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Zalles N, Williamson SR. What Is New in Pathologic Diagnosis and Classification of the Common Renal Cell Neoplasms? Surg Pathol Clin 2025; 18:133-155. [PMID: 39890301 DOI: 10.1016/j.path.2024.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2025]
Abstract
Diagnostic challenges remain among the common renal cell carcinoma (RCC) subtypes. High-grade clear cell RCC may have deceptive patterns, for example BAP1-deficient tumors. Subtyping type 1 and 2 papillary RCC is no longer recommended, as former type 2 tumors may now be contain other diagnostic entities, such as FH-deficient RCC, MITF family RCC, or others. Clear cell papillary tumor is no longer considered carcinoma due to its highly favorable behavior. However, imperfect examples are best considered clear cell RCC. Oncocytic renal neoplasm of low malignant potential has been proposed as a borderline category in the absence of overt malignant features.
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Affiliation(s)
- Nicole Zalles
- Department of Pathology and Laboratory Medicine, Cleveland Clinic, 9500 Euclid Avenue L25, Cleveland, OH 44195, USA
| | - Sean R Williamson
- Department of Pathology and Laboratory Medicine, Cleveland Clinic, 9500 Euclid Avenue L25, Cleveland, OH 44195, USA.
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2
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Song Y, Yang R, Zhang X, Shi J, Pan Q. Diagnostic value of imaging in patients with clear cell papillary renal cell carcinoma: A case series and literature review. JOURNAL OF CLINICAL ULTRASOUND : JCU 2024; 52:939-948. [PMID: 38741262 DOI: 10.1002/jcu.23713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 03/30/2024] [Accepted: 04/15/2024] [Indexed: 05/16/2024]
Abstract
Clear cell papillary renal cell carcinoma (CCPRCC) is a newly classified renal cell carcinoma with a low degree of malignancy. Its imaging features have not been studied deeply. Therefore, we reviewed the imaging features of CCPRCC. Solid CCPRCC shows high echo or isoecho mass on conventional ultrasound. Contrast enhanced ultrasound shows "fast forward and slow backward, uneven high enhancement". Computed tomography shows high enhancement and maximum enhancement in the cortical-medullary phase. Magnetic resonance imaging shows slightly low T1WI and high T2WI. This article aims to improve the understanding of CCPRCC by clinical radiologists and promote the accurate.
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Affiliation(s)
- Yuxuan Song
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Ran Yang
- Department of Ultrasound, Qingdao Municipal Hospital, Qingdao, China
| | - Xiujuan Zhang
- Department of Ultrasound, The second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jiahong Shi
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Qizheng Pan
- Department of Anesthesia, China-Japan Union Hospital of Jilin University, Changchun, China
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3
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Xu H, Taylor-Cho IA, Sara Jiang X, Foo WC. Diagnostic accuracy and clinical impact of renal biopsy cytology. Diagn Cytopathol 2024; 52:505-510. [PMID: 38801188 DOI: 10.1002/dc.25357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Revised: 04/29/2024] [Accepted: 05/14/2024] [Indexed: 05/29/2024]
Abstract
BACKGROUND The role of fine needle biopsy cytology in the workup of renal mass lesions remains controversial. With advances in imaging technology and clinical management for renal masses, a critical reevaluation of the role of renal biopsy is needed. This study was designed to provide a comprehensive evaluation of the performance and clinical impact of fine needle biopsy in patients with renal masses. METHODS A 5-year retrospective study of ultrasound or computer tomography (CT)-guided fine needle biopsies of renal masses diagnosed via cytopathology was conducted. Overall diagnostic rate, sensitivity, and diagnostic accuracy were calculated. Further analysis of the impact of fine needle biopsy cytology on clinical management was performed. RESULTS A total of 227 cases of fine-needle aspiration and/or biopsy (FNA/B) of renal masses were identified, including 76 with subsequent nephrectomies. Complications were rare (<1%). The diagnostic rate and sensitivity of FNA/B were 83.3% and 89.5%, respectively. Diagnostic accuracy was 98.7% at the major categorical level and 94.7% at the tumor subtype level. Subsequent clinical actions were associated with a definitive cytologic diagnosis of malignancy/neoplasia (p < .05) and were affected by tumor subtype (p < .05). CONCLUSION This study demonstrates that FNA/B of renal masses is a safe and reliable minimally invasive diagnostic tool with excellent accuracy in confirmation of malignancy and subclassification of tumors. Diagnoses made on FNA/B play a key role in guiding a personalized clinical treatment plan.
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Affiliation(s)
- Hongzhi Xu
- Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA
| | - Ian A Taylor-Cho
- Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA
| | - Xiaoyin Sara Jiang
- Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA
| | - Wen-Chi Foo
- Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA
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4
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Rotterova P, Alaghehbandan R, Skopal J, Rogala J, Slisarenko M, Strakova Peterikova A, Michalova K, Montiel DP, Farcas M, Ulamec M, Stransky P, Fiala O, Pitra T, Hora M, Michal M, Pivovarcikova K, Hes O. Alpha-methyl CoA racemase (AMACR) reactivity across the spectrum of clear cell renal cell neoplasms. Ann Diagn Pathol 2024; 71:152297. [PMID: 38579443 DOI: 10.1016/j.anndiagpath.2024.152297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 03/19/2024] [Accepted: 03/20/2024] [Indexed: 04/07/2024]
Abstract
a-Methylacyl coenzyme A racemase (AMACR) is traditionally considered to be a marker of papillary renal cell carcinoma. However, AMACR expression can be seen in other renal tumors. The aim of this study was to investigate AMACR immunoreactivity within the spectrum of clear cell renal cell neoplasms. Fifty-three clear cell renal epithelial tumors were used in assembling the following four cohorts: low grade (LG) clear cell renal cell carcinoma (CCRCC), high grade (HG) CCRCC, CCRCC with cystic changes, and multilocular cystic renal neoplasm of low malignant potential (MCRNLMP). Representative blocks were stained for AMACR, using two different clones (SP52 and OV-TL12/30). There were at least some AMACR immunoreactivity in 77.8 % and 68.9 % of CCRCCs (using SP52 and OV-TL12/30 clone, respectively). Moderate to strong positivity, or positivity in more than one third of the tumor (even weak in intensity) was detected in 46.7 % of CCRCCs using SP52 and in 48.9 % of CCRCC using OV-TL12/30 clone. The highest AMACR reactivity was observed in HG CCRCC (60 % by SP52 and 66.7 % by OV-TL12/30). Strong and diffuse AMACR positivity was detected in 8.9 % of all CCRCCs. AMACR immunoreactivity in MCRNLMP was 37.5 % (SP52 clone) and 25 % (OV-TL12/30 clone). We demonstrated relatively high expression rate of AMACR in CCRCC, while very variable in intensity and distribution. This finding may have diagnostic implications especially in limited samples (i.e., core biopsies), as AMACR positivity does not exclude the diagnosis of CCRCC.
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Affiliation(s)
- Pavla Rotterova
- Department of Pathology, Biopticka laborator, Pilsen, Czech Republic
| | - Reza Alaghehbandan
- Robert J. Tomsich Pathology and Laboratory Medicine Institute, Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA
| | - Josef Skopal
- Department of Pathology, Charles University in Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic
| | - Joanna Rogala
- Department of Pathology, University Hospital Wroclaw, Poland
| | - Maryna Slisarenko
- Department of Pathology, Charles University in Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic; Department of Pathology, CSD LAB, Kyiv, Ukraine
| | - Andrea Strakova Peterikova
- Department of Pathology, Biopticka laborator, Pilsen, Czech Republic; Department of Pathology, Charles University in Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic
| | - Kvetoslava Michalova
- Department of Pathology, Biopticka laborator, Pilsen, Czech Republic; Department of Pathology, Charles University in Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic
| | - Delia Perez Montiel
- Department of Pathology, Institute Nacional de Cancerologia, Mexico City, Mexico
| | - Mihaela Farcas
- Department of Pathology, Charles University in Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic; Onco Team Diagnostic, București, Romania
| | - Monika Ulamec
- Department of Pathology and Cytology, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Petr Stransky
- Department of Urology, Charles University in Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic
| | - Ondrej Fiala
- Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - Tomas Pitra
- Department of Urology, Charles University in Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic
| | - Milan Hora
- Department of Urology, Charles University in Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic
| | - Michal Michal
- Department of Pathology, Biopticka laborator, Pilsen, Czech Republic; Department of Pathology, Charles University in Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic
| | - Kristyna Pivovarcikova
- Department of Pathology, Biopticka laborator, Pilsen, Czech Republic; Department of Pathology, Charles University in Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic.
| | - Ondrej Hes
- Department of Pathology, Biopticka laborator, Pilsen, Czech Republic; Department of Pathology, Charles University in Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic
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Sangoi AR, Tsai H, Harik L, Mahlow J, Tretiakova M, Williamson SR, Hirsch MS. Vascular, adipose tissue, and/or calyceal invasion in clear cell tubulopapillary renal cell tumour: potentially problematic diagnostic scenarios. Histopathology 2024; 84:1167-1177. [PMID: 38422612 DOI: 10.1111/his.15166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 02/08/2024] [Accepted: 02/13/2024] [Indexed: 03/02/2024]
Abstract
AIMS The 2022 WHO classification for kidney tumours recently downgraded clear cell tubulopapillary (also known as clear cell papillary) renal cell carcinoma (RCC) to a benign neoplasm (i.e. clear cell tubulopapillary renal cell tumour) based on the overwhelmingly banal nature of this neoplasm. However, it has been recognized that some clear cell tubulopapillary renal cell tumours demonstrate vascular, adipose or pelvicalyceal invasion, raising the possibility of more aggressive behaviour. The goal of this study was to determine if these 'high stage' features have an effect on tumour prognosis, warranting a carcinoma designation. METHODS AND RESULTS After excluding cases with tissue artefact (i.e. prior core biopsy track changes) and other RCC subtypes with next-generation sequencing, nine clear cell tubulopapillary renal cell tumours with these so-called 'high stage' features, and otherwise classic morphologic and immunophenotypic findings, including low-grade cytology and 'cup-like' CA9 expression, were evaluated. Median tumour size was 2.2 cm with a range of 0.8 to 6.7 cm. Eight cases (89%) demonstrated perinephric or hilar adipose tissue invasion, although most of these cases showed a bulging (in contrast to an infiltrative) growth pattern. One case demonstrated renal vascular invasion in addition to hilar adipose tissue invasion, and one case demonstrated extension into the pelvicalyceal system. There were no recurrences or evidence of metastatic disease. CONCLUSION These overall findings continue to support the benign designation for clear cell tubulopapillary renal cell tumours, despite morphologic features that might raise the possibility of a 'higher stage' neoplasm.
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Affiliation(s)
- Ankur R Sangoi
- Department of Pathology, Stanford Medical Center, Stanford, CA, USA
| | - Harrison Tsai
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Center for Advanced Molecular Diagnostics, Brigham and Womens Hospital, Boston, MA, USA
| | - Lara Harik
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Jonathan Mahlow
- Department of Pathology, University of Utah, Salt Lake City, UT, USA
| | - Maria Tretiakova
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
| | | | - Michelle S Hirsch
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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Tretiakova M, Kwon JW, Paner GP. Cystic Features in Renal Epithelial Neoplasms and Their Increasing Clinical and Pathologic Significance. Adv Anat Pathol 2024; 31:157-168. [PMID: 38525552 DOI: 10.1097/pap.0000000000000443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2024]
Abstract
Most cystic renal tumors after resection (Boniak IIF to IV cysts) have an indolent course despite the significantly higher proportion of malignant [ie, renal cell carcinoma (RCC)] diagnosis. Most cystic renal tumors have clear cell histology that include cystic clear cell RCC and multilocular cystic renal neoplasm of low malignant potential (MCNLMP). There is growing evidence to suggest that MCNLMP, cystic clear cell RCC, and noncystic clear cell RCC form a cystic-to-solid biological spectrum with MCNLMP representing the most indolent form and with cystic clear cell RCC behaving better than noncystic (solid) clear cell RCC. Extensively (>75%) cystic clear cell RCC also has an excellent outcome similar to MCNLMP stressing the need to reevaluate the histologic criteria that separate these 2 cystic clear cell tumors. Other tumors with clear cells that can be extensively cystic such as the recently reclassified noncancerous clear cell papillary renal tumor and the newly described MED15::TFE3 RCC also have indolent course and may mimic MCNLMP. Cystic features occur also in renal tumors with nonclear cell histology including tumors capable of metastasis such as acquired cystic disease-associated, tubulocystic, fumarate hydratase-deficient, and eosinophilic solid and cystic RCCs. Cystic imaging presentation of some renal tumors such as papillary RCC can be attributed in part to pseudocystic necrosis and hemorrhage. It is important to know that tubulocystic RCC may have a lower Bosniak class presentation that overlaps with benign renal cysts (Bosniak I to IIF) that are managed conservatively. This review highlights the cystic renal tumors with clear cell and nonclear cell morphologies including some novel RCC subtypes that may have cystic features. The presence of cystic features and their extent may aid in the classification and prognostication of renal neoplasms underscoring its increasing importance in the pathologic diagnosis and reporting of renal neoplasia.
