Clinicopathological features of stratified mucin-producing neoplastic lesions of the cervix

Abstract

Objective: To investigatethe clinicopathological features of stratified mucin-producing intraepithelial lesion (SMILE) and invasive stratified mucin-producing carcinoma (ISMC) of the cervix with review of the literature. Methods: Sixteen patients with SMILE/ISMC components of the cervix were collected from files in the Department of Pathology at Xijing Hospital from January 2007 to March 2019. Clinicopathological data included age at diagnosis, clinical presentation, histological type, depth of invasion measurement, the status of lymphovascular space invasion (LVSI) and lymph node metastasis, FIGO staging and follow-up. Histochemistry AB and PAS-D staining and immunostaining for cytokeratin (CK) 7, p16, p63, p40, PAX8, MUC6, p53 were performed simultaneously. In addition, twelve cases with invasive endocervical adenocarcinoma were evaluated using three-tiered pattern-based system (also called Pattern Classification). Results: The average age at diagnosis for patients was 49.7 years (range, 33 to 65 years), and vaginal bleeding occurred in the majority of cases (13/16). The characteristic morphology of SMILE and ISMC was present as non-invasive and invasive stratified epithelium that the full-thickness cells contained different amount of cytoplasmic mucin, respectively. Five cases of SMILE coexisted with adenocarcinoma in situ (1 case), high-grade squamous intraepithelial lesion (1 case), and invasive adenocarcinoma (3 cases). Thirteen cases with ISMC components included pure ISMC (3 cases), mixed with usual-type endocervical adenocarcinoma (8 cases) or squamous cell carcinoma (2 cases). All pure ISMC had lymph vascular space invasion and depth of invasion exceeded 10 mm. All eleven cases of invasive adenocarcinoma with ISMC components belonged to Pattern C tumors, which typically showed diffusely destructive stromal invasion, solid or poorly differentiated components. The results of histochemical staining confirmed that SMILE/ISMC cells were rich in acidic and neutral mucin. The immunohistochemical staining for CK7 and p16 was diffusely strong positive in SMILE (4/4) and ISMC (8/8) components. The positive expressions of p63 and p40 was located in peripheral cells of stratified epithelial nests or merely in a few cells of SMILE (1/3) and ISMC (2/8) components. In ISMC tissues, there were partial expression of MUC6 (5/7), focal expression of PAX8 (2/8), and wild-type expression pattern (4/10) or completely negative expression (6/10) of p53 protein. All thirteen patients with follow-up data were alive (mean 50.5 months, range 4 to 140). Conclusions: As new tumor entities, SMILE is a rare and unique endocervical intraepithelial lesion, while ISMC belongs to an invasive leison. Given that the tumors with ISMC components may have aggressive behavior, it is important for clinicians and pathologists to fully understand the clinicopathological features of SMILE and ISMC.