Urothelial carcinoma of the upper urinary tract diagnosed via FGFR3 mutation detection in urine: a case report

BACKGROUND: Upper urinary tract cancer is typically diagnosed with urine cytology and imaging techniques. These assays can be limited by sensitivity, specificity, or technical issues making some diagnoses difficult. CASE PRESENTATION: A 73-year old man presented to the clinic with a right renal pelvis filling defect that was detected by a CT-scan performed for unrelated reasons. Urine cytology was negative. Cystoscopy, retrograde pyelogram, and partial ureteroscopy were unable to visualize the lesion resulting in an indeterminate diagnosis. A subsequent CT scan confirmed the renal lesion which appeared to have become larger and was consistent with urothelial carcinoma. A urine based genetic assay was used to test for the presence of urothelial carcinoma. This assay evaluates the presence of mutations in fibroblast growth factor receptor 3 (FGFR3). Mutations in FGFR3 are known to be associated with urothelial carcinoma and have a positive predictive value of 95% when detected in patients with no history of TCC. A mutation in exon 10 (Y375C) of FGFR3 was identified. Nephroureterectomy was performed and the subsequent pathology confirmed urothelial carcinoma. In addition, PCR analysis on isolated tumor tissue indicated the tumor carried the same FGFR3 mutation as that of the DNA isolated from urine, consistent with the tumor being the origin of the mutant DNA. CONCLUSION: This study indicates that the FGFR3 urine assay, which was originally developed to monitor bladder cancer, is also a useful tool for diagnosing upper urinary tract cancer in a real-life setting.