Clear Cell Adenocarcinoma of the Urinary Tract Primary to the Renal Pelvis

Clear cell adenocarcinoma (CCA) of the urinary tract is a rare malignancy and tumors involving the renal pelvis are notably sparse in the literature, with only 5 other patients reported. We present 5 patients, 4 women, and 1 man, with CCA of the renal pelvis. The age at presentation ranged from 29 to 81 years. The tumor size ranged from 4.5 to 8.0 cm. Tumors exhibited shared morphologic and immunohistochemical features with CCA of the female genital tract and those originating in the bladder and urethra, including cells with large nuclei, prominent nucleoli, nuclear hobnailing, and scant clear cytoplasm. Common immunohistochemical findings included reactivity for PAX8, CK7, HNF1β, and Napsin-A. One of the tumors arose in the background of a mixed epithelial and stromal tumor. Another tumor occurred in a renal allograft and tumor cells were positive for the BK virus, demonstrated by SV40 immunohistochemistry. All tumors were negative for TFE3 and TFEB rearrangement and lacked TERT alterations. Follow-up was limited with no recurrence in 4 patients at a maximum of 20 months follow-up and 1 patient died of an unrelated cause at 25 months of follow-up. Next-generation sequencing analysis of all 5 CCAs revealed mutations within genes implicated in DNA damage repair and chromatin remodeling pathways, including ATM, BRCA1, BRCA2, ARID1A, DICER1, SMAD4, NOTCH1, and MYC amplification. These molecular findings underscore the dysregulation of fundamental cellular processes essential for genomic integrity maintenance.