Editing Upper Urinary Tract Urothelial Cancer (section)

== Histology ==

=== Normal upper tract urothelium ===
* '''Bladder is derived from the endoderm; ureter and renal pelvis are derived from the mesoderm'''
* The urothelial lining of the upper urinary tract closely approximates that of the bladder except for the markedly reduced thickness of the muscle layer and the abutting of the urothelium to the renal parenchyma proximally.
* The epithelial layer is continuous from the level of the calyces to the distal ureter.
** It has been suggested that the urothelial layer may even “extend” into the collecting ducts, raising the possibility that collecting duct renal cancers may be closely related to urothelial cancers and perhaps better treated by agents used for urothelial cancers
* '''Renal pelvis and calyces'''
** '''The walls of the calyces and the pelvis''' '''contain''' fibrous connective tissue and 2 layers of '''smooth muscle''' and are lined on their inner surfaces with urothelium
* Ureter
** The 3 muscular layers of the ureter merge with the 3 muscular layers of the bladder

=== Abnormal urothelium ===

==== Benign lesions ====
* '''Papillomas and inverted papillomas'''
** '''Generally considered benign lesions'''
** '''Association with either synchronous or metachronous UTUC'''
*** '''<span style="color:#ff0000">Follow-up for all cases of inverted papilloma should be continued for at least 2 years after initial diagnosis</span>'''
* '''Von Brunn Nests'''
** '''Reactive proliferation, considered a variation of normal urothelium.'''

==== Metaplasia and dysplasia ====
* '''<span style="color:#ff0000">In a significant proportion of patients, UTUCs progress from hyperplasia to dysplasia to frank CIS</span>'''

==== Urothelial carcinoma ====
* '''<span style="color:#ff0000">Majority (90%) of upper tract tumours are urothelial carcinoma</span>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308053/]'''
** Squamous and adenocarcinomas comprise a small minority.
* '''UTUC are histologically similar to urothelial carcinoma of the bladder, but <span style="color:#ff0000">the relative thinness of the muscle layer of the renal pelvis and ureter may allow earlier penetration of invasive upper tract tumors than is seen in bladder neoplasms.</span>'''
** '''<span style="color:#ff0000">UTUC is more often invasive and poorly differentiated than bladder cancers. However, in pathologically matched cohorts, cancer-specific outcomes are comparable between urothelial tumours of the upper tract and bladder</span>'''
* '''Reported variants of urothelial carcinoma are squamous cell, glandular, sarcomatoid, micropapillary, neuroendocrine, and lymphoepithelial'''.
** Although all of these variants are considered aggressive tumors, after adjustment for the rest of clinicopathologic characteristics, '''<span style="color:#ff0000">variant histology has not been shown to predict poor clinical outcome in UTUC (unlike bladder cancer)</span>'''

==== Non-urothelial carcinoma ====
* '''<span style="color:#ff0000">Most commonly squamous cell carcinoma and adenocarcinoma</span>'''

===== Squamous =====
* '''Frequently associated with a condition of chronic inflammation or infection or with analgesic abuse'''
* '''Typically more aggressive at presentation'''
* Occur 6x more frequently in the renal pelvis than in the ureter

===== Adenocarcinoma =====
* Rare
* '''Typically associated with long-term obstruction''', '''inflammation, or urinary calculi'''