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Chromophobe renal cell carcinoma (view source)

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{{ Infobox diagnosis
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Name      = {{PAGENAME}}
| Image      = Oncocytic_chromophobe_rcc_high_mag.jpg
| Image      = Chromophobe renal cell carcinoma -- high mag.jpg  
| Width      =
| Width      =
| Caption    = Oncocytic variant of chromophobe renal cell carcinoma. [[H&E stain]].
| Caption    = Chromophobe renal cell carcinoma showing the characteristic perinuclear clearing and distinctive (plant-like) cellular borders. [[H&E stain]].
| Micro      = pale cytoplasm, with wisps of eosinophilic material, perinuclear clearing (a pale halo surrounds the nucleus), periphery of cell distinct (cell membrane is easy to discern -- plant cell-like)
| Micro      = pale/clear (or eosinophilic) cytoplasm with wisps of eosinophilic material, perinuclear clearing (a pale halo surrounds the nucleus), periphery of cell distinct (cell membrane is easy to discern -- plant cell-like)
| Subtypes  = eosinophilic variant
| Subtypes  = classic, eosinophilic variant
| LMDDx      = [[clear cell renal cell carcinoma]] (classic), [[renal oncocytoma]], [[clear cell renal cell carcinoma]] eosinophilic variant  
| LMDDx      = [[clear cell renal cell carcinoma]] (classic), [[renal oncocytoma]], [[clear cell renal cell carcinoma]] eosinophilic variant, [[renal hybrid oncocytic/chromophobe tumour]], other [[renal tumours with eosinophilic cytoplasm]] 
| Stains    = [[Hale's colloidal iron]] +ve
| Stains    = [[Hale's colloidal iron]] ([[Mueller-Mowry stain]]) +ve
| IHC        = CK7 +ve cell membrane, CD117 +ve, vimentin -ve
| IHC        = CK7 +ve cell membrane, CD117 +ve, vimentin -ve
| EM        =
| EM        =
| Molecular  =
| Molecular  =
| IF        =
| IF        =
| Gross      =
| Gross      = grey-beige, lacks central scar
| Grossing  =
| Grossing  = [[total nephrectomy for tumour grossing]], [[partial nephrectomy grossing]]
| Staging    = [[kidney cancer staging]]
| Site      = [[kidney]] - see [[renal tumours]]
| Site      = [[kidney]] - see [[renal tumours]]
| Assdx      =
| Assdx      =
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| Prognosis  =
| Prognosis  =
| Other      =
| Other      =
| ClinDDx    =
| ClinDDx    = other [[renal tumours]]
| Tx        = surgical resection
}}
}}
'''Chromophobe renal cell carcinoma''', abbreviated ''ChRCC'', is a relatively common form of [[renal cell carcinoma]].
'''Chromophobe renal cell carcinoma''', abbreviated '''ChRCC''', is a relatively common form of [[renal cell carcinoma]].


==General==
==General==
*Least common of the common types of RCC ([[clear cell RCC]], [[papillary RCC]], [[chromophobe RCC]]).
*Least common of the common types of RCC ([[clear cell RCC]], [[papillary RCC]], [[chromophobe RCC]]).
*''Fuhrman grading'' for this entity is controversial, as it does not appear to have any predictive value.<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>
*[[ISUP nucleolar grade|ISUP nucleolar grading]] (replaces ''Fuhrman grading'') not done for this entity, as it does not appear to have any predictive value.<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>
*May be associated with [[Birt–Hogg–Dubé syndrome]].<ref name=Ref_WMSP290>{{Ref WMSP|290}}</ref>
*May be associated with [[Birt–Hogg–Dubé syndrome]].<ref name=Ref_WMSP290>{{Ref WMSP|290}}</ref>
*Can be seen in the context of [[renal oncocytosis]].<ref name=pmid23018240>{{Cite journal  | last1 = Kuroda | first1 = N. | last2 = Tanaka | first2 = A. | last3 = Ohe | first3 = C. | last4 = Mikami | first4 = S. | last5 = Nagashima | first5 = Y. | last6 = Sasaki | first6 = T. | last7 = Inoue | first7 = K. | last8 = Hes | first8 = O. | last9 = Michal | first9 = M. | title = Review of renal oncocytosis (multiple oncocytic lesions) with focus on clinical and pathobiological aspects. | journal = Histol Histopathol | volume = 27 | issue = 11 | pages = 1407-12 | month = Nov | year = 2012 | doi =  | PMID = 23018240 }}</ref>


