EURURO-5666; No. of Pages 4 EUROPEAN UROLOGY XXX (2014) XXX–XXX
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Opinion
International Society of Urological Pathology Grading and Other Prognostic Factors for Renal Neoplasia Brett Delahunt a, John R. Srigley b, Lars Egevad c, Rodolfo Montironi d,* a
Department of Pathology and Molecular Medicine, Wellington School of Medicine, University of Otago, Wellington, New Zealand;
Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Hospital, Solna, Stockholm, Sweden;
d
c
b
Department of
Department of Oncology-Pathology, Karolinska University
Institute of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United
Hospitals, Ancona, Italy
The International Society of Urological Pathology (ISUP) is a specialist society dedicated to the promotion of urologic pathology [1]. The society has developed widely adopted consensus guidelines to promote uniform standards for pathologic reporting, such as those for radical prostatectomy [2]. In 2012, the society convened an international consensus conference and invited those active in renal tumour pathology to review aspects relating to the prognostic assessment, classification, and diagnosis of adult renal malignancy. Work groups focused on prognostic factors, the classification of renal tumours, and the characterisation of novel and emerging forms of renal neoplasia [3,4]. In addition, the groups formulated recommendations for handling and staging of and for diagnostic biomarkers for renal cell carcinoma (RCC) [5,6]. Ultimately, the pathology report is designed to inform clinical care, and interpretation of pathologic data is the role of the urologist. It is incumbent on both urologists and pathologists to work together to improve patient management. For this reason, the detailed recommendations of the conference are reported. 1.
Conference organization
Current data were evaluated by each work group’s members, and key points of controversy were identified through the distribution of a detailed questionnaire to all ISUP members. At the consensus conference, recommendations were formulated following debate and formal electronic voting. As has been the accepted practice of ISUP, a majority vote of 65%
was considered necessary to consider any decisions made to be the consensus of the meeting [7]. The consensus conference was held in Vancouver, Canada, on 17 March 2012 and was attended by 133 members of ISUP, representing 29 countries. International Society of Urological Pathology 2. grading classification As part of the consensus conference, participants considered major changes to the current recommendations for grading the common variants of RCC [3]. The Fuhrman grading system for RCC has gained considerable traction in clinical practice, although its prognostic value has been questioned [8]. In particular, it has been recognised as having poor to moderate interobserver reproducibility, likely due to the subjective nature of the grading process. In several studies, Fuhrman grading has prognostic significance only when data are grouped, effectively reducing the grading to a two-tiered system. Fuhrman grading is based on the simultaneous assessment of nuclear size, nuclear shape, and nucleolar prominence to define the first three grades of the four-tiered system. No direction is provided as to the stratification of these parameters should they individually provide conflicting grading information. To compensate for this, many pathologists utilise nucleolar grading alone; however, this does not satisfy the requirements of Fuhrman grading. In recent studies, grading based on assessment of nucleolar grade alone to define grade 1–3 tumours has
* Corresponding author. Institute of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Via Conca 71, 1-60126 Torrette, Ancona, Italy. Tel. +39 071 5964830; Fax: +39 071 889985. E-mail address: [email protected] (R. Montironi). http://dx.doi.org/10.1016/j.eururo.2014.05.027 0302-2838/# 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Delahunt B, et al. International Society of Urological Pathology Grading and Other Prognostic Factors for Renal Neoplasia. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.05.027
EURURO-5666; No. of Pages 4 2
EUROPEAN UROLOGY XXX (2014) XXX–XXX
Table 1 – The International Society of Urological Pathology grading classification for renal cell carcinoma Grade 1 2 3 4
Definition Tumour cell nucleoli invisible or small and basophilic at 400 magnification Tumour cell nucleoli conspicuous at 400 magnification but inconspicuous at 100 magnification Tumour cell nucleoli eosinophilic and clearly visible at 100 magnification Tumours showing extreme nuclear pleomorphism and/or containing tumour giant cells and/or the presence of any proportion of tumour showing sarcomatoid and/or rhabdoid dedifferentiation
been shown to provide outcome prediction superior to Fuhrman grading for both clear cell RCC and papillary RCC [9,10]. These findings were endorsed by the conference and have been validated in independent survival studies [11]. The conference also acknowledged that the presence of sarcomatoid and rhabdoid morphology within any of the morphotypes of RCC represents an extreme form of tumour dedifferentiation. These combined observations were incorporated into a novel ISUP grading classification for RCC (Table 1, Fig. 1). In this classification, grade 1–3 tumours were graded on the basis of nucleolar prominence, whereas grade 4 tumours were defined by the presence of tumour cells with sarcomatoid and/or rhabdoid morphology and/or tumours containing tumour giant cells or showing extreme nuclear pleomorphism. There was consensus that this classification was recommended for clear cell and papillary RCC. It was also agreed that because no current grading system provides independent prognostic information for chromophobe RCC, those tumours should not be graded. 3.
