Cervical Stratified Mucin-Producing Intraepithelial Lesion: A Systematic Review of Diagnosis and Management.

OBJECTIVES: The aims of the study were to synthesize reported associations of stratified mucin-producing intraepithelial lesion (SMILE) of the cervix with other dysplasia lesions and immunohistochemical (IHC) stains, compare expected patterns of IHC staining to other lesions in the differential diagnosis, and assess follow-up pathology. METHODS: This systematic review includes all case reports and case series of cervical lesions consistent with SMILE based on the histologic diagnosis described in the original case series. MEDLINE, EMBASE, and Cochrane Database were searched through June 2019. Immunohistochemical analysis, concurrent lesions, and pathology on follow-up were compiled for comparison. Weighted averages of concurrent lesions were calculated. RESULTS: Nine case reports and case series were included, published between 2000 and 2019. Of 9 studies, 6 and 5 studies reported strong, diffuse staining of p16 and increased expression of Ki-67, respectively. Stratified mucin-producing intraepithelial lesion is associated with human papillomavirus, especially type 18. The weighted average risk of concurrent high-grade squamous intraepithelial lesion was 79% (range = 33%-93%), adenocarcinoma in situ 39% (2.9%-92%), adenocarcinoma 5% (1%-25%), and squamous cell carcinoma 6% (0%-11%). Patients underwent follow-up ranging from repeat Pap to radical hysterectomy, with pathology on follow-up infrequently and irregularly reported. CONCLUSIONS: Stratified mucin-producing intraepithelial lesion is a rare lesion with a paucity of research on necessary cytology and IHC stains for diagnosis, but p16 and Ki-67 IHC stains can be performed to rule out benign lesions. The lesion is associated with high risk of concurrent high-grade squamous intraepithelial lesion, adenocarcinoma in situ, and invasive carcinoma, but studies on the risk of pursuing fertility-preserving management are needed.