title: Stratified mucin-producing intraepithelial lesions of the cervix: adenosquamous or columnar cell neoplasia?
abstract: BACKGROUND
  Squamous (CIN) and glandular (ACIS) intraepithelial lesions often coexist in the same cervical specimen. However, a less common and little studied variant consists of a stratified epithelium resembling CIN in which conspicuous mucin production is present (Stratified Mucin-producing Intraepithelial LEsions (SMILE). This report describes the phenotypic characteristics of the SMILE, its associated lesions, and its immunophenotype.
  
  
  METHODS
  Eighteen SMILEs were identified by the presence of conspicuous cytoplasmic clearing or vacuoles in lesions otherwise resembling CIN. The morphologic spectrum of SMILEs was detailed; including associated intraepithelial and invasive cervical neoplasms. In addition, selected cases were stained for mucicarmine, markers of squamous cell/reserve cell differentiation (keratin-14 and p63), and proliferative activity (Mib-1).
  
  
  RESULTS
  Stratified neoplastic epithelial cells with a high Mib-1 index and a rounded or lobular contour at the epithelialstromal interface characterized SMILEs. In contrast to CIN, in which mucin droplets are confined to surface cells, mucin was present throughout the epithelium, varying from indistinct cytoplasmic clearing to discrete vacuoles. SMILEs were distinguished from benign metaplasia by nuclear hyperchromasia and a high Mib-1 index. All but three coexisted with either a squamous (CIN) or glandular (ACIS) precursor lesion. Nine of nine coexisting invasive carcinomas contained glandular, adenosquamous differentiation, or both. SMILEs stained negative for keratin-14 and variably for p63. When present, staining with p63 was confined to basal areas of SMILEs and was absent in areas of columnar differentiation.
  
  
  CONCLUSIONS
  SMILEs are unusual cervical intraepithelial lesions best classified as variants of endocervical columnar cell neoplasia based on immunophenotype. The distribution and immunophenotype of SMILEs are consistent with a neoplasm arising in reserve cells in the transformation zone. The coexistence of a wide spectrum of intraepithelial and invasive cell phenotypes suggests that SMILEs are a marker for phenotypic instability, emphasizing the importance of identifying SMILEs and ensuring a complete examination of specimens containing this unusual precursor lesion.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Park
authors.forename: D
authors.initials: D
authors.lastname: Sun
authors.forename: B J
authors.initials: BJ
authors.lastname: Quade
authors.forename: C
authors.initials: C
authors.lastname: Flynn
authors.forename: E E
authors.initials: EE
authors.lastname: Sheets
authors.forename: A
authors.initials: A
authors.lastname: Yang
authors.forename: F
authors.initials: F
authors.lastname: McKeon
authors.forename: C P
authors.initials: CP
authors.lastname: Crum
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D018196:Carcinoma, Adenosquamous / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D009077:Mucins / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000145:classification / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D009077:Mucins