===Subtypes===
There are two subtypes:<ref name=Ref_GUP293>{{Ref GUP|293}}</ref>
There are two subtypes:<ref name=Ref_GUP293>{{Ref GUP|293}}</ref>
*Classic.
*Classic.
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==Gross==
==Gross==
*Tan, light-brown.
*Grey-beige colour.<ref name=pmid12507296>{{Cite journal  | last1 = Kuroda | first1 = N. | last2 = Toi | first2 = M. | last3 = Hiroi | first3 = M. | last4 = Enzan | first4 = H. | title = Review of chromophobe renal cell carcinoma with focus on clinical and pathobiological aspects. | journal = Histol Histopathol | volume = 18 | issue = 1 | pages = 165-71 | month = Jan | year = 2003 | doi =  | PMID = 12507296 }}</ref>
*Solitary.
*Solitary, usually.‡
*Well-circumscribed.
*Well-circumscribed.


Image:
Note:
*‡ Approximately 3% are multifocal.<ref name=pmid22502873>{{Cite journal  | last1 = Siracusano | first1 = S. | last2 = Novara | first2 = G. | last3 = Antonelli | first3 = A. | last4 = Artibani | first4 = W. | last5 = Bertini | first5 = R. | last6 = Carini | first6 = M. | last7 = Carmignani | first7 = G. | last8 = Ciciliato | first8 = S. | last9 = Cunico | first9 = SC. | title = Prognostic role of tumour multifocality in renal cell carcinoma. | journal = BJU Int | volume = 110 | issue = 11 Pt B | pages = E443-8 | month = Dec | year = 2012 | doi = 10.1111/j.1464-410X.2012.11121.x | PMID = 22502873 }}</ref>
 
===Image===
*[http://www.flickr.com/photos/35441329@N05/4273199789/in/photostream/ Chromophobe RCC (flickr.com)].
*[http://www.flickr.com/photos/35441329@N05/4273199789/in/photostream/ Chromophobe RCC (flickr.com)].


==Microscopic==
==Microscopic==
===Classic===
===Classic===
Features - classic type (3 P's [[mnemonic]]):<ref>{{Ref PBoD|1016-7}}</ref><ref name=Ref_GUP293>{{Ref GUP|293}}</ref>
Features - classic type (3 P's memory device):<ref>{{Ref PBoD|1016-7}}</ref><ref name=Ref_GUP293>{{Ref GUP|293}}</ref>
*Pale cytoplasm, with wisps of eosinophilic material; the cells are not completely clear, they have "cobwebs".
*Pale cytoplasm, with wisps of eosinophilic material; the cells are not completely clear, they have "cobwebs".
*Perinuclear clearing, i.e. a pale halo surrounds the nucleus - '''key feature'''.
*Perinuclear clearing, i.e. a pale halo surrounds the nucleus - '''key feature'''.
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**Perinuclear clearing is ''not'' seen in clear cell RCC.
**Perinuclear clearing is ''not'' seen in clear cell RCC.
**ChRCC has wisps in the cytoplasm.
**ChRCC has wisps in the cytoplasm.
*Other [[clear cell tumours]].
*[[Benign clear cell clusters of the kidney]] - somewhat controversial.
====Images====
<gallery>
Image: Chromophobe renal cell carcinoma -- low mag.jpg | ChRCC - low mag. (WC/Nephron)
Image: Chromophobe renal cell carcinoma -- intermed mag.jpg | ChRCC - intermed. mag. (WC/Nephron)
Image: Chromophobe renal cell carcinoma -- high mag.jpg | ChRCC - high mag. (WC/Nephron)
Image: Chromophobe renal cell carcinoma -- very high mag.jpg | ChRCC - very high mag. (WC/Nephron)
Image: Chromophobe renal cell carcinoma - alt -- high mag.jpg | ChRCC - high mag. (WC/Nephron)
Image: Chromophobe renal cell carcinoma - alt -- very high mag.jpg | ChRCC - very high mag. (WC/Nephron)
</gallery>


