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.


==Renal specimens==
Pediatric kidney tumours are dealt with in the ''[[pediatric kidney tumours]]'' article.
*Renal biopsy - usually of medical disease (see ''[[medical kidney]]'').
*Partial nephrectomy.
*Nephrectomy.
*Nephroureterectomy (includes ureter) - done for [[urothelial cell carcinoma]] (UCC) of the renal pelvis and ureteric UCC.
*Radical nephrectomy (includes the [[adrenal gland]]).


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


==Renal cell carcinoma==
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).
===General===
*Relatively common form of cancer.
*Often abbreviated '''RCC'''.
 
===Origin===
*Proximal renal tubule.
 
===Clinical===
*Classically described as a triad:<ref name=schmid>{{cite journal |author=Schmid HP, Szabo J |title=[Renal cell carcinoma--a current review] |language=German |journal=Praxis (Bern 1994) |volume=86 |issue=20 |pages=837?3 |year=1997 |month=May |pmid=9312811 |doi= |url=}}</ref>
**Hematuria (most common symptom).
**Abdominal mass.
**Flank pain.
*Frequently picked-up on imaging (incidentaloma) ~ 1/3 of cases.
 
===Risk factors===
*Smoking.
*Some chemicals.
*Hemodialysis.
*Male>female (~2:1).
*Hereditary - familial syndromes (see [[Hereditary RCC]]).
 
===Subtypes===
RCC (renal cell carcinoma) comes in different subtypes:<ref>PBoD P.1016.</ref>
*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.<ref>PMID 19076149</ref>
*CCRCC tends to be worse than ChRCC and PRCC, probably due to higher incidence of mets.<ref>PMID 17886093</ref>
===IHC - is it RCC?===
*RCC Ma (+), CD10 (+) -- specific for RCC<ref>{{cite journal |author=Zhou M, Roma A, Magi-Galluzzi C |title=The usefulness of immunohistochemical markers in the differential diagnosis of renal neoplasms |journal=Clin. Lab. Med. |volume=25 |issue=2 |pages=247?7 |year=2005 |month=June |pmid=15848735 |doi=10.1016/j.cll.2005.01.004 |url=}}</ref>


===IHC - differentiation of types===
==Anatomy==
*clear cell RCC vs. papillary RCC
Layers (superficial to deep):
** CK7 (-ve CCRCC), AMACR (+ve in PRCC)<ref name=pmid15848735>{{cite journal |author=Zhou M, Roma A, Magi-Galluzzi C |title=The usefulness of immunohistochemical markers in the differential diagnosis of renal neoplasms |journal=Clin. Lab. Med. |volume=25 |issue=2 |pages=247?7 |year=2005 |month=June |pmid=15848735 |doi=10.1016/j.cll.2005.01.004 |url=}}</ref>
#Renal fascia (Gerota's fascia).
*papillary RCC type 1 vs. papillary RCC type 2
#Perinephric fat.
** 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>
#Renal capsule.  
**EMA (MUC1) +ve in PRCC type 1<ref name=pmid14657952/>
#Renal parenchyma (cortex).
*ChRCC vs. oncocytoma (ONC)
** CK7 (ChRCC +ve membrane), CK20, CD15<ref name=pmid15848735/>
** CK7 -- ChRCC 86% +ve vs. ONC 0% +ve<ref name=pmid17683191>{{cite journal |author=Liu L, Qian J, Singh H, Meiers I, Zhou X, Bostwick DG |title=Immunohistochemical analysis of chromophobe renal cell carcinoma, renal oncocytoma, and clear cell carcinoma: an optimal and practical panel for differential diagnosis |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=8 |pages=1290? |year=2007 |month=August |pmid=17683191 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=131&page=1290 }}</ref>
** CD15 -- ChRCC 11% +ve vs. ONC 57% +ve<ref name=pmid15500648>{{cite journal |author=Pan CC, Chen PC, Ho DM |title=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 |journal=Histopathology |volume=45 |issue=5 |pages=452? |year=2004 |month=November |pmid=15500648 |doi=10.1111/j.1365-2559.2004.01962.x |url=}}</ref>
** Hale's colloidal iron +ve in ChRCC, usually neg. in ONC<ref name=pmid18603673>{{cite journal |author=Geramizadeh B, Ravanshad M, Rahsaz M |title=Useful markers for differential diagnosis of oncocytoma, chromophobe renal cell carcinoma and conventional renal cell carcinoma |journal=Indian J Pathol Microbiol |volume=51 |issue=2 |pages=167?1 |year=2008 |pmid=18603673 |doi= |url=http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2008;volume=51;issue=2;spage=167;epage=171;aulast=Geramizadeh }}</ref>
*ChRCC & renal oncocytoma vs. others
** CD117 (ckit) +ve (100% membrane, ~75% cytoplasmic)<ref>{{cite journal |author=Krueger S, Sotlar K, Kausch I, Horny HP |title=Expression of KIT (CD117) in renal cell carcinoma and renal oncocytoma |journal=Oncology |volume=68 |issue=2-3 |pages=269-75 |year=2005 |pmid=16015044 |doi=10.1159/000086783 |url=}}</ref>
*clear cell RCC vs. chromophobe RCC
**Hale's colloidal iron (+ve in ChRCC)<ref name=pmid18603673/>
**CK7 (cell membrane +ve in ChRCC)


Notes:
===Sign out===
*One paper<ref>{{cite journal |author=Martignoni G, Brunelli M, Gobbo S, ''et al'' |title=Role of molecular markers in diagnosis and prognosis of renal cell carcinoma |journal=Anal. Quant. Cytol. Histol. |volume=29 |issue=1 |pages=41? |year=2007 |month=February |pmid=17375873 |doi= |url=}}</ref> describes CD10, parvalbumin, AMACR, CK7 and S100A1 as being useful.
====Missed renal biopsy====
*Another paper I came across:<ref>{{cite journal |author=Avery AK, Beckstead J, Renshaw AA, Corless CL |title=Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasms |journal=Am. J. Surg. Pathol. |volume=24 |issue=2 |pages=203?0 |year=2000 |month=February |pmid=10680888 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0147-5185&volume=24&issue=2&spage=203}}</ref>
{{Main|Missed renal biopsy}}
*ckit (CD117) not useful for differentiating ONC and ChRCC.


