Difference between revisions of "Kidney tumours"

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'''[[Kidney]] tumours''' - includes '''malignant kidney tumours''' and '''benign kidney tumours'''.  Medical renal diseases are dealt with in the [[medical renal diseases]] article.
[[Image:Renal oncocytoma.jpg|thumb|250px|A kidney tumour ([[renal oncocytoma]]). (WC/Emmanuelm)]]
'''[[Kidney]] tumours''' - includes '''malignant kidney tumours''' ('''kidney cancer''') and '''benign kidney tumours'''.  Medical renal diseases are dealt with in the [[medical renal diseases]] article.


Pediatric kidney tumours are dealt with in the ''[[pediatric kidney tumours]]'' article.
Pediatric kidney tumours are dealt with in the ''[[pediatric kidney tumours]]'' article.
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=Renal specimens=
=Renal specimens=
*[[Renal biopsy]] - usually for [[renal oncocytoma]] vs. renal cell carcinoma (RCC) ''or'' medical diseases - see ''[[medical kidney]]''.
*[[Renal biopsy]] - usually for [[renal oncocytoma]] vs. renal cell carcinoma (RCC) ''or'' medical diseases - see ''[[medical kidney]]''.
*Partial nephrectomy.
*[[Partial nephrectomy]].
*Nephrectomy.
*[[Nephrectomy]].
*Nephroureterectomy (includes ureter) - done for [[urothelial cell carcinoma]] (UCC) of the renal pelvis and ureteric UCC.
*[[Nephroureterectomy]] (includes [[ureter]]) - done for [[urothelial cell carcinoma]] (UCC) of the renal pelvis and ureteric UCC.
*Radical nephrectomy - includes Gerota's fascia.
*[[Radical nephrectomy]] - includes Gerota's fascia.
**May include the [[adrenal gland]].<ref name=Ref_WMSP|288>{{Ref WMSP|288}}</ref>
**May include the [[adrenal gland]].<ref name=Ref_WMSP|288>{{Ref WMSP|288}}</ref>


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==Anatomy==
==Anatomy==
The anatomy is important for properly staging renal neoplasms.
Layers (superficial to deep):
Layers (superficial to deep):
#Renal fascia (Gerota's fascia).
#Renal fascia (Gerota's fascia).
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===Sign out===
===Sign out===
====Missed renal biopsy====
====Missed renal biopsy====
<pre>
{{Main|Missed renal biopsy}}
KIDNEY (LESION), LEFT, CORE BIOPSY:
- RENAL PARENCHYMA.
- NEGATIVE FOR MASS LESION, SEE COMMENT.
 
COMMENT:
No mass lesion is apparent in the tissue sampled. A re-biopsy should be considered.
 
Renal parenchyma:
- Glomeruli: seven glomeruli sampled, no apparent glomerular pathology on the H&E sections.
- Interstitium: interstitial fibrosis is not identified.
- Tubules: no pathology is apparent.
- Vessels: mild atherosclerosis, no hyalinization of arterioles apparent.
</pre>


=Tabular comparison (selected tumours)=  
=Tabular comparison (selected tumours)=  
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|-
|-
|IHC
|IHC
| CK7-, EMA+
| [[CK7]]-, EMA+
| AMACR+, EMA+, CK7+
| AMACR+, EMA+, CK7+
| AMACR+, E-cadherin+, CK7-
| AMACR+, E-cadherin+, CK7-
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===Tabular comparison of oncocytoma and chromophobe RCC===
===Tabular comparison of oncocytoma and chromophobe RCC===
Histomorphologic features useful to distinguish chromophobe RCC (eosinophilic variant) and oncocytoma:<ref name=pmid9844591>{{Cite journal  | last1 = Tickoo | first1 = SK. | last2 = Amin | first2 = MB. | title = Discriminant nuclear features of renal oncocytoma and chromophobe renal cell carcinoma. Analysis of their potential utility in the differential diagnosis. | journal = Am J Clin Pathol | volume = 110 | issue = 6 | pages = 782-7 | month = Dec | year = 1998 | doi =  | PMID = 9844591 }}
Histomorphologic features useful to distinguish chromophobe RCC (eosinophilic variant) and oncocytoma:<ref name=pmid9844591>{{Cite journal  | last1 = Tickoo | first1 = SK. | last2 = Amin | first2 = MB. | title = Discriminant nuclear features of renal oncocytoma and chromophobe renal cell carcinoma. Analysis of their potential utility in the differential diagnosis. | journal = Am J Clin Pathol | volume = 110 | issue = 6 | pages = 782-7 | month = Dec | year = 1998 | doi =  | PMID = 9844591 }}</ref>
</ref>
{| class="wikitable sortable"
{| class="wikitable sortable"
! Morphologic feature
! Morphologic feature
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===Common DDx===
===Common DDx===
Spindle cell tumours:
====Spindle cell tumours====
*Malignant:
Malignant spindle cell tumours of the kidney:
**[[Renal cell carcinoma with sarcomatoid differentiation]].
*[[Renal cell carcinoma with sarcomatoid differentiation]].
**[[Renal mucinous tubular and spindle cell carcinoma]].
*[[Renal mucinous tubular and spindle cell carcinoma]].
**[[Wilms tumour]].
*[[Wilms tumour]].
*Benign:
*[[Renal cell carcinoma, unclassified]].
**[[Angiomyolipoma]].
**[[Cystic nephroma]].


=WHO classification=
Benign spindle cell tumours of the kidney:
*[[Angiomyolipoma]].
*[[Cystic nephroma]].
 
====Renal tumours with eosinophilic cytoplasm====
{{Main|Renal tumours with eosinophilic cytoplasm}}
 
=WHO classification of renal neoplasia=
*Based on 2004 iteration - as per WMSP, slightly modified.<ref>{{Ref WMSP|291}}</ref> Online, the classification can [http://www.urosource.com/fileadmin/user_upload/european_urology/PIIS0302283805008316.pdf found here].
*Based on 2004 iteration - as per WMSP, slightly modified.<ref>{{Ref WMSP|291}}</ref> Online, the classification can [http://www.urosource.com/fileadmin/user_upload/european_urology/PIIS0302283805008316.pdf found here].
==Renal cell tumours==
===Renal cell tumours===
Common:
Common:
*[[Clear cell renal cell carcinoma]].
*[[Clear cell renal cell carcinoma]].
*[[Multilocular clear cell renal cell carcinoma]].
*[[Papillary renal cell carcinoma]].
*[[Papillary renal cell carcinoma]].
*[[Renal papillary adenoma|Papillary adenoma]].
*[[Renal papillary adenoma|Papillary adenoma]].
*[[Chromophobe renal cell carinoma]].
*[[Chromophobe renal cell carcinoma]].
*[[Renal oncocytoma|Oncocytoma]].
*[[Renal oncocytoma|Oncocytoma]].


Less common:
Less common:
*[[Multilocular clear cell renal cell carcinoma]].
*[[Carcinoma of the collecting ducts of Bellini]].
*[[Carcinoma of the collecting ducts of Bellini]].
*[[Renal cell carcinoma, unclassified]].
*[[Renal cell carcinoma, unclassified]].
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*Carcinoma associated with neuroblastoma.
*Carcinoma associated with neuroblastoma.


==Metanephric tumours==
===Metanephric tumours===
*[[Metanephric adenoma]].
*[[Metanephric adenoma]].
*[[Metanephric stromal tumour]].
*[[Metanephric stromal tumour]].
*[[Metanephric adenofibroma]].
*[[Metanephric adenofibroma]].


==Nephroblastic tumours==
===Nephroblastic tumours===
*Nephrogenic rests.
*Nephrogenic rests.
*[[Nephroblastoma]].
*[[Nephroblastoma]].


==Mesenchymal tumours==
===Mesenchymal tumours===
Childhood:
Childhood:
*[[Clear cell sarcoma of the kidney]].
*[[Clear cell sarcoma of the kidney]].
*[[Rhabdoid tumour]].
*[[Rhabdoid tumour]].
*[[Mesoblastic nephroma|Congenital mesoblastic nephroma]]
*[[Mesoblastic nephroma|Congenital mesoblastic nephroma]].


Adults:  
Adults:  
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*[[Schwannoma]].
*[[Schwannoma]].


==Mixed mesenchymal and epithelial tumours==
===Mixed mesenchymal and epithelial tumours===
*[[Cystic nephroma]].
*[[Cystic nephroma]].
*[[Mixed epithelial and stromal tumour]].
*[[Mixed epithelial and stromal tumour]].
*[[Synovial sarcoma]].
*[[Synovial sarcoma]].