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Affiliation(s)
- Maria Tretiakova
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA
| | | | - Gladell P Paner
- Departments of Pathology
- Surgery, Section of Urology, University of Chicago, Chicago, IL
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Goswami PR, Singh G, Patel T, Dave R. The WHO 2022 Classification of Renal Neoplasms (5th Edition): Salient Updates. Cureus 2024; 16:e58470. [PMID: 38765391 PMCID: PMC11100973 DOI: 10.7759/cureus.58470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2024] [Indexed: 05/22/2024] Open
Abstract
The first categorization for renal tumours was made by the WHO in 1981 and included only renal cell carcinoma (RCC). After that, classification was continuously altered over five decades. The WHO 2022 Classification of Urinary and Male Genital Tumours 2022 (5th edition) is molecular-driven and contains major revisions compared to the earlier classification from 2016. This revised edition divided renal tumours into four major broad categories: clear cell renal tumours, papillary renal cell tumours, oncocytic and chromophobe renal tumours, and collecting duct tumours. 'Other renal tumours' and 'molecularly defined renal carcinomas' are two other categories that were also included. Transcription factor binding to IGHM enhancer 3 (TFE3)-rearranged, TFEB-altered, elongin C (ELOC)-mutated (formerly TCEB1)-mutated, fumarate hydratase (FH)-deficient, succinate dehydrogenase (SDH)-deficient, anaplastic lymphoma kinase (ALK)-rearranged, and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)-deficient renal cell carcinomas are molecularly defined entities. Eosinophilic vacuolated tumours and low-grade oncocytic tumours are classified as emerging entities. Molecularly characterized renal tumours include those with SMARCB1 deficiencies, TFE3 rearrangements, TFEB alterations, ALK rearrangements, ELOC mutations, etc. Thyroid-like follicular carcinoma, eosinophilic vacuolated tumour, and low-grade oncocytic tumour are a few emerging entities of renal tumours. Improved therapy targets for each kidney tumour can be achieved using immunohistochemistry (IHC) and molecular definition updates. This study aims to highlight new developments in the WHO 2022 categorization of renal tumours with regard to diagnostic, morphological, molecular, IHC, clinical, and prognostic updates.
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Affiliation(s)
- Parth R Goswami
- Pathology, All India Institute of Medical Sciences (AIIMS), Rajkot, Gujarat, IND
| | - Gyanendra Singh
- Pathology, All India Institute of Medical Sciences (AIIMS), Rajkot, IND
| | - Tarang Patel
- Pathology, All India Institute of Medical Sciences (AIIMS), Rajkot, IND
| | - Rushang Dave
- Pathology, Shantabaa Medical College and General Hospital, Amreli, IND
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Li J, Wilkerson ML, Deng FM, Liu H. The Application and Pitfalls of Immunohistochemical Markers in Challenging Diagnosis of Genitourinary Pathology. Arch Pathol Lab Med 2024; 148:13-32. [PMID: 37074862 DOI: 10.5858/arpa.2022-0493-ra] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2023] [Indexed: 04/20/2023]
Abstract
CONTEXT.— The morphologic features of different entities in genitourinary pathology overlap, presenting a diagnostic challenge, especially when diagnostic materials are limited. Immunohistochemical markers are valuable when morphologic features alone are insufficient for definitive diagnosis. The World Health Organization classification of urinary and male genital tumors has been updated for 2022. An updated review of immunohistochemical markers for newly classified genitourinary neoplasms and their differential diagnosis is needed. OBJECTIVE.— To review immunohistochemical markers used in the diagnosis of genitourinary lesions in the kidney, bladder, prostate, and testis. We particularly emphasized difficult differential diagnosis and pitfalls in immunohistochemistry application and interpretation. New markers and new entities in the 2022 World Health Organization classifications of genitourinary tumors are reviewed. Recommended staining panels for commonly encountered difficult differential diagnoses and potential pitfalls are discussed. DATA SOURCES.— Review of current literature and our own experience. CONCLUSIONS.— Immunohistochemistry is a valuable tool in the diagnosis of problematic lesions of the genitourinary tract. However, the immunostains must be carefully interpreted in the context of morphologic findings with a thorough knowledge of pitfalls and limitations.
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Affiliation(s)
- Jianhong Li
- From the Department of Pathology, Geisinger Medical Center, Danville, Pennsylvania (Li, Wilkerson, Liu)
| | - Myra L Wilkerson
- From the Department of Pathology, Geisinger Medical Center, Danville, Pennsylvania (Li, Wilkerson, Liu)
| | - Fang-Ming Deng
- the Department of Pathology, New York University Grossman School of Medicine, New York City (Deng)
| | - Haiyan Liu
- From the Department of Pathology, Geisinger Medical Center, Danville, Pennsylvania (Li, Wilkerson, Liu)
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Wang H, Ma X, Li S, Su J, Fan B, Liu B, Ni X. KIF20A as a potential biomarker of renal and bladder cancers based on bioinformatics and experimental verification. Aging (Albany NY) 2023; 15:204736. [PMID: 37310408 DOI: 10.18632/aging.204736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 05/03/2023] [Indexed: 06/14/2023]
Abstract
BACKGROUND Bladder cancer (BC) is a malignant tumor that occurs in the bladder wall and often appears in elderly individuals. Renal cancer (RC) arises from the renal tubular epithelium, but its molecular mechanism remains unclear. METHODS We downloaded RC datasets (GSE14762 and GSE53757) and a BC dataset (GSE121711) to screen differentially expressed genes (DEGs). We also performed weighted gene coexpression network analysis (WGCNA). We created a protein-protein interaction (PPI) network and performed functional enrichment analysis, such as gene set enrichment analysis (GSEA). Heatmaps were made for gene expression. Survival analysis and immunoinfiltration analysis were performed. Comparative toxicogenomics database (CTD) analysis was performed to find the relationship between disease and hub genes. Western blotting was performed to verify the role of KIF20A in apoptosis. RESULTS A total of 764 DEGs were identified. The GSEA showed that the DEGs were mainly enriched in organic acid metabolism, drug metabolism, mitochondria, and metabolism of cysteine and methionine. The PPI network in GSE121711 showed that KIF20A was a hub gene of renal clear cell carcinoma. Where the expression level of KIF20A was higher, the prognosis of patients was worse. CTD analysis showed that KIF20A was associated with inflammation, proliferation, and apoptosis. KIF20A expression in the RC group was upregulated, as shown by western blotting. The core proteins (including pRB Ser 780, CyclinA, E2F1, CCNE1, and CCNE2) in the pRB Ser 780/CyclinA signaling pathway were also upregulated in the RC group. CONCLUSIONS KIF20A might be a novel biomarker for researching renal and bladder cancers.
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Affiliation(s)
- Haoyuan Wang
- Department of Urology Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, P.R. China
| | - Xiaopeng Ma
- School of Basic Medical Sciences, Hebei Medical University, Shijiazhuang 050000, Hebei, P.R. China
| | - Sijie Li
- School of Basic Medical Sciences, Hebei Medical University, Shijiazhuang 050000, Hebei, P.R. China
| | - Jianzhi Su
- Department of Urology Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, P.R. China
| | - Bo Fan
- Department of Urology Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, P.R. China
| | - Bin Liu
- Department of Urology Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, P.R. China
| | - Xiaochen Ni
- Department of Urology Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, P.R. China
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10
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Chang F, Zhang JH, Wu WS, Tang S, Lv Z, Chen FM. FDC-SP as a diagnostic and prognostic biomarker and modulates immune infiltrates in renal cell carcinoma. BMC Bioinformatics 2023; 24:91. [PMID: 36899339 PMCID: PMC10007807 DOI: 10.1186/s12859-023-05215-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 03/01/2023] [Indexed: 03/12/2023] Open
Abstract
BACKGROUND Renal cell carcinoma (RCC), one of the top 10 causes of cancer death, is responsible for more than 90% of all cases of primary renal cancer worldwide. Follicular dendritic cell-secreted protein (FDC-SP) specifically binds to activated B cells and regulates the generation of antibodies. It is also thought to promote cancer cell invasion and migration, which could help with tumor metastases. This study aimed to assess the efficacy of FDC-SP in the diagnosis and prognosis of RCC and to investigate the relationship between immune infiltration in RCC and these outcomes. RESULTS RCC tissues had significantly higher levels of FDC-SP protein and mRNA than normal tissues. The high level of FDC-SP expression was linked to the T stage, histological grade, pathological stage, N stage, M stage, and OS event. Functional enrichment analysis identified the major pathways that were enriched as immune response regulation, complement, and coagulation. Immunological checkpoints and immune cell infiltration were observed to substantially correlate with the levels of FDC-SP expression. FDC-SP expression levels showed the ability to precisely distinguish high-grade or high-stage renal cancer (area under the curve (AUC) = 0.830, 0.722), and RCC patients with higher FDC-SP expression levels had worse prognoses. The AUC values for one-, two-, and five-year survival rates were all greater than 0.600. Moreover, the FDC-SP expression is an independent predictive biomarker of OS in RCC patients. CONCLUSION FDC-SP may be a prospective therapeutic target in RCC as well as a possible diagnostic and prognostic biomarker associated with immune infiltration.
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Affiliation(s)
- Fan Chang
- Department of Urology, The Third Central Clinical College of Tianjin Medical University, Tianjin, 300170, China
| | - Jiang-Hui Zhang
- Department of Urology, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin, 300170, China.,Department of Urology, Nankai University Affinity the Third Central Hospital, Tianjin, 300170, China
| | - Wen-Song Wu
- Department of Urology, The Third Central Clinical College of Tianjin Medical University, Tianjin, 300170, China
| | - Shuai Tang
- Department of Urology, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin, 300170, China.,Department of Urology, Nankai University Affinity the Third Central Hospital, Tianjin, 300170, China
| | - Zheng Lv
- Department of Urology, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin, 300170, China.,Department of Urology, Nankai University Affinity the Third Central Hospital, Tianjin, 300170, China
| | - Fang-Min Chen
- Department of Urology, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin, 300170, China. .,Department of Urology, Nankai University Affinity the Third Central Hospital, Tianjin, 300170, China.
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11
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Akgul M, Williamson SR. How New Developments Impact Diagnosis in Existing Renal Neoplasms. Surg Pathol Clin 2022; 15:695-711. [PMID: 36344184 DOI: 10.1016/j.path.2022.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
In recent years, several emerging diagnostic entities have been described in renal cell carcinoma (RCC). However, our understanding of well-known and established entities has also grown. Clear cell papillary RCC is now relabeled as a tumor rather than carcinoma in view of its nonaggressive behavior. Renal tumors with a predominantly infiltrative pattern are very important for recognition, as most of these have aggressive behavior, including fumarate hydratase-deficient RCC, SMARCB1-deficient medullary carcinoma, collecting duct carcinoma, urothelial carcinoma, and metastases from other cancers.
