International Society of Urological Pathology Consensus on Cancer Precursor Lesions

Compared with cancers of other organs, precursor lesions of renal cell neoplasms are rarely discussed. However, there are specific scenarios where cysts or microscopic solid lesions are thought to precede tumor formation. In 2024, the International Society of Urological Pathology (ISUP) held a consensus meeting on precursor lesions of urologic neoplasms in Florence, Italy. This report details the findings of Working Group 3-Precursor Lesions of the Kidney. Papillary adenoma is likely the best-established precursor lesion in the kidney, thought to be an incipient form of papillary renal cell carcinoma (RCC) with shared morphology, immunohistochemistry, and genetics. Likewise, in patients with VHL disease, the kidney often contains multiple small nodules of clear cells and/or cysts lined by one or more layers of clear cells, likely representing early tumor or precursor lesions. Interestingly, a precursor counterpart for clear cell RCC in the sporadic setting is not well established. In other scenarios, cysts are considered potential precursors of neoplasia, such as those in acquired cystic kidney disease (ACKD) and possibly in some hereditary renal tumor syndromes. The consensus panel proposes the following terms "cyst with epithelial proliferation" for tufted/hyperplastic/cribriform cyst lining in ACKD without solid tumor, and "papillary hyperplasia" for tufting of cyst lining in autosomal dominant polycystic kidney. Terms such as "tumorlet," "microtumor," or "incipient tumor" are acceptable for incidental unencapsulated microscopic lesions in hereditary syndrome patients. There is insufficient evidence for the diagnosis of "tubular dysplasia" as a precursor to RCC at the present time.