==Others==
===Others===
*[[Neuroendocrine tumours]].
*[[Neuroendocrine tumours]].
*Hematologic tumours.
*Hematologic tumours.
*[[Germ cell tumour]]s.
*[[Germ cell tumour]]s.
*[[Metastases]].
*[[Metastases]].
==Vancouver modification of WHO classification==
In 2012/2013, several additions were made:<ref name=pmid24025519>{{Cite journal  | last1 = Srigley | first1 = JR. | last2 = Delahunt | first2 = B. | last3 = Eble | first3 = JN. | last4 = Egevad | first4 = L. | last5 = Epstein | first5 = JI. | last6 = Grignon | first6 = D. | last7 = Hes | first7 = O. | last8 = Moch | first8 = H. | last9 = Montironi | first9 = R. | title = The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia. | journal = Am J Surg Pathol | volume = 37 | issue = 10 | pages = 1469-89 | month = Oct | year = 2013 | doi = 10.1097/PAS.0b013e318299f2d1 | PMID = 24025519 }}</ref>
*[[Tubulocystic renal cell carcinoma]].
*[[Acquired cystic disease associated renal cell carcinoma]].
*[[Clear cell papillary renal cell carcinoma]] (clear cell tubulopapillary renal cell carcinoma).
*[[Hereditary leiomyomatosis renal cell carcinoma syndrome associated renal cell carcinoma]].
*MiT family translocation renal cell carcinoma - includes:
**[[t(6;11) renal cell carcinoma]].
"Emerging" entities (as per Vancouver) are:
*[[Thyroid-like follicular renal cell carcinoma]].
*[[Succinate dehydrogenase-deficient renal cell carcinoma]].
*[[ALK translocation renal cell carcinoma]].
==An entity proposed after Vancouver==
*[[Eosinophilic, solid and cystic renal cell carcinoma]].
*[[Biphasic hyalinizing psammomatous renal cell carcinoma]].
*[[Papillary renal neoplasm with reverse polarity]].
*[[Low-grade oncocytic renal tumour]].


=Renal cell carcinoma=
=Renal cell carcinoma=
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*Male>female (~2:1).
*Male>female (~2:1).
*Hereditary - familial syndromes (see [[Hereditary RCC]]).
*Hereditary - familial syndromes (see [[Hereditary RCC]]).
*[[Obesity]].<ref name=pmid8770461>{{Cite journal  | last1 = Chow | first1 = WH. | last2 = McLaughlin | first2 = JK. | last3 = Mandel | first3 = JS. | last4 = Wacholder | first4 = S. | last5 = Niwa | first5 = S. | last6 = Fraumeni | first6 = JF. | title = Obesity and risk of renal cell cancer. | journal = Cancer Epidemiol Biomarkers Prev | volume = 5 | issue = 1 | pages = 17-21 | month = Jan | year = 1996 | doi =  | PMID = 8770461 }}</ref>


===Subtypes of RCC===
===Subtypes of RCC===
RCC (renal cell carcinoma) comes in different subtypes:<ref name=Ref_PBoD1016>{{Ref PBoD|1016}}</ref>
RCC (renal cell carcinoma) comes in different subtypes:<ref name=Ref_PBoD1016>{{Ref PBoD|1016}}</ref>
*Clear cell carcinoma (70-80% of RCC) -- abbrev. CCRCC,
*Clear cell carcinoma (70-80% of RCC) -- abbrev. CCRCC.
*Papillary renal cell carcinoma (10-15% of RCC) -- abbrev. PRCC,
*Papillary renal cell carcinoma (10-15% of RCC) -- abbrev. PRCC.
*Chromophobe renal carcinoma (5% of RCC) -- abbrev. ChRCC,
*Chromophobe renal carcinoma (5% of RCC) -- abbrev. ChRCC.
*Collecting duct (Bellini duct) carcinoma (1% of RCC).
*Collecting duct (Bellini duct) carcinoma (1% of RCC).


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*Papillary RCC type 1 vs. papillary RCC type 2:
*Papillary RCC type 1 vs. papillary RCC type 2:
** E-cadherin +ve in PRCC type 2.<ref name=pmid14657952>{{cite journal |author=Langner C, Ratschek M, Rehak P, Schips L, Zigeuner R |title=Expression of MUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases |journal=Mod. Pathol. |volume=17 |issue=2 |pages=180? |year=2004 |month=February |pmid=14657952 |doi=10.1038/modpathol.3800032 |url=}}</ref>
** E-cadherin +ve in PRCC type 2.<ref name=pmid14657952>{{cite journal |author=Langner C, Ratschek M, Rehak P, Schips L, Zigeuner R |title=Expression of MUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases |journal=Mod. Pathol. |volume=17 |issue=2 |pages=180? |year=2004 |month=February |pmid=14657952 |doi=10.1038/modpathol.3800032 |url=}}</ref>
**EMA (MUC1) +ve in PRCC type 1.<ref name=pmid14657952/>
**[[EMA]] (MUC1) +ve in PRCC type 1.<ref name=pmid14657952/>


*ChRCC vs. oncocytoma (ONC):
*ChRCC vs. oncocytoma (ONC):
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*Pathologically, this is not very difficult.   
*Pathologically, this is not very difficult.   
*On gross specimens, it is almost always obvious what one is dealing with:
*On gross specimens, it is almost always obvious what one is dealing with:
**[[UCC]] = ''nephroureterectomy''.
**[[UCC]] = ''[[nephroureterectomy]]''.
**[[RCC]] = ''partial nephrectomy'', ''nephrectomy'' or ''radical nephrectomy''.
**[[RCC]] = ''[[partial nephrectomy]]'', ''nephrectomy'' or ''[[radical nephrectomy]]''.


===Renal cell carcinoma with sarcomatoid differentiation===
===Renal cell carcinoma with sarcomatoid differentiation===
*[[AKA]] ''sarcomatoid renal cell carcinoma''.
*[[AKA]] ''sarcomatoid renal cell carcinoma''.
====General====
{{Main|Renal cell carcinoma with sarcomatoid differentiation}}
Features:<ref name=pmid11224597>{{Cite journal  | last1 = de Peralta-Venturina | first1 = M. | last2 = Moch | first2 = H. | last3 = Amin | first3 = M. | last4 = Tamboli | first4 = P. | last5 = Hailemariam | first5 = S. | last6 = Mihatsch | first6 = M. | last7 = Javidan | first7 = J. | last8 = Stricker | first8 = H. | last9 = Ro | first9 = JY. | title = Sarcomatoid differentiation in renal cell carcinoma: a study of 101 cases. | journal = Am J Surg Pathol | volume = 25 | issue = 3 | pages = 275-84 | month = Mar | year = 2001 | doi =  | PMID = 11224597 }}</ref>
*Not recognized as a distinct entity in 2004 WHO classification.<ref name=pmid16442207>{{Cite journal  | last1 = Lopez-Beltran | first1 = A. | last2 = Scarpelli | first2 = M. | last3 = Montironi | first3 = R. | last4 = Kirkali | first4 = Z. | title = 2004 WHO classification of the renal tumors of the adults. | journal = Eur Urol | volume = 49 | issue = 5 | pages = 798-805 | month = May | year = 2006 | doi = 10.1016/j.eururo.2005.11.035 | PMID = 16442207 }}</ref>
**It is considered an indicator of progression.
**Previously considered a distinct entity.<ref name=pmid16442207/><ref name=pmid10080595>{{Cite journal  | last1 = Cangiano | first1 = T. | last2 = Liao | first2 = J. | last3 = Naitoh | first3 = J. | last4 = Dorey | first4 = F. | last5 = Figlin | first5 = R. | last6 = Belldegrun | first6 = A. | title = Sarcomatoid renal cell carcinoma: biologic behavior, prognosis, and response to combined surgical resection and immunotherapy. | journal = J Clin Oncol | volume = 17 | issue = 2 | pages = 523-8 | month = Feb | year = 1999 | doi =  | PMID = 10080595 | URL = http://jco.ascopubs.org/content/17/2/523.full }}</ref>
*Tend to present at higher stage.
*Worse prognosis when adjusted for stage.
*[[Fuhrman grade]] 4 by definition.
 
====Microscopic====
Features:<ref name=pmid11224597/>
#Renal cell carcinoma.
#Sarcomatoid component:
#*[[Fibrosarcoma]] - most common.
#*[[Pleomorphic undifferentiated sarcoma|Undifferentiated]] - common.
#*[[Rhabdomyosarcoma]] - very rare.
 