===Eosinophilic variant===
===Eosinophilic variant===
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#*Perinuclear clearing is ''not'' seen in clear cell RCC.
#*Perinuclear clearing is ''not'' seen in clear cell RCC.
#*ChRCC has wisps in the cytoplasm.
#*ChRCC has wisps in the cytoplasm.
#[[Renal hybrid oncocytic/chromophobe tumour]].
#Other [[renal tumours with eosinophilic cytoplasm]].
====Images====
=====Case 1=====
<gallery>
Image:Chromophobe renal cell carcinoma, eosinophilic variant - high mag.jpg | Eosinophilic chromophobe RCC. (WC/Nephron)
</gallery>


===Image===  
=====Case 2=====
<gallery>
<gallery>
Image:Oncocytic_chromophobe_rcc_high_mag.jpg | Oncocytic chromophobe RCC. (WC/Nephron)
Image: Eosinophilic variant of chromophobe renal cell carcinoma -- low mag.jpg | EVChRCC - low mag.
</gallery>
Image: Eosinophilic variant of chromophobe renal cell carcinoma -- intermed mag.jpg | EVChRCC - intermed. mag.
www:
Image: Eosinophilic variant of chromophobe renal cell carcinoma - alt -- intermed mag.jpg | EVChRCC - intermed. mag.
Image: Eosinophilic variant of chromophobe renal cell carcinoma -- high mag.jpg | EVChRCC - high mag.
Image: Eosinophilic variant of chromophobe renal cell carcinoma -- very high mag.jpg | EVChRCC - very high mag.
Image: Eosinophilic variant of chromophobe renal cell carcinoma - alt -- very high mag.jpg | EVChRCC - very high mag.  
</gallery>
=====www=====
*[http://path.upmc.edu/cases/case333.html Chromophobe RCC - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case333.html Chromophobe RCC - several images (upmc.edu)].


==Stains==
==Stains==
*[[Hale's colloidal iron]] +ve (blue granular cytoplasmic).
*[[Hale's colloidal iron]] +ve (blue granular cytoplasmic).
**Oncocytoma -ve.
Note:
*This seems to be a difficult stain to get working.


