Discussion:

Primary neoplasms of the renal pelvis are rare, accounting for appx 7% of all renal tumors, with the majority arising from the urothelium.

Urothelial carcinoma (UC) of the renal pelvis are often of high histological grade and present in advanced stages, with poor prognosis when there is large infiltration of the kidney. They are also known for multicentricity and high incidence of recurrence.

Histologically, neoplasticism cells invade as nests, cords, and trabeculae, though a more diffuse, sheet-like pattern can sometimes be seen. The cells have abundant eosinophilic cytoplasm and pleomorphic nuclei.

UC of the renal pelvis tend to display unusual morphologic features and metaplastic phenomena including clear cell appearance, sarcomatoid or rhabdoid features, and intratubular spread (IS).

IS can typically be seen on H&E, and more specifically using positivity for PAX8 to highlight renal tubule cells and p63 to label urothelial carcinoma cells.

Evaluating the type of IS is crucial for accurate staging. Common types based on histopathological patterns include: pagetoid, typical, florid, secondary invasion from intratubular spread; though additional unusual morphological variants have been described.

Pagetoid intratubular spread show the involved tubules contain predominantly renal tubule cells with only a few urothelial carcinoma cells, while Florid spread shows the involved tubules are significantly enlarged and completely occupied with urothelial carcinoma cells with a solid nest pattern.

Difficulty in accurate diagnosis is primarily a result of the difficulty of capturing IS. Preferred biopsy methods from cystoscopy and uteroscopy are typically small and superficial, making it unlikely to capture the intratubular spread portion. PAX and p63 may not always capture IS as some UC variants can be negative for p63, and in rare cases positive for PAX8.