Note:
*In essence, any kidney tumour with [[spindle cell]]s should make one think of this.<ref name=pmid15763002/>
*[[Renal cell carcinoma with rhabdoid morphology|Rhabdoid change in renal cell carcinoma]] is probably analogous to sarcomatoid change.<ref name=pmid21665507>{{Cite journal  | last1 = Chapman-Fredricks | first1 = JR. | last2 = Herrera | first2 = L. | last3 = Bracho | first3 = J. | last4 = Gomez-Fernandez | first4 = C. | last5 = Leveillee | first5 = R. | last6 = Rey | first6 = L. | last7 = Jorda | first7 = M. | title = Adult renal cell carcinoma with rhabdoid morphology represents a neoplastic dedifferentiation analogous to sarcomatoid carcinoma. | journal = Ann Diagn Pathol | volume = 15 | issue = 5 | pages = 333-7 | month = Oct | year = 2011 | doi = 10.1016/j.anndiagpath.2011.03.002 | PMID = 21665507 }}</ref>
 
Images:
*[http://webpathology.com/image.asp?n=2&Case=70 Sarcomatoid change in RCC (webpathology.com)].
*[http://jco.ascopubs.org/content/27/2/235/F1.expansion Sarcomatoid changes in CCRCC (ascopubs.org)].<ref name=pmid19064974>{{Cite journal  | last1 = Golshayan | first1 = AR. | last2 = George | first2 = S. | last3 = Heng | first3 = DY. | last4 = Elson | first4 = P. | last5 = Wood | first5 = LS. | last6 = Mekhail | first6 = TM. | last7 = Garcia | first7 = JA. | last8 = Aydin | first8 = H. | last9 = Zhou | first9 = M. | title = Metastatic sarcomatoid renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. | journal = J Clin Oncol | volume = 27 | issue = 2 | pages = 235-41 | month = Jan | year = 2009 | doi = 10.1200/JCO.2008.18.0000 | PMID = 19064974 }}</ref>
*[http://www.scielo.br/img/revistas/ibju/v31n1/1a03f1.jpg Sarcomatoid changes in RCC (scielo.br)].<ref name=pmid15763002>{{Cite journal  | last1 = Dall'Oglio | first1 = MF. | last2 = Lieberknecht | first2 = M. | last3 = Gouveia | first3 = V. | last4 = Sant'Anna | first4 = AC. | last5 = Leite | first5 = KR. | last6 = Srougi | first6 = M. | title = Sarcomatoid differentiation in renal cell carcinoma: prognostic implications. | journal = Int Braz J Urol | volume = 31 | issue = 1 | pages = 10-6 | month =  | year =  | doi =  | PMID = 15763002 }}</ref>


===Renal cell carcinoma with rhabdoid morphology===
===Renal cell carcinoma with rhabdoid morphology===
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==Hereditary renal cell carcinoma==
==Hereditary renal cell carcinoma==
The classics - which are ''all'' autosomal dominant:<ref name=Ref_PBoD1016>{{Ref PBoD|1016}}</ref>
{{Main|Hereditary renal cell carcinoma}}
# [[Von Hippel-Lindau syndrome]].
#* VHL gene mutation.
#* Clear cell RCC.
# Hereditary [[clear cell renal cell carcinoma]].
#* VHL gene mutation. 
# Hereditary [[papillary renal cell carcinoma]].
#* MET proto-oncogene mutation.
#* PaRCC type 1.<ref name=Ref_WMSP290>{{Ref WMSP|290}}</ref>
# Hereditary leiomyomatosis and renal cell cancer:<ref name=Ref_WMSP290>{{Ref WMSP|290}}</ref>
#* FH (fumarate hydratase) gene mutation.<ref name=omim136850>{{OMIM|136850}}</ref>
#* PaRCC type 2.
#* Benign [[leiomyoma]]s skin/[[uterine leiomyoma|uterus]].
#* Uterine [[leiomyosarcoma]].
# [[Birt–Hogg–Dubé syndrome]]:<ref name=Ref_WMSP290>{{Ref WMSP|290}}</ref>
#* FLCN (folliculin) gene mutation.<ref name=omim135150>{{OMIM|135150}}</ref>
#* Skin lesions (fibrofolliculoma, trichodiscoma, [[acrochordon]]).
#* ChRCC most common, other types seen (e.g. [[renal oncocytoma|oncocytoma]]).
#* Variable penetrance (autosomal dominant).
 
Others:
* Hereditary papillary carcinoma (TFE3 related translocations).<ref name=omim314310>{{OMIM|314310}}</ref>
 
Notes:<br>
*A total of ten hereditary renal cancer syndromes have been described.  In eight of the ten the gene is known.<ref name=pmid20817385>{{Cite journal  | last1 = Verine | first1 = J. | last2 = Pluvinage | first2 = A. | last3 = Bousquet | first3 = G. | last4 = Lehmann-Che | first4 = J. | last5 = de Bazelaire | first5 = C. | last6 = Soufir | first6 = N. | last7 = Mongiat-Artus | first7 = P. | title = Hereditary renal cancer syndromes: an update of a systematic review. | journal = Eur Urol | volume = 58 | issue = 5 | pages = 701-10 | month = Nov | year = 2010 | doi = 10.1016/j.eururo.2010.08.031 | PMID = 20817385 }}</ref>
 
===Molecular===
Recurrent molecular changes in RCC:
*Clear cell RCC:
**Loss of 3p - contains the VHL gene.
*Papillary RCC:
**Sporadic:
***Trisomy 7, 16, 17.
***Loss of Y.
**Familial:
***Trisomy 7 - contains MET gene.<ref>{{OMIM|164860}}</ref>


==Renal cell carcinoma grading==
==Renal cell carcinoma grading==
*[[AKA]] ''Fuhrman grade''.
{{Main|Renal cell carcinoma grading}}
===General===
Some RCC subtypes are graded based on the '''Fuhrman system''' which considers:<ref name=Ref_GUP282>{{Ref GUP|282}}</ref>
*Nuclear pleomorphism (size, shape).
*Chromatin pattern.
*Nucleoli prominence.


Notes:
==Renal cell carcinoma staging==
*The system was validated for [[clear cell RCC]]. 
{{Main|Kidney cancer staging}}
*Fuhrman nuclear grade is '''not''' prognostic in ''chromophobe RCC'' and should not be used in that context.<ref name=pmid17527087>{{Cite journal  | last1 = Delahunt | first1 = B. | last2 = Sika-Paotonu | first2 = D. | last3 = Bethwaite | first3 = PB. | last4 = McCredie | first4 = MR. | last5 = Martignoni | first5 = G. | last6 = Eble | first6 = JN. | last7 = Jordan | first7 = TW. | title = Fuhrman grading is not appropriate for chromophobe renal cell carcinoma. | journal = Am J Surg Pathol | volume = 31 | issue = 6 | pages = 957-60 | month = Jun | year = 2007 | doi = 10.1097/01.pas.0000249446.28713.53 | PMID = 17527087 }}</ref>
*Anything with [[spindle cell]]s<ref name=pmid15763002/> or rhabdoid cells should make one think grade 4, as it is likely a ''[[renal cell carcinoma with sarcomatoid differentiation]]''.


===Criteria & grades===
===Renal sinus invasion===
*Grade 1: no nucleoli, near 'normal' appearance.
{{Main|Kidney cancer staging}}
*Grade 2: finely granular chromatin (key feature), no nuclei visible with 10x objective lens.
*Grade 3: [[nucleoli]] seen easily (key feature).
*Grade 4: prominent pleomorphism (key feature), hyperchromasia, [[macronucleoli]].
**[[Spindle cell]]s<ref name=pmid15763002/> or rhabdoid cells also make something grade 4 (see ''[[renal cell carcinoma with sarcomatoid differentiation]]'').
 
Note:
*Most tumours are grade 2 & 3.
===Fuhrman grading in short===
*1 vs. 2: grade 2 has granular chromatin, grade 2 has nucleoli visible @ 20x objective.<ref>AE. June 2010.</ref>
*2 vs. 3: grade 3 has nucleoli @ 10x objective.
*3 vs. 4: grade 4 has pleomorphism/hyperchromasia (or spindle cells or rhabdoid cells).


==Clear cell renal cell carcinoma==
==Clear cell renal cell carcinoma==
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==Multilocular cystic renal cell carcinoma==
==Multilocular cystic renal cell carcinoma==
===General===
{{Main|Multilocular cystic renal cell carcinoma}}
*No recurrences or metastasis in the literature.<ref name=Ref_WMSP292>{{Ref WMSP|292}}</ref>
**This makes one wonder... is it really cancer.
*Case report rare.<ref name=pmid21366448>{{Cite journal  | last1 = Agarwal | first1 = S. | last2 = Agrawal | first2 = U. | last3 = Mohanty | first3 = NK. | last4 = Saxena | first4 = S. | title = Multilocular cystic renal cell carcinoma: a case report of a rare entity. | journal = Arch Pathol Lab Med | volume = 135 | issue = 3 | pages = 290-2 | month = Mar | year = 2011 | doi = 10.1043/2010-0243-LE.1 | PMID = 21366448 }}</ref>
 
===Gross===
Features:<ref name=Ref_WMSP292>{{Ref WMSP|292}}</ref>
*Cystic with thin septa.
*Well circumscribed.
 
Note:
*This tumour, radiologically, can often be separated from other cystic tumours.<ref name=pmid21722289>{{Cite journal  | last1 = You | first1 = D. | last2 = Shim | first2 = M. | last3 = Jeong | first3 = IG. | last4 = Song | first4 = C. | last5 = Kim | first5 = JK. | last6 = Ro | first6 = JY. | last7 = Hong | first7 = JH. | last8 = Ahn | first8 = H. | last9 = Kim | first9 = CS. | title = Multilocular cystic renal cell carcinoma: clinicopathological features and preoperative prediction using multiphase computed tomography. | journal = BJU Int | volume =  | issue =  | pages =  | month = Jul | year = 2011 | doi = 10.1111/j.1464-410X.2011.10247.x | PMID = 21722289 }}</ref>
===Microscopic===
Features:<ref name=Ref_WMSP292>{{Ref WMSP|292}}</ref>
*Polygonal cells within the septa.
*Clear cytoplasm.
*+/-Calcification (common).
 
DDx:
*[[Cystic renal disease]] with macrophages in the septa.
*Cystic [[clear cell renal cell carcinoma]].
*[[Tubulocystic carcinoma]].
 
===IHC===
*EMA +ve.
*Keratins +ve.
*CD68 -ve.


