Stratified mucin-producing intraepithelial lesion with invasive carcinoma: 12 cases with immunohistochemical and ultrastructural findings

• Published in: Human pathology 2016-09, Vol.55, p.174-181
• Main Authors: Onishi, Junji, MD, PhD, Sato, Yuichiro, MD, PhD, Sawaguchi, Akira, MD, PhD, Yamashita, Atsushi, MD, PhD, Maekawa, Kazunari, MD, Sameshima, Hiroshi, MD, PhD, Asada, Yujiro, MD, PhD
• Format: Article
• Language: English
• Subjects: Adult; Age; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Cellular biology; Chemotherapy; Colleges & universities; Deoxyribonucleic acid; DNA; DNA, Viral - genetics; Electron microscopy; Female; Human papillomavirus; Human papillomavirus 16 - genetics; Human papillomavirus 18 - genetics; Human Papillomavirus DNA Tests; Humans; Hysterectomy; Immunohistochemically; Immunohistochemistry; Invasive stratified mucin-producing carcinoma; Lymphatic system; Metastasis; Microscopy, Electron, Transmission; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Neoplasms, Cystic, Mucinous, and Serous - chemistry; Neoplasms, Cystic, Mucinous, and Serous - classification; Neoplasms, Cystic, Mucinous, and Serous - ultrastructure; Neoplasms, Cystic, Mucinous, and Serous - virology; Pathology; Patients; Predictive Value of Tests; Retrospective Studies; Squamous Intraepithelial Lesions of the Cervix - classification; Squamous Intraepithelial Lesions of the Cervix - metabolism; Squamous Intraepithelial Lesions of the Cervix - pathology; Squamous Intraepithelial Lesions of the Cervix - virology; Stratified mucin-producing intraepithelial lesion; Terminology as Topic; Tumors; Uterine Cervical Neoplasms - chemistry; Uterine Cervical Neoplasms - classification; Uterine Cervical Neoplasms - ultrastructure; Uterine Cervical Neoplasms - virology; Young Adult
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2016.05.007

Stratified mucin-producing intraepithelial lesion (SMILE) is considered to be a variant of adenocarcinoma in situ (AIS; defined as intraepithelial malignant glandular epithelium without invasion) or adenosquamous carcinoma in situ , of the uterine cervix. However, recent study suggested SMILE is more similar to high grade squamous epithelial lesion (HSIL) by their immununohistochemical findings. An invasive form of SMILE “invasive stratified mucin-producing carcinoma (ISMC)”has been also proposed, but immunohistochemical features 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, three of whom had solely intraepithelial disease with SMILE component (mean age: 37 years; range: 30–48 years); and nine with invasive carcinomas (mean age: 47 years: range: 37–66 years; including ISMC). Immunohistochemically, SMILE and ISMC were diffusely positive for p16 and CAM 5.2, focally IMP 3, and almost negative or only focally positive for p63. Nuclear signals in SMILE and invasive carcinomas were detected by human papilloma virus (HPV) in situ hybridization; five cases showed HPV16 and / or HPV18 polymerase chain reaction products. The ultrastructural study of one case showed surface microvilli and small vacuolar structure in SMILE; ISMC had mucous-like vacuoles, many mitochondria, intracytoplasmic lumen, but lacked tonofilament. These findings were more similar to AIS or adenocarcinoma than squamous intraepithelial lesion or squamous cell carcinoma. We suggest SMILE is an intraepithelial neoplasm and ISMC is an invasive form of SMILE.