[Precancerous lesions of the uterine cervix: morphology and molecular pathology]

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).