WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies

Warren, Anne Y.; Harrison, David J.

doi:10.1007/s00345-018-2447-8

Cited by 158 publications

(161 citation statements)

References 139 publications

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“…We speculated that one reason might be the presence of more patients with lower-grade RCC among the metastatic RCC patients with good risk, and combination therapy was unnecessary for these patients, although we could not verify the results of the clinical trial. The WHO/ISUP grading system is widely recognized to be useful for the prognostic prediction of clear cell and papillary RCC and is usually used to evaluate only these two histological types 31 . However, this system could be used to describe the morphological features of all histological types of RCC, and thus we should consider tumour grade across tumour subtypes when evaluating the efficacy of IC inhibitor treatments because it is more versatile than the evaluation of immunohistochemistry in general practice.…”

Section: Discussionmentioning

confidence: 99%

“…The initially diagnosed tumours were staged according to the 7 th American Joint Committee on Cancer staging classification 36 . Pathological diagnosis was evaluated according to WHO/ISUP classification, grading, presence of coagulative necrosis and pathological staging of RCC 31 by two specialized pathologists (N.S., M.E.). Patient characteristics including laboratory findings were evaluated as previously reported 18 .…”

Section: Methodsmentioning

confidence: 99%

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Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma

Kawashima

Kanazawa

Kidani

et al. 2020

Sci Rep

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It is important to evaluate the clinical importance of both CD8 T cells and CD4 T cells expression simultaneously because they have crucial networks in tumour targeting immune responses. In 97 RCC patients, RNA sequencing and gene set enrichment analysis of both CD8 and CD4 T cells based on the expression levels of PD-1 and TIM-3 implied that the populations of PD-1+TIM-3+ CD8 T cells and PD-1lowTIM-3 + CD4 T cells were characterized as exhausted CD8 T cells and regulatory CD4 T cells, respectively. These populations of CD4 and CD8 T cells were significantly upregulated in the patients with RCC of higher WHO/ISUP grade (grades 3, 4) (P < 0.001). Moreover, the cytokine productivities of each population in both CD4 and CD8 T cells of the higher-grade patients were significantly lower than those of the lower-grade patients (P < 0.05). Multivariate analysis showed the prognosis of patients with metastatic RCC of higher WHO/ISUP grade treated by nivolumab to be significantly worse than that of patients with lower grade (P = 0.026). This study showed that tumour grade significantly correlated with dysfunction of both CD4+ and CD8+ TILs and the efficacy of nivolumab treatment. Recently, cancer immunotherapy including monotherapy 1 or combination therapy with anti-PD-1 antibody 2 showed better therapeutic effect than molecular-targeted therapies for metastatic renal cell carcinoma (RCC) patients. However, the therapeutic effect of anti-PD-1 antibody monotherapy against RCC is limited, and both the establishment of biomarkers to predict efficacy and the development of new therapeutic target factors are necessary using tissue infiltrating lymphocytes (TILs). Recently, subpopulations of CD4 and CD8 T cells stratified by PD-1 expression in the tumour microenvironment were reported to be important prognostic factors in cancer immunotherapy 3-5. The transcriptomic data of TILs were published based not only on a single cell 6,7 but also on the intensity of PD-1 expression 3 , and high expression of PD-1 was identified as a predictive marker in non-small cell lung cancer patients. Analysis of TILs according to the expression pattern of multiple immunocheckpoint (IC) molecules revealed the presence of terminally differentiated and stem like CD8 T cells in RCC patients 8. However, few studies have simultaneously evaluated the functions of both CD8 T cells and CD4 T cells, which have crucial networks in establishing immune status in tumour microenvironments 9 and tumour targeting immune responses 10-12 .

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma

Kawashima

Kanazawa

Kidani

et al. 2020

Sci Rep

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“…The presence of sarcomatoid or rhabdoid features in any proportion would classify any clear-cell or papillary RCC as an ISUP grade 4 tumor [14]. Some sRCCs with extensive sarcomatoid dedifferentiation encompassing the whole tumor without clear evidence of any parent histology may be considered as unclassified RCCs [15]. The occurrence of sarcomatoid dedifferentiation may vary according to the parent histology.…”

Section: Pathological Implications Of Sarcomatoid Renal Cell Carcinomamentioning

confidence: 99%

“…This hypermutated phenotype was due to somatic MSH2 and POLE mutations, which could have favored the emergence of the sarcomatoid phenotype in these tumors. A better understanding of sarcomatoid transformation may also be achieved by studying aggressive unclassified RCC (uRCC), which may include tumors with an exclusive sarcomatoid or rhabdoid component [15]. A molecular study of 62 uRCC identified a NF2-deficient subgroup encompassing 26% of tumors and characterized by worse outcomes [30].…”

