Difference between revisions of "Clear cell renal cell carcinoma"

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Clear cell renal cell carcinoma (view source)

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benign clear cell clusters
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| Width      =
| Width      =
| Caption    = Clear cell renal cell carcinoma. [[H&E stain]].
| Caption    = Clear cell renal cell carcinoma. [[H&E stain]].
| Micro      = solid or [[trabecular]] pattern, polygonal cells usually with clear cytoplasm, central nucleus, delicate branching vasculature (chicken wire-like), +/-hyaline bodies
| Synonyms  = conventional renal cell carcinoma
| Subtypes  = classic, eosinophilic variant
| Micro      = solid or [[trabecular]] pattern, polygonal cells usually with clear cytoplasm (may be eosinophilic - esp. in high grade tumours), central nucleus, delicate branching vasculature (chicken wire-like), +/-hyaline bodies
| Subtypes  =  
| LMDDx      = [[chromophobe renal cell carcinoma]], [[clear cell papillary renal cell carcinoma]], [[Xp11.2 translocation carcinoma]], [[adrenocortical carcinoma]], [[alveolar soft part sarcoma]]
| LMDDx      = [[chromophobe renal cell carcinoma]], [[clear cell papillary renal cell carcinoma]], [[Xp11.2 translocation carcinoma]], [[adrenocortical carcinoma]], [[alveolar soft part sarcoma]]
| Stains    = [[Hale's colloidal iron stain]] -ve
| Stains    = [[Hale's colloidal iron stain]] -ve
| IHC        = CK7 -ve, CK20 -ve, TFE3 -ve
| IHC        = [[CA9]] +ve, CK7 -ve, CK20 -ve, TFE3 -ve, PAX8 +ve, vimentin +ve
| EM        =
| EM        =
| Molecular  =
| Molecular  =
| IF        =
| IF        =
| Gross      = golden/yellow colour, +/-hemorrhagic, +/-cystic, +/-necrosis
| Gross      = golden/yellow colour, +/-hemorrhagic, +/-cystic, +/-[[necrosis]]
| Grossing  = [[total nephrectomy for tumour grossing]], [[partial nephrectomy grossing]]
| Grossing  = [[total nephrectomy for tumour grossing]], [[partial nephrectomy grossing]]
| Staging    = [[kidney cancer staging]]
| Site      = [[kidney]] - see [[kidney tumours]]
| Site      = [[kidney]] - see [[kidney tumours]]
| Assdx      =
| Assdx      =
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| Other      =
| Other      =
| ClinDDx    = other [[renal tumours]]
| ClinDDx    = other [[renal tumours]]
| Tx        = surgery, targeted therapies, other drugs
}}
}}
'''Clear cell renal cell carcinoma''', abbreviated '''CRCC''' or '''CCRCC''', is the most common type of [[renal cell carcinoma]].
'''Clear cell renal cell carcinoma''', abbreviated '''CCRCC''', is the most common type of [[renal cell carcinoma]].
 
It is also known as '''conventional renal cell carcinoma''' (abbreviated '''CRCC''').


