Papillary Hyperplasia in Autosomal Dominant Polycystic Kidney Disease

Renal cysts in autosomal dominant polycystic kidney disease (ADPKD) frequently harbor small intracystic epithelial proliferations that arise in continuity with the cyst lining and are distinct from other recognized proliferative lesions or well-defined renal tumors and lack a formal designation. We aim to provide the histomorphologic, immunohistochemical (IHC), and molecular characteristics of these lesions, determine their incidence, and employ the term papillary hyperplasia (PH), consistent with the recent International Society of Urological Pathology (ISUP) consensus meeting report on precursor lesions of the kidney. A multi-institutional retrospective study of nephrectomies affected by ADPKD was reviewed for PH, histomorphologic features, and clinicopathologic data. PH was defined by intracystic tufted or papillary epithelial proliferations composed of a single layer of bland cuboidal epithelial cells with minimal amphophilic to eosinophilic cytoplasm. IHC stains and molecular analysis using whole-genome sequencing were performed on a subset of cases. Eighty-five nephrectomies from 48 patients demonstrated PH in 88% (75/85) of kidneys. Predominant architectural patterns were tufting (97%), papillary (72%), hobnail (72%), and micropapillary (51%). All PH exhibited low-grade nuclei without atypia, with amphophilic (95%) and/or eosinophilic cytoplasm (63%). The most well-developed PH per case measured 0.3 by 3.1 mm (mean height by width) and occurred within small cysts with an average diameter of 3 mm. PH were positive for KRT7, GATA3, L1CAM, variably positive for AMACR, and negative for CA9 and showed no definitive molecular alterations. PH are common microscopic findings in kidneys affected by ADPKD. PH show a distinct combined histomorphologic, IHC, and molecular profile.