==Papillary renal cell carcinoma==
==Papillary renal cell carcinoma==
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{{Main|Chromophobe renal cell carcinoma}}
{{Main|Chromophobe renal cell carcinoma}}


==Clear cell papillary renal cell carcinoma==
==Clear cell papillary renal cell tumour==
{{Main|Clear cell papillary renal cell carcinoma}}
In the past, it was known as ''clear cell papillary renal cell carcinoma''.
{{Main|Clear cell papillary renal cell tumour}}


==Unclassified renal cell carcinoma==
==Unclassified renal cell carcinoma==
*Abbreviated ''URCC''.
*Abbreviated ''URCC''.
===General===
{{Main|Unclassified renal cell carcinoma}}
*Uncommon.
*A WHO classification ''diagnosis of exclusion''.
*Worse prognosis than [[clear cell renal cell carcinoma]].<ref name=pmid17822461>{{Cite journal  | last1 = Karakiewicz | first1 = PI. | last2 = Hutterer | first2 = GC. | last3 = Trinh | first3 = QD. | last4 = Pantuck | first4 = AJ. | last5 = Klatte | first5 = T. | last6 = Lam | first6 = JS. | last7 = Guille | first7 = F. | last8 = de La Taille | first8 = A. | last9 = Novara | first9 = G. | title = Unclassified renal cell carcinoma: an analysis of 85 cases. | journal = BJU Int | volume = 100 | issue = 4 | pages = 802-8 | month = Oct | year = 2007 | doi = 10.1111/j.1464-410X.2007.07148.x | PMID = 17822461 }}</ref>
*High variation in the prevalence (when comparing institutions); this suggests a lack of uniformity in the diagnosis of this subtype.<ref name=pmid17822461/>
 
===Microscopic===
Features:
*Malignant tumour that is one of the following:<ref name=Ref_WMSP293>{{Ref WMSP|293}}</ref><ref name=pmid22404824>{{Cite journal  | last1 = Lopez-Beltran | first1 = A. | last2 = Kirkali | first2 = Z. | last3 = Montironi | first3 = R. | last4 = Blanca | first4 = A. | last5 = Algaba | first5 = F. | last6 = Scarpelli | first6 = M. | last7 = Yorukoglu | first7 = K. | last8 = Hartmann | first8 = A. | last9 = Cheng | first9 = L. | title = Unclassified renal cell carcinoma: a report of 56 cases. | journal = BJU Int | volume = 110 | issue = 6 | pages = 786-93 | month = Sep | year = 2012 | doi = 10.1111/j.1464-410X.2012.10934.x | PMID = 22404824 }}</ref>
*#A combination of other RCC histologic types (~35% of cases of URCC).
*#Has a "non-identifiable" pattern/unrecognizable cell type (~60% of cases of URCC).
*#Pure [[sarcomatoid RCC]] without an identifiable (epithelioid) RCC subtype (~5% of cases of URCC).<ref name=pmid22404824/>
 
DDx:
*[[Clear cell renal cell carcinoma]].
*[[Collecting duct carcinoma]].
*Undifferentiated carcinoma.
*[[Metastatic]] carcinoma.


=Renal translocation carcinomas=
=Renal translocation carcinomas=
Line 472: Line 364:


==Renal tumour with t(6;11) translocation==
==Renal tumour with t(6;11) translocation==
===General===
*[[AKA]] ''t(6;11) renal cell carcinoma''.
*Not common.
{{main|Renal tumour with t(6;11) translocation}}
*[[Lymph node metastases]] are common.
*Essentially a pediatric tumour - case report of an adult.<ref name=pmid21884304>{{Cite journal  | last1 = Ishihara | first1 = A. | last2 = Yamashita | first2 = Y. | last3 = Takamori | first3 = H. | last4 = Kuroda | first4 = N. | title = Renal carcinoma with (6;11)(p21;q12) translocation: Report of an adult case. | journal = Pathol Int | volume = 61 | issue = 9 | pages = 539-45 | month = Sep | year = 2011 | doi = 10.1111/j.1440-1827.2011.02711.x | PMID = 21884304 }}</ref>
 
===Microscopic===
Features:
*Hyaline material between nests.
*Large cells with clear to eosinophilic cytoplasm.
 
===Molecular===
*t(6;11)(p21;q12) Alpha/TFEB.<ref name=Ref_WMSP281>{{Ref WMSP|281}}</ref>


=Benign tumours=
=Benign tumours=
==Papillary adenoma of the kidney==
==Papillary adenoma of the kidney==
*[[AKA]] ''renal papillary adenoma''.
*[[AKA]] ''renal papillary adenoma''.
===General===
{{Main|Papillary adenoma of the kidney}}
*Benign.
*Considered a precursor for ''[[papillary renal cell carcinoma]]'' (PaRCC).<ref name=pmid17056094>{{Cite journal  | last1 = Wang | first1 = KL. | last2 = Weinrach | first2 = DM. | last3 = Luan | first3 = C. | last4 = Han | first4 = M. | last5 = Lin | first5 = F. | last6 = Teh | first6 = BT. | last7 = Yang | first7 = XJ. | title = Renal papillary adenoma--a putative precursor of papillary renal cell carcinoma. | journal = Hum Pathol | volume = 38 | issue = 2 | pages = 239-46 | month = Feb | year = 2007 | doi = 10.1016/j.humpath.2006.07.016 | PMID = 17056094 }}</ref>
**Stains like PaRCC.
**Found with an increased frequency within the content of PaRCC.
 
===Microscopic===
Features:
#Histomorphology of ''[[papillary renal cell carcinoma]]''.
#'''''Must''''' be <=0.5 cm.<ref name=Ref_GUP288>{{Ref GUP|288}}</ref><ref name=pmid18846240>{{Cite journal  | last1 = Algaba | first1 = F. | title = Renal adenomas: pathological differential diagnosis with malignant tumors. | journal = Adv Urol | volume =  | issue =  | pages = 974848 | month =  | year = 2008 | doi = 10.1155/2008/974848 | PMID = 18846240 | PMC = 2563151 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2563151/?tool=pubmed }}</ref>
#*[[Diagnostic size cutoff]] - larger lesions are ''papillary renal cell carcinoma''.
 
DDx:
*[[Papillary renal cell carcinoma]].
*[[Metanephric adenoma]].
 
Images:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2563151/figure/fig2/ Renal papillary adenoma (nih.gov)].<ref name=pmid18846240/>
 
===IHC===
*AMACR +ve.<ref name=pmid17056094/>


==Renal oncocytoma==
==Renal oncocytoma==
Line 515: Line 377:
==Angiomyolipoma==
==Angiomyolipoma==
*Abbreviated ''AML''.
*Abbreviated ''AML''.
===General===
{{Main|Angiomyolipoma}}
*Benign mesenchymal tumour.
*Presentations: flank pain, hematuria, incidentaloma.<ref name=pmid18805573>{{Cite journal  | last1 = Seyam | first1 = RM. | last2 = Bissada | first2 = NK. | last3 = Kattan | first3 = SA. | last4 = Mokhtar | first4 = AA. | last5 = Aslam | first5 = M. | last6 = Fahmy | first6 = WE. | last7 = Mourad | first7 = WA. | last8 = Binmahfouz | first8 = AA. | last9 = Alzahrani | first9 = HM. | title = Changing trends in presentation, diagnosis and management of renal angiomyolipoma: comparison of sporadic and tuberous sclerosis complex-associated forms. | journal = Urology | volume = 72 | issue = 5 | pages = 1077-82 | month = Nov | year = 2008 | doi = 10.1016/j.urology.2008.07.049 | PMID = 18805573 }}</ref>
**Tumours >4 cm considered a risk for bleeding.<ref name=pmid21571778>{{Cite journal  | last1 = Abrams | first1 = J. | last2 = Yee | first2 = DC. | last3 = Clark | first3 = TW. | title = Transradial embolization of a bleeding renal angiomyolipoma. | journal = Vasc Endovascular Surg | volume = 45 | issue = 5 | pages = 470-3 | month = Jul | year = 2011 | doi = 10.1177/1538574411408352 | PMID = 21571778 }}</ref>
*AMLs occur may be elsewhere in the body, e.g. liver,<ref name=pmid15498214>{{Cite journal  | last1 = Zhang | first1 = SH. | last2 = Cong | first2 = WM. | last3 = Xian | first3 = ZH. | last4 = Wu | first4 = WQ. | last5 = Dong | first5 = H. | last6 = Wu | first6 = MC. | title = [Morphologic variants and immunohistochemical features of hepatic angiomyolipoma.] | journal = Zhonghua Bing Li Xue Za Zhi | volume = 33 | issue = 5 | pages = 437-40 | month = Oct | year = 2004 | doi =  | PMID = 15498214 }}
</ref> but are most common in the kidney.
*In the [[PEComa]] group of tumours.
 
