Are CIN2 Lesions Overdiagnosed? Selected Immunopanel Can Prevent Unnecessary Cervical Excisions.
Rouzan Karabakhtsian, Michael Cibull, Christopher DeSimone. UKMC, Lexington, KY
Background: Atypical cellular changes reflecting inflammation, immature squamous metaplasia and atrophy can be diagnostically challenging in small cervical biopsies (bx) when evaluating for high-grade (HG) cervical intraepithelial neoplasia (CIN). Such changes may mimic HG dysplasia and can lead to unnecessary cervical excision. The aim of this study was to retrospectively re-evaluate CIN2 lesions diagnosed on cervical bx in patients with no residual HG lesion in subsequent cervical excision, utilizing a panel of immunohistochemical (IHC) stains.
Design: 211 cervical bx from 151 patients with histologic diagnosis (Dx) of CIN2 who underwent cervical LEEP/Cone excision from 2000 to 2007 were retrieved from pathology files. Residual CIN2 was present in cervical excision in 89/151 (59%) patients (group 1, 130 bx) and absent in 62/151 (41%) (group 2, 81bx). 9/81 bx did not have sufficient tissue for IHC work-up. Tissue blocks of 72/81 cervical bx (group 2) were stained for 3 IHC markers: p16INK4a (CINtec, MTM) and proliferation markers MIB-1 (Dako) and proExTMC (BD). H&E and immunostained slides were independently reviewed by two pathologists. Diffuse nuclear and cytoplasmic staining of cells for p16 in at least half of the epithelial thickness was interpreted as positive for CIN2, and negative otherwise. Co-expression of nuclear staining for MIB-1 and proExC in cells within at least half of the epithelium was interpreted as supportive of CIN2, and negative otherwise.
Results: Histologic Dx of CIN2 (group 2) was supported by 3 stains in 61% (44/72) cervical bx and by 2 stains (p16-) in 13% (9/72). In 26% (19/72) of bx stains failed to support the presence of CIN2. Overall, CIN2 was overdiagnosed in 9% (19/211) cervical bx. Immunoreactivity for p16 was present in 83% (44/53) and absent in 17% (9/53) of true CIN2 lesions. In-situ hybridization (ISH) for HPV was performed in p16 (-) group (9 bx). In 4/9 tissue was insufficient for additional work-up. HPV 16/18 by ISH was (+) in remaining 3/5 and (-) in 2/5.
Conclusions: 1) In 25% (53/211) the absence of CIN2 in subsequent excision may be due to small lesion size with complete removal by colposcopic bx, or regression.
2) CIN2 was overdiagnosed in 9% cervical bx in this study.
3) Immunopanel of p16, MIB-1 and ProExC can be useful in separating CIN2 lesions from its benign mimics.
4) While not extremely sensitive for CIN2 (83%), p16 appears highly specific “key” biomarker and critical when dealing with diagnostic challenges.
5) ISH for HPV can be helpful in rare p16 (-) cases.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 205, Tuesday Morning