===Tabular comparison===
=Tabular comparison (selected tumours)=  


Selected common tumours of the kidney:<ref>GUP PP.281-304.</ref><ref name=pmid19494850>PMID 19494850.</ref>
Selected common tumours of the kidney:<ref name=Ref_GUP281>{{Ref GUP|281-304}}</ref><ref name=pmid19494850>{{Cite journal  | last1 = Srigley | first1 = JR. | last2 = Delahunt | first2 = B. | title = Uncommon and recently described renal carcinomas. | journal = Mod Pathol | volume = 22 Suppl 2 | issue =  | pages = S2-S23 | month = Jun | year = 2009 | doi = 10.1038/modpathol.2009.70 | PMID = 19494850 }}</ref>
{| class="wikitable"
{| class="wikitable"
| ||'''Clear cell RCC''' ||'''Papillary RCC<br>type 1''' ||'''Papillary RCC<br>type 2''' ||'''Chromophobe RCC<br>classic variant''' || '''Chromophobe RCC<br>eosinophilic variant''' || '''Oncocytoma'''
|
| '''Clear cell RCC'''
| '''Papillary RCC<br>type 1'''
| '''Papillary RCC<br>type 2'''  
| '''Chromophobe RCC<br>classic variant'''
| '''Chromophobe RCC<br>eosinophilic variant'''
| '''Oncocytoma'''
|-
|-
|Gross ||Golden yellow, solid || friable || friable ||light brown ||light brown ||mahogany/brown, +/-central scar
|Gross
| Golden yellow, solid
| friable
| friable
| light brown
| light brown
| mahogany/brown, +/-central scar
|-
|-
|Architecture ||nests, sheets || papillary, simple || papillary,<br>pseudostratified ||nests, sheets ||nests, sheets ||nests, sheets
|Architecture
| nests, sheets
| papillary, simple
| papillary,<br>pseudostratified
| nests, sheets
| nests, sheets
| nests, sheets
|-
|-
|Nuclear atypia ||low-high<br>typically medium-high ||low-medium || medium-high ||low-high ||low-high ||low-medium, round nuclei
|Nuclear atypia
| low-high<br>typically medium-high  
| low-medium
| medium-high  
| low-high, "raisinoid" <br>nuc. membrane
| low-high, "raisinoid" <br>nuc. membrane
| low-medium, round nuclei
|-
|-
|Cytoplasm ||clear ||eosinophilic ||eosinophilic ||cobwebs/clear ||eosinophilic/cobwebs ||eosinophilic/<br>granular & abundant
|Cytoplasm
| clear
| eosinophilic
| eosinophilic
| cobwebs/clear
| eosinophilic/cobwebs
| eosinophilic/<br>granular & abundant
|-
|-
|Other ||delicate vessels,<br>necrosis common ||histiocytes<br> in fibrovascular cores ||histiocytes<br> in fibrovascular cores ||perinuclear clearing, thick vessels ||perinuclear clearing, thick vessels ||in loose fibrous/hyaline stroma
|Other
| delicate vessels,<br>[[necrosis]] common
| histiocytes<br> in fibrovascular cores, >0.5 cm
| histiocytes<br> 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+
|IHC
| [[CK7]]-, EMA+
| AMACR+, EMA+, CK7+
| AMACR+, E-cadherin+, CK7-
| CD117+, CK7+ (membrane)
| CD117+, CK7+ (membrane)
| Vimentin-, EMA+
|-
|-
|Main DDx ||chromophobe<br>classic variant ||PaRCC type 2, mets ||PaRCC type 1, mets||clear cell RCC ||oncocytoma ||chromophobe<br>eosinophilic variant
|Main DDx
| chromophobe<br>classic variant
| PaRCC type 2, mets  
| PaRCC type 1, mets
| clear cell RCC
| oncocytoma
| chromophobe<br>eosinophilic variant
|-
|-
|Key features ||clear cells, vascular || papillae, histiocytes<br>simple epithelium ||papillae, histiocytes,<br>stratified ||perinuc. clearing<br>wispy cytoplasm ||wispy eosinophilic<br>cytoplasm ||eosinophilic, granular cytoplasm
|Key features
| clear cells, vascular  
| papillae, histiocytes<br>simple epithelium  
| papillae, histiocytes,<br>stratified
| perinuc. clearing,<br>wispy cytoplasm
| perinuc. clearing,<br>wispy eosinophilic<br>cytoplasm
| eosinophilic, granular cytoplasm
|-
|Image(s)
| [[Image:Renal_clear_cell_ca_%281%29_Nephrectomy.jpg|thumb|150px| CCRCC (WC)]]
| [[Image:Papillary_renal_cell_carcinoma_intermed_mag.jpg|thumb|150px| PaRCC - intermed. (WC)]], [[Image:Papillary_renal_cell_carcinoma_very_high_mag.jpg | thumb|150px| PaRCC - high (WC)]]
|
|
| [[Image:Oncocytic_chromophobe_rcc_high_mag.jpg|thumb|150px| ChRCC (WC)]]
| [[Image:Renal_oncocytoma2.jpg|thumb|150px| Oncocytoma (WC)]]
|}
|}
Notes:
Notes:
*Cell shape: all have epithelioid morphology.
*Cell shape: all have epithelioid morphology.