Other prognostic factors for renal tumours
Numerous prognostic factors have been investigated for RCC in addition to tumour grading and sarcomatoid and rhabdoid differentiation. Of these, only tumour necrosis, microvascular invasion, and tumour morphotype were identified by the consensus conference’s prognostic factors work group as parameters worthy of consideration for routine reporting in clinical practice [3]. 3.1.
Sarcomatoid and rhabdoid morphology
For the assessment of sarcomatoid dedifferentiation within any of the morphotypes of RCC, there was agreement that a minimum percentage of sarcomatoid carcinoma was not required to make the diagnosis and that, consequently, it was unnecessary to report the percentage of tumour showing sarcomatoid morphology. For tumours showing rhabdoid morphology, it was similarly agreed that it was unnecessary to report the percentage of rhabdoid tumour present. For both of these dedifferentiation patterns, it was agreed that the underlying morphotype should be recorded and that if this was not evident, then the tumour should be reported as an undifferentiated carcinoma with a sarcomatoid/rhabdoid component. 3.2.
Tumour necrosis and microvascular invasion
There was consensus that tumour necrosis was of prognostic significance and that assessment should be based on
both macroscopic and microscopic examination of tumours. It was further recommended for clear cell RCC that the amount of necrosis should be quantified as a percentage of the sampled tumour. In the absence of conclusive evidence as to the significance of intratumoural microvascular invasion as a prognostic parameter, there was consensus that, at present, microvascular invasion should not be considered a potential TNM pT staging criterion for RCC. 3.3.
Tumour morphotype
It was agreed that the main morphotypes of RCC are of prognostic significance. In particular, it was noted that clear cell RCC, stage for stage, has a less favourable outcome than either papillary or chromophobe RCC. There was also consensus that division of papillary RCC according to type 1 and type 2 morphology provides prognostic information. 4.
The Vancouver classification of renal neoplasia
4.1.
Newly recognized tumour entities
The conference made a number of recommendations relating to modifications to the 2004 World Health Organization classification of renal tumours [4]. There was consensus that five entities should be recognised as new and distinctive renal epithelial malignancies. These were acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, hereditary leiomyomatosis-associated RCC, microphthalmia transcription factor family (MiTF) translocation RCCs, and tubulocystic RCC. The conference concluded that for most of these newly defined tumour types, the number of reported cases was too limited to allow for prognostic assessment. An exception to this was clear cell (tubulo) papillary RCC, which was considered to be a low-grade malignancy with a very favourable prognosis. Within the clear cell RCC group, there was consensus that because multilocular cystic clear cell RCC has shown a universally favourable outcome to date, these tumours should be renamed multilocular clear cell renal cell neoplasm of low malignant potential. 4.2.
