Papillary renal cell carcinoma: Difference between revisions

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| Caption    = Papillary renal cell carcinoma. [[H&E stain]].
| Caption    = Papillary renal cell carcinoma. [[H&E stain]].
| Micro      = cuboidal or low columnar cells (simple or pseudostratified) on papillae, interstitial foam cells in the vascular cores
| Micro      = cuboidal or low columnar cells (simple or pseudostratified) on papillae, interstitial foam cells in the vascular cores
| Subtypes  = type 1, type 2, oncocytic variant
| Subtypes  = no ''World Health Organization'' recognized subtypes; defunct subtypes: "type 1" and "type 2", oncocytic variant
| LMDDx      = [[clear cell renal cell carcinoma]], [[clear cell papillary renal cell carcinoma]], [[metanephric adenoma]] (esp. solid PaRCC type 1), [[collecting duct carcinoma]] (esp. PaRCC type 2), [[renal papillary adenoma]], [[acquired cystic disease-associated renal cell carcinoma]], [[urothelial carcinoma]], [[renal mucinous tubular and spindle cell carcinoma]]
| LMDDx      = [[clear cell renal cell carcinoma]], [[clear cell papillary renal cell carcinoma]], [[metanephric adenoma]], [[collecting duct carcinoma]], [[renal papillary adenoma]], [[acquired cystic disease-associated renal cell carcinoma]], [[urothelial carcinoma]], [[renal mucinous tubular and spindle cell carcinoma]], [[ALK translocation renal cell carcinoma]], [[Xp11 translocation renal cell carcinoma]], [[FH-deficient renal cell carcinoma]]
| Stains    =
| Stains    =
| IHC        =
| IHC        =
| EM        =
| EM        =
| Molecular  =
| Molecular  = MET mutation (hereditary papillary renal cell carcinoma)
| IF        =
| IF        =
| Gross      = may be multifocal, must be >1.5 cm (otherwise [[renal papillary adenoma]]), often necrotic-appearing (brown, soft, friable)
| Gross      = may be multifocal, must be >1.5 cm (if low ISUP grade), often necrotic-appearing (brown, soft, friable)
| Grossing  = [[total nephrectomy for tumour grossing]], [[partial nephrectomy grossing]]
| Grossing  = [[total nephrectomy for tumour grossing]], [[partial nephrectomy grossing]]
| Staging    = [[kidney cancer staging]]
| Staging    = [[kidney cancer staging]]
| Site      = [[kidney]] - see [[kidney tumours]]
| Site      = [[kidney]] - see [[kidney tumours]]
| Assdx      = [[acquired renal cystic disease]] ([[end-stage renal disease]])
| Assdx      = [[acquired renal cystic disease]] ([[end-stage renal disease]])
| Syndromes  = hereditary papillary renal cell carcinoma, [[hereditary leiomyomatosis and renal cell cancer]]
| Syndromes  = hereditary papillary renal cell carcinoma
| Clinicalhx =
| Clinicalhx =
| Signs      =
| Signs      =
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==General==
==General==
*Often subclassified<ref name=Ref_GUP289>{{Ref GUP|289}}</ref> into ''type 1'' and ''type 2'' -- see ''microscopic''.
*Historically, PaRCC was subclassified<ref name=Ref_GUP289>{{Ref GUP|289}}</ref> into ''type 1'' and ''type 2''.
**Type 1 and Type 2 are different on a cytogenetic and molecular basis.<ref>{{Cite journal  | last1 = Klatte | first1 = T. | last2 = Pantuck | first2 = AJ. | last3 = Said | first3 = JW. | last4 = Seligson | first4 = DB. | last5 = Rao | first5 = NP. | last6 = LaRochelle | first6 = JC. | last7 = Shuch | first7 = B. | last8 = Zisman | first8 = A. | last9 = Kabbinavar | first9 = FF. | title = Cytogenetic and molecular tumor profiling for type 1 and type 2 papillary renal cell carcinoma. | journal = Clin Cancer Res | volume = 15 | issue = 4 | pages = 1162-9 | month = Feb | year = 2009 | doi = 10.1158/1078-0432.CCR-08-1229 | PMID = 19228721 }}</ref>
**Type 1 and Type 2 are different on a cytogenetic and molecular basis.<ref>{{Cite journal  | last1 = Klatte | first1 = T. | last2 = Pantuck | first2 = AJ. | last3 = Said | first3 = JW. | last4 = Seligson | first4 = DB. | last5 = Rao | first5 = NP. | last6 = LaRochelle | first6 = JC. | last7 = Shuch | first7 = B. | last8 = Zisman | first8 = A. | last9 = Kabbinavar | first9 = FF. | title = Cytogenetic and molecular tumor profiling for type 1 and type 2 papillary renal cell carcinoma. | journal = Clin Cancer Res | volume = 15 | issue = 4 | pages = 1162-9 | month = Feb | year = 2009 | doi = 10.1158/1078-0432.CCR-08-1229 | PMID = 19228721 }}</ref>


