Stratified mucin-producing intraepithelial lesions of the cervix - Adenosquamous or columnar cell neoplasia?

BACKGROUND: Squamous (CIN) and glandular (ACIS) intraepithelial lesions oft en coexist in the same cervical specimen. However, a less common and little studied Variant consists of a stratified epithelium resembling CIN in whic h conspicuous mucin production is present (Stratified Mucin-producing Intra epithelial LEsions (SMILE). This report describes the phenotypic characteri stics of the SMILE, its associated lesions, and its immunophenotype. METHOD S: Eighteen SMILEs were identified by the presence of conspicuous cytoplasm ic clearing or vacuoles in lesions otherwise resembling CIN. The morphologi c 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 neopl astic epithelial cells with a high Mib-1 index and a rounded or lobular con tour at the epithelial-stromal interface characterized SMILEs. In contrast to CIN, in which mucin droplets are confined to surface cells, mucin was pr esent throughout the epithelium, varying from indistinct cytoplasmic cleari ng to discrete vacuoles. SMILEs were distinguished from benign metaplasia b y nuclear hyperchromasia and a high Mib-1 index. All but three coexisted wi th either a squamous (CIN) or glandular (ACIS) precursor lesion. Nine of ni ne coexisting invasive carcinomas contained glandular, adenosquamous differ entiation. or both. SMILEs stained negative fur 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 a re unusual cervical intraepithelial lesions best classified as variants of endocervical columnar cell neoplasia based on immunophenotype. The distribu tion and immunophenotype of SMILEs are consistent with a neoplasm arising i n reserve cells in the transformation zone. The coexistence of a wide spect rum of intraepithelial and invasive cell phenotypes suggests that SMILEs ar e a marker for phenotypic instability, emphasizing the importance of identi fying SMILEs and ensuring a complete examination of specimens containing th is unusual precursor lesion.