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Affiliation(s)
- Mahmut Akgul
- Department of Pathology and Laboratory Medicine, Albany Medical Center, 47 New Scotland Ave, Room F110S, MC81 Albany, NY 12208, USA
| | - Sean R Williamson
- Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Mail Code L25 Cleveland, OH 44195, USA.
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12
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Gverović-Antunica A, Puzović V, Fabris Miletić Z, Arapović Slavić D, Šikić M, Kaštelan S. Metamorphopsia as the first clinical sign of renal cell carcinoma. Int J Ophthalmol 2022; 15:1407-1409. [PMID: 36017043 DOI: 10.18240/ijo.2022.08.27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 05/14/2022] [Indexed: 11/23/2022] Open
Affiliation(s)
- Antonela Gverović-Antunica
- Department of Ophthalmology, General Hospital Dubrovnik; University of Dubrovnik, Dubrovnik, Dr. Roka Mišetića 2, Dubrovnik 20000, Croatia
| | - Velibor Puzović
- Department of Pathology, General Hospital Dubrovnik, Dr. Roka Mišetića 2, Dubrovnik 20000, Croatia
| | - Zrinka Fabris Miletić
- Department of Radiology, General Hospital Dubrovnik, Dr. Roka Mišetića 2, Dubrovnik 20000, Croatia
| | - Diana Arapović Slavić
- Department of Radiology, General Hospital Dubrovnik, Dr. Roka Mišetića 2, Dubrovnik 20000, Croatia
| | - Maja Šikić
- Medical Centre Dubrovnik, Dr. Ante Starčevićeva 1, Dubrovnik 20000, Croatia
| | - Snježana Kaštelan
- Department of Ophthalmology, Clinical Hospital Dubrava; School of Medicine, University of Zagreb, Zagreb Avenija Gojka Šuška 6, Zagreb 10000, Croatia
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13
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Chan E, Stohr BA, Butler RS, Cox RM, Myles JL, Nguyen JK, Przybycin CG, Reynolds JP, Williamson SR, McKenney JK. Papillary Renal Cell Carcinoma With Microcystic Architecture Is Strongly Associated With Extrarenal Invasion and Metastatic Disease. Am J Surg Pathol 2022; 46:392-403. [PMID: 34881751 DOI: 10.1097/pas.0000000000001802] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Papillary renal cell carcinoma (PRCC) is well-recognized as a morphologically and molecularly heterogenous group of kidney tumors with variable clinical behavior. Our goal was to analyze a unique histologic pattern of PRCC we have observed in routine practice to evaluate for potential clinical significance or distinct molecular signature. We identified 42 cases of PRCC showing a morphologically distinct architecture characterized by numerous epithelial-lined cysts containing the papillary tumor (herein called "microcysts"), which are typically separated by fibrous stroma. Of the initial 42 case test set with microcystic features, 23 (55%) were stage pT3a or higher. Most tumors had strong and diffuse cytoplasmic immunoreactivity for CK7 (93%, 37/40) and AMACR (100%, 40/40). Fumarate hydratase staining was retained in all cases tested (39/39). We performed next-generation sequencing on 15 of these cases with available tissue and identified chromosomal alterations commonly reported in historically "type 1" PRCC, notably multiple chromosomal gains, particularly of chromosomes 7 and 17, and MET alterations. However, alterations in pathways associated with more aggressive behavior (including SETD2, CDKN2A, and members of the NRF pathway) were also identified in 6 of 15 cases tested (40%). Given this molecular and immunophenotypic data, we subsequently reviewed an additional group of 60 consecutive pT2b-pT3 PRCCs to allow for comparisons between cases with and without microcysts, to assess for potential associations with other recently described histologic patterns (ie, "unfavorable architecture": micropapillary, solid, and hobnail), and to assess interobserver reproducibility for diagnosing architectural patterns and grade. Of the total combined 102 PRCCs, 67 (66%) had microcystic architecture within the intrarenal component but were commonly admixed with other patterns (39% had micropapillary, 31% solid, and 31% hobnail). Twenty-seven cases (26%) had metastatic disease, and 24 of these 27 (89%) had microcystic architecture in the intrarenal tumor. Within the pT3 subset, 21 of 22 cases with metastases (95%) had extrarenal invasion as either individual microcysts in renal sinus fat or aggregates of microcysts bulging beyond the confines of the capsule. Backward elimination and stepwise regression methods to detect features significantly associated with adverse outcome identified solid architecture (hazard ratio [HR]: 6.3; confidence interval [CI]: 2.1-18.8; P=0.001), hobnail architecture (HR: 5.3; CI: 1.7-16.7; P=0.004), and microcystic architecture at the tumor-stromal interface (HR: 4.2; CI: 1.1-16.7; P=0.036) as strongest. Of architectural patterns and grade, the microcystic pattern had a substantial interobserver agreement (κ score=0.795) that was highest among the 6 observers. In summary, PRCCs with microcystic architecture represents a subset of historically "type 1" PRCC with a predilection for morphologically distinctive extrarenal involvement and metastatic disease. Microcysts co-vary with other "unfavorable" architectural patterns also associated with higher risk for aggressive disease (ie, micropapillary, hobnail, and solid), but microcysts were more common and have superior interobserver reproducibility. These findings suggest that microcystic PRCC should be recognized as a potentially aggressive histologic pattern of growth in PRCC.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Papillary/diagnosis
- Carcinoma, Papillary/genetics
- Carcinoma, Papillary/metabolism
- Carcinoma, Papillary/pathology
- Carcinoma, Renal Cell/diagnosis
- Carcinoma, Renal Cell/genetics
- Carcinoma, Renal Cell/metabolism
- Carcinoma, Renal Cell/pathology
- Cysts/diagnosis
- Cysts/genetics
- Cysts/metabolism
- Cysts/pathology
- Female
- Follow-Up Studies
- Humans
- Immunohistochemistry
- Kidney Neoplasms/diagnosis
- Kidney Neoplasms/genetics
- Kidney Neoplasms/metabolism
- Kidney Neoplasms/pathology
- Male
- Middle Aged
- Neoplasm Invasiveness
- Neoplasm Metastasis
- Observer Variation
- Prognosis
- Reproducibility of Results
- Retrospective Studies
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Affiliation(s)
- Emily Chan
- Department of Pathology, University of California San Francisco (UCSF), San Francisco, CA
| | - Bradley A Stohr
- Department of Pathology, University of California San Francisco (UCSF), San Francisco, CA
| | - Robert S Butler
- Department of Quantitative Health Sciences, Cleveland Clinic
| | - Roni M Cox
- Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH
| | - Jonathan L Myles
- Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH
| | - Jane K Nguyen
- Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH
| | - Christopher G Przybycin
- Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH
| | - Jordan P Reynolds
- Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH
| | - Sean R Williamson
- Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH
| | - Jesse K McKenney
- Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH
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14
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Alaghehbandan R, Siadat F, Trpkov K. What's new in the WHO 2022 classification of kidney tumours? Pathologica 2022; 115:8-22. [PMID: 36645398 DOI: 10.32074/1591-951x-818] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 10/27/2022] [Indexed: 01/17/2023] Open
Abstract
The World Health Organization (WHO) 2022 classification of urinary and male genital tumours (5th edition) has significantly improved our understanding of the morphologic, immunohistochemical, and molecular characteristics of renal tumours. The aim of this review is to outline the most important changes and diagnostic updates in the WHO 2022 classification of kidney tumours. A major change in this edition is the grouping of renal tumours into broader categories that include "clear cell renal tumours", "papillary renal tumours", "oncocytic and chromophobe renal tumours", "collecting duct tumours" as well as adding two categories of "other renal tumours" and "molecularly defined renal carcinomas". Novel entities included in the WHO 2022 classification are eosinophilic solid and cystic renal cell carcinoma (ESC RCC), anaplastic lymphoma kinase (ALK)-rearranged RCC and ELOC (formerly TCEB1)-mutated RCC. The category of "other renal tumours" includes a group of diverse, unrelated renal tumours that do not fit into other categories. The group of "molecularly defined renal carcinomas" reflects recent discoveries in the renal tumour genomics. These molecularly-defined renal entities demonstrate a set of morphologic features reflecting genotype-phenotype relationships. Final diagnosis of such entities rests on phenotypic and immunohistochemical (IHC) correlation, usually associated with IHC surrogate makers that reflect specific genetic abnormalities.
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Affiliation(s)
- Reza Alaghehbandan
- Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Farshid Siadat
- Cumming School of Medicine, University of Calgary and Alberta Precision Laboratories, Calgary, AB, Canada
| | - Kiril Trpkov
- Cumming School of Medicine, University of Calgary and Alberta Precision Laboratories, Calgary, AB, Canada
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15
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Rysz J, Franczyk B, Ławiński J, Gluba-Brzózka A. Characteristics of Clear Cell Papillary Renal Cell Carcinoma (ccpRCC). Int J Mol Sci 2021; 23:ijms23010151. [PMID: 35008576 PMCID: PMC8745490 DOI: 10.3390/ijms23010151] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 12/16/2021] [Accepted: 12/20/2021] [Indexed: 02/07/2023] Open
Abstract
Renal cell carcinomas (RCCs) is a group of various malignant tumours of the renal cortex displaying distinct clinical, morphologic, and genetic features. Clear cell papillary renal cell carcinoma (ccpRCC), belonging to this group, shares morphologic features with both clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) and therefore, more strict diagnostic criteria should be developed to avoid misdiagnosis. Despite overlapping features, ccpRCC has also distinct clinical behaviour, histologic characteristics (morphologic and immunohistochemical), and genomic features. The concepts concerning this tumour are constantly developing since its biological potential and molecular basis remains to be fully unravelled. First reports indicated the presence of ccpRCC in end-stage renal disease, and they underlined the enriched development in this group of patients; however, currently, it is known that such tumours can also occur spontaneously in the normal kidney. Numerous studies have demonstrated that clinical outcomes and prognosis of ccpRCC patients is highly favourable. Till now, no convincing evidence of metastatic ccpRCC or death caused by the disease has been found. Therefore, it is of high importance to correctly differentiate ccpRCC from other subtypes of RCC with a much worse prognosis and to introduce appropriate management.
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Affiliation(s)
- Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 113 Zeromskiego Street, 90-549 Lodz, Poland; (J.R.); (B.F.)
| | - Beata Franczyk
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 113 Zeromskiego Street, 90-549 Lodz, Poland; (J.R.); (B.F.)
| | - Janusz Ławiński
- Department of Urology, Institute of Medical Sciences, Medical College of Rzeszow University, 35-055 Rzeszow, Poland;
| | - Anna Gluba-Brzózka
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 113 Zeromskiego Street, 90-549 Lodz, Poland; (J.R.); (B.F.)
- Correspondence: or ; Tel.: +48-42-639-3750
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16
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Jia L, Deng FM, Kong MX, Wu CL, Yang XJ. Common Diagnostic Challenges and Pitfalls in Genitourinary Organs, With Emphasis on Immunohistochemical and Molecular Updates. Arch Pathol Lab Med 2021; 145:1387-1404. [PMID: 34673910 DOI: 10.5858/arpa.2021-0107-ra] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/11/2021] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Lesions in the genitourinary (GU) organs, both benign and malignant, can demonstrate overlapping morphology, and practicing surgical pathologists should be aware of these potential pitfalls and consider a broad differential diagnosis for each specific type of lesion involving the GU organs. The following summary of the contents presented at the 6th Annual Chinese American Pathologists Association (CAPA) Diagnostic Course (October 10-11, 2020), supplemented with relevant literature review, exemplifies the common diagnostic challenges and pitfalls for mass lesions of the GU system of adults, including adrenal gland, with emphasis on immunohistochemical and molecular updates when relevant. OBJECTIVE.— To describe the common mass lesions in the GU system of adults, including adrenal gland, with emphasis on the diagnostic challenges and pitfalls that may arise in the pathologic assessment, and to highlight immunohistochemical workups and emerging molecular findings when relevant. DATA SOURCES.— The contents presented at the course and literature search comprise our data sources. CONCLUSIONS.— The diagnostic challenges and pitfalls that arise in the pathologic assessment of the mass lesions in the GU system of adults, including adrenal gland, are common. We summarize the contents presented at the course, supplemented with relevant literature review, and hope to provide a diagnostic framework to evaluate these lesions in routine clinical practice.