==Hereditary RCC==
===Tabular comparison of oncocytoma and chromophobe RCC===
# [[Von Hippel-Lindau syndrome]] (clear cell tumours),
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>
# hereditary clear cell carcinoma (VHL gene),
{| class="wikitable sortable"
# hereditary papillary carcinoma (MET proto-oncogene mutation)
! Morphologic feature
 
! [[ChRCC]] (eosinophilic<br> variant)
Note: ''all'' of the above are autosomal dominant<ref>PBoD P.1016.</ref>
! [[Renal oncocytoma]]
 
|-
==Grading==
| Nuclear morphology
Grading based on '''Fuhrman system''' which considers:<ref>GUP P.282.</ref>
| "raisinoid"/wrinkled appearance
*Nuclear pleomorphism (size, shape),
| round with small nucleolus, <br>usu. little size variation
*Chromatin pattern,
|-
*Nucleoli prominence.
| Multinucleation
| common - binucleation
| uncommon
|-
| Chromatin
| coarse
| fine
|-
| Architecture
| solid, crowded nests
| spaced nests / <br>archipelago-like, solid
|-
| Cytoplasm
| perinuclear halo, may be focal
| no perinuclear halo
|-
| Degenerative foci<br>(focal atypia & pleomorphism)
| absent
| present in ~20% of cases
|-
| Image
| [[Image:Oncocytic_chromophobe_rcc_high_mag.jpg |thumb|150px|ChRCC (WC/Nephron)]]
| [[Image:Renal_oncocytoma2.jpg |thumb|150px|Oncocytoma (WC/Nephron)]]
|}


===Criteria & grades===
===Common DDx===
*Grade 1: no nucleoli, near 'normal' appearance.
====Spindle cell tumours====
*Grade 2: finely granular chromatin (key feature), no nuclei visible with 10x objective lens.
Malignant spindle cell tumours of the kidney:
*Grade 3: nucleoli seen easily (key feature).
*[[Renal cell carcinoma with sarcomatoid differentiation]].
*Grade 4: prominent pleomorphism (key feature), hyperchromasia, macronucleoli.
*[[Renal mucinous tubular and spindle cell carcinoma]].
Note: Most tumours are grade 2 & 3.
*[[Wilms tumour]].
*[[Renal cell carcinoma, unclassified]].


===Fuhrman grading in short===
Benign spindle cell tumours of the kidney:
*1 vs. 2: grade 2 has granular chromatin, grade 2 has nucleoli visible @ 5x objective.<ref>AE. June 2010.</ref>
*[[Angiomyolipoma]].
*2 vs. 3: grade 3 has nucleoli @ 10x objective.
*[[Cystic nephroma]].
*3 vs. 4: grade 4 has pleomorphism/hyperchromasia.


==Clear cell carcinoma==
====Renal tumours with eosinophilic cytoplasm====
===Gross===
{{Main|Renal tumours with eosinophilic cytoplasm}}
*Gold/yellow.
*+/-Haemorrhage (common).
*+/-Necrosis (common in large tumours).


===Microscopic===
=WHO classification of renal neoplasia=
Features:<ref>PBoD P.1017-8</ref>
*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].
*Clear cells.
===Renal cell tumours===
*Solid or trabecular pattern.
Common:
*Delicate branching vasculature.
*[[Clear cell renal cell carcinoma]].
*[[Papillary renal cell carcinoma]].
*[[Renal papillary adenoma|Papillary adenoma]].
*[[Chromophobe renal cell carcinoma]].
*[[Renal oncocytoma|Oncocytoma]].


*Hyaline bodies common.<ref>AFIP Renal Tumours Book.</ref>
Less common:
**Not common in papillary RCC.
*[[Multilocular clear cell renal cell carcinoma]].
*[[Carcinoma of the collecting ducts of Bellini]].
*[[Renal cell carcinoma, unclassified]].
*[[Renal medullary carcinoma]].
*[[Renal tumour with Xp11.2 translocation|Xp11 translocation carcinoma]].
*[[Mucinous tubular and spindle cell carcinoma]].
*Carcinoma associated with neuroblastoma.


===IHC===
===Metanephric tumours===
*CK7 -ve.  
*[[Metanephric adenoma]].
*CK20 -ve.
*[[Metanephric stromal tumour]].
*Hale's colloidal iron -ve.
*[[Metanephric adenofibroma]].
**+ve in chromophobe.


Note: ''[[Hale's colloidal iron]]'' does not stain iron... it stains hemosiderin.<ref>Latta Jan 27, '09</ref>
===Nephroblastic tumours===
*Nephrogenic rests.
*[[Nephroblastoma]].


Clear cell vs. chromophobe:
===Mesenchymal tumours===
*Chromophobe: "translucent" (NOT quite clear), reticulated, +Hale's colloidal iron stain, CK7+ (cell membrane).
Childhood:
*[[Clear cell sarcoma of the kidney]].
*[[Rhabdoid tumour]].
*[[Mesoblastic nephroma|Congenital mesoblastic nephroma]].


Clear cell vs. [[adrenocortical carcinoma]]:
Adults:
*ACC: EMA- (epithelial membrane antigen), cytokeratin mostly neg., inhibin+ (neg. in RCC).<ref>GUP P.285.</ref>
*Unique to kidney:
**[[Juxtaglomerular cell tumour]].
**[[Renomedullary interstitial cell tumour]].
Other:
*[[Angiomyolipoma]].
*[[Epithelioid angiomyolipoma]].
*[[Leiomyosarcoma]].
*[[Angiosarcoma]].
*[[Pleomorphic undifferentiated sarcoma]].
*[[Hemangiopericytoma]].
*[[Solitary fibrous tumour]].
*[[Osteosarcoma]].
*[[Schwannoma]].