====Epidemiology====
*May be associated with [[tuberous sclerosis]] -- 70% have an AML.
**When compared to sporadic cases:
***More often bilateral.
***Usually bigger.
*There is a suggestion that an ''epithelioid'' variant is more worisome.<ref name=pmid12352384>{{Cite journal  | last1 = Nelson | first1 = CP. | last2 = Sanda | first2 = MG. | title = Contemporary diagnosis and management of renal angiomyolipoma. | journal = J Urol | volume = 168 | issue = 4 Pt 1 | pages = 1315-25 | month = Oct | year = 2002 | doi = 10.1097/01.ju.0000028200.86216.b2 | PMID = 12352384 }}</ref>
**This is not confirmed by all studies.<ref name=pmid18852677>{{Cite journal  | last1 = Aydin | first1 = H. | last2 = Magi-Galluzzi | first2 = C. | last3 = Lane | first3 = BR. | last4 = Sercia | first4 = L. | last5 = Lopez | first5 = JI. | last6 = Rini | first6 = BI. | last7 = Zhou | first7 = M. | title = Renal angiomyolipoma: clinicopathologic study of 194 cases with emphasis on the epithelioid histology and tuberous sclerosis association. | journal = Am J Surg Pathol | volume = 33 | issue = 2 | pages = 289-97 | month = Feb | year = 2009 | doi = 10.1097/PAS.0b013e31817ed7a6 | PMID = 18852677 }}</ref>
 
===Microscopic===
Features:
*Smooth muscle.
*Adipose tissue - not always present<ref name=pmid15584043>{{Cite journal  | last1 = Crapanzano | first1 = JP. | title = Fine-needle aspiration of renal angiomyolipoma: cytological findings and diagnostic pitfalls in a series of five cases. | journal = Diagn Cytopathol | volume = 32 | issue = 1 | pages = 53-7 | month = Jan | year = 2005 | doi = 10.1002/dc.20179 | PMID = 15584043 }}</ref> - '''key feature'''.
*Abundant blood vessels.
 
====Epithelioid angiomyolipoma====
Features:
*Carcinoma-like morphology.
*+/-Spindle cells.
*"High grade" nuclei.
**Pleomorphic nuclei.
 
DDx:
*[[Clear cell renal cell carcinoma]] eosinophilic variant - esp. if epithelioid.
 
Images:
*[http://bjr.birjournals.org/content/82/984/e249/F3.expansion.html Epithelioid AML (birjournals.org)].
*[http://radiographics.rsna.org/content/30/6/1525/F2.expansion.html Epithelioid AML (rsna.org)].
*[http://www.archivesofpathology.org/action/showFullPopup?id=i1543-2165-128-10-1176-f01&doi=10.1043%2F1543-2165%282004%29128%3C1176%3APQCAYW%3E2.0.CO%3B2 Atypical epithelioid AML (archivesofpathology.org)].<ref>{{Cite journal  | last1 = Aljerian | first1 = K. | last2 = Evans | first2 = AJ. | title = Pathologic quiz case: a 44-year-old woman with an incidental asymptomatic renal mass. Atypical epithelioid angiomyolipoma. | journal = Arch Pathol Lab Med | volume = 128 | issue = 10 | pages = 1176-8 | month = Oct | year = 2004 | doi = 10.1043/1543-2165(2004)1281176:PQCAYW2.0.CO;2 | PMID = 15387699 }}</ref>
 
====Cytologic====
Features<ref name=pmid15584043>{{Cite journal  | last1 = Crapanzano | first1 = JP. | title = Fine-needle aspiration of renal angiomyolipoma: cytological findings and diagnostic pitfalls in a series of five cases. | journal = Diagn Cytopathol | volume = 32 | issue = 1 | pages = 53-7 | month = Jan | year = 2005 | doi = 10.1002/dc.20179 | PMID = 15584043 }}</ref>
*Nuclei - round/ovoid.
*Chromatin - bland.
 
===IHC===
*Melanocytic markers +ve.<ref name=Ref_GUP324>{{Ref GUP|324}}</ref>
**HMB-45 +ve in all cases (15/15).<ref name=pmid23932749>{{Cite journal  | last1 = Esheba | first1 = Gel S. | last2 = Esheba | first2 = Nel S. | title = Angiomyolipoma of the kidney: clinicopathological and immunohistochemical study. | journal = J Egypt Natl Canc Inst | volume = 25 | issue = 3 | pages = 125-34 | month = Sep | year = 2013 | doi = 10.1016/j.jnci.2013.05.002 | PMID = 23932749 }}
</ref>
**Melan A +ve in ~87% of cases (13/15).
*Epithelial markers -ve.<ref name=Ref_GUP324>{{Ref GUP|324}}</ref>
*SMA +ve.
*CD117 +ve/-ve.
 
*Ki-67:<ref name=pmid18839327>{{Cite journal  | last1 = Ooi | first1 = SM. | last2 = Vivian | first2 = JB. | last3 = Cohen | first3 = RJ. | title = The use of the Ki-67 marker in the pathological diagnosis of the epithelioid variant of renal angiomyolipoma. | journal = Int Urol Nephrol | volume = 41 | issue = 3 | pages = 559-65 | month =  | year = 2009 | doi = 10.1007/s11255-008-9473-1 | PMID = 18839327 }}</ref>
**Epithelioid variant of AML +ve.
**Conventional AML -ve.


=Mimics=
=Mimics=
Line 580: Line 389:
=Rare stuffs=
=Rare stuffs=
==Juxtaglomerular cell tumour==
==Juxtaglomerular cell tumour==
*[[AKA]] juxtaglomerular tumour, reninoma.<ref name=pmid18192852/>
*[[AKA]] juxtaglomerular tumour, reninoma.<ref name=pmid18192852>{{Cite journal  | last1 = Wong | first1 = L. | last2 = Hsu | first2 = TH. | last3 = Perlroth | first3 = MG. | last4 = Hofmann | first4 = LV. | last5 = Haynes | first5 = CM. | last6 = Katznelson | first6 = L. | title = Reninoma: case report and literature review. | journal = J Hypertens | volume = 26 | issue = 2 | pages = 368-73 | month = Feb | year = 2008 | doi = 10.1097/HJH.0b013e3282f283f3 | PMID = 18192852 }}</ref>
===General===
{{Main|Juxtaglomerular cell tumour}}
*Rare.
*Etiology: increased renin.
 
Clinical:<ref name=pmid18192852>{{Cite journal  | last1 = Wong | first1 = L. | last2 = Hsu | first2 = TH. | last3 = Perlroth | first3 = MG. | last4 = Hofmann | first4 = LV. | last5 = Haynes | first5 = CM. | last6 = Katznelson | first6 = L. | title = Reninoma: case report and literature review. | journal = J Hypertens | volume = 26 | issue = 2 | pages = 368-73 | month = Feb | year = 2008 | doi = 10.1097/HJH.0b013e3282f283f3 | PMID = 18192852 }}</ref>
*[[Hypertension]].
*Increased aldosterone.
**Causes hypokalemia.
*Increased plasma renin.
 
===Microscopic===
Features:<ref name=pmid21191395/>
*Polygonal cells.
*Abundant granular, eosinophilic cytoplasm.<ref name=pmid436071/>
*Perinuclear halo.
 
DDx:
*[[Chromophobe renal cell carcinoma]], eosinophilic variant.
 
Image:
*[http://www.nature.com/ki/journal/v79/n2/fig_tab/ki2010445f1.html#figure-title Reninoma (nature.com)].<ref name=pmid21191395/>
 
===Stains===
Cytoplasmic granules.<ref name=pmid436071>{{Cite journal  | last1 = Hanna | first1 = W. | last2 = Tepperman | first2 = B. | last3 = Logan | first3 = AG. | last4 = Robinette | first4 = MA. | last5 = Colapinto | first5 = R. | last6 = Phillips | first6 = MJ. | title = Juxtaglomerular cell tumour (reninoma) with paroxysmal hypertension. | journal = Can Med Assoc J | volume = 120 | issue = 8 | pages = 957-9 | month = Apr | year = 1979 | doi =  | PMID = 436071 PMC = 1819229 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1819229/?tool=pubmed }}</ref>
*PAS +ve.
*PASD +ve.
 
===IHC===
Features:<ref name=pmid21191395>{{Cite journal  | last1 = Chao | first1 = CT. | last2 = Chang | first2 = FC. | last3 = Wu | first3 = VC. | last4 = Chen | first4 = JC. | title = Reninoma. | journal = Kidney Int | volume = 79 | issue = 2 | pages = 260 | month = Jan | year = 2011 | doi = 10.1038/ki.2010.445 | PMID = 21191395 }}</ref>
*Actin +ve.
*Cytokeratin -ve.
*HMB-45 -ve.
 
===EM===
Features:
*Vesicles - contain renin.<ref name=upmc29>URL: [http://path.upmc.edu/cases/case29/micro.html http://path.upmc.edu/cases/case29/micro.html]. Accessed on: 18 December 2011.</ref>


==Renomedullary interstitial cell tumour==
==Renomedullary interstitial cell tumour==
Line 635: Line 409:
==Mixed epithelial and stromal tumour==
==Mixed epithelial and stromal tumour==
*Abbreviated ''MEST''.
*Abbreviated ''MEST''.
 
