Preinvasive endocervical glandular lesions, termed cervical glandular intraepithelial
neoplasia, are increasing in incidence. The distinction of cervical glandular intraepithelial
neoplasia from benign mimics, especially tubo-endometrial
metaplasia,
endometriosis and microglandular
hyperplasia, can be difficult. This study investigates the value of immunohistochemical staining with MIB1, bcl2 and p16 in the distinction of cervical glandular intraepithelial
neoplasia from these benign mimics.
METHODS AND RESULTS: Immunohistochemical staining using the
monoclonal antibodies MIB1, bcl2 and p16 was performed on cases of cervical glandular intraepithelial
neoplasia (n = 21), tubo-endometrial
metaplasia (n = 13),
endometriosis (n = 7) and microglandular
hyperplasia (n = 14). With tubo-endometrial
metaplasia and microglandular
hyperplasia staining with MIB1 was either negative or involved <10% of cells, while with cervical glandular intraepithelial
neoplasia the majority of cases (86%) exhibited >10% positive cells. Two cases of
endometriosis exhibited a MIB1 index of 10-30% while in the other cases <10% cells stained. With bcl2 the cells of microglandular
hyperplasia were negative although there was staining of associated reserve cells in 43% of cases. All cases of tubo-endometrial
metaplasia except one and all cases of
endometriosis stained diffusely positive with bcl2. Cases of cervical glandular intraepithelial
neoplasia were negative or exhibited focal staining. With p16 all cases of cervical glandular intraepithelial
neoplasia exhibited diffuse strong positivity, generally involving 100% of cells, while all cases of microglandular
hyperplasia were negative. Sixty-two percent of cases of tubo-endometrial
metaplasia showed focal positivity, the remainder being negative. Cases of tubo-endometrial
metaplasia were never diffusely positive with p16. In three cases of
endometriosis there was staining of >50% of cells while the other cases were either focally positive or negative.
CONCLUSIONS: A panel of
antibodies, comprising MIB1, bcl2 and p16, is a useful adjunct to histology in distinguishing cervical glandular intraepithelial
neoplasia from tubo-endometrial
metaplasia,
endometriosis and microglandular
hyperplasia. Cases of cervical glandular intraepithelial
neoplasia are diffusely positive for p16 and generally exhibit a high proliferation index with MIB1, while bcl2 is negative or, at most, focally positive. Tubo-endometrial
metaplasia and
endometriosis are characterized by strong diffuse positivity with bcl2 and a low proliferation index with MIB1 (although occasional cases of
endometriosis show moderate proliferative activity). p16 is negative or exhibits focal positivity in tubo-endometrial
metaplasia but in
endometriosis there may be quite widespread positivity. Microglandular
hyperplasia shows a low proliferation index with MIB1 and is negative for bcl2 and p16.