==Papillary RCC==
===Mixed mesenchymal and epithelial tumours===
===General===
*[[Cystic nephroma]].
*Often subclassified<ref>GUP P.289.</ref> into ''type 1'' and ''type 2'' -- see below.
*[[Mixed epithelial and stromal tumour]].
*May be abbreviated ''PRCC''.
*[[Synovial sarcoma]].


===Epidemiology===
===Others===
*Associated with ''dialysis associated cystic disease''.<ref>PBoD PP.1017-8</ref>
*[[Neuroendocrine tumours]].
*Hematologic tumours.
*[[Germ cell tumour]]s.
*[[Metastases]].


===Microsopy===
==Vancouver modification of WHO classification==
Histo.<ref>PBoD P.1017-8.</ref>
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>
*Cuboidal or low columnar cell in papillae.
*[[Tubulocystic renal cell carcinoma]].
*Interstitial foam cells in vascular cores - '''key feature'''.<ref>ALS Feb 9, 2009.</ref>
*[[Acquired cystic disease associated renal cell carcinoma]].
**Most sensitive and specific feature of PRCC.<ref>{{cite journal |author=Granter SR, Perez-Atayde AR, Renshaw AA |title=Cytologic analysis of papillary renal cell carcinoma |journal=Cancer |volume=84 |issue=5 |pages=303?8 |year=1998 |month=October |pmid=9801205 |doi= |url=http://dx.doi.org/10.1002/(SICI)1097-0142(19981025)84:5<303::AID-CNCR6>3.0.CO;2-7}}</ref>
*[[Clear cell papillary renal cell carcinoma]] (clear cell tubulopapillary renal cell carcinoma).
*Highly vascular.
*[[Hereditary leiomyomatosis renal cell carcinoma syndrome associated renal cell carcinoma]].
Mnemonic ''HIP'': '''h'''ighly vascular, '''i'''nterstitial foam cells, '''p'''apillae.
*MiT family translocation renal cell carcinoma - includes:
**[[t(6;11) renal cell carcinoma]].


Histological subtyping:<ref>GUP P.289.</ref>
"Emerging" entities (as per Vancouver) are:
*''Type 1'' - single layer of cells on basement membrane.
*[[Thyroid-like follicular renal cell carcinoma]].
** usually low grade nuclear features, i.e. low Fuhrman grade.
*[[Succinate dehydrogenase-deficient renal cell carcinoma]].
*''Type 2'' - pseudostratification of cells.
*[[ALK translocation renal cell carcinoma]].
** Usually high grade nuclear features, i.e. high Fuhrman grade.


===IHC===
==An entity proposed after Vancouver==
Features:<ref>GUP P. 289.</ref>
*[[Eosinophilic, solid and cystic renal cell carcinoma]].
*AMACR +ve.<ref>ALS Feb 9, 2009.</ref>
*[[Biphasic hyalinizing psammomatous renal cell carcinoma]].
*HMWCK (34betaE12) +ve.
*[[Papillary renal neoplasm with reverse polarity]].
*Panker (AE1/AE3) +ve.
*[[Low-grade oncocytic renal tumour]].
*CK7 +ve ~90% of type 1, 20% of type 2.


More reading:
=Renal cell carcinoma=
*[http://www.e-immunohistochemistry.info/web/Papillary_renal_cell_carcinoma.htm e-immunohistochemistry.info]
==Overview==
 
===Clear cell vs. papillary===
*Papillary: +histiocytes, +intracellular hemosiderin, [[CK7]]+.
 
==Chromophobe RCC==
===General===
===General===
*Sometimes abbreviated ''ChRCC''.
*Relatively common form of cancer.
*Often abbreviated '''RCC'''.
*[[AKA]] ''hypernephroma''.<ref>URL:[http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001544/ http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001544/]. Accessed on: 14 July 2011.</ref>
*RCC represents approx. 90% of malignancies in kidneys of adults.<ref name=Ref_WMSP289>{{Ref WMSP|289}}</ref>
===Origin===
*Proximal renal tubule.


There are two subtypes:<ref>GUP P.293.</ref>
===Clinical===
*Classic.
*Classically described as a triad:<ref name=schmid>{{cite journal |author=Schmid HP, Szabo J |title=[Renal cell carcinoma--a current review] |language=German |journal=Praxis (Bern 1994) |volume=86 |issue=20 |pages=837?3 |year=1997 |month=May |pmid=9312811 |doi= |url=}}</ref>
*Eosinophilic variant.
**Hematuria (most common symptom).
**Abdominal mass.
**Flank pain.
*Frequently picked-up on imaging (incidentaloma) ~ 1/3 of cases.


===Gross===
===Risk factors===
*Tan, light-brown.
*[[Smoking]] - most important.<ref name=Ref_WMSP289>{{Ref WMSP|289}}</ref>
*Solitary.
*Chemical exposures (arsenic, asbestos, cadmium, organic solvents, pesticides, fungal toxins).<ref name=Ref_WMSP289>{{Ref WMSP|289}}</ref>
*Well-circumscribed.
*Chronic renal failure.
**[[Acquired cystic renal disease]].
*Male>female (~2:1).
*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>


===Microscopy===
===Subtypes of RCC===
Classic Histo.<ref>PBoD P.1016-7</ref><ref>GUP P.293.</ref>, 3 P's [[mnemonic]]:
RCC (renal cell carcinoma) comes in different subtypes:<ref name=Ref_PBoD1016>{{Ref PBoD|1016}}</ref>
*Pale cytoplasm, with wisps of eosinophilic material; the cells are not completely clear, they have "cobwebs".
*Clear cell carcinoma (70-80% of RCC) -- abbrev. CCRCC.
*Perinuclear clearing, i.e. a pale halo surrounds the nucleus - '''key feature'''.
*Papillary renal cell carcinoma (10-15% of RCC) -- abbrev. PRCC.
*Periphery of cell distinct, i.e. cell membrane is easy to discern.
*Chromophobe renal carcinoma (5% of RCC) -- abbrev. ChRCC.  
 
