Editing Kidney Cancer: Pathology

[[Category:Kidney Cancer]]

== Classification of renal masses ==

=== 2016 WHO Classification of renal neoplasms[https://pubmed.ncbi.nlm.nih.gov/26935559/] ===
(abbreviated)
{| class="wikitable"
|
* '''<span style="color:#ff0000">Renal cell tumours (16)</span>'''
** Clear cell renal cell carcinoma
** Multilocular cystic renal neoplasm of low malignant potential
** Papillary renal cell carcinoma
** Hereditary leiomyomatosis and renal cell carcinoma associated renal cell carcinoma
** Chromophobe renal cell carcinoma
** Collecting duct carcinoma
** Renal medullary carcinoma
** MiT family translocation renal cell carcinomas
** Succinate dehydrogenase deficient renal cell carcinoma
** Mucinous tubular and spindle cell carcinoma
** Tubulocystic renal cell carcinoma
** Acquired cystic disease associated renal cell carcinoma
** Clear cell papillary renal cell carcinoma
** Renal cell carcinoma, unclassified
** Papillary adenoma
** Oncocytoma

* '''Metanephric tumors'''
** Metanephric adenoma
** Metanephric adenofibroma
** Metanephric stromal tumor

* '''Nephroblastic and cystic tumors occurring mainly in children'''
** Nephrogenic rests
** Nephroblastoma
** Cystic partially differentiated nephroblastoma
** Pediatric cystic nephroma
|
* '''Mesenchymal tumors occurring mainly in children'''
** Clear cell sarcoma
** Rhabdoid tumor
** Congenital mesoblastic nephroma
** Ossifying renal tumor of infancy

* '''Mesenchymal tumors occurring mainly in adults'''
** Leiomyosarcoma (including renal vein leiomyosarcoma)
** Angiosarcoma
** Rhabdomyosarcoma
** Osteosarcoma
** Synovial sarcoma
** Ewing sarcoma
** Angiomyolipoma
** Epithelioid angiomyolipoma
** Leiomyoma
** Hemangioma
** Lymphangioma
** Hemangioblastoma
** Juxtaglomerular cell tumor
** Renomedullary interstitial cell tumor
** Schwannoma
** Solitary fibrous tumor
** Mixed epithelial and stromal tumor family
** Adult cystic nephroma
** Mixed epithelial and stromal tumor

* '''Neuroendocrine tumors'''
** Well differentiated neuroendocrine tumor
** Large cell neuroendocrine carcinoma
** Small cell neuroendocrine carcinoma
** Paraganglioma

* '''Miscellaneous tumors'''
**Renal hematopoietic neoplasms
**Germ cell tumors
* '''Metastatic tumors'''
* '''Tumor-like lesions'''
** Xanthogranulomatous pyelonephritis
** IgG4 related disease
|}
There are additional described entities not currently in WHO

=== Classification by malignant vs. benign vs. inflammatory ===
{| class="wikitable"
|
* '''Malignant'''
** Renal cell carcinoma (RCC)
**# Clear cell RCC
**# Multilocular cystic renal neoplasm of low malignant potential
**# Papillary RCC
**# Hereditary leiomyomatosis RCC
**# Chromophobe RCC
**# Collecting duct carcinoma
**# Renal medullary carcinoma
**# MiT Family translocation carcinomas
**# Succinate dehydrogenase (SDH) deficient RCC
**# Mucinous tubular and spindle cell carcinoma
**# Tubulocystic RCC
**# Acquired cystic disease associated RCC
**# Clear cell papillary RCC
**# RCC, unclassified
** Urothelium-based cancers
*** Urothelial carcinoma
*** Squamous cell carcinoma
*** Adenocarcinoma
** Sarcomas
*** Leiomyosarcoma
*** Liposarcoma
*** Angiosarcoma
*** Hemangiopericytoma
*** Malignant fibrous histiocytoma
*** Synovial sarcoma
*** Osteogenic sarcoma
*** Clear cell sarcoma
*** Rhabdomyosarcoma
** Wilms tumor
** Primitive neuroectodermal tumor
** Carcinoid tumor
** Lymphoma/leukemia
** Metastasis
** Invasion by adjacent neoplasm
|
* '''Benign'''
** Cystic lesions
*** Simple cyst
*** Hemorrhagic cyst
** Solid lesions
*** Angiomyolipoma
*** Oncocytoma
*** Renal adenoma
*** Metanephric adenoma
*** Cystic nephroma
*** Mixed epithelial-stromal tumor
*** Reninoma (juxtaglomerular cell tumor)
*** Leiomyoma
*** Fibroma
*** Hemangioma
** Vascular lesions
*** Renal artery aneurysm
*** Arteriovenous malformation
** Pseudotumor

* '''Inflammatory'''
** Abscess
** Focal pyelonephritis
** Xanthogranulomatous pyelonephritis
** Infected renal cyst
** Tuberculosis
** Rheumatic granuloma
|}

== 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>'''

== Grade ==

* Based primarily on nuclear size, shape, and presence of predominant nucleoli
* Fuhrman Grading system
** Described in 1982
* International Society of Urological Pathology (ISUP) Grading system
** Proposed in 2012, updated in 2016
** Incorporates aspects of the Fuhrman Grading system but includes more objective criteria for nuclear characteristics.
** Sarcomatoid and rhabdoid tumors, tumors with giant cells, and tumors with extreme nuclear pleomorphism are included within grade 4 tumors.
** Chromophobe RCC is no longer graded in the ISUP system.
* In general, higher grade is associated with larger tumor size and more aggressive tumors.</span>
== Questions ==

# What the prognosis of ccRCC relative to chromophobe and papillary RCC? Which papillary RCC subtype is associated with better prognosis relative to the other?
# Patients with ESRD or acquired renal cystic disease are more likely to develop which type of RCC?
# Which RCC histology stains for Hale colloidal iron?
# Which RCC histologies arise from the proximal tubule vs. collecting duct?

== Answers ==

# What the prognosis of ccRCC relative to chromophobe and papillary RCC? Which papillary RCC subtype is associated with better prognosis relative to the other?
#* Prognosis of ccRCC is worse than chromophobe and papillary RCC
#* Type II papillary RCC has worse prognosis than type I
# Patients with ESRD or acquired renal cystic disease are more likely to develop with type of RCC?
#* Papillary
# Which RCC histology stains for Hale colloidal iron?
#* Chromophobe
# Which RCC histologies arise from the proximal tubule vs. collecting duct?
## Proximal tubule:
### Clear cell
### Papillary
## Collecting duct
### Chromophobe
### Collecting duct
### Medullary

== Next Chapter: [[Kidney Cancer: TNM Staging|TNM Staging]] ==

== References ==

* Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 57
* Campbell, Steven C., et al. "Renal Mass and Localized Renal Cancer: Evaluation, Management, and Follow-Up: AUA Guideline Part I." ''The Journal of urology'' (2021): 10-1097.