title: Stratified mucin-producing intraepithelial lesion (SMILE): report of a case series with associated pathological findings.
abstract: OBJECTIVE
  Stratified mucin-producing intraepithelial lesion (SMILE) is an uncommon premalignant cervical lesion showing morphological overlap with cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS)/cervical glandular intraepithelial neoplasia. Given the limited literature on SMILE, we aimed to document its frequency and assess the associated pathology in a large series of cases.
  
  
  RESULTS
  Over a 6-year period, we documented all cases of SMILE and the associated findings. SMILE was diagnosed in 69 specimens from 60 patients (50 loop excisions and 19 punch biopsy specimens), constituting 0.6% of cervical specimens. Overall, SMILE coexisted with high-grade CIN in 93% of cases, AIS in 42%, and a carcinoma in 10%. When SMILE was diagnosed on a cervical punch biopsy, there was high-grade CIN in the follow-up loop in most cases. SMILE was consistently diffusely p16-positive and IMP3-negative.
  
  
  CONCLUSIONS
  Given the morphological overlap and significant association with high-grade CIN and AIS, we believe that SMILE is best regarded as a form of high-grade reserve cell dysplasia, probably arising from reserve or stem cells with the capacity for multidirectional differentiation. We recommend that management of SMILE should be as for AIS.
authors.affiliation: Department of Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland.
authors.forename: David P
authors.initials: DP
authors.lastname: Boyle
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
mesh_terms: D065311:Adenocarcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C498780:IGF2BP3 protein, human; D009077:Mucins; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins
keywords: IMP3; adenocarcinoma in situ (AIS); cervical intraepithelial neoplasia (CIN); cervix; stratified mucin-producing intraepithelial lesion (SMILE)