*Collecting duct (Bellini duct) carcinoma (1% of RCC).
Eosinophilic variant:<ref>GUP P.293.</ref>
*Eosinophilic (finely granular) cytoplasm.
*Perinuclear clearing - '''key feature'''.
*Periphery of cell distinct.
*Smaller cells than classic subtype.


Notes:
Notes:
*May have psammoma bodies.
*Subtype is an independent predictor of mortality - but adds very little to multivariate models with staging information.<ref name=pmid19076149>{{Cite journal  | last1 = Capitanio | first1 = U. | last2 = Cloutier | first2 = V. | last3 = Zini | first3 = L. | last4 = Isbarn | first4 = H. | last5 = Jeldres | first5 = C. | last6 = Shariat | first6 = SF. | last7 = Perrotte | first7 = P. | last8 = Antebi | first8 = E. | last9 = Patard | first9 = JJ. | title = A critical assessment of the prognostic value of clear cell, papillary and chromophobe histological subtypes in renal cell carcinoma: a population-based study. | journal = BJU Int | volume = 103 | issue = 11 | pages = 1496-500 | month = Jun | year = 2009 | doi = 10.1111/j.1464-410X.2008.08259.x | PMID = 19076149 }}</ref>
*CCRCC tends to be worse than ChRCC and PRCC, probably due to higher incidence of mets.<ref name=pmid17886093>{{Cite journal  | last1 = Delahunt | first1 = B. | last2 = Bethwaite | first2 = PB. | last3 = Nacey | first3 = JN. | title = Outcome prediction for renal cell carcinoma: evaluation of prognostic factors for tumours divided according to histological subtype. | journal = Pathology | volume = 39 | issue = 5 | pages = 459-65 | month = Oct | year = 2007 | doi = 10.1080/00313020701570061 | PMID = 17886093 }}</ref>
*The exam answer (worst to best): clear cell RCC, papillary RCC, chromophobe RCC.


Image: [http://commons.wikimedia.org/wiki/File:Oncocytic_chromophobe_rcc_high_mag.jpg Oncocytic chromophobe RCC (wikimedia.org)].
===IHC - is it RCC?===
*RCC Ma (+), CD10 (+) -- specific for RCC<ref>{{cite journal |author=Zhou M, Roma A, Magi-Galluzzi C |title=The usefulness of immunohistochemical markers in the differential diagnosis of renal neoplasms |journal=Clin. Lab. Med. |volume=25 |issue=2 |pages=247?7 |year=2005 |month=June |pmid=15848735 |doi=10.1016/j.cll.2005.01.004 |url=}}</ref>


===IHC===
===IHC - differentiation of types===
*CK7+ cell membrane<ref>GUP P.293.</ref>
*Clear cell RCC vs. papillary RCC:
** CK7 (-ve CCRCC), AMACR (+ve in PRCC).<ref name=pmid15848735>{{cite journal |author=Zhou M, Roma A, Magi-Galluzzi C |title=The usefulness of immunohistochemical markers in the differential diagnosis of renal neoplasms |journal=Clin. Lab. Med. |volume=25 |issue=2 |pages=247?7 |year=2005 |month=June |pmid=15848735 |doi=10.1016/j.cll.2005.01.004 |url=}}</ref>
*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>
**[[EMA]] (MUC1) +ve in PRCC type 1.<ref name=pmid14657952/>


DDx:
*ChRCC vs. oncocytoma (ONC):
*May appear similar to oncotyoma -- particularily the eosinophilic variant.
** CK7 (ChRCC +ve membrane), CK20, CD15.<ref name=pmid15848735/>
**IHC: CK7: chromophobe = cell membrane CK7+; oncoctyoma = patchy cytoplasmic +ve
** CK7 -- ChRCC 86% +ve vs. ONC 0% +ve.<ref name=pmid17683191>{{cite journal |author=Liu L, Qian J, Singh H, Meiers I, Zhou X, Bostwick DG |title=Immunohistochemical analysis of chromophobe renal cell carcinoma, renal oncocytoma, and clear cell carcinoma: an optimal and practical panel for differential diagnosis |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=8 |pages=1290? |year=2007 |month=August |pmid=17683191 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=131&page=1290 }}</ref>
*Classic ChRCC may be challenging to differentiate from clear cell RCC.
** CD15 -- ChRCC 11% +ve vs. ONC 57% +ve.<ref name=pmid15500648>{{cite journal |author=Pan CC, Chen PC, Ho DM |title=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 |journal=Histopathology |volume=45 |issue=5 |pages=452? |year=2004 |month=November |pmid=15500648 |doi=10.1111/j.1365-2559.2004.01962.x |url=}}</ref>
**Perinuclear clearing is ''not'' seen in clear cell RCC.
** Hale's colloidal iron +ve in ChRCC, usually neg. in ONC.<ref name=pmid18603673>{{cite journal |author=Geramizadeh B, Ravanshad M, Rahsaz M |title=Useful markers for differential diagnosis of oncocytoma, chromophobe renal cell carcinoma and conventional renal cell carcinoma |journal=Indian J Pathol Microbiol |volume=51 |issue=2 |pages=167?1 |year=2008 |pmid=18603673 |doi= |url=http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2008;volume=51;issue=2;spage=167;epage=171;aulast=Geramizadeh }}</ref>
**ChRCC has wisps in the cytoplasm
** PAX2 -- ChRCC (1/11) +ve vs. ONC (20/23) +ve.<ref name=pmid17210525>{{cite journal |author=Memeo L, Jhang J, Assaad AM, ''et al.'' |title=Immunohistochemical analysis for cytokeratin 7, KIT, and PAX2: value in the differential diagnosis of chromophobe cell carcinoma |journal=Am. J. Clin. Pathol. |volume=127 |issue=2 |pages=225–9 |year=2007 |month=February |pmid=17210525 |doi=10.1309/9KWEA4W9Y94D1AEE |url=http://ajcp.ascpjournals.org/cgi/pmidlookup?view=long&pmid=17210525}}</ref>
**Kidney-specific cadherin (Ksp-cadherin) -- ChRCC 97% +ve (distinctive membrane pattern) vs. ONC only 3% +ve.<ref name=pmid15712178>{{cite journal |author=Mazal PR, Exner M, Haitel A, ''et al.'' |title=Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma |journal=Hum. Pathol. |volume=36 |issue=1 |pages=22–8 |year=2005 |month=January |pmid=15712178 |doi=10.1016/j.humpath.2004.09.011 |url=}}</ref>