Images:
===Images===
*[http://www.nature.com/modpathol/journal/v18/n2/fig_tab/3800286f1.html ChRCC Hale's colloidal iron - several images (nature.com)].
*[http://www.nature.com/modpathol/journal/v18/n2/fig_tab/3800286f1.html ChRCC Hale's colloidal iron - several images (nature.com)].
*[http://www.ultrapath.org/oldsite/cases99/sep99/images/figure-3.jpg ChRCC Hale's colloidal iron (ultrapath.org)].<ref>URL: [http://www.ultrapath.org/oldsite/cases99/sep99/cotm9-2.html http://www.ultrapath.org/oldsite/cases99/sep99/cotm9-2.html]. Accessed on: 9 October 2011.</ref>
*[http://www.ultrapath.org/oldsite/cases99/sep99/images/figure-3.jpg ChRCC Hale's colloidal iron (ultrapath.org)].<ref>URL: [http://www.ultrapath.org/oldsite/cases99/sep99/cotm9-2.html http://www.ultrapath.org/oldsite/cases99/sep99/cotm9-2.html]. Accessed on: 9 October 2011.</ref>
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==IHC==
==IHC==
*CK7 +ve cell membrane.<ref name=Ref_GUP293>{{Ref GUP|293}}</ref>
*[[CK7]] +ve cell membrane.<ref name=Ref_GUP293>{{Ref GUP|293}}</ref>
**Useful for differentiating from oncocytoma.
*[[CD117]] +ve.
*Vimentin -ve.<ref name=pmid22455881>{{Cite journal  | last1 = Zhang | first1 = W. | last2 = Yu | first2 = WJ. | last3 = Jiang | first3 = YX. | last4 = Li | first4 = YJ. | last5 = Han | first5 = F. | last6 = Liu | first6 = Y. | last7 = Han | first7 = ZL. | title = [Chromophobe renal cell carcinoma: a clinicopathologic study and immunophenotypes of 42 cases]. | journal = Zhonghua Bing Li Xue Za Zhi | volume = 41 | issue = 2 | pages = 76-80 | month = Feb | year = 2012 | doi =  | PMID = 22455881 }}</ref><ref name=pmid24095630>{{Cite journal  | last1 = Din | first1 = NU. | last2 = Fatima | first2 = S. | last3 = Ahmad | first3 = Z. | title = Chromophobe renal cell carcinoma: a morphologic and immunohistochemical study of 45 cases. | journal = Ann Diagn Pathol | volume = 17 | issue = 6 | pages = 508-13 | month = Dec | year = 2013 | doi = 10.1016/j.anndiagpath.2013.06.005 | PMID = 24095630 }}</ref>
 
Others:<ref name=pmid18603673>{{Cite journal  | last1 = Geramizadeh | first1 = B. | last2 = Ravanshad | first2 = M. | last3 = Rahsaz | first3 = 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 = 167-71 | month =  | year =  | doi =  | PMID = 18603673 }}</ref>
*CD10 -ve.
*RCC -ve.
Uncommon stains for ChRCC versus oncocytoma:
*PAX2 -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>
**ChRCC 10 of 11 -ve versus Oncocytoma 3 of 23 -ve.
*Amylase α-1A -ve.<ref name=pmid24225843>{{Cite journal  | last1 = Jain | first1 = S. | last2 = Roy | first2 = S. | last3 = Amin | first3 = M. | last4 = Acquafondata | first4 = M. | last5 = Yin | first5 = M. | last6 = Laframboise | first6 = W. | last7 = Bastacky | first7 = S. | last8 = Pantanowitz | first8 = L. | last9 = Dhir | first9 = R. | title = Amylase α-1A (AMY1A): A Novel Immunohistochemical Marker to Differentiate Chromophobe Renal Cell Carcinoma From Benign Oncocytoma. | journal = Am J Surg Pathol | volume = 37 | issue = 12 | pages = 1824-30 | month = Dec | year = 2013 | doi = 10.1097/PAS.0000000000000108 | PMID = 24225843 }}</ref>
 
===ChRCC versus [[clear cell RCC]]===
[[ISUP]] recommends:<ref name=pmid25025364 >{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*CD117 +ve.
*CD117 +ve.
*Vimentin -ve.
**-ve in CCRCC.
*CA9 ([[carbonic anhydrase 9]]) -ve.
**+ve (strong membranous) in CCRCC.<ref name=pmid21677535>{{cite journal |author=Al-Ahmadie HA, Alden D, Fine SW, ''et al.'' |title=Role of immunohistochemistry in the evaluation of needle core biopsies in adult renal cortical tumors: an ex vivo study |journal=Am. J. Surg. Pathol. |volume=35 |issue=7 |pages=949–61 |year=2011 |month=July |pmid=21677535 |doi=10.1097/PAS.0b013e31821e25cd |url=}}</ref>
*CK7 +ve.
**-ve in CCRCC.
 