{{Main|Mixed epithelial and stromal tumour of the kidney}}
===General===
*Rare - approx. 1.5% of renal neoplasms.<ref name=pmid17454754>{{Cite journal  | last1 = Mai | first1 = KT. | last2 = Elkeilani | first2 = A. | last3 = Veinot | first3 = JP. | title = Mixed epithelial and stromal tumour (MEST) of the kidney: report of 14 cases with male and PEComatous variants and proposed histopathogenesis. | journal = Pathology | volume = 39 | issue = 2 | pages = 235-40 | month = Apr | year = 2007 | doi = 10.1080/00313020701230799 | PMID = 17454754 }}</ref>
*Benign.
*Prevalence: males > females.
 
Note:
*Turbiner ''et al.''<ref name=pmid17414095>{{Cite journal  | last1 = Turbiner | first1 = J. | last2 = Amin | first2 = MB. | last3 = Humphrey | first3 = PA. | last4 = Srigley | first4 = JR. | last5 = De Leval | first5 = L. | last6 = Radhakrishnan | first6 = A. | last7 = Oliva | first7 = E. | title = Cystic nephroma and mixed epithelial and stromal tumor of kidney: a detailed clinicopathologic analysis of 34 cases and proposal for renal epithelial and stromal tumor (REST) as a unifying term. | journal = Am J Surg Pathol | volume = 31 | issue = 4 | pages = 489-500 | month = Apr | year = 2007 | doi = 10.1097/PAS.0b013e31802bdd56 | PMID = 17414095 }}</ref>  have suggested that ''cystic nephroma'' and ''mixed epithelial and stromal tumour (MEST)'' are one tumour.
**The lumping term ''renal epithelial and stromal tumour'', abbreviated ''REST''.
 
===Microscopic===
Features:
*Cysts lined by simple epithelium with hobnailing - '''key feature'''.
*Stroma has an ovarian look:
**''Blue'' (basophilic).
**''Spindle cells''.
 
Notes:
*Parenchymal elements (e.g. glomueruli, tubules) are not found in the septa between the cysts.
 
====Images====
<gallery>
Image:Cystic_nephroma_low_mag.jpg |Cystic nephroma - low mag. (WC/Nephron)
Image:Cystic_nephroma_intermed_mag.jpg |Cystic nephroma - intermed. mag. (WC/Nephron)
</gallery>
===IHC===
Features:<ref name=pmid17454754>{{Cite journal  | last1 = Mai | first1 = KT. | last2 = Elkeilani | first2 = A. | last3 = Veinot | first3 = JP. | title = Mixed epithelial and stromal tumour (MEST) of the kidney: report of 14 cases with male and PEComatous variants and proposed histopathogenesis. | journal = Pathology | volume = 39 | issue = 2 | pages = 235-40 | month = Apr | year = 2007 | doi = 10.1080/00313020701230799 | PMID = 17454754 }}
</ref>
*ER +ve.
*PR +ve.
*CD10 +ve.
 
===DDx===
*Tubulocystic carcinoma.


==Cystic nephroma==
==Cystic nephroma==
 
{{Main|Cystic nephroma}}
===General===
*Turbiner ''et al.''<ref name=pmid17414095>{{Cite journal  | last1 = Turbiner | first1 = J. | last2 = Amin | first2 = MB. | last3 = Humphrey | first3 = PA. | last4 = Srigley | first4 = JR. | last5 = De Leval | first5 = L. | last6 = Radhakrishnan | first6 = A. | last7 = Oliva | first7 = E. | title = Cystic nephroma and mixed epithelial and stromal tumor of kidney: a detailed clinicopathologic analysis of 34 cases and proposal for renal epithelial and stromal tumor (REST) as a unifying term. | journal = Am J Surg Pathol | volume = 31 | issue = 4 | pages = 489-500 | month = Apr | year = 2007 | doi = 10.1097/PAS.0b013e31802bdd56 | PMID = 17414095 }}</ref>  has suggested that ''[[cystic nephroma]]'' and ''[[mixed epithelial and stromal tumour]] (MEST)'' are one tumour.
**The lumping term is ''renal epithelial and stromal tumour'', abbreviated ''REST''.
 
===Gross===
*Bubble wrap-like appearance.
 
====Image====
<gallery>
Image:Bubble_Wrap.jpg| Bubble wrap. (WC)
</gallery>
===Microscopic===
Features:
*Cysts lined by simple epithelium with hobnailing - '''key feature'''.
*Stroma has an ovarian look:
**''Blue'' (basophilic).
**''Spindle cells''.
 
Notes:
*Parenchymal elements (e.g. glomueruli, tubules) are not found in the septa between the cysts.
====Images====
<gallery>
Image:Cystic_nephroma_low_mag.jpg |Cystic nephroma - low mag. (WC/Nephron)
Image:Cystic_nephroma_intermed_mag.jpg |Cystic nephroma - intermed. mag. (WC/Nephron)
</gallery>
 
===IHC===
Features:
*ER +ve.
*PR +ve.
*CD10 +ve.


==Renal mucinous tubular and spindle cell carcinoma==
==Renal mucinous tubular and spindle cell carcinoma==
Line 713: Line 423:


==Renal medullary carcinoma==
==Renal medullary carcinoma==
===General===
{{Main|Renal medullary carcinoma}}
*Rare.
*Usually young adults.
*Associated with sickle cell trait (heterozygotes for the sickle cell allele).<ref name=pmid7528470>{{cite journal |author=Davis CJ, Mostofi FK, Sesterhenn IA |title=Renal medullary carcinoma. The seventh sickle cell nephropathy |journal=Am. J. Surg. Pathol. |volume=19 |issue=1 |pages=1–11 |year=1995 |month=January |pmid=7528470 |doi= |url=}}</ref>
*Aggressive/poor prognosis.<ref name=pmid17643096>{{Cite journal  | last1 = Watanabe | first1 = IC. | last2 = Billis | first2 = A. | last3 = Guimarães | first3 = MS. | last4 = Alvarenga | first4 = M. | last5 = de Matos | first5 = AC. | last6 = Cardinalli | first6 = IA. | last7 = Filippi | first7 = RZ. | last8 = de Castro | first8 = MG. | last9 = Suzigan | first9 = S. | title = Renal medullary carcinoma: report of seven cases from Brazil. | journal = Mod Pathol | volume = 20 | issue = 9 | pages = 914-20 | month = Sep | year = 2007 | doi = 10.1038/modpathol.3800934 | PMID = 17643096 |url = http://www.nature.com/modpathol/journal/v20/n9/full/3800934a.html }}</ref>
 
Aside:
*Kidney disease assoc. with sickle cell disorders:<ref name=pmid7528470/>
*#Papillary necrosis.
*#[[Nephrotic syndrome]].
*#Renal [[infarction]].
*#[[Pyelonephritis]].
 
===Gross===
Features:<ref name=pmid17643096>{{cite journal |author=Watanabe IC, Billis A, Guimarães MS, ''et al.'' |title=Renal medullary carcinoma: report of seven cases from Brazil |journal=Mod. Pathol. |volume=20 |issue=9 |pages=914–20 |year=2007 |month=September |pmid=17643096 |doi=10.1038/modpathol.3800934 |url=}}</ref>
*Well circumscribed.
*Renal medulla.
 
===Microscopic===
Features:<ref name=pmid7528470/><ref name=pmid17643096>{{cite journal |author=Watanabe IC, Billis A, Guimarães MS, ''et al.'' |title=Renal medullary carcinoma: report of seven cases from Brazil |journal=Mod. Pathol. |volume=20 |issue=9 |pages=914–20 |year=2007 |month=September |pmid=17643096 |doi=10.1038/modpathol.3800934 |url=}}</ref>
*Variable architecture:
**Reticular - classic.
**[[Adenoid cystic carcinoma]]-like appearance:
***Cystic spaces.
**Yolk sac-like.
**Tubular.
*Desmoplastic stroma - prominent.
*Inflammation:
**Lymphocytes.
**Neutrophils - margination in vessels.
 
DDx:
*[[Yolk sac tumour]].
*[[Collecting duct carcinoma]].
 
Image:
*[http://www.nature.com/modpathol/journal/v20/n9/fig_tab/3800934f3.html#figure-title RMC (nature.com)].
 
===IHC===
*SMARCB1 (INI1) -ve.<ref name=Ref_WMSP286>{{Ref WMSP|286}}</ref>


==Tubulocystic carcinoma of the kidney==
==Tubulocystic carcinoma of the kidney==
Line 759: Line 430:
==Acquired cystic disease-associated renal cell carcinoma==
==Acquired cystic disease-associated renal cell carcinoma==
{{Main|Acquired cystic disease-associated renal cell carcinoma}}
{{Main|Acquired cystic disease-associated renal cell carcinoma}}
==Kidney metastasis==
*[[AKA]] ''renal metastasis'', ''metastatic kidney disease''.
{{Main|Kidney metastasis}}


=Pediatric=
=Pediatric=

Latest revision as of 21:41, 15 August 2024

A kidney tumour (renal oncocytoma). (WC/Emmanuelm)

Kidney tumours - includes malignant kidney tumours (kidney cancer) and benign kidney tumours. Medical renal diseases are dealt with in the medical renal diseases article.

Pediatric kidney tumours are dealt with in the pediatric kidney tumours article.

Renal specimens

In excisions done for tumours, a comment should be made about kidney distant from the tumour. People with less renal mass, i.e. less kidney, are predisposed to focal segmental glomerulosclerosis (FSGS).

