Benign stratified intraepithelial mucinous proliferation of the uterine cervix: Significance of a previously unreported potential mimic of SMILE.

Stratified mucin-producing intraepithelial lesion (SMILE) is a histologic subtype of HPV-associated endocervical adenocarcinoma in situ. We have observed benign endocervical changes resembling SMILE. We aim to characterize this pattern and explore its potential association with dysplasia. We retrospectively retrieved all 296 consecutive cases accessioned as endocervical biopsies. Some included multiple specimens, totaling 483 biopsies and 219 endocervical curettages (ECC), n = 702. We included cases showing endocervical epithelial stratification often with pencillate (triangular-shaped) nuclei. We rejected cases in which layering represented tangential sectioning, metaplasia, microglandular hyperplasia, gastric type epithelial changes, and dysplasia. We found benign stratified intraepithelial mucinous proliferation in 51 patients, either with a multilayered (n = 27) or a two-layered appearance (n = 24). Overall, multilayered proliferation occurred in 6 % (29/483) of biopsies and in 0.9 % of ECCs (2/219). Two-layering was identified in 4 % of all biopsies (20/482) and was not seen in ECCs. Histologic findings included stratification, intracytoplasmic mucin, paler cytoplasm, low nuclear-to-cytoplasmic ratio, often pencillate nuclei, rare mitoses, and no apoptotic bodies. P16 immunohistochemistry (n = 12) was negative, suggesting absence of underlying high-risk HPV infection. HSIL was concomitant in 29.6 % (8/27) of patients with multilayered proliferation. Concurrent SMILE was not observed. We also reviewed 13 SMILE cases. Concurrent multilayered benign proliferation was identified in 54 % (7/13) of cases. We describe benign stratified intraepithelial mucinous proliferation of the cervix, which morphologically may overlap with SMILE. Its presence in most SMILE cases suggests a potential relationship. The multilayered form represents a diagnostic pitfall when mitotically active. Because of the often-coexistent HSIL, we propose that its presence should prompt scrutiny to rule out any associated dysplasia.