==General==
==General==
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Treatment:
Treatment:
*Surgery.
*Surgery.
*[[Tyrosine kinase inhibitors]].<ref name=pmid25467013>{{Cite journal  | last1 = Elaidi | first1 = R. | last2 = Harbaoui | first2 = A. | last3 = Beuselinck | first3 = B. | last4 = Eymard | first4 = JC. | last5 = Bamias | first5 = A. | last6 = De Guillebon | first6 = E. | last7 = Porta | first7 = C. | last8 = Vano | first8 = Y. | last9 = Linassier | first9 = C. | title = Outcomes from second-line therapy in long-term responders to first-line tyrosine kinase inhibitor in clear-cell metastatic renal cell carcinoma. | journal = Ann Oncol | volume = 26 | issue = 2 | pages = 378-85 | month = Feb | year = 2015 | doi = 10.1093/annonc/mdu552 | PMID = 25467013 }}</ref><ref name=pmid21484781>{{Cite journal  | last1 = Verma | first1 = J. | last2 = Jonasch | first2 = E. | last3 = Allen | first3 = P. | last4 = Tannir | first4 = N. | last5 = Mahajan | first5 = A. | title = Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma. | journal = Cancer | volume = 117 | issue = 21 | pages = 4958-65 | month = Nov | year = 2011 | doi = 10.1002/cncr.26138 | PMID = 21484781 }}</ref>
*Various drugs.
*Targeted therapies.
**[[Tyrosine kinase inhibitors]] (e.g. [[sunitinib]], sorafenib).<ref name=pmid25467013>{{Cite journal  | last1 = Elaidi | first1 = R. | last2 = Harbaoui | first2 = A. | last3 = Beuselinck | first3 = B. | last4 = Eymard | first4 = JC. | last5 = Bamias | first5 = A. | last6 = De Guillebon | first6 = E. | last7 = Porta | first7 = C. | last8 = Vano | first8 = Y. | last9 = Linassier | first9 = C. | title = Outcomes from second-line therapy in long-term responders to first-line tyrosine kinase inhibitor in clear-cell metastatic renal cell carcinoma. | journal = Ann Oncol | volume = 26 | issue = 2 | pages = 378-85 | month = Feb | year = 2015 | doi = 10.1093/annonc/mdu552 | PMID = 25467013 }}</ref><ref name=pmid21484781>{{Cite journal  | last1 = Verma | first1 = J. | last2 = Jonasch | first2 = E. | last3 = Allen | first3 = P. | last4 = Tannir | first4 = N. | last5 = Mahajan | first5 = A. | title = Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma. | journal = Cancer | volume = 117 | issue = 21 | pages = 4958-65 | month = Nov | year = 2011 | doi = 10.1002/cncr.26138 | PMID = 21484781 }}</ref>
**Anti-VEGF antibodies (e.g. bevacizumab).<ref name=pmid21330923>{{Cite journal  | last1 = Singer | first1 = EA. | last2 = Gupta | first2 = GN. | last3 = Srinivasan | first3 = R. | title = Update on targeted therapies for clear cell renal cell carcinoma. | journal = Curr Opin Oncol | volume = 23 | issue = 3 | pages = 283-9 | month = May | year = 2011 | doi = 10.1097/CCO.0b013e32834479c0 | PMID = 21330923 }}</ref>


==Gross==
==Gross==
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==Microscopic==
==Microscopic==
Features:<ref name=Ref_PBoD1017-8>{{Ref PBoD|1017-8}}</ref>
Features:<ref name=Ref_PBoD1017-8>{{Ref PBoD|1017-8}}</ref>
*Clear cytoplasm.
**May have eosinophilic cytoplasm (in high-grade tumours) - usually focal.
*Delicate branching vasculature - '''key feature'''.
**Often called "chicken wire-like" vasculature.
*Solid or [[trabecular]] pattern.
*Solid or [[trabecular]] pattern.
*Polygonal cells.
*Polygonal cells.
*Clear cytoplasm.
*Central nucleus.
*Central nucleus.
*Delicate branching vasculature.
*+/-[[Renal cell carcinoma with rhabdoid morphology|Rhabdoid cells]]:
**Often called "chicken wire-like" vasculature.
*+/-Rhabdoid cells:
**Eccentric nucleus.
**Eccentric nucleus.
**Abundant eosinophilic cytoplasma.
**Abundant eosinophilic cytoplasm.


Notes:
Notes:
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**Not common in papillary RCC.
**Not common in papillary RCC.
*Clear cytoplasm - due to lipid content.
*Clear cytoplasm - due to lipid content.
*[[Necrosis]] is independent predictor of outcome - if present in a significant quantity:<ref name=pmid25474516>{{Cite journal  | last1 = Renshaw | first1 = AA. | last2 = Cheville | first2 = JC. | title = Quantitative tumour necrosis is an independent predictor of overall survival in clear cell renal cell carcinoma. | journal = Pathology | volume = 47 | issue = 1 | pages = 34-7 | month = Jan | year = 2015 | doi = 10.1097/PAT.0000000000000193 | PMID = 25474516 }}</ref>
**>30% is significant for pT3a tumours.
**>20% is significant for pT1-2 pN0 tumours.


