The Utility of HPV In Situ Hybridization and the PAS Test in Improving the Specificity of the Diagnosis of CIN 1

Department of Immunology, Oswaldo Cruz Foundation, Rio de Janiero, Brazil.
International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists (Impact Factor: 1.67). 12/2008; 28(1):83-9. DOI: 10.1097/PGP.0b013e318181b41c
Source: PubMed


The histologic features of cervical intraepithelial neoplasia (CIN 1), caused by infection by the human papillomavirus (HPV), can overlap with those of its mimics that can lead to an over diagnosis of this sexually transmitted disease. In this study, 67 consecutive cervical biopsies that were diagnosed as CIN 1 from the surgical files of Ohio State University Medical Center were analyzed. Twenty controls (10 CIN 1 cervical biopsies and 10 normal cervical tissues) were also studied. The 87 biopsies were reevaluated blinded to the original diagnosis and the results were correlated with detection of HPV DNA by in situ hybridization and glycogen by the periodic acid solution (PAS)/PAS-D stain, respectively. HPV was detected by in situ hybridization in 55/67 cases (82%); no virus was evident in the negative controls whereas each of the 10 CIN 1 controls was virus positive. A PAS test demonstrated in the mature squamous component of the negative controls a strong signal in cells with prominent and uniform halos, which was lost with diastase treatment, indicative of abundant glycogen. The PAS/PAS-D tests in the CIN 1 lesions showed rare variable sized glycogen deposits in the dysplastic cells. Nine (15%) cases initially diagnosed as CIN 1 were HPV negative by in situ hybridization and had halolike cells that were strongly and uniformly positive for glycogen. This data underscores the value of glycogen and HPV analyses in improving the specificity of the diagnosis of CIN 1.

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    ABSTRACT: HPV-induced alterations of the uterine cervix are frequently biopsied because of suspicious findings on a Pap smear and/or colposcopy. Precancerous lesions occur at the so called transformation zone. For those representing squamous differentiation, the traditional three-tier grading system in CIN 1 to 3 is used. CIN 1 and CIN 2 represent (spontaneous) regression in 60-90% and 50%, respectively. In CIN 3 lesions progression is seen in 20-50%. For appropriate grading, improvement of inter- and intraobserver correlation as well as the exclusion of non-precancerous lesions, p16 immunohistochemistry might be helpful. The terms endocervical glandular dysplasia and low-grade glandular intraepithelial neoplasia have been suggested for glandular lesions less than adenocarcinoma in situ (AIS). Until now reproducible histological criteria have not been established. Additional studies using HPV analysis, p16 and Ki-67 immunohistochemistry have not been proved for these lesions. In accordance with international consensus meetings, these diagnostic terms are not recommended for use in practice. AIS, characterised by the replacement of glandular epithelium by cytologically malignant cells, has been established as the precancerous lesion of the endocervix. AIS is much less common than CIN 3 with a reported range of 1:50-100. But, AIS is found in association with CIN 3 with 25-75%. The differential diagnosis between AIS and non-neoplastic glandular lesion may be aided by immunohistochemistry (e.g. p16, Ki-67, bcl-2, vimentin). All specimens obtained after the clinical diagnosis of cervical precancerous lesions should be examined using step sectioning to rule out microinvasive growth. Important information for clinicians includes the quality of the specimen (cautery artefacts, transformation zone enclosed within the probe), exact grading of CIN lesions, identification of other lesions responsible for suspicious findings of a Pap smear or at colposcopy, and in the case of conisation the distance of the lesion from the resection margins (endo- and ectocervical and circumferential margin).
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