Emerging tumour entities
In addition to these newly recognised forms of renal neoplasia, thyroid-like follicular RCC, succinic dehydrogenase B deficiency-associated RCC, and ALK-translocation RCC were classified as emerging or provisional new entities. It was agreed that although there was sufficient information to recognise these three rare morphotypes of carcinoma as distinctive forms of renal neoplasia, further reports were
Please cite this article in press as: Delahunt B, et al. International Society of Urological Pathology Grading and Other Prognostic Factors for Renal Neoplasia. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.05.027
EURURO-5666; No. of Pages 4 EUROPEAN UROLOGY XXX (2014) XXX–XXX
3
Fig. 1 – The International Society of Urological Pathology grading classification for renal cell carcinoma: (a) grade 1, (b) grade 2, (c) grade 3, (d–f) grade 4.
required to permit a clearer understanding of the nature and behaviour of these highly unusual malignancies. There was consensus that subtyping of papillary RCC (type 1, type 2, and other) should be undertaken, although it was agreed that the oncocytic variant of papillary RCC should
not be considered as a distinct entity. The hybrid oncocytic/ chromophobe tumour is an apparently indolent tumour that occurs in three settings, namely, Birt-Hogg-Dube´ syndrome, renal oncocytosis, and as a sporadic neoplasm; for the time being, it was placed within the chromophobe RCC category.
Please cite this article in press as: Delahunt B, et al. International Society of Urological Pathology Grading and Other Prognostic Factors for Renal Neoplasia. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.05.027
EURURO-5666; No. of Pages 4 4
EUROPEAN UROLOGY XXX (2014) XXX–XXX
4.3.
Nonepithelial tumours
[3] Delahunt B, Cheville JC, Martignoni G, et al. The International Society of Urological Pathology (ISUP) grading classification for
Beyond epithelial tumours of the kidney, advances in our understanding of the behaviour of angiomyolipoma, including the epithelioid and cystic variants, were considered. It was agreed that epithelioid angiomyolipoma should be subdivided according to the presence or absence of atypia because this was considered to more accurately predict behaviour than the simple presence of an epithelioid morphology. In addition, the apparent relationship between cystic nephroma and mixed epithelial and stromal tumour was discussed, with consensus that these tumours represent the same spectrum of neoplasia. Finally, it was agreed that the synovial sarcoma should be removed from the mixed epithelial and mesenchymal category and placed within the sarcoma group. Conflicts of interest: The authors have nothing to disclose.
renal cell carcinoma and other prognostic parameters. Am J Surg Pathol 2013;37:1490–504. [4] Srigley JR, Delahunt B, Eble JN, et al. The International Society of Urological Pathology (ISUP) Vancouver classification of renal neoplasia. Am J Surg Pathol 2013;37:1469–89. [5] Trpkov K, Grignon DJ, Bonsib SM, et al. Handing and staging of renal cell carcinoma: the International Society of Urological Pathology (ISUP) consensus conference recommendations. Am J Surg Pathol 2013;37:1505–17. [6] Tan PH, Cheng L, Rioux-Leclercq N, et al. Renal tumors: diagnostic and prognostic markers. Am J Surg Pathol 2013;37:1518–31. [7] Delahunt B, Egevad L, Montironi R, Srigley JR. International Society of Urological Pathology (ISUP) consensus conference on renal neoplasia: rationale and Organization. Am J Surg Pathol 2013;37: 1463–8. [8] Delahunt B. Advances and controversies in grading and staging of renal cell carcinoma. Mod Pathol 2009;22:S24–36. [9] Delahunt B, Sika-Paotonu D, Bethwaite PB, et al. Grading of clear cell
References [1] Delahunt B, Srigley JR, Montironi R, Egevad L. Urological pathology comes of age. Pathology 2012;44:389–90. [2] Egevad L, Srigley JR, Delahunt B. International Society of Urological
renal cell carcinoma should be based upon nucleolar prominence. Am J Surg Pathol 2011;135:1134–9. [10] Sika-Paotonu D, Bethwaite PB, McCredie MRE, et al. Nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma. Am J Surg Pathol 2006;30:1091–6.
Pathology (ISUP) consensus conference on handling and staging of
[11] Delahunt B, McKenney JK, Lohse CM, et al. A novel grading system
radical prostatectomy specimens: rationale and organization. Mod
for clear cell renal cell carcinoma incorporating tumor necrosis. Am
Pathol 2011;24:1–5.
J Surg Pathol 2013;37:311–22.