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Affiliation(s)
- Liwei Jia
- From the Department of Pathology, University of Texas Southwestern Medical Center, Dallas (Jia)
| | - Fang-Ming Deng
- the Department of Pathology, New York University Grossman School of Medicine, New York City (Deng)
| | - Max X Kong
- Northern California Kaiser, Kaiser Sacramento Medical Center, Sacramento (Kong)
| | - Chin-Lee Wu
- the Department of Pathology and Urology, Massachusetts General Hospital, Boston (Wu)
| | - Ximing J Yang
- the Department of Pathology, Northwestern University, Chicago, Illinois (Yang)
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17
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Lobo J, Ohashi R, Helmchen BM, Rupp NJ, Rüschoff JH, Moch H. The Morphological Spectrum of Papillary Renal Cell Carcinoma and Prevalence of Provisional/Emerging Renal Tumor Entities with Papillary Growth. Biomedicines 2021; 9:1418. [PMID: 34680535 PMCID: PMC8533532 DOI: 10.3390/biomedicines9101418] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 10/04/2021] [Accepted: 10/06/2021] [Indexed: 12/11/2022] Open
Abstract
Renal cell carcinoma (RCC) represents a heterogeneous disease, encompassing an increasing number of tumor subtypes. Post-2016, the World Health Organization (WHO) classification recognized that the spectrum of papillary renal cell carcinoma is evolving and has long surpassed the dichotomic simplistic "type 1 versus type 2" classification. The differential diagnosis of pRCC includes several new provisional/emerging entities with papillary growth. Type 2 tumors have been cleared out of several confounding entities, now regarded as independent tumors with specific clinical and molecular backgrounds. In this work we describe the prevalence and characteristics of emerging papillary tumor entities in two renal tumor cohorts (one consisting of consecutive papillary tumors from a single institute, the other consisting of consultation cases from several centers). After a review of 154 consecutive pRCC cases, 58% remained type 1 pRCC, and 34% type 2 pRCC. Papillary renal neoplasm with reversed polarity (1.3%), biphasic hyalinizing psammomatous RCC (1.3%), and biphasic squamoid/alveolar RCC (4.5%) were rare. Among 281 consultation cases, 121 (43%) tumors had a dominant papillary growth (most frequently MiT family translocation RCCs, mucinous tubular and spindle cell carcinoma and clear cell papillary RCC). Our data confirm that the spectrum of RCCs with papillary growth represents a major diagnostical challenge, frequently requiring a second expert opinion. Papillary renal neoplasm with reversed polarity, biphasic hyalinizing psammomatous RCC, and biphasic squamoid/alveolar RCC are rarely sent out for a second opinion, but correct classification and knowledge of these variants will improve our understanding of the clinical behavior of renal tumors with papillary growth.
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Affiliation(s)
- João Lobo
- Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal;
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
- Department of Pathology and Molecular Immunology, ICBAS—School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
| | - Riuko Ohashi
- Histopathology Core Facility, Faculty of Medicine, Niigata University, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata 951-8510, Japan;
- Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata 951-8510, Japan
| | - Birgit M. Helmchen
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland; (B.M.H.); (N.J.R.); (J.H.R.)
| | - Niels J. Rupp
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland; (B.M.H.); (N.J.R.); (J.H.R.)
| | - Jan H. Rüschoff
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland; (B.M.H.); (N.J.R.); (J.H.R.)
| | - Holger Moch
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland; (B.M.H.); (N.J.R.); (J.H.R.)
- Faculty of Medicine, University of Zurich, Rämistrasse 71, 8006 Zurich, Switzerland
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18
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Tian X, Xu WH, Wu JL, Gan HL, Wang HK, Gu WJ, Qu YY, Zhang HL, Ye DW. Clear Cell Papillary Renal Cell Carcinoma Shares Distinct Molecular Characteristics and may be Significantly Associated With Higher Risk of Developing Second Primary Malignancy. Pathol Oncol Res 2021; 27:1609809. [PMID: 34512202 PMCID: PMC8432294 DOI: 10.3389/pore.2021.1609809] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 08/12/2021] [Indexed: 12/12/2022]
Abstract
Traditionally, clear cell papillary renal cell carcinoma (ccpRCC) was considered to share similar molecular and histological characteristics with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Here we aimed to identify somatic and germline variants of ccpRCC. For this purpose, we conducted whole-exome sequencing to detect somatic variants in the tissues of 18 patients with pathologically confirmed ccpRCC, who underwent surgical treatment at Fudan University Shanghai Cancer Center. Targeted sequencing was conducted to detect germline variants in paired tumor or normal tissues or blood. Somatic and germline variants of ccRCC and Renal cell carcinoma included in The Cancer Genome Atlas data and other published data were analyzed as well. The molecular profiles of ccpRCC, ccRCC and pRCC were compared. Among the 387 somatic variants identified, TCEB1 (3/18) and VHL (3/18) variants occurred at the highest frequencies. Germline mutation detection showed that nine variants associated with Fanconi anemia (VAFAs) pathway (FANCA, 6/18; FANCI, 3/18) were identified in 18 ccpRCC patients. Among ccpRCC patients with VAFAs, five out of eight patients had second primary malignancy or family history of cancer. Somatic variants characteristics may distinguish ccpRCC from ccRCC or pRCC and germline VAFAs may be a molecular characterization of ccpRCC. Compared with ccRCC or pRCC, ccpRCC patients may be significantly correlated with higher risk of developing second primary malignancy.
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Affiliation(s)
- Xi Tian
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wen-Hao Xu
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jun-Long Wu
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hua-Lei Gan
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Hong-Kai Wang
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wei-Jie Gu
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yuan-Yuan Qu
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hai-Liang Zhang
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ding-Wei Ye
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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19
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Webster BR, Rompre-Brodeur A, Daneshvar M, Pahwa R, Srinivasan R. Kidney cancer: from genes to therapy. Curr Probl Cancer 2021; 45:100773. [PMID: 34261604 DOI: 10.1016/j.currproblcancer.2021.100773] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 06/24/2021] [Accepted: 06/24/2021] [Indexed: 11/30/2022]
Abstract
Renal cell carcinoma incidence is rising worldwide with increasing subtype stratification by the World Health Organization. Each subtype has unique genetic alterations, cell biology changes and clinical findings. Such genetic alterations offer the potential for individualized therapeutic approaches that are rapidly progressing. This review highlights the most common subtypes of renal cell carcinoma, including both hereditary and sporadic forms, with a focus on genetic changes, clinical findings and ongoing clinical trials.
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Affiliation(s)
- Bradley R Webster
- Center for Cancer Research, Urologic Oncology Branch, National Cancer Institute/NIH, 10 Center Drive, CRC Room 2W-5940, Bethesda, MD 20892, USA
| | - Alexis Rompre-Brodeur
- Center for Cancer Research, Urologic Oncology Branch, National Cancer Institute/NIH, 10 Center Drive, CRC Room 2W-5940, Bethesda, MD 20892, USA
| | - Michael Daneshvar
- Center for Cancer Research, Urologic Oncology Branch, National Cancer Institute/NIH, 10 Center Drive, CRC Room 2W-5940, Bethesda, MD 20892, USA
| | - Roma Pahwa
- Center for Cancer Research, Urologic Oncology Branch, National Cancer Institute/NIH, 10 Center Drive, CRC Room 2W-5940, Bethesda, MD 20892, USA
| | - Ramaprasad Srinivasan
- Center for Cancer Research, Urologic Oncology Branch, National Cancer Institute/NIH, 10 Center Drive, CRC Room 2W-5940, Bethesda, MD 20892, USA.
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20
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Weng S, DiNatale RG, Silagy A, Mano R, Attalla K, Kashani M, Weiss K, Benfante NE, Winer AG, Coleman JA, Reuter VE, Russo P, Reznik E, Tickoo SK, Hakimi AA. The Clinicopathologic and Molecular Landscape of Clear Cell Papillary Renal Cell Carcinoma: Implications in Diagnosis and Management. Eur Urol 2021; 79:468-477. [PMID: 33046271 PMCID: PMC8327325 DOI: 10.1016/j.eururo.2020.09.027] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 09/10/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND Clear cell papillary renal cell carcinoma (CCPRCC) is a recently described tumor entity. Several questions remain about its epidemiology, molecular features, and clinical behavior. OBJECTIVE To comprehensively evaluate clinicopathologic and molecular features of CCPRCC, and compare it with more common kidney cancer subtypes. DESIGN, SETTING, AND PARTICIPANTS We identified 89 CCPRCC patients and compared their clinicopathologic features with 1120 localized clear cell renal cell carcinoma (ccRCC) and 129 type 1 papillary renal cell carcinoma (pRCC) patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Nonparametric statistical testing was used to compare relevant features between tumor types. Overall, cancer-specific survival (CSS) and metastasis-free survival estimates were calculated from initial diagnosis using the Kaplan-Meier method. Patients with ipsilateral multifocal disease were explored further. A subset of CCPRCC tumors underwent genomic analysis and were compared with other RCC subtypes. RESULTS AND LIMITATIONS A higher proportion of female (45% vs 32%) and African-American (19% vs 3%) patients were observed in the CCPRCC cohort than in the ccRCC and pRCC cohorts. CCPRCC tumors also had increased odds of presenting with additional ipsilateral masses (odds ratio [OR]: 4.41 [confidence interval {CI}: 2.34, 8.15], p < 0.001) and bilateral disease (OR: 4.80 [CI: 2.40, 9.59], p < 0.001) compared with ccRCC tumors. On molecular analysis, CCPRCC tumors showed fewer somatic aberrations and a greater degree of mitochondrial DNA depletion. In multifocal CCPRCC tumors, histologic concordance among the different renal cell carcinoma masses was estimated at 44% (7/16), and none of the individuals presenting exclusively with CCPRCC tumors developed metastatic disease after 5 yr. In contrast, multifocal tumors with CCPRCC and other nonconcordant histologies were more likely to experience adverse outcomes (CSS, log rank p = 0.034). CONCLUSIONS CCPRCC is characterized by distinct molecular and epidemiologic features that could be used to refine current diagnostic approaches. Although their clinical course is generally indolent, multifocal CCPRCC tumors represent a unique diagnostic challenge. In this context, single-mass biopsies could miss concomitant aggressive disease, with a potential negative impact on patient outcomes. Furthermore, high discordance rates in multifocal CCPRCC tumors have important clinical implications in management. PATIENT SUMMARY We explored the molecular and clinical features of clear cell papillary renal cell carcinoma (CCPRCC) relative to other kidney cancer subtypes. While CCPRCC generally conveys a good prognosis, additional caution should be taken when it is diagnosed using biopsy if multiple kidney masses are present.