==Collecting duct carcinoma==
*ChRCC & renal oncocytoma vs. others:
===Epidemiology===
** CD117 (ckit) +ve (100% membrane, ~75% cytoplasmic).<ref>{{cite journal |author=Krueger S, Sotlar K, Kausch I, Horny HP |title=Expression of KIT (CD117) in renal cell carcinoma and renal oncocytoma |journal=Oncology |volume=68 |issue=2-3 |pages=269-75 |year=2005 |pmid=16015044 |doi=10.1159/000086783 |url=}}</ref>
*Rare.
*Clear cell RCC vs. chromophobe RCC:
 
**Hale's colloidal iron (+ve in ChRCC).<ref name=pmid18603673/>
===Microscopy===
**CK7 (cell membrane +ve in ChRCC).
Features:<ref>GUP P.295.</ref>
*Tubular structures with tapered ends.
*High grade nuclear features (nuclear pleomorphism).
*High mitotic rate.
*[[Hobnail pattern]] - cell width smaller at basement membrane than free surface ??? <ref>PBoD P.1018.</ref>


Notes:
*One paper<ref>{{cite journal |author=Martignoni G, Brunelli M, Gobbo S, ''et al'' |title=Role of molecular markers in diagnosis and prognosis of renal cell carcinoma |journal=Anal. Quant. Cytol. Histol. |volume=29 |issue=1 |pages=41? |year=2007 |month=February |pmid=17375873 |doi= |url=}}</ref> describes CD10, parvalbumin, AMACR, CK7 and S100A1 as being useful.
*Another paper I came across:<ref>{{cite journal |author=Avery AK, Beckstead J, Renshaw AA, Corless CL |title=Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasms |journal=Am. J. Surg. Pathol. |volume=24 |issue=2 |pages=203?0 |year=2000 |month=February |pmid=10680888 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0147-5185&volume=24&issue=2&spage=203}}</ref>
*c-kit (CD117) not useful for differentiating ONC and ChRCC.<ref name=pmid17210525>{{cite journal |author=Memeo L, Jhang J, Assaad AM, ''et al.'' |title=Immunohistochemical analysis for cytokeratin 7, KIT, and PAX2: value in the differential diagnosis of chromophobe cell carcinoma |journal=Am. J. Clin. Pathol. |volume=127 |issue=2 |pages=225–9 |year=2007 |month=February |pmid=17210525 |doi=10.1309/9KWEA4W9Y94D1AEE |url=http://ajcp.ascpjournals.org/cgi/pmidlookup?view=long&pmid=17210525}}</ref>
*E-cadherin ''not'' useful for differentiating ChRCC and ONC.<ref name=pmid12613443>{{cite journal |author=Kim MK, Kim S |title=Immunohistochemical profile of common epithelial neoplasms arising in the kidney |journal=Appl. Immunohistochem. Mol. Morphol. |volume=10 |issue=4 |pages=332–8 |year=2002 |month=December |pmid=12613443 |doi= |url=}}</ref>


==Urothelial cell carcinoma==
===RCC vs. Urothelial cell carcinoma===
{{main|Urothelium}}
*Clinically/radiologically, it may not be possible to differentiate renal pelvis UCC and RCC if the tumour is large.
*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.   
*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 = ''nephrectomy'' or ''radical nephrectomy''.
**[[RCC]] = ''[[partial nephrectomy]]'', ''nephrectomy'' or ''[[radical nephrectomy]]''.


=Benign & mimics=
===Renal cell carcinoma with sarcomatoid differentiation===
*[[AKA]] ''sarcomatoid renal cell carcinoma''.
{{Main|Renal cell carcinoma with sarcomatoid differentiation}}


==Oncocytoma==
===Renal cell carcinoma with rhabdoid morphology===
===General===
*[[AKA]] ''renal cell carcinoma with rhabdoid change''.
*Can be difficult to distinguish radiologically from RCC (chromophobe subtype).
{{Main|Renal cell carcinoma with rhabdoid morphology}}
** ... and pathologists occasionally struggle like the radiologists.
*Benign tumour - the reason it is excised is... one cannot be certain it isn't a RCC.


===Gross===
==Hereditary renal cell carcinoma==
*Brown, mahogany brown.
{{Main|Hereditary renal cell carcinoma}}
*1/3 have a characteristic central scar.<ref>GUP P.302.</ref>


Image: [http://en.wikipedia.org/wiki/File:Renal_oncocytoma.jpg Renal oncocytoma with central scar (wikipedia.org)].
==Renal cell carcinoma grading==
{{Main|Renal cell carcinoma grading}}


===Histology===
==Renal cell carcinoma staging==
*Eosinophilic cytoplasm '''key feature'''.
{{Main|Kidney cancer staging}}
*Cells arranged in nests.
*Slightly enlarged nuclei, but no significant pleomorphism (size variation).
*Nuclei uniform and round.<ref>GUP P.302.</ref>


Notes:
===Renal sinus invasion===
*May look like eosinophilic variant of chromophobe RCC -- this is the main DDx.
{{Main|Kidney cancer staging}}
**May need IHC to differentiate (CK7: oncocytoma = cytoplasm +ve, chromophobe = cell membrane +ve).