Anatomy

Layers (superficial to deep):

  1. Renal fascia (Gerota's fascia).
  2. Perinephric fat.
  3. Renal capsule.
  4. Renal parenchyma (cortex).

Sign out

Missed renal biopsy

Main article: Missed renal biopsy

Tabular comparison (selected tumours)

Selected common tumours of the kidney:[2][3]

Clear cell RCC Papillary RCC
type 1 		Papillary RCC
type 2 		Chromophobe RCC
classic variant 		Chromophobe RCC
eosinophilic variant 		Oncocytoma
Gross Golden yellow, solid friable friable light brown light brown mahogany/brown, +/-central scar
Architecture nests, sheets papillary, simple papillary,
pseudostratified 		nests, sheets nests, sheets nests, sheets
Nuclear atypia low-high
typically medium-high 		low-medium medium-high low-high, "raisinoid"
nuc. membrane 		low-high, "raisinoid"
nuc. membrane 		low-medium, round nuclei
Cytoplasm clear eosinophilic eosinophilic cobwebs/clear eosinophilic/cobwebs eosinophilic/
granular & abundant
Other delicate vessels,
necrosis common 		histiocytes
in fibrovascular cores, >0.5 cm 		histiocytes
in fibrovascular cores, >0.5 cm 		perinuclear clearing, thick vessels perinuclear clearing, thick vessels in loose fibrous/hyaline stroma
IHC CK7-, EMA+ AMACR+, EMA+, CK7+ AMACR+, E-cadherin+, CK7- CD117+, CK7+ (membrane) CD117+, CK7+ (membrane) Vimentin-, EMA+
Main DDx chromophobe
classic variant 		PaRCC type 2, mets PaRCC type 1, mets clear cell RCC oncocytoma chromophobe
eosinophilic variant
Key features clear cells, vascular papillae, histiocytes
simple epithelium 		papillae, histiocytes,
stratified 		perinuc. clearing,
wispy cytoplasm 		perinuc. clearing,
wispy eosinophilic
cytoplasm 		eosinophilic, granular cytoplasm
Image(s)
CCRCC (WC)
PaRCC - intermed. (WC)
,
PaRCC - high (WC)
ChRCC (WC)
Oncocytoma (WC)

Notes:

  • Cell shape: all have epithelioid morphology.

Tabular comparison of oncocytoma and chromophobe RCC

Histomorphologic features useful to distinguish chromophobe RCC (eosinophilic variant) and oncocytoma:[4]

Morphologic feature ChRCC (eosinophilic
variant) 		Renal oncocytoma
Nuclear morphology "raisinoid"/wrinkled appearance round with small nucleolus,
usu. little size variation
Multinucleation common - binucleation uncommon
Chromatin coarse fine
Architecture solid, crowded nests spaced nests /
archipelago-like, solid
Cytoplasm perinuclear halo, may be focal no perinuclear halo
Degenerative foci
(focal atypia & pleomorphism) 		absent present in ~20% of cases
Image
ChRCC (WC/Nephron)
Oncocytoma (WC/Nephron)

Common DDx

Spindle cell tumours

Malignant spindle cell tumours of the kidney:

Benign spindle cell tumours of the kidney:

Renal tumours with eosinophilic cytoplasm

Main article: Renal tumours with eosinophilic cytoplasm

WHO classification of renal neoplasia

  • Based on 2004 iteration - as per WMSP, slightly modified.[5] Online, the classification can found here.

Renal cell tumours

Common:

Less common:

Metanephric tumours

Nephroblastic tumours

Mesenchymal tumours

Childhood:

Adults:

Other:

Mixed mesenchymal and epithelial tumours

Others

Vancouver modification of WHO classification

In 2012/2013, several additions were made:[6]

"Emerging" entities (as per Vancouver) are:

An entity proposed after Vancouver

Renal cell carcinoma

Overview

General

  • Relatively common form of cancer.
  • Often abbreviated RCC.
  • AKA hypernephroma.[7]
  • RCC represents approx. 90% of malignancies in kidneys of adults.[8]

Origin

  • Proximal renal tubule.

Clinical

  • Classically described as a triad:[9]
    • Hematuria (most common symptom).
    • Abdominal mass.
    • Flank pain.
  • Frequently picked-up on imaging (incidentaloma) ~ 1/3 of cases.

Risk factors

Subtypes of RCC

RCC (renal cell carcinoma) comes in different subtypes:[11]

  • Clear cell carcinoma (70-80% of RCC) -- abbrev. CCRCC.
  • Papillary renal cell carcinoma (10-15% of RCC) -- abbrev. PRCC.
  • Chromophobe renal carcinoma (5% of RCC) -- abbrev. ChRCC.
  • Collecting duct (Bellini duct) carcinoma (1% of RCC).

Notes:

  • Subtype is an independent predictor of mortality - but adds very little to multivariate models with staging information.[12]
  • CCRCC tends to be worse than ChRCC and PRCC, probably due to higher incidence of mets.[13]
  • The exam answer (worst to best): clear cell RCC, papillary RCC, chromophobe RCC.

IHC - is it RCC?

  • RCC Ma (+), CD10 (+) -- specific for RCC[14]

IHC - differentiation of types

  • Clear cell RCC vs. papillary RCC:
    • CK7 (-ve CCRCC), AMACR (+ve in PRCC).[15]
  • Papillary RCC type 1 vs. papillary RCC type 2:
    • E-cadherin +ve in PRCC type 2.[16]
    • EMA (MUC1) +ve in PRCC type 1.[16]
  • ChRCC vs. oncocytoma (ONC):
    • CK7 (ChRCC +ve membrane), CK20, CD15.[15]
    • CK7 -- ChRCC 86% +ve vs. ONC 0% +ve.[17]
    • CD15 -- ChRCC 11% +ve vs. ONC 57% +ve.[18]
    • Hale's colloidal iron +ve in ChRCC, usually neg. in ONC.[19]
    • PAX2 -- ChRCC (1/11) +ve vs. ONC (20/23) +ve.[20]
    • Kidney-specific cadherin (Ksp-cadherin) -- ChRCC 97% +ve (distinctive membrane pattern) vs. ONC only 3% +ve.[21]
  • ChRCC & renal oncocytoma vs. others:
    • CD117 (ckit) +ve (100% membrane, ~75% cytoplasmic).[22]
  • Clear cell RCC vs. chromophobe RCC:
    • Hale's colloidal iron (+ve in ChRCC).[19]
    • CK7 (cell membrane +ve in ChRCC).

Notes:

  • One paper[23] describes CD10, parvalbumin, AMACR, CK7 and S100A1 as being useful.
  • Another paper I came across:[24]
  • c-kit (CD117) not useful for differentiating ONC and ChRCC.[20]
  • E-cadherin not useful for differentiating ChRCC and ONC.[25]

RCC vs. Urothelial cell carcinoma

Main article: Urothelium
  • Clinically/radiologically, it may not be possible to differentiate renal pelvis UCC and RCC if the tumour is large.
  • Pathologically, this is not very difficult.
  • On gross specimens, it is almost always obvious what one is dealing with:

Renal cell carcinoma with sarcomatoid differentiation

  • AKA sarcomatoid renal cell carcinoma.
Main article: Renal cell carcinoma with sarcomatoid differentiation

Renal cell carcinoma with rhabdoid morphology

  • AKA renal cell carcinoma with rhabdoid change.
Main article: Renal cell carcinoma with rhabdoid morphology

Hereditary renal cell carcinoma

Main article: Hereditary renal cell carcinoma

Renal cell carcinoma grading

Main article: Renal cell carcinoma grading

Renal cell carcinoma staging

Main article: Kidney cancer staging

Renal sinus invasion

Main article: Kidney cancer staging

Clear cell renal cell carcinoma

Main article: Clear cell renal cell carcinoma

Multilocular cystic renal cell carcinoma

Main article: Multilocular cystic renal cell carcinoma

Papillary renal cell carcinoma

Main article: Papillary renal cell carcinoma

Chromophobe renal cell carcinoma

Main article: Chromophobe renal cell carcinoma

Clear cell papillary renal cell tumour

In the past, it was known as clear cell papillary renal cell carcinoma.

Main article: Clear cell papillary renal cell tumour

Unclassified renal cell carcinoma

  • Abbreviated URCC.
Main article: Unclassified renal cell carcinoma

Renal translocation carcinomas

Renal tumour with Xp11.2 translocation

Main article: Renal tumour with Xp11.2 translocation

Renal tumour with t(6;11) translocation

  • AKA t(6;11) renal cell carcinoma.
Main article: Renal tumour with t(6;11) translocation

Benign tumours

Papillary adenoma of the kidney

  • AKA renal papillary adenoma.
Main article: Papillary adenoma of the kidney

Renal oncocytoma

Main article: Renal oncocytoma

Angiomyolipoma

  • Abbreviated AML.
Main article: Angiomyolipoma

Mimics

Xanthogranulomatous pyelonephritis

  • Abbreviated XGP.
Main article: Xanthogranulomatous pyelonephritis

Malakoplakia

Main article: Malakoplakia

Rare stuffs

Juxtaglomerular cell tumour

  • AKA juxtaglomerular tumour, reninoma.[26]
Main article: Juxtaglomerular cell tumour

Renomedullary interstitial cell tumour

Main article: Renomedullary interstitial cell tumour

Metanephric adenoma

  • Should not be confused mesonephric adenoma, another term for nephrogenic adenoma.
    • Memory device: metanephric adenoma is a tumour.
Main article: Metanephric adenoma

Renal epithelial and stromal tumour

Abbreviated REST.

