Histologic heterogeneity in bladder neoplasia: Identification of coexisting urothelial dysplasia, papillary lesions of low malignant potential, and muscle-invasive urothelial carcinoma

Moultrie, GA

BACKGROUND: Urothelial bladder carcinoma (UBC) accounts for approximately 90% of bladder cancers with a male to female prevalence of 3:1. Established risk factors include exposure to tobacco smoking, and environmental and occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines. Additional risk factors include air pollution, advanced age, and occupational exposure to carcinogens present in dyes, paints, petroleum products, and metals. UBC are recognized for their heterogeneous characteristics due to urothelial epithelium exhibiting diverse transcriptional and mutational profiles that evolve within the tumor microenvironment. Additionally, bladder cancers are often found to be multifocal, highlighting the importance of thorough examination of the bladder in patients suspected of bladder cancer, along with confirmatory diagnosis involving Transurethral Resection of Bladder Tumor (TURBT). Urothelial carcinoma typically progresses from hyperplasia or dysplasia to papillary non-invasive lesions and may ultimately advance to muscle-invasive bladder cancer (MIBC). This study describes the gross and histologic findings of bladder neoplasia identified in an 89-year-old male cadaver with a history of occupational paint exposure, demonstrating a multifocal heterogeneous bladder tumor containing areas of papillary urothelial dysplasia and MIBC.

METHODS: Dissection was performed as part of medical student anatomical education at the Philadelphia College of Osteopathic Medicine–South Georgia. A midline pelvic hemisection was completed using standard dissection techniques, including longitudinal incision of midline soft tissues followed by osteotomy of the pubic symphysis, sacrum, and coccyx to the level of L5. A transverse incision from the iliac crest with osteotomy at L4–L5 allowed removal of one hemipelvis and the ipsilateral lower extremity. The urinary bladder was subsequently excised from the pelvic cavity, opened, and the internal mucosal surface was inspected for intraluminal masses or mucosal abnormalities. Suspicious lesions were documented and submitted for histologic analysis.

RESULTS: Gross examination revealed an irregular exophytic mucosal outgrowth with focal bladder wall thickening suggestive of neoplastic pathology. Histologic evaluation demonstrated heterogeneous urothelial changes. Some sections showed papillary urothelial architecture with low malignant potential and areas of urothelial dysplasia. Other regions exhibited inflammatory infiltrates with epithelial detachment consistent with chronic inflammatory changes. Additional sections demonstrated invasive nests of atypical urothelial cells infiltrating the muscularis propria, confirming focal MIBC. Tumor cells displayed nuclear and architectural atypia with invasion between detrusor muscle fibers. Diffuse lymphadenopathy was observed in para-aortic, inguinal, axillary, and submandibular lymph nodes; histologic evaluation showed reactive lymphoid hyperplasia without evidence of metastatic carcinoma.

CONCLUSION: These findings demonstrate histopathologic heterogeneity within a single bladder tumor, including coexistence of low-grade papillary urothelial neoplasia and focal MIBC. The case highlights the complex progression of urothelial carcinoma and underscores the importance of environmental and occupational exposures in bladder carcinogenesis. Recognition of such heterogeneity is clinically significant, as tumor biology and progression may vary across different regions of the same lesion, influencing diagnostic interpretation and therapeutic decision-making.