P16 Expression in Biopsies with Tubal Metaplasia from Patients with Atypical Glandular Cells on Pap Smear
G Yu, G Nolan, M Amin, M De Peralta-Venturina. William Beaumont Hospital, Royal Oak, MI
Background: A finding of atypical glandular cells (AGC) on pap smear is significant requiring further work-up. A proportion of these cases can be attributed to tubal metaplasia (TM), a known potential pitfall. P16 staining has been used as an adjunct in diagnosis and confirmation of significant squamous and endocervical dysplastic lesions. p16 immunostain can be positive in endocervical TM and this can be another potential pitfall when used in isolation to evaluate such lesions. The aim of this study is to evaluate p16 immunostaining in tissue specimens from patients who had TM accounting for AGC on their pap smears.
Design: Patients who had a diagnosis of AGC on their Thin-prep pap smears and with subsequent tissue diagnosis of endocervical TM were selected. Cases with coexisting squamous intraepithelial lesion (SIL) were excluded. Paraffin-embedded tissue of 16 cases including 9 cervical cone and 7 endocervical curettage (ECC) specimens were immunostained for p16 (clone 16PO4;1:300 dilution, Cell Marque Corp, Hotsprings, AZ). For comparison, 22 cases of endocervical AIS (13 cervical cones, 9 ECC) and 10 hysterectomy specimens with endometrial TM were also stained. Immunoreactivity was scored for both intensity (weak, intermediate and strong) and extent. Localization of staining (nuclear and/or cytoplasmic) was also noted.
Results: Cases with AGC on pap smear attributed to endocervical TM cells showed weak to strong p16 staining in 94% of cases with patchy staining confined to the TM cells giving a mosaic appearance. In contrast, endocervical AIS showed intermediate to strong, diffuse uniform staining in the dysplastic endocervical epithelium. Staining was noted in both nucleus and cytoplasm in TM and AIS. Endometrial TM showed patchy mild to moderate p16 immunostaining in 90% of cases. Some endometrial glands without TM, normal and reactive endocervical cells may also show rare cells with weak staining that appears insignificant.
Conclusions: Significant p16 immunostaining may be seen in tissue biopsies with endocervical tubal metaplasia that presented as AGC on pap smear. Tubal metaplasia can mimic AIS both on pap smears and tissue specimens. A combination of morphologic features and patchy mosaic staining pattern with p16 are supportive of tubal metaplasia. There are recent articles suggesting utility of p16 immunostain in pap smears for diagnosis of SIL, and in our opinion this interpretation may need caution when evaluating cases presenting as AGC.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 22, Wednesday Morning