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Affiliation(s)
- Stanley Weng
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Urology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA
| | - Renzo G DiNatale
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Computational Oncology, Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrew Silagy
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Roy Mano
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kyrollis Attalla
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mahyar Kashani
- Department of Urology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA
| | - Kate Weiss
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nicole E Benfante
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrew G Winer
- Department of Urology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA
| | - Jonathan A Coleman
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Victor E Reuter
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Paul Russo
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ed Reznik
- Computational Oncology, Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Satish K Tickoo
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - A Ari Hakimi
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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21
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Steward JE, Kern SQ, Cheng L, Boris RS, Tong Y, Bahler CD, Masterson TA, Cary KC, Kaimakliotis H, Gardner T, Sundaram CP. Clear cell papillary renal cell carcinoma: Characteristics and survival outcomes from a large single institutional series. Urol Oncol 2021; 39:370.e21-370.e25. [PMID: 33771410 DOI: 10.1016/j.urolonc.2021.02.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 01/27/2021] [Accepted: 02/01/2021] [Indexed: 11/17/2022]
Abstract
OBJECTIVES To investigate the clinical characteristics and survival outcomes of a large clear cell papillary renal cell carcinoma cohort. METHODS AND MATERIALS A retrospective review of patients with clear cell papillary renal cell carcinoma at a single academic center was performed after Institutional Review Board approval. Patients underwent either partial or radical nephrectomy from September 2009 to July 2019. Demographic and clinical characteristics, recurrence, and cancer specific and overall survival were reported. RESULTS A total of 90 patients were included in the study. Median follow up was 26.5 months. Median age was 61 (range 27 to 87). 47.8% of patients were African American. 26.7% of patients had end stage renal disease. 37.8% had multifocal renal tumors. 48.9% underwent partial nephrectomy, while the remainder underwent radical nephrectomy. 43.3% underwent an open surgical approach, 40.0% a robotic approach, and 16.7% a laparoscopic approach. Pathologic stage included T1a (90.0%), T1b (1.1%), and T2b (8.9%). Fuhrman grades 1-3 were present in 18.9%, 77.8%, and 3.3% of patients, respectively. There were no cancer specific deaths. There was one local recurrence and no metastases. The overall survival at a median follow up of 26.5 months was 92.1% (95% confidence interval 83.1%-96.4%). CONCLUSIONS Clear cell papillary renal cell carcinoma typically presents at a low stage and grade and has favorable survival outcomes. A nephron-sparing approach to treatment should be considered when feasible due to the tumor's indolent nature and propensity towards multifocality.
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Affiliation(s)
- James E Steward
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Sean Q Kern
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Liang Cheng
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, IN, USA
| | - Ronald S Boris
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Yan Tong
- Department of Biostatistics, Indiana University School of Medicine, IN, USA
| | - Clint D Bahler
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Timothy A Masterson
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - K Clint Cary
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Hristos Kaimakliotis
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Thomas Gardner
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Chandru P Sundaram
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
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22
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Athanazio DA, Amorim LS, da Cunha IW, Leite KRM, da Paz AR, de Paula Xavier Gomes R, Tavora FRF, Faraj SF, Cavalcanti MS, Bezerra SM. Classification of renal cell tumors – current concepts and use of ancillary tests: recommendations of the Brazilian Society of Pathology. SURGICAL AND EXPERIMENTAL PATHOLOGY 2021. [DOI: 10.1186/s42047-020-00084-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AbstractClassification of renal cell carcinomas has become more challenging. The 2016 WHO classification included 14 different subtypes and 4 emerging/provisional entities, and recent literature indicates new entities to be incorporated. Nomenclature is based on cytoplasmic appearance, architecture, combination of morphologies, anatomic location, underlying disease, familial syndromes, and specific genetic alterations. Immunohistochemistry is useful in selected cases while it can be insufficient in entities that require molecular confirmation of a specific gene alteration. The aim of these recommendations is to provide a reasonable and optimized approach for the use of ancillary tests in subtyping renal tumors, particularly in resource-limited settings.
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23
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Application of Chromosome Microarray Analysis for the Differential Diagnosis of Low-grade Renal Cell Carcinoma With Clear Cell and Papillary Features. Appl Immunohistochem Mol Morphol 2020; 28:123-129. [PMID: 32044880 DOI: 10.1097/pai.0000000000000704] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) are the 2 most common RCCs. However, some RCCs can have both clear cell and papillary features, including clear cell papillary RCC (ccpRCC). They can be a diagnostic challenge in daily practice. Accurate diagnosis of these tumors is important for both patient prognosis and appropriate treatment. Fourteen RCCs with papillary architecture, clear cytoplasm and low Fuhrman grade were analyzed by SNP-based chromosome microarray (CMA). Seven cases had pathologic features of ccpRCC, and all had normal genomic profiles except one that had copy neutral loss of heterozygosity (cnLOH) of chromosome 3 and loss of one copy of the X chromosome. The remaining 7 cases also had papillae and clear cytoplasm. Two of these cases showed losses of chromosome 3 which are typically found in ccRCC. One had a gain of chromosome 7, which is commonly seen in pRCC. The remaining 4 had no alterations of chromosome 3 or 7. However, 3 of these 4 had monosomy 8, which are consistent with RCC with monosomy 8. The remaining case had no copy number alterations. This study shows that low-grade RCC with papillae and clear cell phenotype represents a heterogeneous group, including ccpRCC, ccRCC, pRCC, and RCC with monosomy 8. CMA analysis can be useful for the differential diagnosis of these neoplasms.
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24
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Williamson SR. Clear cell papillary renal cell carcinoma: an update after 15 years. Pathology 2020; 53:109-119. [PMID: 33223139 DOI: 10.1016/j.pathol.2020.10.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 10/13/2020] [Indexed: 12/19/2022]
Abstract
Fifteen years since the first recognition of clear cell papillary renal cell carcinoma, this distinct renal tumour type is now well accepted as a distinct entity in major classification schemes. It occurs both with and without end-stage renal disease and may be multifocal or bilateral in both scenarios. Recognisable morphological features include clear cells lining branching glands and variable papillary formations with nuclear alignment. Most tumours are small (pT1a) and nucleolar grade 1-2. Immunohistochemistry consistently shows positivity for carbonic anhydrase IX and cytokeratin 7, and often high molecular weight cytokeratin or GATA3, the latter suggesting distal nephron phenotype. Labeling for AMACR and CD10 is consistently negative or minimal. Despite a resemblance to clear cell renal cell carcinoma, molecular alterations of VHL and chromosome 3p are typically lacking, with debatable rare exceptions. Potential mimics include clear cell renal cell carcinoma (with branching architecture or nuclear alignment), papillary renal cell carcinoma with clear cytoplasm, or rarely MITF family translocation renal cell carcinoma. Clinical behaviour is highly favourable with rare, debatable reports of aggressive behaviour. Combined with striking similarity to several extrarenal benign neoplasms, it would be reasonable to reclassify this entity as a benign or low malignant potential neoplasm. Using the nomenclature of the extrarenal counterparts, clear cell papillary (cyst)adenoma is proposed.
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Affiliation(s)
- Sean R Williamson
- Department of Pathology, Robert J Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
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25
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Griffin BB, Lin X. Cytomorphologic analysis of clear cell papillary renal cell carcinoma: Distinguishing diagnostic features. Cancer Cytopathol 2020; 129:192-203. [PMID: 33036062 DOI: 10.1002/cncy.22355] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 07/30/2020] [Accepted: 08/07/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Clear cell papillary renal cell carcinoma (CCPRCC) shares histomorphologic and immunophenotypic features with clear cell RCC (CCRCC) and papillary RCC (PRCC). METHODS We compared the cytomorphology, immunoprofile, and clinical management of CCPRCC (n = 18), CCRCC (n = 20), and PRCC (n = 18). RESULTS Useful cytomorphologic features for comparing CCPRCC with CCRCC include 3-dimensional clusters (72% vs 0%), papillae (50% vs 0%) and sheets (22% vs 70%), vasculature (papillary vs traversing), naked nuclei (17% vs 100%), prominent nucleoli (0% vs 65%), and amount of cytoplasm (small vs large). Useful cytomorphologic features for comparing CCPRCC with PRCC include sheets (22% vs 61%), naked nuclei (17% vs 67%), nuclear grooves (5% vs 67%) and inclusions (17% vs 67%), and pigmented cytoplasm (17% vs 83%). At on-site evaluation, 16 of 18 (86%) CCPRCC specimens were deemed adequate, with suspicion for CCPRCC in 5 of 16 (31%) cases. Core histology of CCPRCC showed low-grade malignant cells in nests (67%), tubules (100%), and papillae (72%), frequently in myxohyaline stroma (67%). Immunostains demonstrated expression of cytokeratin 7 (CK7; 100%), carbonic anhydrase IX (CA IX; 100%, cup-like), CD10 (53%, reverse cup-like), and α-methylacyl-CoA racemase (AMACR; 35%). Among 18 CCPRCC patients, 9 (50%) underwent nephrectomy, 5 (28%) underwent cryo-ablation, and 4 (22%) were under surveillance with serial imaging. CONCLUSION Certain morphologic features represent diagnostic criteria of CCPRCC in cytology specimens and help distinguish CCPRCC from CCRCC and PRCC. Immunostaining patterns with CK7, CA IX, CD10, and AMACR can confirm the diagnosis. Delineating CCPRCC from more biologically aggressive RCC types in cytology specimens enhances presurgical and clinical management of patients given CCPRCC's low-grade, indolent behavior.
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Affiliation(s)
- Brannan B Griffin
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Xiaoqi Lin
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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26
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Kancherla P, Daneshvar M, Sager RA, Mollapour M, Bratslavsky G. Fumarate hydratase as a therapeutic target in renal cancer. Expert Opin Ther Targets 2020; 24:923-936. [PMID: 32744123 DOI: 10.1080/14728222.2020.1804862] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Renal cell carcinoma (RCC) is a heterogeneous group of cancers that can occur sporadically or as a manifestation of various inherited syndromes. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is one such inherited syndrome that predisposes patients to HLRCC-associated RCC. These tumors are notoriously aggressive and often exhibit early metastases. HLRCC results from germline mutations in the FH gene, which encodes the citric acid cycle enzyme fumarate hydratase (FH). FH loss leads to alterations in oxidative carbon metabolism, necessitating a switch to aerobic glycolysis, as well as a pseudohypoxic response and consequent upregulation of various pro-survival pathways. Mutations in FH also alter tumor cell migratory potential, response to oxidative stress, and response to DNA damage. AREAS COVERED We review the mechanisms by which FH loss leads to HLRCC-associated RCC and how these mechanisms are being rationally targeted. EXPERT OPINION FH loss results in the activation of numerous salvage pathways for tumor cell survival in HLRCC-associated RCC. Tumor heterogeneity requires individualized characterization via next-generation sequencing, ultimately resulting in HLRCC-specific treatment regimens. As HLRCC-associated RCC represents a classic Warburg tumor, targeting aerobic glycolysis is particularly promising as a future therapeutic avenue.
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Affiliation(s)
- Priyanka Kancherla
- Department of Urology, SUNY Upstate Medical University , Syracuse, NY, USA.,Cancer Center, SUNY Upstate Medical University , Syracuse, NY, USA
| | - Michael Daneshvar
- Department of Urology, SUNY Upstate Medical University , Syracuse, NY, USA.,Cancer Center, SUNY Upstate Medical University , Syracuse, NY, USA
| | - Rebecca A Sager
- Department of Urology, SUNY Upstate Medical University , Syracuse, NY, USA.,Cancer Center, SUNY Upstate Medical University , Syracuse, NY, USA.,Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University , Syracuse, NY, USA
| | - Mehdi Mollapour
- Department of Urology, SUNY Upstate Medical University , Syracuse, NY, USA.,Cancer Center, SUNY Upstate Medical University , Syracuse, NY, USA.,Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University , Syracuse, NY, USA
| | - Gennady Bratslavsky
- Department of Urology, SUNY Upstate Medical University , Syracuse, NY, USA.,Cancer Center, SUNY Upstate Medical University , Syracuse, NY, USA.,Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University , Syracuse, NY, USA
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Tretiakova MS. Renal Cell Tumors: Molecular Findings Reshaping Clinico-pathological Practice. Arch Med Res 2020; 51:799-816. [PMID: 32839003 DOI: 10.1016/j.arcmed.2020.08.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 08/11/2020] [Indexed: 02/07/2023]
Abstract
Over the past 20 years, the number of subtypes of renal epithelial cell neoplasia has grown. This growth has resulted from detailed histological and immunohistochemical characterization of these tumors and their correlation with clinical outcomes. Distinctive molecular phenotypes have validated the unique nature of many of these tumors. This growth of unique renal neoplasms has continued after the 2016 World Health Organization (WHO) Classification of Tumours. A consequence is that both the pathologists who diagnose the tumors and the clinicians who care for these patients are confronted with a bewildering array of renal cell carcinoma variants. Many of these variants have important clinical features, i.e. familial or syndromic associations, genomics alterations that can be targeted with systemic therapy, and benignancy of tumors previously classified as carcinomas. Our goal in the review is to provide a practical guide to help recognize these variants, based on small and distinct sets of histological features and limited numbers of immunohistochemical stains, supplemented, as necessary, with molecular features.