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*Associated with ''[[acquired renal cystic disease]]''.<ref name=Ref_DARP438>{{Ref DARP|438}}</ref>
*Associated with ''[[acquired renal cystic disease]]''.<ref name=Ref_DARP438>{{Ref DARP|438}}</ref>
*May be familial - uncommon.<ref name=pmid12629341>{{Cite journal  | last1 = Czene | first1 = K. | last2 = Hemminki | first2 = K. | title = Familial papillary renal cell tumors and subsequent cancers: a nationwide epidemiological study from Sweden. | journal = J Urol | volume = 169 | issue = 4 | pages = 1271-5 | month = Apr | year = 2003 | doi = 10.1097/01.ju.0000052373.36963.12 | PMID = 12629341 }}</ref>
*May be familial - uncommon.<ref name=pmid12629341>{{Cite journal  | last1 = Czene | first1 = K. | last2 = Hemminki | first2 = K. | title = Familial papillary renal cell tumors and subsequent cancers: a nationwide epidemiological study from Sweden. | journal = J Urol | volume = 169 | issue = 4 | pages = 1271-5 | month = Apr | year = 2003 | doi = 10.1097/01.ju.0000052373.36963.12 | PMID = 12629341 }}</ref>
**MET mutation<ref name=pmid22717761>{{Cite journal  | last1 = Wadt | first1 = KA. | last2 = Gerdes | first2 = AM. | last3 = Hansen | first3 = TV. | last4 = Toft | first4 = BG. | last5 = Friis-Hansen | first5 = L. | last6 = Andersen | first6 = MK. | title = Novel germline c-MET mutation in a family with hereditary papillary renal carcinoma. | journal = Fam Cancer | volume = 11 | issue = 3 | pages = 535-7 | month = Sep | year = 2012 | doi = 10.1007/s10689-012-9542-6 | PMID = 22717761 }}</ref> - autosomal dominant transmission, PaRCC type 1.
**MET mutation<ref name=pmid22717761>{{Cite journal  | last1 = Wadt | first1 = KA. | last2 = Gerdes | first2 = AM. | last3 = Hansen | first3 = TV. | last4 = Toft | first4 = BG. | last5 = Friis-Hansen | first5 = L. | last6 = Andersen | first6 = MK. | title = Novel germline c-MET mutation in a family with hereditary papillary renal carcinoma. | journal = Fam Cancer | volume = 11 | issue = 3 | pages = 535-7 | month = Sep | year = 2012 | doi = 10.1007/s10689-012-9542-6 | PMID = 22717761 }}</ref> - autosomal dominant transmission (previously ''PaRCC type 1'').


==Gross==
==Gross==
*Renal cortical mass > 1.5 cm.<ref name=pmid26935559>{{Cite journal  | last1 = Moch | first1 = H. | last2 = Cubilla | first2 = AL. | last3 = Humphrey | first3 = PA. | last4 = Reuter | first4 = VE. | last5 = Ulbright | first5 = TM. | title = The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. | journal = Eur Urol | volume =  | issue =  | pages =  | month = Feb | year = 2016 | doi = 10.1016/j.eururo.2016.02.029 | PMID = 26935559 }}</ref> †
*Renal cortical mass usually >1.5 cm.
*May be multifocal. ‡
*May be multifocal. ‡
*Often necrotic appearing - light-to-dark brown, soft/mushy, friable.
*Often necrotic appearing - light-to-dark brown, soft/mushy, friable.


Note:
Note:
*† The size cut in the 2004 [[WHO]] GU (blue) book was 0.5 cm.<ref>{{Ref WHOGU|28}}</ref>
*‡ Approximately 10% of PaRCCs are multifocal (based on a set of 5378 patients);<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> it is the renal tumour that is most commonly multifocal.
*‡ Approximately 10% of PaRCCs are multifocal (based on a set of 5378 patients);<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> it is the renal tumour that is most commonly multifocal.