Section: Molecular Landscape Of Sarcomatoid Renal Cell Carcinomamentioning

confidence: 99%

Sarcomatoid Dedifferentiation in Renal Cell Carcinoma: From Novel Molecular Insights to New Clinical Opportunities

Debien

Thouvenin

Lindner³

et al. 2019

Cancers

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Sarcomatoid features in renal cell carcinoma (RCC) have long been associated with dismal prognosis and poor response to therapy, while biological mechanisms underpinning sarcomatoid dedifferentiation remained obscure. Several efforts have been conducted to break down the molecular profile of sarcomatoid RCC and investigate different targeted therapeutic approaches. Mutations enriched for in sarcomatoid RCC involve, notably, TP53, BAP1, cell cycle, and chromatin-remodeling genes. The immunological landscape of these tumors is also gradually being uncovered, showing frequent expression of programmed cell death ligand-1 (PD-L1) and high levels of tumor-infiltrating lymphocytes. These features may be major determinants for the activity of immune checkpoint inhibitors in this population, which has been confirmed by retrospective studies and subgroup analyses of large randomized phase 3 trials. Combinations based on PD-1/PD-L1 inhibition have demonstrated response rates and complete responses in >50% and >10% of patients in the first-line metastatic setting, respectively, with median overall survival exceeding two years. This remarkable improvement in outcomes effectively establishes immune checkpoint inhibitor combinations as a new standard of care in patients with sarcomatoid RCC. New research fields, including epigenetic regulations and tumor–microenvironment interactions, may further sharpen understanding of sarcomatoid RCC and advance therapeutic developments.

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“…We hope that this will serve as a comprehensive up-to-date resource for urologists, specifically for those not involved in genomic research. Similarly, the review on the most recent WHO classification, staging and grading of renal tumours by Warren and Harrison [5] outlines standards and controversies from the perspective of pathologists. It remains important to look beyond our own immediate specialty to provide high-quality care.…”

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confidence: 99%

Renal cell carcinoma: standards and controversies

Klatte

Stewart

2018

World J Urol

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The purpose of this topic issue of the World Journal of Urology is to relay novel developments and controversies in renal cell carcinoma (RCC). To achieve this, we have selected renowned experts to review various scientific and clinical aspects of RCC . The pace of basic, translational and clinical RCC research development is rapid. We have selected, as outlined below, those topics where we felt that we must improve our knowledge and understanding to provide improved prevention, diagnostic and treatment strategies to our patients.With the widespread use of modern cross-sectional abdominal imaging, the incidence of asymptomatic renal tumours has been increasing, especially in patients over the age of 70 [1,2]. Many of these incidentalomas do not have and will not develop adverse pathological or clinical features meaning any intervention may not change the natural history of the disease. Unfortunately, while imaging is an essential part of the workup, precise criteria to determine the biology of a renal tumour are lacking [2]. However, this "opportunistic", unspecific screening by non-urological specialities has decreased the number of patients presenting with advanced RCC [1], which results from a shift to an earlier stage where RCC is curable or does not cause harm if left alone. "Smart" ultrasound-based screening of a target population defined by established risk factors (age, sex, body mass index, smoking history) and promising plasma markers such as kidney injury molecule-1 [3] may be even more beneficial. Such a strategy may increase the incidence of the disease but would hopefully further decrease mortality rates. If we utilise renal tumour biopsy and active surveillance wisely, intervention rates will remain on a similar level. Overtreatment of screendetected tumours must be avoided at all costs.Research into the biology and the genetic basis of RCC has led to a greater understanding of molecular pathways, refinements in pathological classification, development of drugs and new prognostic factors. The trunk-branch model of key genetic events and heterogeneity is now generally accepted, with many of these events occurring years to decades before tumours become clinically evident [4]. Many more landmark studies will be published from the TRAC-ERx Renal Consortium and other initiatives in the foreseeable future. The review article in this topic issue includes a summary of recent evidence, but also a methodological overview and a glossary of terms used to describe genetic changes [4]. We hope that this will serve as a comprehensive up-to-date resource for urologists, specifically for those not involved in genomic research. Similarly, the review on the most recent WHO classification, staging and grading of renal tumours by Warren and Harrison [5] outlines standards and controversies from the perspective of pathologists. It remains important to look beyond our own immediate specialty to provide high-quality care.Despite several efforts with adjuvant phase III trials in high-risk non-metastatic RCC, a clinically s...

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WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies

Abstract: Much has been done to standardise pathological assessment of renal cell carcinomas in recent years, but there still remain areas of difficulty in classification and grading of these heterogeneous tumours.

Cited by 158 publications

References 139 publications

Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma

Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma

Sarcomatoid Dedifferentiation in Renal Cell Carcinoma: From Novel Molecular Insights to New Clinical Opportunities

Renal cell carcinoma: standards and controversies

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