Images:
==Clear cell renal cell carcinoma==
*[http://commons.wikimedia.org/wiki/File:Renal_oncocytoma2.jpg High mag. oncocytoma (mediawiki.org)].
{{Main|Clear cell renal cell carcinoma}}
*[http://commons.wikimedia.org/wiki/File:Renal_oncocytoma3.jpg Intermed. mag. oncocytoma (mediawiki.org)].
*[http://commons.wikimedia.org/wiki/File:Renal_oncocytoma4.jpg Low mag. oncocytoma (mediawiki.org)].


==Angiomyolipoma==
==Multilocular cystic renal cell carcinoma==
===General===
{{Main|Multilocular cystic renal cell carcinoma}}
*Mostly benign mesenchymal tumour.
*Presentations: flank pain, hematuria, incidentaloma.<ref name=pmid18805573>PMID 18805573</ref>
*AMLs occur may be elsewhere in the body, e.g. liver,<ref name=pmid15498214>PMID 15498214</ref> but are most common in the kidney.


===Epidemiology===
==Papillary renal cell carcinoma==
*May be assoc. with tuberous sclerosis -- 70% have an AML.
{{Main|Papillary renal cell carcinoma}}
**When compared to sporadic cases:
***More often bilateral.
***Usually bigger.


===Microscopy===
==Chromophobe renal cell carcinoma==
*Muscle.
{{Main|Chromophobe renal cell carcinoma}}
*Adipose tissue - not always present.<ref name=pmid15584043>PMID 15584043</ref>
*Blood vessels.


====Cytologic features<ref>PMID 15584043</ref>====
==Clear cell papillary renal cell tumour==
*Nuclei - round/ovoid.
In the past, it was known as ''clear cell papillary renal cell carcinoma''.
*Chromatin - bland.
{{Main|Clear cell papillary renal cell tumour}}


===IHC===
==Unclassified renal cell carcinoma==
*Melanocytic markers +ve<ref>GUP P.324.</ref> (e.g. HMB-45 +ve).
*Abbreviated ''URCC''.
*Epithelial markers -ve.<ref>GUP P.324.</ref>
{{Main|Unclassified renal cell carcinoma}}
*SMA +ve.
*CD117 +/-.
Additional paper: <ref name=pmid15584043>PMID 15584043</ref>


Notes:
=Renal translocation carcinomas=
*There is a suggestion that an ''epithelioid'' variant is more worisome,<ref>PMID 12352384</ref> but this is not the case in all studies.<ref>PMID 18852677</ref>
==Renal tumour with Xp11.2 translocation==
Ki-67 can be used to help distinguish btw 'em -- epithelioid variant Ki-67 +ve.<ref>PMID 18839327</ref>
{{Main|Renal tumour with Xp11.2 translocation}}


==Xanthogranulomatous pyelonephritis==
==Renal tumour with t(6;11) translocation==
===General===
*[[AKA]] ''t(6;11) renal cell carcinoma''.
*May mimic RCC (esp. radiologically).
{{main|Renal tumour with t(6;11) translocation}}
*Usually lower pole ???
*Associated with:
**Diabetes mellitus,
**History of UTI,<ref name=pmid17987581>{{cite journal |author=Afgan F, Mumtaz S, Ather MH |title=Preoperative diagnosis of xanthogranulomatous pyelonephritis |journal=Urol J |volume=4 |issue=3 |pages=169–73 |year=2007 |pmid=17987581 |doi= |url=}}</ref>
**Nephrolithiasis,
**GU obstruction.<ref name=pmid17098659>{{cite journal |author=Al-Ghazo MA, Ghalayini IF, Matalka II, Al-Kaisi NS, Khader YS |title=Xanthogranulomatous pyelonephritis: Analysis of 18 cases |journal=Asian J Surg |volume=29 |issue=4 |pages=257–61 |year=2006 |month=October |pmid=17098659 |doi= |url=}}</ref>
*Occasionally an indication of nephrectomy.<ref name=pmid17987581/><ref name=pmid17098659/>
*Most common organism (in the context of nephrectomy specimens) - ''Proteus mirabilis''.<ref name=pmid17098659/>


===Microscopy===
=Benign tumours=
*Abundant macrophages.
==Papillary adenoma of the kidney==
*+/-Giant cells.
*[[AKA]] ''renal papillary adenoma''.
{{Main|Papillary adenoma of the kidney}}


Image:
==Renal oncocytoma==
*[http://commons.wikimedia.org/wiki/File:Xanthogranulomatous_pyelonephritis_cd68.jpg Xanthogranulomatous_pyelonephritis - CD68 IHC (mediawiki.org)].
{{Main|Renal oncocytoma}}


===IHC===
==Angiomyolipoma==
*CD68 +ve.
*Abbreviated ''AML''.
*RCC markers (CD10, RCC) all negative.
{{Main|Angiomyolipoma}}


DDx:
=Mimics=
*[[Malacoplakia]].
==Xanthogranulomatous pyelonephritis==
**Basophilic inclusions -- inside or outside of macrophages - often size of RBC or larger ([[Michaelis-Gutmann bodies]]).
*Abbreviated ''XGP''.
*RCC - esp. PaRCC (as this has foamy macrophages).
{{Main|Xanthogranulomatous pyelonephritis}}
*Granulomatous disease.