Others:
*[[DOG1]] +ve (Swalchick ''et al.''<ref name=pmid26678977>{{Cite journal  | last1 = Swalchick | first1 = W. | last2 = Shamekh | first2 = R. | last3 = Bui | first3 = MM. | title = Is DOG1 Immunoreactivity Specific to Gastrointestinal Stromal Tumor? | journal = Cancer Control | volume = 22 | issue = 4 | pages = 498-504 | month = Oct | year = 2015 | doi =  | PMID = 26678977 }}</ref> 32 +ve of 37 cases; Zhao ''et al.''<ref name=pmid25596994>{{Cite journal  | last1 = Zhao | first1 = W. | last2 = Tian | first2 = B. | last3 = Wu | first3 = C. | last4 = Peng | first4 = Y. | last5 = Wang | first5 = H. | last6 = Gu | first6 = WL. | last7 = Gao | first7 = FH. | title = DOG1, cyclin D1, CK7, CD117 and vimentin are useful immunohistochemical markers in distinguishing chromophobe renal cell carcinoma from clear cell renal cell carcinoma and renal oncocytoma. | journal = Pathol Res Pract | volume = 211 | issue = 4 | pages = 303-7 | month = Apr | year = 2015 | doi = 10.1016/j.prp.2014.12.014 | PMID = 25596994 }}</ref> 32 +ve of 32 cases).
**Useful in ChRCC versus clear cell RCC.
 
A panel:
*CK7, [[PAX8]], CD117, CD10, [[Mueller-Mowry stain]].
 
===Comparison between some renal tumours with eosinophilic cytoplasm===
{| class="wikitable sortable"
!Tumour
![[CK7]]
![[CD117]]
![[GATA3]]
|-
| [[Renal oncocytoma]]
| -ve †
| +ve
| -ve/+ve
|-
| Chromophobe renal cell carcinoma
| +ve ‡
| +ve
| -ve
|-
| [[Low-grade oncocytic tumour]]
| +ve
| -ve
| +ve
|-
|}
† may have scattered positive cells<br>
‡ diffuse and strong


==Molecular==
==Molecular==
*Extensive aneusomy (monosomy?):<ref name=Ref_WMSP292>{{Ref WMSP|292}}</ref>
*Extensive aneusomy (monosomy?):<ref name=Ref_WMSP292>{{Ref WMSP|292}}</ref>
**Loss of chromosomes: 1, 2, 6, 10, 13, 17, 21.
**Loss of chromosomes: 1, 2, 6, 10, 13, 17, 21.
==EM==
Ultrastructural features:<ref name=pmid21713152>{{Cite journal  | last1 = Lee | first1 = W. | title = Imprint cytology of the chromophobe renal cell carcinoma: Correlation with the histological and ultrastructural features. | journal = J Cytol | volume = 28 | issue = 2 | pages = 77-80 | month = Apr | year = 2011 | doi = 10.4103/0970-9371.80749 | PMID = 21713152 }}</ref>
*Microvesicles.
*Complex plicated cell membrane.
===Images===
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111713/figure/F5/ Microvesicles in ChRCC (nih.gov)].<ref name=pmid21713152/>
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111713/figure/F6/ Cell membrane in ChRCC (nih.gov)].


==Sign out==
==Sign out==
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Negative: AMACR, CD10, CD68, RCC, vimentin.
Negative: AMACR, CD10, CD68, RCC, vimentin.
</pre>
</pre>
===Micro===
The sections show a sheeting tumour with abundant and eosinophilic cytoplasm. The tumour cell cell membranes are prominent and plant-like. Perinuclear clearing is present. Binucleation is frequent and the nuclear membranes moderately irregular. No definite papillae or macrophages are present. Nucleoli are not prominent. Small blood vessels are not prominent.
====Alternate====
The sections show a tumour composed of compact nests. The cytoplasm is abundant and eosinophilic. Perinuclear clearing is prominent. Binucleation is frequent and the nuclear membranes moderately irregular to round. No definite papillae or macrophages are present. Nucleoli are not prominent.


==See also==
==See also==
Michael
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