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Affiliation(s)
- Maria S Tretiakova
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
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28
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Surgical pathology of cystic renal cell carcinomas: is there an overestimation of malignancy? ACTA ACUST UNITED AC 2020. [DOI: 10.1016/j.mpdhp.2020.04.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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29
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Williamson SR, Gill AJ, Argani P, Chen YB, Egevad L, Kristiansen G, Grignon DJ, Hes O. Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: III: Molecular Pathology of Kidney Cancer. Am J Surg Pathol 2020; 44:e47-e65. [PMID: 32251007 PMCID: PMC7289677 DOI: 10.1097/pas.0000000000001476] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Renal cell carcinoma (RCC) subtypes are increasingly being discerned via their molecular underpinnings. Frequently this can be correlated to histologic and immunohistochemical surrogates, such that only simple targeted molecular assays, or none at all, are needed for diagnostic confirmation. In clear cell RCC, VHL mutation and 3p loss are well known; however, other genes with emerging important roles include SETD2, BAP1, and PBRM1, among others. Papillary RCC type 2 is now known to include likely several different molecular entities, such as fumarate hydratase (FH) deficient RCC. In MIT family translocation RCC, an increasing number of gene fusions are now described. Some TFE3 fusion partners, such as NONO, GRIPAP1, RBMX, and RBM10 may show a deceptive fluorescence in situ hybridization result due to the proximity of the genes on the same chromosome. FH and succinate dehydrogenase deficient RCC have implications for patient counseling due to heritable syndromes and the aggressiveness of FH-deficient RCC. Immunohistochemistry is increasingly available and helpful for recognizing both. Emerging tumor types with strong evidence for distinct diagnostic entities include eosinophilic solid and cystic RCC and TFEB/VEGFA/6p21 amplified RCC. Other emerging entities that are less clearly understood include TCEB1 mutated RCC, RCC with ALK rearrangement, renal neoplasms with mutations of TSC2 or MTOR, and RCC with fibromuscular stroma. In metastatic RCC, the role of molecular studies is not entirely defined at present, although there may be an increasing role for genomic analysis related to specific therapy pathways, such as for tyrosine kinase or MTOR inhibitors.
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MESH Headings
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Renal Cell/diagnosis
- Carcinoma, Renal Cell/genetics
- Carcinoma, Renal Cell/metabolism
- Carcinoma, Renal Cell/pathology
- Humans
- Immunohistochemistry
- In Situ Hybridization, Fluorescence
- Kidney Neoplasms/diagnosis
- Kidney Neoplasms/genetics
- Kidney Neoplasms/metabolism
- Kidney Neoplasms/pathology
- Mutation
- Neoplasm Metastasis
- Neoplastic Syndromes, Hereditary/diagnosis
- Neoplastic Syndromes, Hereditary/genetics
- Neoplastic Syndromes, Hereditary/metabolism
- Neoplastic Syndromes, Hereditary/pathology
- Pathology, Clinical
- Pathology, Molecular
- Prognosis
- Societies, Medical
- Urology
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Affiliation(s)
- Sean R Williamson
- Department of Pathology and Laboratory Medicine and Henry Ford Cancer Institute, Henry Ford Health System
- Department of Pathology, Wayne State University School of Medicine, Detroit, MI
| | - Anthony J Gill
- NSW Health Pathology, Department of Anatomical Pathology
- Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards
- Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - Pedram Argani
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ying-Bei Chen
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Lars Egevad
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
| | | | - David J Grignon
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN
| | - Ondrej Hes
- Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czechia
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30
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Somorácz Á, Kuthi L, Micsik T, Jenei A, Hajdu A, Vrabély B, Rásó E, Sápi Z, Bajory Z, Kulka J, Iványi B. Renal Cell Carcinoma with Clear Cell Papillary Features: Perspectives of a Differential Diagnosis. Pathol Oncol Res 2020; 26:1767-1776. [PMID: 31656019 PMCID: PMC7297853 DOI: 10.1007/s12253-019-00757-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 10/01/2019] [Indexed: 02/06/2023]
Abstract
Thirty-one cases of low-grade renal cell carcinoma (RCC) with clear cells and tubulopapillary/papillary architecture were analyzed retrospectively with immunohistochemical and genetic markers to gain more experience with the differential diagnosis of such cases. All samples coexpressed CK7 and CA9; the TFE3 or TFEB reactions were negative; the CD10 and the AMACR stainings were negative in 27 cases and 30 cases, respectively. The FISH assays for papillary RCC, available in 27 cases, and deletion of chromosome 3p, available in 29 cases, gave negative results. The results for 3p deletion, VHL gene mutation or VHL gene promoter region hypermethylation testing, along with the diffuse CD10-positivity in 2 cases confirmed 21 cases as clear cell papillary RCC (CCPRCC; CK7+, CA9+; no 3p loss, no VHL abnormality) and 10 cases as clear cell RCC (CCRCC; CK7+, CA9+; no 3p loss, VHL abnormality mutation/hypermethylation present). In CCPRCCs, the representative growth pattern was branching tubulo-acinar, commonly accompanied by cyst formation. The linear nuclear arrangement or cup-shaped staining of CA9 did not necessarily indicate CCPRCC, and the absence of these did not exclude the diagnosis of CCPPRC. One tumor infiltrated the renal sinus; the others exhibited pT1 stage; and metastatic outcome was not recorded. The CCRCC cases were in pT1 stage; 6 exhibited cup-shaped staining of CA9, and 1 displayed lymph node metastasis at the time of surgery. Distant metastatic disease was not observed. In summary, the VHL abnormalities distinguished the subset of CCRCC with diffuse CK7-positivity and no 3p loss from cases of CCPRCC.
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Affiliation(s)
- Áron Somorácz
- 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, H-1091, Hungary.
| | - Levente Kuthi
- Department of Pathology, University of Szeged, Szeged, Hungary
| | - Tamás Micsik
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Alex Jenei
- Department of Pathology, University of Szeged, Szeged, Hungary
| | - Adrienn Hajdu
- Department of Pathology, University of Szeged, Szeged, Hungary
| | - Brigitta Vrabély
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Erzsébet Rásó
- 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, H-1091, Hungary
| | - Zoltán Sápi
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Zoltán Bajory
- Department of Urology, University of Szeged, Szeged, Hungary
| | - Janina Kulka
- 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, H-1091, Hungary
| | - Béla Iványi
- Department of Pathology, University of Szeged, Szeged, Hungary
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31
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Giunchi F, Franceschini T, Gruppioni E, Altimari A, Capizzi E, Massari F, Schiavina R, Brunelli M, Martignoni G, Fiorentino M. Similarities and Differences between Clear Cell Tubulo-Papillary and Conventional Clear Cell Renal Cell Carcinoma: A Comparative Phenotypical and Mutational Analysis. Diagnostics (Basel) 2020; 10:diagnostics10020123. [PMID: 32102250 PMCID: PMC7168142 DOI: 10.3390/diagnostics10020123] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 02/21/2020] [Accepted: 02/22/2020] [Indexed: 01/13/2023] Open
Abstract
Background: Clear cell tubulo-papillary renal cell carcinoma (cctpRCC) is characterized by clear cell morphology, but differs from conventional clear cell carcinoma (ccRCC) for its indolent clinical behavior and genetic background. The differential diagnosis between the two is based on histology and immunohistochemistry (IHC). Methods: We performed a comparative case-control histological, IHC, and genetic analysis by next generation sequencing (NGS), to point out the differences in 10 cases of cctpRCC, and six controls of ccRCC with low stage and grade. Results: All 16 cases showed the IHC profile with cytokeratin 7, racemase, and carbonic anhydrase IX expected for the histological features of each tumor type. By contrast, the NGS mutation analysis that covered 207 amplicons of 50 oncogenes or tumor suppressor genes provided conflicting results. Among the 10 cctpRCC cases, eight (80%) were wild type for all of the genes in the panel, while two (20%) harbored VHL mutations typical of ccRCC. Three of the six (50%) ccRCC control cases showed expected VHL mutations; two (33%) harbored pathogenic mutations in the p53 or the CKIT genes; and one (16%) was wild type. Conclusion: We can assume that histology and ICH are not sufficient for a definitive diagnosis of cctpRCC or ccRCC. Although with a panel covering 50 genes, we found that 80% of cctpRCC were genetically silent; thus, suggesting an indolent biology of these tumors. The differential diagnosis between ccptRCC and ccRCC for the choice of the best therapeutic strategy likely requires the comprehensive evaluation of histology, IHC, and at least VHL mutations.
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Affiliation(s)
- Francesca Giunchi
- Department of Pathology, University of Bologna, 40138 Bologna, Italy; (F.G.); (T.F.); (E.G.); (A.A.); (E.C.)
| | - Tania Franceschini
- Department of Pathology, University of Bologna, 40138 Bologna, Italy; (F.G.); (T.F.); (E.G.); (A.A.); (E.C.)
| | - Elisa Gruppioni
- Department of Pathology, University of Bologna, 40138 Bologna, Italy; (F.G.); (T.F.); (E.G.); (A.A.); (E.C.)
| | - Annalisa Altimari
- Department of Pathology, University of Bologna, 40138 Bologna, Italy; (F.G.); (T.F.); (E.G.); (A.A.); (E.C.)
| | - Elisa Capizzi
- Department of Pathology, University of Bologna, 40138 Bologna, Italy; (F.G.); (T.F.); (E.G.); (A.A.); (E.C.)
| | - Francesco Massari
- Department of Oncology, University of Bologna, 40138 Bologna, Italy;
| | | | - Matteo Brunelli
- Department of Pathology, University of Verona, 37129 Verona, Italy; (M.B.); (G.M.)
| | - Guido Martignoni
- Department of Pathology, University of Verona, 37129 Verona, Italy; (M.B.); (G.M.)
| | - Michelangelo Fiorentino
- Department of Pathology, University of Bologna, 40138 Bologna, Italy; (F.G.); (T.F.); (E.G.); (A.A.); (E.C.)