DDx:
DDx:
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**EMA -ve, CKs mostly -ve, inhibin +ve (neg. in RCC).<ref name=Ref_GUP285>{{Ref GUP|285}}</ref>
**EMA -ve, CKs mostly -ve, inhibin +ve (neg. in RCC).<ref name=Ref_GUP285>{{Ref GUP|285}}</ref>
*[[Alveolar soft part sarcoma]].
*[[Alveolar soft part sarcoma]].
*[[Adrenal gland]], normal.
*[[Adrenal gland]], normal cortex - wispy, vacuolated.
*[[Epithelioid angiomyolipoma]].
*[[Epithelioid angiomyolipoma]].
*[[Benign clear cell clusters of the kidney]].


===Images===
===Images===
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*CD10 +ve.
*CD10 +ve.
*Vimentin +ve.
*Vimentin +ve.
*CK7 -ve.  
*CK7 -ve.
**Strong CK7 staining is more in keeping with [[clear cell papillary renal cell carcinoma]]<ref name=pmid26457355>{{Cite journal  | last1 = Williamson | first1 = SR. | last2 = Gupta | first2 = NS. | last3 = Eble | first3 = JN. | last4 = Rogers | first4 = CG. | last5 = Michalowski | first5 = S. | last6 = Zhang | first6 = S. | last7 = Wang | first7 = M. | last8 = Grignon | first8 = DJ. | last9 = Cheng | first9 = L. | title = Clear Cell Renal Cell Carcinoma With Borderline Features of Clear Cell Papillary Renal Cell Carcinoma: Combined Morphologic, Immunohistochemical, and Cytogenetic Analysis. | journal = Am J Surg Pathol | volume = 39 | issue = 11 | pages = 1502-10 | month = Nov | year = 2015 | doi = 10.1097/PAS.0000000000000514 | PMID = 26457355 }}</ref> or the evolving entity of [[TCEB1-mutated renal cell carcinoma]]. 
*CK20 -ve.
*CK20 -ve.
*Glut-1 >85% of CCRCC (membranous pattern).<ref name=pmid17638658>{{Cite journal  | last1 = Ozcan | first1 = A. | last2 = Shen | first2 = SS. | last3 = Zhai | first3 = QJ. | last4 = Truong | first4 = LD. | title = Expression of GLUT1 in primary renal tumors: morphologic and biologic implications. | journal = Am J Clin Pathol | volume = 128 | issue = 2 | pages = 245-54 | month = Aug | year = 2007 | doi = 10.1309/HV6NJVRQKK4QHM9F | PMID = 17638658 }}</ref>
*Glut-1 >85% of CCRCC (membranous pattern).<ref name=pmid17638658>{{Cite journal  | last1 = Ozcan | first1 = A. | last2 = Shen | first2 = SS. | last3 = Zhai | first3 = QJ. | last4 = Truong | first4 = LD. | title = Expression of GLUT1 in primary renal tumors: morphologic and biologic implications. | journal = Am J Clin Pathol | volume = 128 | issue = 2 | pages = 245-54 | month = Aug | year = 2007 | doi = 10.1309/HV6NJVRQKK4QHM9F | PMID = 17638658 }}</ref>
*E-cadherin +ve - usually weak, often -ve in higher stage tumours.<ref name=pmid23939157>{{Cite journal  | last1 = Hu | first1 = H. | last2 = Chen | first2 = JW. | last3 = Xu | first3 = KX. | last4 = Wang | first4 = D. | last5 = Wang | first5 = Y. | last6 = Wang | first6 = GW. | last7 = Zhang | first7 = SY. | last8 = Wang | first8 = XF. | title = [Expressions of CMTM8 and E-cadherin in primary and metastatic clear cell renal cell carcinoma]. | journal = Beijing Da Xue Xue Bao | volume = 45 | issue = 4 | pages = 537-41 | month = Aug | year = 2013 | doi =  | PMID = 23939157 }}</ref>
*CAIX (also CA9) +ve.


A panel to confirm the diagnosis:
A panel to confirm the diagnosis:
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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>
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 (+ve in ChRCC).
*CD117 -ve (+ve in ChRCC).
*CAIX (carbonic anhydrase CA IX) +ve (membranous).<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>
**Aguilar-León ''et al.'' found ~8% of CCRCC are CD117 +ve.<ref name=pmid25643775>{{Cite journal  | last1 = Aguilar-León | first1 = D. | last2 = Del Ángel-Millán | first2 = G. | last3 = Zepeda-Quiroz | first3 = I. | last4 = Soria-Céspedes | first4 = D. | title = [Immunohistochemical Expression of CD117 (c-kit) in 75 Renal Cell Tumors]. | journal = Gac Med Mex | volume = 150 Suppl 2 | issue =  | pages = 156-60 | month = Dec | year = 2014 | doi =  | PMID = 25643775 }}</ref>
*CK7 -ve (+ve in ChRCC).
**Liu ''et al.'' found ~80% of ChRCC are CD117 +ve.<ref name=pmid17683191/>
*CA9 ([[carbonic anhydrase 9]]) +ve (membranous).<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 ChRCC).


