Gutierrez CM, et al. - The researchers carried out one of the biggest studies to date of invasive high-grade urothelial carcinoma (with an inverted/endophytic growth pattern, it can, sometimes, imitate inverted urothelial papilloma and pose diagnostic challenges when evaluating the presence or absence of invasion) originating in a background of urothelial carcinoma with an inverted growth pattern. The bladder, renal pelvis, ureter, and prostatic urethra were primary sites investigated. Clinicopathologic parameters like the extent of invasion, variant histology, presence of urothelial carcinoma in situ, and clinical follow-up were collected. A total of 91 cases from 82 patients were involved. In 81%, 60%, 20% and 100% of the bladder, ureter, renal pelvis, and of prostatic urethra cases, respectively, the lamina propria invasion was present, while in 19%, 14% and 20% of the bladder, ureter, and renal pelvis cases, respectively, the muscularis propria invasion was recognized. Urothelial carcinoma invaded periureteric fat and the renal parenchyma in 29% of ureter cases and in 60% of renal pelvis cases, respectively. Recurrent urothelial carcinoma in 63/82, 16/82 and 20/77 patients, continued, progressed with metastatic disease, and in those with bladder involvement led to death, respectively. Hence, the study highlighted the significance of differentiating these tumors from benign mimickers of urothelial carcinoma. Moreover, in a subset of these patients, identification of invasive foci was also critical in view of the potentially high frequency of recurrence, and the possibility of advanced disease.