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Size criterion:
Size criterion:
*Papillary lesions with low [[ISUP grade]] '''''must''''' be >1.5 cm to be called ''carcinoma''; smaller lesions (<=1.5 cm) with low ISUP grade are called ''[[renal papillary adenoma|papillary adenoma]]s''.<ref name=Ref_GUP288>{{Ref GUP|288}}</ref><ref name=pmid26935559/>
*Papillary lesions with low [[ISUP nucleolar grade|ISUP grade]] '''''must''''' be >1.5 cm to be called ''carcinoma''; smaller lesions (<=1.5 cm) with low ISUP grade are called ''[[renal papillary adenoma|papillary adenoma]]s''.<ref name=pmid26935559>{{Cite journal  | last1 = Moch | first1 = H. | last2 = Cubilla | first2 = AL. | last3 = Humphrey | first3 = PA. | last4 = Reuter | first4 = VE. | last5 = Ulbright | first5 = TM. | title = The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. | journal = Eur Urol | volume =  | issue =  | pages =  | month = Feb | year = 2016 | doi = 10.1016/j.eururo.2016.02.029 | PMID = 26935559 }}</ref><ref name=Ref_GUP288>{{Ref GUP|288}}</ref> †


Mnemonic ''HIP'':  '''h'''ighly vascular, '''i'''nterstitial foam cells, '''p'''apillae.
Mnemonic ''HIP'':  '''h'''ighly vascular, '''i'''nterstitial foam cells, '''p'''apillae.
Note:
*† The [[diagnostic size cut-off]] in the 2004 [[WHO]] GU (blue) book was 0.5 cm.<ref name=pmid26935559/><ref>{{Ref WHOGU|28}}</ref>


DDx:
DDx:
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*[[Renal mucinous tubular and spindle cell carcinoma]].
*[[Renal mucinous tubular and spindle cell carcinoma]].
*[[Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma]] - for ''type 2 PaRCC''; CK7 -ve, prominent eosinophilic nucleoli.   
*[[Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma]] - for ''type 2 PaRCC''; CK7 -ve, prominent eosinophilic nucleoli.   
*[[ALK translocation renal cell carcinoma]].
*[[Mixed epithelial and stromal tumour]].<ref name=pmid31862520>{{cite journal |authors=Rogala J, Kojima F, Alaghehbandan R, Agaimy A, Martinek P, Ondic O, Ulamec M, Sperga M, Michalova K, Pivovarcikova K, Pitra T, Hora M, Ferak I, Marečková J, Michal M, Hes O |title=Papillary renal cell carcinoma with prominent spindle cell stroma - tumor mimicking mixed epithelial and stromal tumor of the kidney: Clinicopathologic, morphologic, immunohistochemical and molecular genetic analysis of 6 cases |journal=Ann Diagn Pathol |volume=44 |issue= |pages=151441 |date=February 2020 |pmid=31862520 |doi=10.1016/j.anndiagpath.2019.151441 |url=}}</ref>
*[[Papillary renal neoplasm with reverse polarity]] (PRNRP) - nuclei at luminal aspect of cell (rather than closer to the basement membrane).<ref name=pmid31135486>{{cite journal |authors=Al-Obaidy KI, Eble JN, Cheng L, Williamson SR, Sakr WA, Gupta N, Idrees MT, Grignon DJ |title=Papillary Renal Neoplasm With Reverse Polarity: A Morphologic, Immunohistochemical, and Molecular Study |journal=Am J Surg Pathol |volume=43 |issue=8 |pages=1099–1111 |date=August 2019 |pmid=31135486 |doi=10.1097/PAS.0000000000001288 |url=}}</ref>
**May be considered a subtype of papillary renal cell carcinoma (rather than a distinct entity).
*[[Xp11 translocation renal cell carcinoma]].


===Images===
===Images===
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</gallery>
</gallery>


===Histological subtyping===
===Histological subtyping===  
Generally accepted subtypes:<ref name=Ref_GUP289>{{Ref GUP|289}}</ref><ref>{{Cite journal  | last1 = Delahunt | first1 = B. | last2 = Eble | first2 = JN. | title = Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors. | journal = Mod Pathol | volume = 10 | issue = 6 | pages = 537-44 | month = Jun | year = 1997 | doi =  | PMID = 9195569 }}</ref>
====Historical type 1 and type 2====
Historically, PaRCC was subtyped:<ref name=Ref_GUP289>{{Ref GUP|289}}</ref><ref>{{Cite journal  | last1 = Delahunt | first1 = B. | last2 = Eble | first2 = JN. | title = Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors. | journal = Mod Pathol | volume = 10 | issue = 6 | pages = 537-44 | month = Jun | year = 1997 | doi =  | PMID = 9195569 }}</ref>
*''Type 1'' - single layer of cells on basement membrane - '''most important'''.
*''Type 1'' - single layer of cells on basement membrane - '''most important'''.
** Usually low grade nuclear features, i.e. low [[ISUP nucleolar grade]].
** Usually low grade nuclear features, i.e. low [[ISUP nucleolar grade]].
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*** Cells larger.
*** Cells larger.