==Malakoplakia==
==Malakoplakia==
{{main|Malakoplakia}}
{{main|Malakoplakia}}


==Medullary fibroma==
=Rare stuffs=
===General===
==Juxtaglomerular cell tumour==
*Rare.
*[[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>
{{Main|Juxtaglomerular cell tumour}}


===Epidemiology===
==Renomedullary interstitial cell tumour==
*Benign.
*[[AKA]] ''medullary fibroma''.<ref name=pmid11054036 >{{Cite journal  | last1 = Bircan | first1 = S. | last2 = Orhan | first2 = D. | last3 = Tulunay | first3 = O. | last4 = Safak | first4 = M. | title = Renomedullary interstitial cell tumor. | journal = Urol Int | volume = 65 | issue = 3 | pages = 163-6 | month =  | year = 2000 | doi =  | PMID = 11054036 }}</ref>
{{Main|Renomedullary interstitial cell tumour}}


===Gross===
==Metanephric adenoma==
*Small, white well circumscribed nodule in medulla.
*Should '''not''' be confused ''[[mesonephric adenoma]]'', another term for ''nephrogenic adenoma''.
**Memory device: me'''t'''anephric adenoma is a '''t'''umour.
{{Main|Metanephric adenoma}}


===Microscopy===
==Renal epithelial and stromal tumour==
*Spindle cells.
:Abbreviated ''REST''.
The lumping term for both:<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>
#[[Mixed epithelial and stromal tumour]].
#[[Cystic nephroma]].


=Rare stuffs=
==Mixed epithelial and stromal tumour==
==Metanephric adenoma==
*Abbreviated ''MEST''.
===General===
{{Main|Mixed epithelial and stromal tumour of the kidney}}
*Benign.
 
==Cystic nephroma==
{{Main|Cystic nephroma}}


===Micro===
==Renal mucinous tubular and spindle cell carcinoma==
Features:
*[[AKA]] ''renal mucinous tubular spindle cell carcinoma''.
*Small uniform cells with:
*[[AKA]] ''mucinous tubular and spindle cell carcinoma of the kidney''.<ref name=pmid16258504>{{Cite journal  | last1 = Brandal | first1 = P. | last2 = Lie | first2 = AK. | last3 = Bassarova | first3 = A. | last4 = Svindland | first4 = A. | last5 = Risberg | first5 = B. | last6 = Danielsen | first6 = H. | last7 = Heim | first7 = S. | title = Genomic aberrations in mucinous tubular and spindle cell renal cell carcinomas. | journal = Mod Pathol | volume = 19 | issue = 2 | pages = 186-94 | month = Feb | year = 2006 | doi = 10.1038/modpathol.3800499 | PMID = 16258504 }}</ref>
**Fine chromatin.
{{Main|Renal mucinous tubular and spindle cell carcinoma}}
**No apparent [[w:nucleolus|nucleolus]].
**A relatively smooth nuclear membrane.  


DDx:
==Collecting duct carcinoma==
*Wilm tumour (nephroblastoma) - these typically have:
{{Main|Collecting duct carcinoma}}
**Irregular nuclear membrane.
**Nucleoli.
**Mitoses.


Images:
==Renal medullary carcinoma==
*[http://commons.wikimedia.org/wiki/File:Metanephric_adenoma_high_mag.jpg Metanephric adenoma (WC)].
{{Main|Renal medullary carcinoma}}
*[http://commons.wikimedia.org/wiki/File:Metanephric_adenoma_high_mag_cropped.jpg Metanephric adenoma - cropped (WC)].


==Cystic nephroma==
==Tubulocystic carcinoma of the kidney==
*AKA ''renal epithelial stromal tumour (REST)'' and ''mixed epithelial stromal tumour (MEST)''.
{{Main|Tubulocystic carcinoma of the kidney}}
*Rare - approx. 1.5% of renal neoplasms.<ref name=pmid17454754>PMID 17454754.</ref>
*Benign.
*Prevalence: males > females.


===Micro===
==Acquired cystic disease-associated renal cell carcinoma==
*Cysts lined by simple epithelium with hobnailing.
{{Main|Acquired cystic disease-associated renal cell carcinoma}}
*Stroma has an ovarian look:
**''Blue'' (basophilic).
**''Spindle cells''.


Image: [http://commons.wikimedia.org/wiki/File:Cystic_nephroma_low_mag.jpg Cystic nephroma (wikimedia.org)].
==Kidney metastasis==
===IHC===
*[[AKA]] ''renal metastasis'', ''metastatic kidney disease''.
Features:<ref name=pmid17454754>PMID 17454754</ref>
{{Main|Kidney metastasis}}
*ER +ve.
*PR +ve.
*CD10 +ve.


===DDx===
=Pediatric=
*Tubulocystic carcinoma.
{{Main|Pediatric kidney tumours}}


==Mucinous spindle cell carcinoma==
The most common is [[nephroblastoma]] (Wilms tumour).
*Rare.<ref name=pmid19494850>PMID 19494850</ref>


===Microscopy===
Others include:
*Mucin - may be scant.
*[[Metanephric stromal tumour]].
*Spindle cells.
*[[Metanephric adenofibroma]]
*[[Metanephric adenoma]].
*[[Clear cell sarcoma of the kidney]].


==See also==
=See also=
*[[Urinary bladder]].
*[[Urinary bladder]].
*[[Medical kidney]].
*[[Medical kidney]].
*[[Malakoplakia]] - yellow lesion on gross; may mimic RCC.


==References==
=References=
{{reflist|2}}
{{reflist|2}}
=External links=
*[http://www.uscap.org/site~/99th/pdf/companion13h03.pdf Renal tumours with eosinophilic cytoplasm (uscap.org)].


[[Category: Genitourinary pathology]]
[[Category: Genitourinary pathology]]

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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