Another set of stains:<ref name=pmid17683191>{{Cite journal  | last1 = Liu | first1 = L. | last2 = Qian | first2 = J. | last3 = Singh | first3 = H. | last4 = Meiers | first4 = I. | last5 = Zhou | first5 = X. | last6 = Bostwick | first6 = 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 = 1290-7 | month = Aug | year = 2007 | doi = 10.1043/1543-2165(2007)131[1290:IAOCRC]2.0.CO;2 | PMID = 17683191 }}</ref>
May also be useful:
*Vimentin +ve.
*Vimentin +ve.
**-ve in ChRCC.
**-ve in ChRCC.<ref name=pmid17683191>{{Cite journal  | last1 = Liu | first1 = L. | last2 = Qian | first2 = J. | last3 = Singh | first3 = H. | last4 = Meiers | first4 = I. | last5 = Zhou | first5 = X. | last6 = Bostwick | first6 = 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 = 1290-7 | month = Aug | year = 2007 | doi = 10.1043/1543-2165(2007)131[1290:IAOCRC]2.0.CO;2 | PMID = 17683191 }}</ref>
*CD117 -ve.
**+ve ~80% of ChRCC.


===CCRCC versus [[CCPRCC]]===
===CCRCC versus [[CCPRCC]]===
[[ISUP]] recommends:<ref name=pmid25025364/>
[[ISUP]] recommends:<ref name=pmid25025364/>
*CAIX +ve (strong membranous).
*CA9 +ve (strong membranous).
*CK7 -ve.
*CK7 -ve.
**Usually +ve in [[clear cell papillary renal cell carcinoma]].
*AMACR -ve.
*AMACR -ve.


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<pre>
<pre>
Kidney Mass, Left, Core Biopsy:
Kidney Mass, Left, Core Biopsy:
- CLEAR CELL RENAL CELL CARCINOMA, preliminary nucleolar grade 2 (see comment)
- CLEAR CELL RENAL CELL CARCINOMA, preliminary ISUP nucleolar grade 2 (see comment).
- No renal parenchyma identified
- No renal parenchyma identified.


Comment:
Comment:
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*The surgeon wants the diagnosis and margin status; thus, these are included in the diagnosis line with the tumour stage.
*The surgeon wants the diagnosis and margin status; thus, these are included in the diagnosis line with the tumour stage.


<pre>
Left Kidney, Radical Nephrectomy:
    - CLEAR CELL RENAL CELL CARCINOMA.
    -- Margins clear.
    -- Please see synoptic report.
</pre>
====Block letters====
<pre>
<pre>
KIDNEY, LEFT, NEPHRECTOMY:
KIDNEY, LEFT, NEPHRECTOMY:
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The sections show a tumour with a chicken wire-like vasculature composed of clear cells with basally stratified nuclei. Hemosiderin-laden macrophages are present. Necrosis is present. Abundant hyaline globules are present.   
The sections show a tumour with a chicken wire-like vasculature composed of clear cells with basally stratified nuclei. Hemosiderin-laden macrophages are present. Necrosis is present. Abundant hyaline globules are present.   


There is no perinuclear clearing.  The cytoplasm is not whispy. Collections of macrophages are not identified within the stroma of the tumour.  Papillae are not evident.
There is no perinuclear clearing.  The cytoplasm is not wispy. Papillae are not evident.


Rare, small nucleoli are visible with the 10x objective.  The tumour nuclei are approximately 15 micrometers.
Rare, small nucleoli are visible with the 10x objective.  The tumour nuclei are approximately 15 micrometers.
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==See also==
==See also==
*[[Kidney tumours]].
*[[Kidney tumours]].
*[[TCEB1-mutated renal cell carcinoma]].
*[[Renal cell carcinoma with rhabdoid morphology]].


==References==
==References==
Michael
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