Another subtype:
The WHO GU Blue Book 5th Ed. recommends against subtyping.
 
How are ''Type 1'' and ''Type 2'' now classified?
*The defunct ''Type 1'' is ''papillary renal cell carcinoma''.  It is classically associated with a MET gene alteration.
*The defunct ''Type 2'' is a mix of different RCCs, e.g. ALK-RCC, translocation RCC, FH-deficient RCC.
 
===Oncocytic subtype===
*''Oncocytic'' - oncocytic cytoplasm.
*''Oncocytic'' - oncocytic cytoplasm.
**Extremely rare ~ largest series is 12 cases.<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>
**Extremely rare ~ a few dozen reported.<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><ref name=pmid16730306>{{Cite journal  | last1 = Hes | first1 = O. | last2 = Brunelli | first2 = M. | last3 = Michal | first3 = M. | last4 = Cossu Rocca | first4 = P. | last5 = Hora | first5 = M. | last6 = Chilosi | first6 = M. | last7 = Mina | first7 = M. | last8 = Boudova | first8 = L. | last9 = Menestrina | first9 = F. | title = Oncocytic papillary renal cell carcinoma: a clinicopathologic, immunohistochemical, ultrastructural, and interphase cytogenetic study of 12 cases. | journal = Ann Diagn Pathol | volume = 10 | issue = 3 | pages = 133-9 | month = Jun | year = 2006 | doi = 10.1016/j.anndiagpath.2005.12.002 | PMID = 16730306 }}</ref>
***One "large" series was 14 cases.<ref name=pmid27931799>{{Cite journal  | last1 = Han | first1 = G. | last2 = Yu | first2 = W. | last3 = Chu | first3 = J. | last4 = Liu | first4 = Y. | last5 = Jiang | first5 = Y. | last6 = Li | first6 = Y. | last7 = Zhang | first7 = W. | title = Oncocytic papillary renal cell carcinoma: A clinicopathological and genetic analysis and indolent clinical course in 14 cases. | journal = Pathol Res Pract | volume = 213 | issue = 1 | pages = 1-6 | month = Jan | year = 2017 | doi = 10.1016/j.prp.2016.04.009 | PMID = 27931799 }}</ref>


==IHC==
==IHC==
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*CK7 +ve ~90% of type 1, 20% of type 2.
*CK7 +ve ~90% of type 1, 20% of type 2.
*CD10 +ve.<ref>[http://surgpathcriteria.stanford.edu/kidney/papillary-renal-cell-carcinoma/differential-diagnosis.html http://surgpathcriteria.stanford.edu/kidney/papillary-renal-cell-carcinoma/differential-diagnosis.html]. Accessed on: 6 May 2014.</ref>
*CD10 +ve.<ref>[http://surgpathcriteria.stanford.edu/kidney/papillary-renal-cell-carcinoma/differential-diagnosis.html http://surgpathcriteria.stanford.edu/kidney/papillary-renal-cell-carcinoma/differential-diagnosis.html]. Accessed on: 6 May 2014.</ref>
More reading:
*[http://www.e-immunohistochemistry.info/web/Papillary_renal_cell_carcinoma.htm PaRCC (e-immunohistochemistry.info)].


Type 1 versus Type 2:<ref name=pmid9234615>{{Cite journal | last1 = Ono | first1 = Y. | last2 = Ito | first2 = T. | last3 = Tsujino | first3 = S. | last4 = Aizawa | first4 = S. | last5 = Suzuki | first5 = M. | title = [A study of papillary renal cell carcinoma. Clinicopathological, immunohistochemical features and its typing]. | journal = Nihon Hinyokika Gakkai Zasshi | volume = 88 | issue = 6 | pages = 587-95 | month = Jun | year = 1997 | doi = | PMID = 9234615 }}</ref>
Others:
*CK7:
*[[GATA3]] +ve - oncocytic variant of PaRCC; negative in other PaRCC subtypes.<ref name=pmid28984673>{{cite journal |authors=Saleeb RM, Brimo F, Farag M, Rompré-Brodeur A, Rotondo F, Beharry V, Wala S, Plant P, Downes MR, Pace K, Evans A, Bjarnason G, Bartlett JMS, Yousef GM |title=Toward Biological Subtyping of Papillary Renal Cell Carcinoma With Clinical Implications Through Histologic, Immunohistochemical, and Molecular Analysis |journal=Am J Surg Pathol |volume=41 |issue=12 |pages=1618–1629 |date=December 2017 |pmid=28984673 |doi=10.1097/PAS.0000000000000962 |url=}}</ref>
**Type 1 ~ 100%.
*[[ABCC2]] brush border staining = worse survival.<ref name=pmid37680023>{{cite journal |authors=Castillo VF, Masoomian M, Trpkov K, Downes M, Brimo F, van der Kwast T, Yousef GM, Zakhary A, Rotondo F, Saad G, Nguyen VN, Kidanewold W, Streutker C, Rowsell C, Hamdani M, Saleeb RM |title=ABCC2 brush-border expression predicts outcome in papillary renal cell carcinoma: a multi-institutional study of 254 cases |journal=Histopathology |volume=83 |issue=6 |pages=949–958 |date=December 2023 |pmid=37680023 |doi=10.1111/his.15042 |url=}}</ref>
**Type 2 ~ 19%.
*CK19:
**Type 1 ~ 100%.
**Type 2 ~ 53%.