The lumping term for both:[28]

  1. Mixed epithelial and stromal tumour.
  2. Cystic nephroma.

Mixed epithelial and stromal tumour

  • Abbreviated MEST.
Main article: Mixed epithelial and stromal tumour of the kidney

Cystic nephroma

Main article: Cystic nephroma

Renal mucinous tubular and spindle cell carcinoma

  • AKA renal mucinous tubular spindle cell carcinoma.
  • AKA mucinous tubular and spindle cell carcinoma of the kidney.[29]
Main article: Renal mucinous tubular and spindle cell carcinoma

Collecting duct carcinoma

Main article: Collecting duct carcinoma

Renal medullary carcinoma

Main article: Renal medullary carcinoma

Tubulocystic carcinoma of the kidney

Main article: Tubulocystic carcinoma of the kidney

Acquired cystic disease-associated renal cell carcinoma

Main article: Acquired cystic disease-associated renal cell carcinoma

Kidney metastasis

  • AKA renal metastasis, metastatic kidney disease.
Main article: Kidney metastasis

Pediatric

Main article: Pediatric kidney tumours

The most common is nephroblastoma (Wilms tumour).

Others include:

See also

References

  1. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 288. ISBN 978-0781765275.
  2. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 281-304. ISBN 978-0443066771.
  3. ↑ Srigley, JR.; Delahunt, B. (Jun 2009). "Uncommon and recently described renal carcinomas.". Mod Pathol 22 Suppl 2: S2-S23. doi:10.1038/modpathol.2009.70. PMID 19494850.
  4. ↑ Tickoo, SK.; Amin, MB. (Dec 1998). "Discriminant nuclear features of renal oncocytoma and chromophobe renal cell carcinoma. Analysis of their potential utility in the differential diagnosis.". Am J Clin Pathol 110 (6): 782-7. PMID 9844591.
  5. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 291. ISBN 978-0781765275.
  6. ↑ Srigley, JR.; Delahunt, B.; Eble, JN.; Egevad, L.; Epstein, JI.; Grignon, D.; Hes, O.; Moch, H. et al. (Oct 2013). "The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia.". Am J Surg Pathol 37 (10): 1469-89. doi:10.1097/PAS.0b013e318299f2d1. PMID 24025519.
  7. ↑ URL:http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001544/. Accessed on: 14 July 2011.
  8. ↑ 8.0 8.1 8.2 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 289. ISBN 978-0781765275.
  9. ↑ Schmid HP, Szabo J (May 1997). "[Renal cell carcinoma--a current review]" (in German). Praxis (Bern 1994) 86 (20): 837?3. PMID 9312811.
  10. ↑ Chow, WH.; McLaughlin, JK.; Mandel, JS.; Wacholder, S.; Niwa, S.; Fraumeni, JF. (Jan 1996). "Obesity and risk of renal cell cancer.". Cancer Epidemiol Biomarkers Prev 5 (1): 17-21. PMID 8770461.
  11. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1016. ISBN 0-7216-0187-1.
  12. ↑ Capitanio, U.; Cloutier, V.; Zini, L.; Isbarn, H.; Jeldres, C.; Shariat, SF.; Perrotte, P.; Antebi, E. et al. (Jun 2009). "A critical assessment of the prognostic value of clear cell, papillary and chromophobe histological subtypes in renal cell carcinoma: a population-based study.". BJU Int 103 (11): 1496-500. doi:10.1111/j.1464-410X.2008.08259.x. PMID 19076149.
  13. ↑ Delahunt, B.; Bethwaite, PB.; Nacey, JN. (Oct 2007). "Outcome prediction for renal cell carcinoma: evaluation of prognostic factors for tumours divided according to histological subtype.". Pathology 39 (5): 459-65. doi:10.1080/00313020701570061. PMID 17886093.
  14. ↑ Zhou M, Roma A, Magi-Galluzzi C (June 2005). "The usefulness of immunohistochemical markers in the differential diagnosis of renal neoplasms". Clin. Lab. Med. 25 (2): 247?7. doi:10.1016/j.cll.2005.01.004. PMID 15848735.
  15. ↑ 15.0 15.1 Zhou M, Roma A, Magi-Galluzzi C (June 2005). "The usefulness of immunohistochemical markers in the differential diagnosis of renal neoplasms". Clin. Lab. Med. 25 (2): 247?7. doi:10.1016/j.cll.2005.01.004. PMID 15848735.
  16. ↑ 16.0 16.1 Langner C, Ratschek M, Rehak P, Schips L, Zigeuner R (February 2004). "Expression of MUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases". Mod. Pathol. 17 (2): 180?. doi:10.1038/modpathol.3800032. PMID 14657952.
  17. ↑ Liu L, Qian J, Singh H, Meiers I, Zhou X, Bostwick DG (August 2007). "Immunohistochemical analysis of chromophobe renal cell carcinoma, renal oncocytoma, and clear cell carcinoma: an optimal and practical panel for differential diagnosis". Arch. Pathol. Lab. Med. 131 (8): 1290?. PMID 17683191. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=131&page=1290.
  18. ↑ Pan CC, Chen PC, Ho DM (November 2004). "The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases". Histopathology 45 (5): 452?. doi:10.1111/j.1365-2559.2004.01962.x. PMID 15500648.
  19. ↑ 19.0 19.1 Geramizadeh B, Ravanshad M, Rahsaz M (2008). "Useful markers for differential diagnosis of oncocytoma, chromophobe renal cell carcinoma and conventional renal cell carcinoma". Indian J Pathol Microbiol 51 (2): 167?1. PMID 18603673. http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2008;volume=51;issue=2;spage=167;epage=171;aulast=Geramizadeh.
  20. ↑ 20.0 20.1 Memeo L, Jhang J, Assaad AM, et al. (February 2007). "Immunohistochemical analysis for cytokeratin 7, KIT, and PAX2: value in the differential diagnosis of chromophobe cell carcinoma". Am. J. Clin. Pathol. 127 (2): 225–9. doi:10.1309/9KWEA4W9Y94D1AEE. PMID 17210525. http://ajcp.ascpjournals.org/cgi/pmidlookup?view=long&pmid=17210525.
  21. ↑ Mazal PR, Exner M, Haitel A, et al. (January 2005). "Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma". Hum. Pathol. 36 (1): 22–8. doi:10.1016/j.humpath.2004.09.011. PMID 15712178.
  22. ↑ Krueger S, Sotlar K, Kausch I, Horny HP (2005). "Expression of KIT (CD117) in renal cell carcinoma and renal oncocytoma". Oncology 68 (2-3): 269-75. doi:10.1159/000086783. PMID 16015044.
  23. ↑ Martignoni G, Brunelli M, Gobbo S, et al (February 2007). "Role of molecular markers in diagnosis and prognosis of renal cell carcinoma". Anal. Quant. Cytol. Histol. 29 (1): 41?. PMID 17375873.
  24. ↑ Avery AK, Beckstead J, Renshaw AA, Corless CL (February 2000). "Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasms". Am. J. Surg. Pathol. 24 (2): 203?0. PMID 10680888. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0147-5185&volume=24&issue=2&spage=203.
  25. ↑ Kim MK, Kim S (December 2002). "Immunohistochemical profile of common epithelial neoplasms arising in the kidney". Appl. Immunohistochem. Mol. Morphol. 10 (4): 332–8. PMID 12613443.
  26. ↑ Wong, L.; Hsu, TH.; Perlroth, MG.; Hofmann, LV.; Haynes, CM.; Katznelson, L. (Feb 2008). "Reninoma: case report and literature review.". J Hypertens 26 (2): 368-73. doi:10.1097/HJH.0b013e3282f283f3. PMID 18192852.
  27. ↑ Bircan, S.; Orhan, D.; Tulunay, O.; Safak, M. (2000). "Renomedullary interstitial cell tumor.". Urol Int 65 (3): 163-6. PMID 11054036.
  28. ↑ Turbiner, J.; Amin, MB.; Humphrey, PA.; Srigley, JR.; De Leval, L.; Radhakrishnan, A.; Oliva, E. (Apr 2007). "Cystic nephroma and mixed epithelial and stromal tumor of kidney: a detailed clinicopathologic analysis of 34 cases and proposal for renal epithelial and stromal tumor (REST) as a unifying term.". Am J Surg Pathol 31 (4): 489-500. doi:10.1097/PAS.0b013e31802bdd56. PMID 17414095.
  29. ↑ Brandal, P.; Lie, AK.; Bassarova, A.; Svindland, A.; Risberg, B.; Danielsen, H.; Heim, S. (Feb 2006). "Genomic aberrations in mucinous tubular and spindle cell renal cell carcinomas.". Mod Pathol 19 (2): 186-94. doi:10.1038/modpathol.3800499. PMID 16258504.

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