Editing Kidney Cancer: Pathology (section)

== Renal cell carcinoma (RCC) ==

* '''<span style="color:#ff0000">Most common (>90%) non-metastatic malignant histology of kidney tumours</span>'''
** Most common benign tumours of the kidney include oncocytoma and angiomyolipoma (AML).
* '''<span style="color:#ff0000">Most common renal tumour in pregnancy[https://pubmed.ncbi.nlm.nih.gov/3756780/]</span>'''
* '''<span style="color:#ff0000">All RCCs are adenocarcinomas</span>'''
** '''<span style="color:#ff0000">Most are derived from</span> renal tubular epithelial cells <span style="color:#ff0000">of the proximal convoluted tubule</span>'''
*** Exceptions include chromophobe, collecting duct, and medullary RCC (see below)

=== <span style="color:#ff0000">Subtypes</span> ===
{| class="wikitable"
|'''<span style="color:#ff0000">Histology</span>'''
|'''<span style="color:#ff0000">Characteristics</span>'''
|'''<span style="color:#ff0000">Familial form and genetic factors</span>'''
|-
|'''<span style="color:#ff0000">Clear cell RCC (ccRCC)</span>'''

'''<span style="color:#ff0000">(70-80%, most common)</span>'''
|'''<span style="color:#ff0000">Originates from proximal tubule</span>'''

'''<span style="color:#ff0000">Prognosis generally worse compared to papillary or chromophobe</span>'''

'''Responds to systemic therapy'''
|'''<span style="color:#ff0000">von Hippel-Lindau disease</span>'''

'''Chromosome 3p deletions''' (VHL inactivation by mutation or promoter hypermethylation occurs in 70-90% of clear cell renal tumors)
|-
|'''Multilocular cystic'''

'''ccRCC'''

'''(uncommon)'''
|'''Almost uniformly benign clinical behavior'''
|'''Identical to ccRCC'''
|-
|'''<span style="color:#ff0000">Papillary RCC</span>'''

'''<span style="color:#ff0000">(10-15%, 2nd most common)</span>'''
|'''<span style="color:#ff0000">Originates from proximal tubule</span>'''

'''<span style="color:#ff0000">Commonly multifocal</span>'''

'''<span style="color:#ff0000">Common in ESRD and acquired renal cystic disease</span>'''

'''<span style="color:#ff0000">Type 1: good prognosis</span>'''

'''<span style="color:#ff0000">Type 2: worse prognosis</span>'''

'''Grade may be of greater prognostic significance than type 1 vs. 2'''

'''<span style="color:#ff0000">Current systemic therapies are ineffective against papillary RCC</span>'''

Papillary adenomas are small (≤5mm) tumours that resemble papillary RCC under the microscope, are often well encapsulated and low grade, commonly found at autopsy, possess many of the same genetic alterations found in larger papillary RCCs, but are benign neoplasms
|'''<span style="color:#ff0000">Type 1: Hereditary papillary RCC (HPRCC) syndrome</span>'''

'''<span style="color:#ff0000">Type 2: Hereditary leiomyomatosis and RCC syndrome (HLRCC)</span>'''

'''Trisomy of chromosomes 7 and 17 and loss of the Y chromosome.'''
|-
|'''<span style="color:#ff0000">Chromophobe RCC</span>'''

'''<span style="color:#ff0000">(3-5%)</span>'''
|'''<span style="color:#ff0000">Originates from</span>''' intercalated cells of '''<span style="color:#ff0000">distal tubule/collecting duct</span>'''

'''Stains positive for Hale colloidal iron'''

'''<span style="color:#ff0000">Generally good prognosis</span>''', compared to clear cell and papillary

* Rates of disease-specific (recurrence, metastasis, or death due disease) events following nephrectomy:[https://pubmed.ncbi.nlm.nih.gov/21602658/]
** 5 years: 3.7%
** 10 years: 6.4%
* Features associated with disease-specific events (4):[https://pubmed.ncbi.nlm.nih.gov/21602658/]
*# Tumour size
*# Small-vessel invasion
*# Sarcomatoid features
*# Microscopic necrosis
** pT stage or nodal metastasis tended to show some association, without reaching statistical significance
|'''<span style="color:#ff0000">Commonly seen Birt-Hogg-Dubé syndrome;</span> most cases are sporadic'''
|-
|'''<span style="color:#ff0000">Collecting duct carcinoma (<1%)</span>'''
|'''<span style="color:#ff0000">Originates from collecting duct</span>'''

'''Stains positive with Ulex europaeus lectin'''

'''Poor prognosis;''' most reported cases have been high grade, advanced stage, and unresponsive to conventional therapies

'''May share features in common with urothelial carcinoma;''' '''advanced collecting duct carcinoma may respond to cisplatin or gemcitabine-based chemotherapy'''
|Unknown

Multiple chromosomal losses
|-
|'''<span style="color:#ff0000">Renal medullary carcinoma</span> (rare)'''
|'''<span style="color:#ff0000">Originates from collecting duct</span>'''

'''Dismal prognosis'''; '''many cases are both locally advanced and metastatic at the time of diagnosis'''
|'''<span style="color:#ff0000">Associated with sickle cell trait (NOT disease);</span>''' typically diagnosed in young African-Americans
|-
|'''Unclassified RCC'''

'''(1%-3%)'''
|'''Origin not defined'''

'''Poor prognosis''', most are poorly differentiated and are associated with a highly aggressive biologic behavior
|Unknown
|-
|'''RCC associated with Xp11.2'''

'''translocations/TFE3'''

'''gene fusions (rare)'''
|'''Occurs in children and young adults;''' 40% of pediatric RCC

Prognosis similar to ccRCC
|Various mutations involving chromosome Xp11.2

resulting in TFE3 gene fusion
|-
|Post-neuroblastoma

RCC (rare)
|Occurs exclusively in children with prior neuroblastoma
|Unknown
|-
|Mucinous tubular and spindle cell (rare)
|Favorable prognosis
|Unknown
|}

=== <span style="color:#ff0000">Other histologic features</span> ===

* '''<span style="color:#ff0000">Sarcomatoid differentiation</span>'''
** Found in 1-5% of RCCs
** '''Not a distinct histologic subtype of RCC''', '''<span style="color:#ff0000">most commonly in association with ccRCC and chromophobe RCC</span>'''
** '''<span style="color:#ff0000">Associated with worse prognosis;</span> multimodal approaches should be considered'''
* '''Cystic degeneration'''
** Found in 10-25% of RCCs
** '''Associated with better prognosis''' compared with purely solid RCC

* '''Laterality and focality'''
** '''<span style="color:#ff0000">Most sporadic RCCs are unilateral and unifocal</span>'''
** '''<span style="color:#ff0000">Bilateral involvement</span>'''
*** Occurs in 2-4% of sporadic RCCs
**** '''More common in patients with familial forms of RCC ('''e.g'''.''' von Hippel-Lindau disease).
*** Can be synchronous or asynchronous
**** '''<span style="color:#ff0000">If synchronous, likely an independent growth</span>'''
**** '''<span style="color:#ff0000">If asynchronous, likely a metastasis</span>'''
** '''<span style="color:#ff0000">Multifocality'''
*** '''<span style="color:#ff0000">Occurs in 10-20% of cases</span>'''
*** '''<span style="color:#ff0000">More common with papillary histology and familial RCC</span>'''
*** '''<span style="color:#ff0000">Microsatellite analysis suggests a clonal origin for most multifocal RCC</span>'''