Metanephric adenoma vs. PaRCC type 1:<ref name=pmid24083046>{{Cite journal  | last1 = Watanabe | first1 = S. | last2 = Naganuma | first2 = H. | last3 = Shimizu | first3 = M. | last4 = Ota | first4 = S. | last5 = Murata | first5 = S. | last6 = Nihei | first6 = N. | last7 = Matsushima | first7 = J. | last8 = Mikami | first8 = S. | last9 = Kuroda | first9 = N. | title = Adult nephroblastoma with predominant epithelial component: a differential diagnostic candidate of papillary renal cell carcinoma and metanephric adenoma-report of three cases. | journal = Case Rep Pathol | volume = 2013 | issue =  | pages = 675875 | month =  | year = 2013 | doi = 10.1155/2013/675875 | PMID = 24083046 }}</ref>
Metanephric adenoma vs. PaRCC type 1:<ref name=pmid24083046>{{Cite journal  | last1 = Watanabe | first1 = S. | last2 = Naganuma | first2 = H. | last3 = Shimizu | first3 = M. | last4 = Ota | first4 = S. | last5 = Murata | first5 = S. | last6 = Nihei | first6 = N. | last7 = Matsushima | first7 = J. | last8 = Mikami | first8 = S. | last9 = Kuroda | first9 = N. | title = Adult nephroblastoma with predominant epithelial component: a differential diagnostic candidate of papillary renal cell carcinoma and metanephric adenoma-report of three cases. | journal = Case Rep Pathol | volume = 2013 | issue =  | pages = 675875 | month =  | year = 2013 | doi = 10.1155/2013/675875 | PMID = 24083046 }}</ref>
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<pre>
<pre>
KIDNEY, RIGHT, RADICAL NEPHRECTOMY:
KIDNEY, RIGHT, RADICAL NEPHRECTOMY:
- PAPILLARY RENAL CELL CARCINOMA, TYPE 1, ISUP NUCLEOLAR GRADE 3, pT2a(2), pNx.
- PAPILLARY RENAL CELL CARCINOMA, WHO/ISUP NUCLEOLAR GRADE 3, pT2a(2), pNx.
-- SURGICAL MARGINS NEGATIVE.
-- SURGICAL MARGINS NEGATIVE.
-- PLEASE SEE TUMOUR SUMMARY.
-- PLEASE SEE TUMOUR SUMMARY.
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Multiple small lesions, like the largest tumour, less than 1.5 cm are present.
Multiple small lesions, like the largest tumour, less than 1.5 cm are present.
=====Alternate=====
The sections show a tumour in the kidney with fibrovascular cores (papillae) that contain macrophages. The papillae predominantly have a single layer of tumour cells. Nucleoli are not prominent with the 10x objective (ISUP nucleolar grade 2).


===Oncocytic variant===
===Oncocytic variant===
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KIDNEY, RIGHT, NEPHRECTOMY:
KIDNEY, RIGHT, NEPHRECTOMY:
- PAPILLARY RENAL CELL CARCINOMA, ONCOCYTIC -- SEE COMMENT;
- PAPILLARY RENAL CELL CARCINOMA, ONCOCYTIC -- SEE COMMENT;
- FUHRMANN GRADE 2;
- WHO/ISUP GRADE 2;
- SURGICAL MARGINS NEGATIVE;
- SURGICAL MARGINS NEGATIVE;
- PLEASE SEE TUMOUR SUMMARY.
- PLEASE SEE TUMOUR SUMMARY.
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