title: Stratified mucin-producing intraepithelial lesion with invasive carcinoma: 12 cases with immunohistochemical and ultrastructural findings.
abstract: Stratified mucin-producing intraepithelial lesion (SMILE) is considered to be a variant of adenocarcinoma in situ (defined as intraepithelial malignant glandular epithelium without invasion) or adenosquamous carcinoma in situ of the uterine cervix. However, recent study suggested that SMILE is more similar to high-grade squamous epithelial lesion by their immunohistochemical findings. An invasive form of SMILE "invasive stratified mucin-producing carcinoma (ISMC)" has been also proposed, but immunohistochemical features are not well documented. Therefore, this study aimed to clarify the immunohistochemical characteristics of SMILE and ISMC. Twelve cases of SMILE were found among 445 patients (2.7%) with high-grade intraepithelial lesions or invasive carcinomas, 3 of whom had solely intraepithelial disease with SMILE component (mean age, 37 years; range, 30-48 years) and 9 with invasive carcinomas (mean age, 47 years; range, 37-66 years; including ISMC). Immunohistochemically, SMILE and ISMC were diffusely positive for p16 and CAM5.2, focally for IMP3, and almost negative or only focally positive for p63. Nuclear signals in SMILE and invasive carcinomas were detected by human papillomavirus (HPV) in situ hybridization; 5 cases showed HPV16 and/or HPV18 polymerase chain reaction products. The ultrastructural study of 1 case showed surface microvilli and small vacuolar structure in SMILE; ISMC had mucous-like vacuoles, many mitochondria and intracytoplasmic lumen but lacked tonofilament. These findings were more similar to adenocarcinoma in situ or adenocarcinoma than squamous intraepithelial lesion or squamous cell carcinoma. We suggest that SMILE is an intraepithelial neoplasm and ISMC is an invasive form of SMILE.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan. Electronic address: junji_onishi@med.miyazaki-u.ac.jp.
authors.forename: Junji
authors.initials: J
authors.lastname: Onishi
authors.affiliation: Department of Diagnostic Pathology, University of Miyazaki Hospital, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan. Electronic address: yuichiro_sato@med.miyazaki-u.ac.jp.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Anatomy, Ultrastructural Cell Biology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan. Electronic address: akira_sawaguchi@med.miyazaki-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawaguchi
authors.affiliation: Department of Pathology, University of Miyazaki, Miyazaki, Japan, Faculty of Medicine, Miyazaki 889-1692, Japan. Electronic address: atsushi_yamashita@med.miyazaki-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Department of Pathology, University of Miyazaki, Miyazaki, Japan, Faculty of Medicine, Miyazaki 889-1692, Japan. Electronic address: kznmaekawa@med.miyazaki-u.ac.jp.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Maekawa
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan. Electronic address: hsameshima@med.miyazaki-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sameshima
authors.affiliation: Department of Anatomy, Ultrastructural Cell Biology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Asada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D061809:Human Papillomavirus DNA Tests; D052162:Human papillomavirus 16 / Q000235:genetics; D052161:Human papillomavirus 18 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000737:chemistry* / Q000145:classification / Q000648:ultrastructure* / Q000821:virology; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000145:classification / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D009626:Terminology as Topic; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000145:classification / Q000648:ultrastructure* / Q000821:virology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral
keywords: Electron microscopy; Immunohistochemically; Invasive stratified mucin-producing carcinoma; Stratified mucin-producing intraepithelial lesion