Stratified Mucin Producing Intraepithelial Lesion (SMILE): Report of Two Cases

Abstract

Abstract Introduction/Objective Stratified mucin producing intraepithelial lesion (SMILE) is an uncommon variant of adenocarcinoma in-situ (AIS), often confused with immature squamous metaplasia or high-grade intraepithelial lesion (HG-SIL). This premalignant lesion is often found in proximity to HG-SIL, AIS and invasive carcinomas. SMILE is also a precursor for Invasive Stratified Mucinous Carcinoma. As was first described in the original article, SMILE lesions are considered derived from the reserve cells at the transformation zone where HPV infections lead to varied phenotypes. Methods Two cases of SMILE were collected from our files. A 31-year-old female with a previous abnormal Pap smear result. She underwent cervical biopsy and subsequent LEEP.The second patient, a 26-year-old female, underwent a cervical biopsy after an abnormal Pap smear. Results Histologically, stratified cells with presence of conspicuous mucin production with abundant cytoplasm separating cells in mid and lower layer of epithelium accompanied with conspicuous spacing of nuclei in the lower to middle epithelial layer are seen. Additionally, there is nuclear pleomorphism with absence of gland formation. Mucicarmine stain was performed and showed positive staining in mucin producing dysplastic cells throughout the epithelium. Immunoperoxidase stains demonstrated positivity for p16 (nuclear and cytoplasmic) and p63 in the basal cells. The Ki67 proliferation index was high (approximately 90%). These results supported the diagnostic interpretation of SMILE. Conclusion SMILE is a rare variant of glandular precursor lesion in the cervix. It is frequently associated with HG-SIL and/or AIS, but may rarely appear as an isolated finding. The differential diagnosis include adenocarcinoma in-situ, atypical immature squamous metaplasia and squamous intraepithelial lesion. Since these lesions are cervical glandular intraepithelial neoplasms, the morphologic recognition of a SMILE in a biopsy is important for patient follow up, particularly in cases were only squamous intraepithelial lesion is present in the sample.