Significance of atypical repair in liquid-based gynecologic cytology: a follow-up study with molecular analysis for human papillomavirus.

Abstract

"Atypical repair" is a controversial topic in gynecologic cytology. Although some cases do represent reparative change of dysplastic epithelium, the overall significance of identifying atypical reparative cells, especially in liquid-based cytology specimens, has not been investigated thoroughly. All the liquid-based cytology cases with the diagnostic connotation of atypical repair were retrieved from the files of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a 4.5-year period from early 1998 to mid 2002. The clinical data and follow-up cytology/surgical biopsy findings were analyzed to explain the atypical cytologic change. Retrospective molecular analysis for human papillomavirus (HPV) using polymerase chain reaction and restriction fragment length polymorphism was also carried out on the liquid-based cytology samples. During the study period, the authors identified 21 patients with a cytologic diagnosis of atypical repair, for which follow-up information was available. The liquid-based cytology samples revealed scattered atypical squamoid cells demonstrating reparative change, including the presence of prominent nucleoli. In addition to typical repair, these cells showed more obvious nuclear pleomorphism, anisonucleosis, irregularities of nuclear outline, slight coarsening of the chromatin, and focal loss of nuclear polarity. Of the 21 patients, 4 did not have a significant history of cervical/vaginal pathology before or after the cytologic examination, whereas the 17 remaining patients had squamous intraepithelial lesions (SIL; n = 9), genital prolapse (n = 3), endocervical polyps (n = 2), SIL/cervical carcinoma with local radiotherapy (n = 2), or uterine malignancy with cervical extension (n = 1). These associations could not be delineated solely on the basis of morphologic assessment of the liquid-based cytology preparations. However, HPV DNA was detected frequently in cases of atypical repair associated with subsequent development of SIL (positive predictive value = 71.4%; negative predictive value = 77.8%). The presence of atypical reparative cells in liquid-based cytology is associated with a variety of conditions ranging from reactive to neoplastic conditions. Close follow-up with clinical correlation and further investigations (if indicated) are necessary for this group of high-risk patients. Reflex molecular analysis for HPV performed on liquid-based cytology samples is also helpful in predicting the possible association with an underlying SIL.