- Correspondence: ; Tel.: +39-051-317-2114
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32
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Deng FM, Zhai QJ. Application of Immunohistochemistry in Diagnosis of Renal Cell Neoplasms. KIDNEY CANCER 2020. [DOI: 10.1007/978-3-030-28333-9_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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33
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New and Emerging Subtypes of Renal Cell Carcinoma. KIDNEY CANCER 2020. [DOI: 10.1007/978-3-030-28333-9_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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34
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Lin X, Goyal R, Yang XJ. Pathologic characterization of renal epithelial neoplasms arising in nonfunctioning kidneys. Hum Pathol 2019; 97:1-7. [PMID: 31857138 DOI: 10.1016/j.humpath.2019.09.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 09/17/2019] [Accepted: 09/19/2019] [Indexed: 11/18/2022]
Abstract
Nonfunctioning kidneys secondary to various etiologies display different histopathological features. Studies focused on incidence and types of renal neoplasms using the new World Health Organization and International Society of Urological Pathology classification system in various types of nonfunctioning kidneys are very limited. We identified 311 nephrectomies of nonfunctioning kidneys and categorized them into 5 categories: acquired cystic kidney disease (ACKD, n = 61); end-stage renal disease, nonspecific (ESRD, n = 63); adult polycystic kidney disease (APKD, n = 49); failed transplant kidney (FTK, n = 96); and those caused by obstructive conditions in the kidney (OCK, n = 42). ACKD (70%) and ESRD (43%) had higher cancer incidences than the other 3 groups (APKD = 2%, FTK = 0%, and OCK = 5%). Besides clear cell renal cell carcinoma (RCC) and papillary RCC, clear cell papillary RCC had a much higher incidence within ACKD patients (13/61) compared to other groups. ACKD-associated RCC was only identified in ACKD patients. ACKD patients had significantly longer dialysis duration compared to ESRD, APKD, and FTK. Although they had similar risk for clear cell RCC and papillary RCC, ACKD patients had a much higher risk for ACKD-associated RCC and clear cell papillary RCC than ESRD patients. Although most RCCs arising in these nonfunctioning kidneys were early pT1 stage, 6 ACKD patients and 3 ESRD patients had higher-stage diseases, which can be fatal if not treated appropriately. Therefore, precise clinicopathological classification of these nonfunctioning kidneys is important for predicting kidney cancer risk. These results indicate the need for active monitoring of the patients with high-risk nonfunctioning kidney diseases and appropriate surgical treatment when necessary.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Carcinoma, Renal Cell/epidemiology
- Carcinoma, Renal Cell/pathology
- Carcinoma, Renal Cell/physiopathology
- Carcinoma, Renal Cell/surgery
- Female
- Humans
- Incidence
- Kidney Diseases, Cystic/epidemiology
- Kidney Diseases, Cystic/pathology
- Kidney Diseases, Cystic/physiopathology
- Kidney Diseases, Cystic/therapy
- Kidney Failure, Chronic/epidemiology
- Kidney Failure, Chronic/pathology
- Kidney Failure, Chronic/physiopathology
- Kidney Failure, Chronic/therapy
- Kidney Neoplasms/epidemiology
- Kidney Neoplasms/pathology
- Kidney Neoplasms/physiopathology
- Kidney Neoplasms/surgery
- Kidney Transplantation
- Male
- Middle Aged
- Nephrectomy
- Polycystic Kidney Diseases/epidemiology
- Polycystic Kidney Diseases/pathology
- Polycystic Kidney Diseases/physiopathology
- Polycystic Kidney Diseases/therapy
- Prognosis
- Renal Dialysis
- Risk Assessment
- Risk Factors
- Treatment Failure
- Young Adult
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Affiliation(s)
- Xiaoqi Lin
- Department of Pathology, Northwestern University, Chicago, IL 60611
| | - Rajen Goyal
- Department of Pathology, Northwestern University, Chicago, IL 60611
| | - Ximing J Yang
- Department of Pathology, Northwestern University, Chicago, IL 60611.
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Clear Cell Papillary Renal Cell Carcinoma: A Recent Entity With Distinct Imaging Patterns. AJR Am J Roentgenol 2019; 214:579-587. [PMID: 31770020 DOI: 10.2214/ajr.19.21681] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
OBJECTIVE. Clear cell papillary renal cell carcinoma (RCC), an entity with strikingly indolent behavior, recently was added to the World Health Organization classification of renal tumors and represents the fourth most common histologic type of renal cell carcinoma. This article aims to describe the imaging features of clear cell papillary RCC along with its clinical and pathologic characteristics. MATERIALS AND METHODS. This retrospective study consisted of 27 patients with 44 clear cell papillary RCC tumors. The inclusion criteria were a pathologically proven clear cell papillary RCC and the availability of preoperative imaging including at least CT or MRI. Two experienced radiologists performed the imaging analysis independently. RESULTS. Patients (mean age, 62 years old) presented with renal failure in 26% of cases, and four had a tumor-predisposing disease. Multiple clear cell papillary RCC tumors occurred in 5 of the 27 patients. Two imaging patterns were recognizable. Solid clear cell papillary RCC (n = 23, 52%) presented as heterogeneous tumors with minor cystic changes (74%) and rarely exhibited calcifications (10%). All solid tumors showed hyperintensity on T2-weighted images compared with renal cortex and maximal enhancement on corticomedullary phase with a delayed washout. Cystic clear cell papillary RCC (n = 21, 48%) were classified as Bosniak IV (57%), III (33%), or IIF (10%), with a predominant unilocular pattern (76%). Pathologic stage according to TNM classification was mostly pT1a and low grade on nucleolar grade. All patients were alive at the date of last follow-up after treatment with no metastasis or recurrence. CONCLUSION. Clear cell papillary RCC exhibits two imaging patterns including cystic and solid in almost equal proportion. Imaging characteristics of solid clear cell papillary RCC including high signal T2 intensity and early arterial enhancement are unexpectedly distinct from papillary RCC and very similar to clear cell RCC.
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37
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Williamson SR. Renal cell carcinomas with a mesenchymal stromal component: what do we know so far? Pathology 2019; 51:453-462. [DOI: 10.1016/j.pathol.2019.04.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 04/16/2019] [Accepted: 04/28/2019] [Indexed: 02/07/2023]
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38
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Patel S, Asarian A, Xiao P. Clear cell papillary renal cell carcinoma: a case report and literature review. J Surg Case Rep 2019; 2019:rjz177. [PMID: 31249659 PMCID: PMC6581136 DOI: 10.1093/jscr/rjz177] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 05/11/2019] [Accepted: 06/03/2019] [Indexed: 12/13/2022] Open
Abstract
Clear cell papillary renal cell carcinoma (CCPRCC), a type of low-grade renal cell neoplasm was recently included in the 2016 WHO classification of renal tumors (Tickoo SK, dePeralta-Venturina Mariza N, Harik LR, Worcester Heath D, Salama ME, Young AN et al. Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia. Am J Surg Pathol 30:141–153, 2006). While being recognized as its own entity, there is little research on CCPRCC. The specific tumor comprises of 9.3% of all renal tumors in young adults with an age range of 18-88 years (Wang Y, Ding Y, Wang J, Gu M, Wang Z, Qin C et al. Clinical features and survival of clear cell papillary renal cell carcinoma: 10-year retrospective study from two institutions. Oncology letters 16:1010–22, 2018.). In this article we provide recent understanding of CCPRCC and how to identify its distinct pathological entity. It is strongly positive for cytokeratin 7 (CK7), vimentin and mostly negative for CD10 and AMACR (Zhanyong B and John TE Clear cell papillary renal cell carcinoma in bilateral native kidneys after 2 year of renal transplantation: report of a case and review of literature. Case Reports in Transplantation 2011:11–4, 2011). Histopathologically, all cases of CCPRCC exhibited a tubular and papillary architecture, cuboidal tumor cells with clear cytoplasm and low Fuhrman grade (Wang Y, Ding Y, Wang J, Gu M, Wang Z, Qin C et al. Clinical features and survival of clear cell papillary renal cell carcinoma: 10-year retrospective study from two institutions. Oncology letters 16:1010–22, 2018; Kuroda N, Ohe C, Kawakami F, Mikami S, Furuya M, Matsuura K et al. Clear cell papillary renal cell carcinoma: a review. Int J Clin Exp Pathol 7: 7312–18, 2004.; Srigley JR, Delahunt B, Eble JN, Egevad L, Epstein JI, Grignon D, et al. The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia. Am J surg Pathol. 37:1469–89, 2013). This case report and literature review highlights the cryptomorphic, immunohistochemical and cytogenic features of CCPRCC which will assist in understanding and managing these tumors.
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Affiliation(s)
- Simmi Patel
- St George's University School of Medicine, True Blue, Grenada, WI, USA
| | - Armand Asarian
- Department of Surgery, The Brooklyn Hospital Center, Icahn School of Medicine at Mount Sinai, Brooklyn, NY, USA
| | - Philip Xiao
- Department of Pathology, The Brooklyn Hospital Center, Icahn School of Medicine at Mount Sinai, Brooklyn, NY, USA
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Diaz de Leon A, Pirasteh A, Costa DN, Kapur P, Hammers H, Brugarolas J, Pedrosa I. Current Challenges in Diagnosis and Assessment of the Response of Locally Advanced and Metastatic Renal Cell Carcinoma. Radiographics 2019; 39:998-1016. [PMID: 31199711 DOI: 10.1148/rg.2019180178] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Locally advanced and metastatic renal cell carcinoma (RCC) present a specific set of challenges to the radiologist. The detection of metastatic disease is confounded by the ability of RCC to metastasize to virtually any part of the human body long after surgical resection of the primary tumor. This includes sites not commonly included in routine surveillance, which come to light after the patient becomes symptomatic. In the assessment of treatment response, the phenomenon of tumor heterogeneity, where clone selection through systemic therapy drives the growth of potentially more aggressive phenotypes, can result in oligoprogression despite overall disease control. Finally, advances in therapy have resulted in the development of immuno-oncologic agents that may result in changes that are not adequately evaluated with conventional size-based response criteria and may even be misinterpreted as progression. This article reviews the common challenges a radiologist may encounter in the evaluation of patients with locally advanced and metastatic RCC. ©RSNA, 2019.
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Affiliation(s)
- Alberto Diaz de Leon
- From the Department of Radiology (A.D.d.L., A.P., D.N.C., I.P.), Advanced Imaging Research Center (D.N.C., I.P.), Department of Pathology (P.K.), Department of Urology (P.K.), Kidney Cancer Program-Simmons Comprehensive Cancer Center (P.K., H.H., J.B., I.P.), and Department of Internal Medicine (H.H., J.B.), UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
| | - Ali Pirasteh
- From the Department of Radiology (A.D.d.L., A.P., D.N.C., I.P.), Advanced Imaging Research Center (D.N.C., I.P.), Department of Pathology (P.K.), Department of Urology (P.K.), Kidney Cancer Program-Simmons Comprehensive Cancer Center (P.K., H.H., J.B., I.P.), and Department of Internal Medicine (H.H., J.B.), UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
| | - Daniel N Costa
- From the Department of Radiology (A.D.d.L., A.P., D.N.C., I.P.), Advanced Imaging Research Center (D.N.C., I.P.), Department of Pathology (P.K.), Department of Urology (P.K.), Kidney Cancer Program-Simmons Comprehensive Cancer Center (P.K., H.H., J.B., I.P.), and Department of Internal Medicine (H.H., J.B.), UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
| | - Payal Kapur
- From the Department of Radiology (A.D.d.L., A.P., D.N.C., I.P.), Advanced Imaging Research Center (D.N.C., I.P.), Department of Pathology (P.K.), Department of Urology (P.K.), Kidney Cancer Program-Simmons Comprehensive Cancer Center (P.K., H.H., J.B., I.P.), and Department of Internal Medicine (H.H., J.B.), UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
| | - Hans Hammers
- From the Department of Radiology (A.D.d.L., A.P., D.N.C., I.P.), Advanced Imaging Research Center (D.N.C., I.P.), Department of Pathology (P.K.), Department of Urology (P.K.), Kidney Cancer Program-Simmons Comprehensive Cancer Center (P.K., H.H., J.B., I.P.), and Department of Internal Medicine (H.H., J.B.), UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
| | - James Brugarolas
- From the Department of Radiology (A.D.d.L., A.P., D.N.C., I.P.), Advanced Imaging Research Center (D.N.C., I.P.), Department of Pathology (P.K.), Department of Urology (P.K.), Kidney Cancer Program-Simmons Comprehensive Cancer Center (P.K., H.H., J.B., I.P.), and Department of Internal Medicine (H.H., J.B.), UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
| | - Ivan Pedrosa
- From the Department of Radiology (A.D.d.L., A.P., D.N.C., I.P.), Advanced Imaging Research Center (D.N.C., I.P.), Department of Pathology (P.K.), Department of Urology (P.K.), Kidney Cancer Program-Simmons Comprehensive Cancer Center (P.K., H.H., J.B., I.P.), and Department of Internal Medicine (H.H., J.B.), UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
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40
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Chen C, Fang H, Jiao Y, Zhou Y, Guo Q, Lv Z. Clinical Efficacy and Complication Rate of Sunitinib 2/1 Versus 4/2 Schedule for the Treatment of Metastatic Renal Cell Cancer: A Systematic Review and Meta-Analysis. Clin Genitourin Cancer 2019; 17:319-331. [PMID: 31371223 DOI: 10.1016/j.clgc.2019.06.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 05/26/2019] [Accepted: 06/03/2019] [Indexed: 12/24/2022]
Abstract
The treatment of renal cell carcinoma has achieved certain curative effects with the innovation of clinical drugs, such as sunitinib. However, the clinical efficacy and complication rate of the sunitinib 2/1 and 4/2 schedule in metastatic renal cell cancer remain unclear. In this study we aimed to resolve this issue by using meta-analysis to provide more theoretical guidance for clinical use. Several outcome measurements were included in this study to compare the 2 schedules such as complete response, partial response, stable disease, progressive disease, progression-free survival, overall survival, and complications. In the contrast analysis, the sunitinib 2/1 and 4/2 schedule resulted in significant improvements in prognosis. However, the sunitinib 2/1 schedule was superior to the 4/2 schedule in terms of controlling stable disease and causing fewer complications.
