[Clinicopathological and molecular features of acquired cystic kidney disease and associated renal cell carcinoma].

Abstract

Objective: To investigate the clinicopathological and genetic features of acquired cystic kidney disease (ACKD) and secondary renal cell carcinoma (RCC) in end-stage renal disease (ESRD) patients undergoing dialysis.

Methods: The clinicopathological data of 9 patients with ACKD, of whom, 7 had concurrent RCC, of the Department of Pathology, Peking University Third Hospital from 2020 to 2025 were retrospectively analyzed. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to detect RCC-related proteins and targeted-drug associated gene variations/microsatellite instability (MSI) status.

Results: The 9 patients were all male, aged 29-64 years. Causes of ESRD included hypertension, IgA nephropathy, chronic glomerulonephritis, and diabetes. Dialysis duration ranged from 1 to 30 years (median 9.0 years), and 3 patients had kidney transplantation history. Imaging showed reduced kidney size and multiple cysts, including complex cysts. Solid lesions were found in the cyst wall of 5 patients with secondary RCC. The maximum diameter of tumors was 1.3-7.0 cm (median 3.0 cm). Histologically, except for typical morphological changes of ACKD and atypical renal cysts, some cases had papillary adenoma and hemorrhage. Six ACKD-associated RCC (ACKD-RCC) patients and 1 papillary RCC (pRCC) patient were diagnosed. Most ACKD-RCC tumor cells had eosinophilic cytoplasm; 5 patients predominantly showed papillary structure, and 1 patient mainly presented sieve-cystic with acinar/solid/micropapillary structures. Oxalate crystals were found in all ACKD-RCC cases, and most patients were accompanied by necrosis and calcification. P504S and CK7 were diffusely or focally positive in all the cases, while CAⅨ was negative. The World Health Organization/International Society of Urological Pathology (WHO/ISUP) nuclear grading of ACKD-RCC and pRCC were 2-3 and 3-4, respectively. Pathological staging of 5 RCC patients was pT1 and of the other 2 patients was pT3a. NGS results identified one PIK3CA point mutation and SETD2 deletion in one ACKD-RCC patient and the pRCC patient, which were accompanied by marked necrosis and pT3a staging. The RCC patients were regularly followed up for 1-32 months postoperatively without additional treatment, and no recurrence or metastasis was observed.

Conclusion: ACKD is a common complication in ESRD patients undergoing dialysis. In our cohort, ACKD-RCC was predominantly characterized by papillary architecture histologically with oxalate crystals in all cases. Immunohistochemically, P504S and CK7 were positive. Regardless of secondary occurrent tumor, atypical renal cysts were present in all ACKD cases in this study. NGS detected PIK3CA and SETD2 (Tier Ⅱ) variants in 2 RCC patients, respectively, accompanied by coagulative necrosis and advanced pathological stage, which may indicate a poor prognosis. This study suggests that imaging screening for RCC should be strengthened in young and middle-aged male ESRD patients with long-term dialysis, and adequate sample examination should be performed to detect potentially precancerous lesions, such as atypical renal cysts. The prognosis of ACKD-RCC requires comprehensive analysis combining clinicopathological and molecular genetic features.