Please cite this article in press as: Delahunt B, et al. International Society of Urological Pathology Grading and Other Prognostic Factors for Renal Neoplasia. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.05.027
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Opinion
International Society of Urological Pathology Grading and Other Prognostic Factors for Renal Neoplasia Brett Delahunt a, John R. Srigley b, Lars Egevad c, Rodolfo Montironi d,* a
Department of Pathology and Molecular Medicine, Wellington School of Medicine, University of Otago, Wellington, New Zealand;
Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Hospital, Solna, Stockholm, Sweden;
d
c
b
Department of
Department of Oncology-Pathology, Karolinska University
Institute of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United
Hospitals, Ancona, Italy
The International Society of Urological Pathology (ISUP) is a specialist society dedicated to the promotion of urologic pathology [1]. The society has developed widely adopted consensus guidelines to promote uniform standards for pathologic reporting, such as those for radical prostatectomy [2]. In 2012, the society convened an international consensus conference and invited those active in renal tumour pathology to review aspects relating to the prognostic assessment, classification, and diagnosis of adult renal malignancy. Work groups focused on prognostic factors, the classification of renal tumours, and the characterisation of novel and emerging forms of renal neoplasia [3,4]. In addition, the groups formulated recommendations for handling and staging of and for diagnostic biomarkers for renal cell carcinoma (RCC) [5,6]. Ultimately, the pathology report is designed to inform clinical care, and interpretation of pathologic data is the role of the urologist. It is incumbent on both urologists and pathologists to work together to improve patient management. For this reason, the detailed recommendations of the conference are reported. 1.
Conference organization
Current data were evaluated by each work group’s members, and key points of controversy were identified through the distribution of a detailed questionnaire to all ISUP members. At the consensus conference, recommendations were formulated following debate and formal electronic voting. As has been the accepted practice of ISUP, a majority vote of 65%
was considered necessary to consider any decisions made to be the consensus of the meeting [7]. The consensus conference was held in Vancouver, Canada, on 17 March 2012 and was attended by 133 members of ISUP, representing 29 countries. International Society of Urological Pathology 2. grading classification As part of the consensus conference, participants considered major changes to the current recommendations for grading the common variants of RCC [3]. The Fuhrman grading system for RCC has gained considerable traction in clinical practice, although its prognostic value has been questioned [8]. In particular, it has been recognised as having poor to moderate interobserver reproducibility, likely due to the subjective nature of the grading process. In several studies, Fuhrman grading has prognostic significance only when data are grouped, effectively reducing the grading to a two-tiered system. Fuhrman grading is based on the simultaneous assessment of nuclear size, nuclear shape, and nucleolar prominence to define the first three grades of the four-tiered system. No direction is provided as to the stratification of these parameters should they individually provide conflicting grading information. To compensate for this, many pathologists utilise nucleolar grading alone; however, this does not satisfy the requirements of Fuhrman grading. In recent studies, grading based on assessment of nucleolar grade alone to define grade 1–3 tumours has
* Corresponding author. Institute of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Via Conca 71, 1-60126 Torrette, Ancona, Italy. Tel. +39 071 5964830; Fax: +39 071 889985. E-mail address: [email protected] (R. Montironi). http://dx.doi.org/10.1016/j.eururo.2014.05.027 0302-2838/# 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Delahunt B, et al. International Society of Urological Pathology Grading and Other Prognostic Factors for Renal Neoplasia. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.05.027
EURURO-5666; No. of Pages 4 2
EUROPEAN UROLOGY XXX (2014) XXX–XXX
Table 1 – The International Society of Urological Pathology grading classification for renal cell carcinoma Grade 1 2 3 4
Definition Tumour cell nucleoli invisible or small and basophilic at 400 magnification Tumour cell nucleoli conspicuous at 400 magnification but inconspicuous at 100 magnification Tumour cell nucleoli eosinophilic and clearly visible at 100 magnification Tumours showing extreme nuclear pleomorphism and/or containing tumour giant cells and/or the presence of any proportion of tumour showing sarcomatoid and/or rhabdoid dedifferentiation
been shown to provide outcome prediction superior to Fuhrman grading for both clear cell RCC and papillary RCC [9,10]. These findings were endorsed by the conference and have been validated in independent survival studies [11]. The conference also acknowledged that the presence of sarcomatoid and rhabdoid morphology within any of the morphotypes of RCC represents an extreme form of tumour dedifferentiation. These combined observations were incorporated into a novel ISUP grading classification for RCC (Table 1, Fig. 1). In this classification, grade 1–3 tumours were graded on the basis of nucleolar prominence, whereas grade 4 tumours were defined by the presence of tumour cells with sarcomatoid and/or rhabdoid morphology and/or tumours containing tumour giant cells or showing extreme nuclear pleomorphism. There was consensus that this classification was recommended for clear cell and papillary RCC. It was also agreed that because no current grading system provides independent prognostic information for chromophobe RCC, those tumours should not be graded. 3.
