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

Objective: To investigate the clinicopathological features, immunophenotype, molecular characteristics and prognosis of acquired cystic disease-associated renal cell carcinoma (ACD-RCC). Methods: The clinicopathological data of four ACD-RCC cases diagnosed at the Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China and one case at the Ningbo Clinical Pathology Diagnostic Center, Ningbo, China between 2018 and 2025 were collected. The clinical, histological, and immunohistochemical characteristics were analyzed. FISH and high-throughput DNA targeted next generation sequencing (NGS) were carried out. Follow-up was conducted with review of relevant literature. Results: Among the five patients, four were male and one was female, aged 45-71 years. All patients had a history of chronic kidney disease (duration 9-30 years) and received dialysis treatment. Three cases occurred in the right kidney and two in the left kidney. All were single lesions with a maximum diameter of 2.0-15.0 cm. Grossly, the tumors showed a solid-cystic appearance. Histologically, various histological patterns were observed, including cystic (4 cases), tubular (4 cases), papillary (4 cases), solid (2 cases), cribriform (2 cases), and microcystic structures (1 case). Two cases were accompanied by tumor necrosis, and one case was accompanied by sarcomatoid differentiation. The tumor cells had abundant eosinophilic cytoplasm with intracytoplasmic vacuoles, conspicuous nucleoli, and high nuclear grades (World Health Organization/International Society of Urological Pathology nuclear grade 3 or 4). Two cases had focal, clear cytoplasm. Oxalate crystals were present in all tumors. In all cases, the surrounding renal parenchyma was atrophic with multiple cysts. The cysts in three cases were lined by single-or multiple-layered eosinophilic cells, which had abundant cytoplasm and visible nucleoli. Tumor cells in all five cases expressed PAX8, CD10 and P504s. Two cases partially expressed carbonic anhydrase Ⅸ(CAⅨ). Two cases focally expressed CK7, CD117, HMB45, Melan A, TFE3, TFEB, GATA3, 2SC and ALK were negative in all cases. FH, SDHB and SMARCB1 (INI1) proteins were not deficient. TFE3 gene rearrangement was not detected in two cases using FISH with break-apart probes. High-throughput DNA targeted NGS showed that one tumor had a KMT2C mutation, one had KMT2B, TSC1, SETD2 and TP53 mutations, one had an MTOR mutation, one had a TSC2 mutation, and one had an SETD2 mutation. The five cases were followed up for 6-70 months and had no recurrence or metastasis, except one case with local recurrence and retroperitoneal lymph node metastasis four years after the surgery. Conclusions: ACD-RCC is a rare renal cell carcinoma that occurs in patients with end-stage renal disease and has unique morphological features. It is often associated with favorable prognosis and alterations in genes related to the MTOR/TSC pathway or chromatin modification.