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Although collecting duct carcinoma is a subtype of renal cell carcinoma, several studies implicate association with urothelial carcinoma. The coexistence of collecting duct carcinoma and another renal neoplasm is rare. Endemic nephropathy is a renal disease causing chronic renal failure. It is highly associated with urothelial neoplasm and occurs in endemic villages in Bosnia, Croatia, Bulgaria, Romania and Serbia. Recent studies have confirmed the important role of exposure to aristolochic acid as an etiologic factor. We present three cases of collecting duct carcinoma with literature overview. In one case, we describe collecting duct carcinoma with metachronous urothelial carcinoma of the pyelon and urinary bladder in an endemic nephropathy patient. To our knowledge, this is the first case report describing this coexistence. Certain similarities between collecting duct carcinoma and urothelial carcinoma were found, e.g., higher incidence in female compared to male, higher mean age, and multifocal and multicentric occurrence of the tumor. Our observations support the hypothesis that collecting duct carcinoma and urothelial carcinoma could be connected.

Aristolochic acid (AA) is a potent dietary cytotoxin and carcinogen, and an established etiological agent underlying severe human nephropathies and associated upper urinary tract urothelial cancers, collectively designated aristolochic acid nephropathy (AAN). Its genome-wide mutational signature, marked by predominant A:T > T:A transversions occurring in the 5'-CpApG-3' trinucleotide context and enriched on the nontranscribed gene strand, has been identified in human upper urinary tract urothelial carcinomas from East Asian patients and in experimental systems. Here we report a whole-exome sequencing screen performed on DNA from formalin-fixed, paraffin-embedded renal cell carcinomas (RCC) arising in chronic renal disease patients from a Balkan endemic nephropathy (EN) region. In the EN regions, the disease results from the consumption of bread made from wheat contaminated by seeds of Aristolochia clematitis, an AA-containing plant. In five of eight (62.5%) tested RCC tumor specimens, we observed the characteristic global mutational signature consistent with the mutagenic effects of AA. This signature was absent in the control RCC samples obtained from patients from a nonendemic, metropolitan region. By identifying a new tumor type associated with the AA-driven genome-wide mutagenic process in the context of renal disease, our results suggest new epidemiological and public health implications for the RCC incidence worldwide, particularly for the high-risk regions with unregulated use of AA-containing traditional herbal medicines., (© 2014 UICC.)

Objective: The aim of this study was to correlate the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) with pathological renal artery changes in patients with renal cell carcinoma (RCC). A further aim was to correlate intratumoral microvessel density (MVD) with VEGF and HIF-1α expression and prognostic factors for RCC, including tumour necrosis., Material and Methods: Formalin-fixed and paraffin-embedded tissue blocks from 150 patients with RCC and 50 patients with non-tumorous kidney diseases were analysed. The control group consisted of specimens from both renal arteries obtained from 25 decedents at routine autopsy (50 cases in total). Immunohistochemistry was performed using primary antibodies to VEGF, HIF-1α and CD31., Results: Pathological renal artery changes were more common in patients with RCC and non-tumorous kidney diseases than in the control group. MVD was higher in the RCCs of patients with pathological renal artery changes. Tumours with higher HIF-1α expression had higher MVD; however, VEGF expression was not associated with MVD. A significant association was also found between MVD and the extent of tumour necrosis, in that less necrotic tumours had higher MVD. No association between renal artery changes and VEGF and HIF-1α expression was established., Conclusion: Considering the results of this study, the evaluation of renal artery changes in forthcoming research on RCC would be helpful for several reasons: to estimate their incidence in a larger number of patients, to clarify their connection with RCC and to reveal their relationship with MVD in RCC.

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial renal disease of a still unknown etiology, associated with an increased frequency of urothelial carcinoma, particularly of the upper urinary tract (UUT). The aim of the study was to compare the occurrence of UUT carcinomas between Brodsko-Posavska Region (BPR) which is the region with endemic villages and the non-endemic region of Zagreb (ZG) in two six-year periods with a 20 year period separating the two, pointing out a possible difference in occurrence regarding war in Croatia (1991-1995). Comparing BPR and ZG regions we found a more then 5 times higher frequency of UUT carcinomas in BPR in the first period and more than 4.5 times higher frequency in the second period. Women in BPR were more frequently affected with UUT carcinomas.

Necrosis, cysts, hemorrhage, and calcification represent common findings in renal cell carcinoma. Different lesions, including arteriosclerosis or fibromuscular dysplasia, or both, may involve the main renal artery. This study analyzed the relationship between the presence and extent of necrosis in renal cell carcinoma with renal artery changes in a consecutive series of 112 patients (71 men, 41 women) with mean renal cell carcinoma of 7.7 cm (range, 2 to 20 cm). Necrosis was seen macroscopically and confirmed microscopically in 88 cases (78.6%), with 64 tumors having less than 50% and 24 more than 50% necrosis. Fibromuscular dysplasia was found in 41 patients (36.6%; 17 men, 24 women) and atherosclerotic changes in 21 patients (18.8%; 18 men, 3 women). The results suggest that necrosis of renal cell carcinoma was significantly more common in women with associated fibromuscular dysplasia (especially type I) and men with atherosclerotic changes of renal artery.