Other prognostic factors for renal tumours
Numerous prognostic factors have been investigated for RCC in addition to tumour grading and sarcomatoid and rhabdoid differentiation. Of these, only tumour necrosis, microvascular invasion, and tumour morphotype were identified by the consensus conference’s prognostic factors work group as parameters worthy of consideration for routine reporting in clinical practice [3]. 3.1.
Sarcomatoid and rhabdoid morphology
For the assessment of sarcomatoid dedifferentiation within any of the morphotypes of RCC, there was agreement that a minimum percentage of sarcomatoid carcinoma was not required to make the diagnosis and that, consequently, it was unnecessary to report the percentage of tumour showing sarcomatoid morphology. For tumours showing rhabdoid morphology, it was similarly agreed that it was unnecessary to report the percentage of rhabdoid tumour present. For both of these dedifferentiation patterns, it was agreed that the underlying morphotype should be recorded and that if this was not evident, then the tumour should be reported as an undifferentiated carcinoma with a sarcomatoid/rhabdoid component. 3.2.
Tumour necrosis and microvascular invasion
There was consensus that tumour necrosis was of prognostic significance and that assessment should be based on
both macroscopic and microscopic examination of tumours. It was further recommended for clear cell RCC that the amount of necrosis should be quantified as a percentage of the sampled tumour. In the absence of conclusive evidence as to the significance of intratumoural microvascular invasion as a prognostic parameter, there was consensus that, at present, microvascular invasion should not be considered a potential TNM pT staging criterion for RCC. 3.3.
Tumour morphotype
It was agreed that the main morphotypes of RCC are of prognostic significance. In particular, it was noted that clear cell RCC, stage for stage, has a less favourable outcome than either papillary or chromophobe RCC. There was also consensus that division of papillary RCC according to type 1 and type 2 morphology provides prognostic information. 4.
The Vancouver classification of renal neoplasia
4.1.
Newly recognized tumour entities
The conference made a number of recommendations relating to modifications to the 2004 World Health Organization classification of renal tumours [4]. There was consensus that five entities should be recognised as new and distinctive renal epithelial malignancies. These were acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, hereditary leiomyomatosis-associated RCC, microphthalmia transcription factor family (MiTF) translocation RCCs, and tubulocystic RCC. The conference concluded that for most of these newly defined tumour types, the number of reported cases was too limited to allow for prognostic assessment. An exception to this was clear cell (tubulo) papillary RCC, which was considered to be a low-grade malignancy with a very favourable prognosis. Within the clear cell RCC group, there was consensus that because multilocular cystic clear cell RCC has shown a universally favourable outcome to date, these tumours should be renamed multilocular clear cell renal cell neoplasm of low malignant potential. 4.2.
