Difference between revisions of "Clear cell renal cell carcinoma"

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benign clear cell clusters
m (benign clear cell clusters)
 
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| Caption    = Clear cell renal cell carcinoma. [[H&E stain]].
| Caption    = Clear cell renal cell carcinoma. [[H&E stain]].
| Synonyms  = conventional renal cell carcinoma
| Synonyms  = conventional renal cell carcinoma
| Micro      = solid or [[trabecular]] pattern, polygonal cells usually with clear cytoplasm, central nucleus, delicate branching vasculature (chicken wire-like), +/-hyaline bodies
| 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  = classic, eosinophilic variant
| 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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*Various drugs.
*Various drugs.
*Targeted therapies.
*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>
**[[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>
**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>


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Features:<ref name=Ref_PBoD1017-8>{{Ref PBoD|1017-8}}</ref>
Features:<ref name=Ref_PBoD1017-8>{{Ref PBoD|1017-8}}</ref>
*Clear cytoplasm.
*Clear cytoplasm.
**May have eosinophilic cytoplasm (in high-grade tumours) - usually focal.
*Delicate branching vasculature - '''key feature'''.
*Delicate branching vasculature - '''key feature'''.
**Often called "chicken wire-like" vasculature.
**Often called "chicken wire-like" vasculature.
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*Polygonal cells.
*Polygonal cells.
*Central nucleus.
*Central nucleus.
*+/-Rhabdoid cells:
*+/-[[Renal cell carcinoma with rhabdoid morphology|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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*[[Adrenal gland]], normal cortex - wispy, vacuolated.
*[[Adrenal gland]], normal cortex - wispy, vacuolated.
*[[Epithelioid angiomyolipoma]].
*[[Epithelioid angiomyolipoma]].
*[[Benign clear cell clusters of the kidney]].


===Images===
===Images===
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*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>
*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]].
**Usually +ve in [[clear cell papillary renal cell carcinoma]].
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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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*[[Kidney tumours]].
*[[Kidney tumours]].
*[[TCEB1-mutated renal cell carcinoma]].
*[[TCEB1-mutated renal cell carcinoma]].
*[[Renal cell carcinoma with rhabdoid morphology]].


==References==
==References==
48,470

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