Primary adenocarcinoma of the urinary tract and its precursors: Diagnostic criteria and classification

Primary adenocarcinoma of the urinary bladder is a rare malignancy, comprising up to 2% of bladder cancers, predominantly in males. Its rarity and similarity to urothelial carcinoma and secondary adenocarcinomas pose diagnostic challenges. A comprehensive literature review was conducted on the diagnosis, classification, morphological and immunophenotypic characteristics, and molecular profiles of primary adenocarcinoma, urachal adenocarcinoma, and precursor lesions.

Primary adenocarcinoma exhibits diverse morphological patterns, including enteric, mucinous, signet ring cell, and mixed types. Immunohistochemistry is useful in differentiating primary adenocarcinoma from metastatic adenocarcinomas and secondary involvement. Genetic studies reveal mutations common in colorectal and bladder adenocarcinomas (KRAS, TP53, PIK3CA) and novel primary adenocarcinoma-specific mutations (OR2L5). Urachal adenocarcinoma shares morphological features with primary adenocarcinoma but typically occurs in younger patients with unique genomic and distinct immunoprofile. Potential precursor lesions include villous adenoma, cystitis glandularis, and intestinal metaplasia, and warrant close clinical follow-up. Despite advances in histopathological and molecular diagnostics, primary adenocarcinoma remains challenging to diagnose due to its rarity and morphological heterogeneity. Ongoing research into its molecular characteristics is essential to refine diagnostic criteria and therapeutic approaches. Thorough clinical and pathological assessment is crucial for accurate diagnosis, classification, and clinical management.