Emerging tumour entities
In addition to these newly recognised forms of renal neoplasia, thyroid-like follicular RCC, succinic dehydrogenase B deficiency-associated RCC, and ALK-translocation RCC were classified as emerging or provisional new entities. It was agreed that although there was sufficient information to recognise these three rare morphotypes of carcinoma as distinctive forms of renal neoplasia, further reports were
Please cite this article in press as: Delahunt B, et al. International Society of Urological Pathology Grading and Other Prognostic Factors for Renal Neoplasia. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.05.027
EURURO-5666; No. of Pages 4 EUROPEAN UROLOGY XXX (2014) XXX–XXX
3
Fig. 1 – The International Society of Urological Pathology grading classification for renal cell carcinoma: (a) grade 1, (b) grade 2, (c) grade 3, (d–f) grade 4.
required to permit a clearer understanding of the nature and behaviour of these highly unusual malignancies. There was consensus that subtyping of papillary RCC (type 1, type 2, and other) should be undertaken, although it was agreed that the oncocytic variant of papillary RCC should
not be considered as a distinct entity. The hybrid oncocytic/ chromophobe tumour is an apparently indolent tumour that occurs in three settings, namely, Birt-Hogg-Dube´ syndrome, renal oncocytosis, and as a sporadic neoplasm; for the time being, it was placed within the chromophobe RCC category.
Please cite this article in press as: Delahunt B, et al. International Society of Urological Pathology Grading and Other Prognostic Factors for Renal Neoplasia. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.05.027
EURURO-5666; No. of Pages 4 4
EUROPEAN UROLOGY XXX (2014) XXX–XXX
4.3.
Nonepithelial tumours
[3] Delahunt B, Cheville JC, Martignoni G, et al. The International Society of Urological Pathology (ISUP) grading classification for
Beyond epithelial tumours of the kidney, advances in our understanding of the behaviour of angiomyolipoma, including the epithelioid and cystic variants, were considered. It was agreed that epithelioid angiomyolipoma should be subdivided according to the presence or absence of atypia because this was considered to more accurately predict behaviour than the simple presence of an epithelioid morphology. In addition, the apparent relationship between cystic nephroma and mixed epithelial and stromal tumour was discussed, with consensus that these tumours represent the same spectrum of neoplasia. Finally, it was agreed that the synovial sarcoma should be removed from the mixed epithelial and mesenchymal category and placed within the sarcoma group. Conflicts of interest: The authors have nothing to disclose.
renal cell carcinoma and other prognostic parameters. Am J Surg Pathol 2013;37:1490–504. [4] Srigley JR, Delahunt B, Eble JN, et al. The International Society of Urological Pathology (ISUP) Vancouver classification of renal neoplasia. Am J Surg Pathol 2013;37:1469–89. [5] Trpkov K, Grignon DJ, Bonsib SM, et al. Handing and staging of renal cell carcinoma: the International Society of Urological Pathology (ISUP) consensus conference recommendations. Am J Surg Pathol 2013;37:1505–17. [6] Tan PH, Cheng L, Rioux-Leclercq N, et al. Renal tumors: diagnostic and prognostic markers. Am J Surg Pathol 2013;37:1518–31. [7] Delahunt B, Egevad L, Montironi R, Srigley JR. International Society of Urological Pathology (ISUP) consensus conference on renal neoplasia: rationale and Organization. Am J Surg Pathol 2013;37: 1463–8. [8] Delahunt B. Advances and controversies in grading and staging of renal cell carcinoma. Mod Pathol 2009;22:S24–36. [9] Delahunt B, Sika-Paotonu D, Bethwaite PB, et al. Grading of clear cell
References [1] Delahunt B, Srigley JR, Montironi R, Egevad L. Urological pathology comes of age. Pathology 2012;44:389–90. [2] Egevad L, Srigley JR, Delahunt B. International Society of Urological
renal cell carcinoma should be based upon nucleolar prominence. Am J Surg Pathol 2011;135:1134–9. [10] Sika-Paotonu D, Bethwaite PB, McCredie MRE, et al. Nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma. Am J Surg Pathol 2006;30:1091–6.
Pathology (ISUP) consensus conference on handling and staging of
[11] Delahunt B, McKenney JK, Lohse CM, et al. A novel grading system
radical prostatectomy specimens: rationale and organization. Mod
for clear cell renal cell carcinoma incorporating tumor necrosis. Am
Pathol 2011;24:1–5.
J Surg Pathol 2013;37:311–22.
Please cite this article in press as: Delahunt B, et al. International Society of Urological Pathology Grading and Other Prognostic Factors for Renal Neoplasia. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.05.027
