31 SC junction (-) and SC junction (+) cases with followups averaging 34 and 28 months, HSIL was documented by consensus agreement of a biopsy or smear in 0 (0%) and 7 (23%) respectively. Interestingly, six SC junction (-) LSILs had succeeded a cone biopsy for HSIL, suggesting that ablation of the prior SC junction influenced the type of recurrent SIL.
Conclusions: LSILs arising in the SC junction are significantly more likely to: 1) be classified as HSIL on pathology reports, 2) contain high risk HPVs, 3) and have a consensus outcome diagnosis of HSIL. Although outcome data will be influenced by the original diagnosis, together these findings are compelling evidence for the existence of two categories of SIL with low grade nuclear features based on putative SC junction origin. A model for precursor classification, including LSIL, HSIL and "QSIL" - problematic SC junction marker-positive (L)SILs - will be discussed.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 8:15 AM
Proffered Papers: Section E, Tuesday Morning