Clinical and Cytopathological Significance of Intracytoplasmic Lumina and Immunohistochemical Mucin Expression in Non‐Muscle‐Invasive Urothelial Carcinoma of the Bladder

BACKGROUND: Intracytoplasmic lumina (ICL) are mucin-containing structures identified in histological and cytological specimens of urothelial carcinoma and are associated with high-grade tumors and poor prognosis. However, their biological significance remains unclear. This study investigated mucin expression in ICL and its association with clinical, cytopathological, and prognostic features in non-muscle-invasive urothelial carcinoma of the bladder. METHODS: A total of 105 cases of non-muscle-invasive urothelial carcinoma of the bladder diagnosed were examined. Immunohistochemical staining for MUC1, MUC2, MUC4, MUC5AC, and MUC6 was performed in 47 cases in which ICL were identified histologically, and the staining patterns of ICL and tumor cells were evaluated. The presence of ICL in urine cytology specimens was assessed, and its associations with tumor-specific survival and recurrence were analyzed statistically. RESULTS: ICL were identified in 47 cases histologically and in 33 cases cytologically. ICL-positive tumors were more frequently observed in high-grade histology and were more often diagnosed as malignant or suspicious for malignancy in urine cytology. Immunohistochemically, MUC1 was the most frequently expressed mucin, with localization along the microvilli of the ICL lumen and within luminal mucin. Increased expression of MUC4 and MUC5AC showed a trend toward decreased survival. CONCLUSION: ICL in non-muscle-invasive urothelial carcinoma is more frequently observed in high-grade tumors and shows characteristic mucin expression patterns, particularly MUC1 localization within ICL structures. Increased expression of MUC4 and MUC5AC may be associated with unfavorable clinical outcomes. These findings suggest that combined evaluation of ICL and mucin expression may provide additional prognostic information in urothelial carcinoma.