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Affiliation(s)
- Chenglong Chen
- Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, P.R. China
| | - Huan Fang
- Urology Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, P.R. China
| | - Yurui Jiao
- Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, P.R. China
| | - Yi Zhou
- First Clinical Medical School of Southern Medical University, Guangzhou, P.R. China
| | - Qiang Guo
- Urology Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, P.R. China
| | - Zhi Lv
- Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, P.R. China.
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41
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Robila V, Kraft AO, Smith SC. New entities, new technologies, new findings: A review of the cytologic features of recently established subtypes of renal cell carcinoma. Cancer Cytopathol 2019; 127:79-97. [PMID: 30690877 DOI: 10.1002/cncy.22093] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 11/08/2018] [Accepted: 11/26/2018] [Indexed: 02/06/2023]
Abstract
Several new renal tumor types with distinctive pathologic, epidemiologic, and genetic signatures have recently been adopted in the fourth edition of the World Health Organization classification. In succeeding years, the cytologic features of most of these new types have been described, adding to the trend of increasing diagnostic accuracy for most common renal cell carcinoma subtypes and the important diagnostic role of cytologic sampling in the management and personalization of therapy. The current article reviews the cytologic findings from these recently established renal cell carcinoma subtypes. Emphasis is placed on cytologic diagnostic clues, confirmatory ancillary testing, salient differential diagnoses, and challenges that can be encountered in an attempt to render accurate interpretations in small samples.
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Affiliation(s)
- Valentina Robila
- Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Adele O Kraft
- Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Steven Christopher Smith
- Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.,Division of Urology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia
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42
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Abstract
Clear cell papillary renal cell carcinoma (ccpRCC) is a recently recognized entity and represents the fourth most common variant of renal cell carcinoma (RCC). It has unique morphologic and immunohistochemical features and demonstrates an indolent clinical behavior. Microscopically, it may mimic other RCCs with clear cell features, such as clear cell RCC, translocation RCC, and papillary RCC with clear cell changes. A high index of suspicion is required to keep ccpRCC in the differential diagnosis of RCCs with features of clear cell and/or papillary architecture. In equivocal cases, immunohistochemistry is generally sufficient to substantiate the diagnosis of ccpRCC. In this review, we discuss the clinical, gross, and histopathologic features, immunohistochemical and genetic profiling, and prognosis of ccpRCC.
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Affiliation(s)
- Jianping Zhao
- From the Department of Pathology, University of Texas Medical Branch, Galveston
| | - Eduardo Eyzaguirre
- From the Department of Pathology, University of Texas Medical Branch, Galveston
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43
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Kim SH, Kwon WA, Joung JY, Seo HK, Lee KH, Chung J. Clear cell papillary renal cell carcinoma: A case report and review of the literature. World J Nephrol 2018; 7:155-160. [PMID: 30596034 PMCID: PMC6305527 DOI: 10.5527/wjn.v7.i8.155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 10/29/2018] [Accepted: 11/08/2018] [Indexed: 02/06/2023] Open
Abstract
Clear cell papillary renal cell carcinoma (ccpRCC) was recently established as a distinct type of epithelial neoplasm by the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. Here, we report a case of partial nephrectomy for a ccpRCC detected during the routine follow-up of a previously treated liposarcoma in a 70-year-old male patient. The patient was referred to the urology department for a right-sided renal mass (size: 2 cm) detected during routine annual imaging follow-up for a malignant right inguinal fibrous histocytoma and liposarcoma that had been diagnosed 6 and 4 years earlier, respectively, and treated with surgery and adjuvant radiation therapy. Following partial nephrectomy, the renal mass was pathologically diagnosed as ccpRCC, and immunohistochemistry revealed carbonic anhydrase 9 (CA9) expression. No recurrences or metastases were detected on follow-up imaging for 6 months. This is the first report of partial nephrectomy for incidentally discovered CA9-positive ccpRCC.
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Affiliation(s)
- Sung Han Kim
- Department of Urology, Center for Prostate Cancer, National Cancer Center, Goyang 410-769, South Korea
| | - Whi-An Kwon
- Department of Urology, Center for Prostate Cancer, National Cancer Center, Goyang 410-769, South Korea
| | - Jae Young Joung
- Department of Urology, Center for Prostate Cancer, National Cancer Center, Goyang 410-769, South Korea
| | - Ho Kyung Seo
- Department of Urology, Center for Prostate Cancer, National Cancer Center, Goyang 410-769, South Korea
| | - Kang Hyun Lee
- Department of Urology, Center for Prostate Cancer, National Cancer Center, Goyang 410-769, South Korea
| | - Jinsoo Chung
- Department of Urology, Center for Prostate Cancer, National Cancer Center, Goyang 410-769, South Korea
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44
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Andeen NK, Qu X, Antic T, Tykodi SS, Fang M, Tretiakova MS. Clinical Utility of Chromosome Genomic Array Testing for Unclassified and Advanced-Stage Renal Cell Carcinomas. Arch Pathol Lab Med 2018; 143:494-504. [DOI: 10.5858/arpa.2018-0104-oa] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Context.—
Cytogenomic analysis provides a useful adjunct to traditional pathology in the categorization of renal cell carcinomas (RCCs), particularly in morphologically ambiguous cases, but it has disadvantages, including cost.
Objective.—
To define the clinical scenarios in which this technology has direct clinical applications.
Design.—
DNA was isolated from paraffin-embedded tissue from 40 selected cases of RCC. Chromosome genomic array testing was performed using the OncoScan.
Results.—
Of 23 cases of unclassified renal tumors, 19 (83%) were reclassified with incorporation of cytogenetic and histologic features, including 10 as clear cell RCC, 2 as collecting duct carcinoma, 2 as papillary RCC, and 1 as novel TFEB-amplified tumor lacking TFEB translocation. Of 5 tumors with “hybrid” oncocytic features, 3 were reclassified as an eosinophilic variant of chromophobe RCC and 1 as oncocytoma. Appropriate staging in 2 patients was determined by identifying distinct, nonshared cytogenetic profiles. Of 11 cases of metastatic clear cell RCC, 7 (63%) had cytogenetic features associated with a poor prognosis.
Conclusions.—
We identified 5 scenarios in which chromosome genomic array testing has direct clinical utility: (1) to investigate unclassified RCCs, (2) to understand tumors with “hybrid” features and “collision” tumors, (3) to determine appropriate staging in questions of bilateral tumors and/or metastases, (4) to identify chromosomal aberrations in metastatic clear cell RCCs associated with a worse prognosis, and (5) to identify new entities. This has practical value in our institution, where a molecular profile diagnostically separating morphologically difficult to classify clear cell, papillary, chromophobe, and unclassified RCC influences treatment recommendations and clinical trial eligibility.
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Affiliation(s)
- Nicole K. Andeen
- From the Department of Pathology, University of Washington, Seattle (Drs Andeen and Tretiakova); the Department of Pathology, Oregon Health & Science University, Portland (Dr Andeen); Cytogenetics, Seattle Cancer Care Alliance, Seattle, Washington (Dr Qu); the Department of Pathology, University of Chicago, Chicago, Illinois (Dr Antic); and the Division of Medical Oncology, Department of Medicine
| | - Xiaoyu Qu
- From the Department of Pathology, University of Washington, Seattle (Drs Andeen and Tretiakova); the Department of Pathology, Oregon Health & Science University, Portland (Dr Andeen); Cytogenetics, Seattle Cancer Care Alliance, Seattle, Washington (Dr Qu); the Department of Pathology, University of Chicago, Chicago, Illinois (Dr Antic); and the Division of Medical Oncology, Department of Medicine
| | - Tatjana Antic
- From the Department of Pathology, University of Washington, Seattle (Drs Andeen and Tretiakova); the Department of Pathology, Oregon Health & Science University, Portland (Dr Andeen); Cytogenetics, Seattle Cancer Care Alliance, Seattle, Washington (Dr Qu); the Department of Pathology, University of Chicago, Chicago, Illinois (Dr Antic); and the Division of Medical Oncology, Department of Medicine
| | - Scott S. Tykodi
- From the Department of Pathology, University of Washington, Seattle (Drs Andeen and Tretiakova); the Department of Pathology, Oregon Health & Science University, Portland (Dr Andeen); Cytogenetics, Seattle Cancer Care Alliance, Seattle, Washington (Dr Qu); the Department of Pathology, University of Chicago, Chicago, Illinois (Dr Antic); and the Division of Medical Oncology, Department of Medicine
| | - Min Fang
- From the Department of Pathology, University of Washington, Seattle (Drs Andeen and Tretiakova); the Department of Pathology, Oregon Health & Science University, Portland (Dr Andeen); Cytogenetics, Seattle Cancer Care Alliance, Seattle, Washington (Dr Qu); the Department of Pathology, University of Chicago, Chicago, Illinois (Dr Antic); and the Division of Medical Oncology, Department of Medicine
| | - Maria S. Tretiakova
- From the Department of Pathology, University of Washington, Seattle (Drs Andeen and Tretiakova); the Department of Pathology, Oregon Health & Science University, Portland (Dr Andeen); Cytogenetics, Seattle Cancer Care Alliance, Seattle, Washington (Dr Qu); the Department of Pathology, University of Chicago, Chicago, Illinois (Dr Antic); and the Division of Medical Oncology, Department of Medicine
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Tsuzuki T, Iwata H, Murase Y, Takahara T, Ohashi A. Renal tumors in end-stage renal disease: A comprehensive review. Int J Urol 2018; 25:780-786. [DOI: 10.1111/iju.13759] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 06/25/2018] [Indexed: 12/14/2022]
Affiliation(s)
- Toyonori Tsuzuki
- Department of Surgical Pathology; Aichi Medical University Hospital; Nagakute Aichi Japan
| | - Hidehiro Iwata
- Department of Surgical Pathology; Aichi Medical University Hospital; Nagakute Aichi Japan
- Department of Pathology; Japanese Red Cross Nagoya Daini Hospital; Nagoya Aichi Japan
| | - Yota Murase
- Department of Surgical Pathology; Aichi Medical University Hospital; Nagakute Aichi Japan
- Department of Pathology; Japanese Red Cross Nagoya Daini Hospital; Nagoya Aichi Japan
| | - Taishi Takahara
- Department of Surgical Pathology; Aichi Medical University Hospital; Nagakute Aichi Japan
| | - Akiko Ohashi
- Department of Surgical Pathology; Aichi Medical University Hospital; Nagakute Aichi Japan
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Wang Y, Ding Y, Qin C, Gu M, Wang Z, Han C, Liu X, Li H, Hua H. Expression of vitamin D receptor in clear cell papillary renal cell carcinoma. Ann Diagn Pathol 2018; 36:1-4. [PMID: 29966830 DOI: 10.1016/j.anndiagpath.2018.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Revised: 05/17/2018] [Accepted: 06/20/2018] [Indexed: 12/31/2022]
Abstract
Clear cell papillary renal cell carcinoma (ccpRCC) is a recently recognized subtype of renal cell carcinoma. In this study, we investigated the clinicopathological and immunohistochemical features in a group of 26 cases of ccpRCC, with a special emphasis on the expression of vitamin D receptor (VDR). The mean age of patients was 53.3 years (range 36-74 years), and the mean tumor size was 2.5 cm (range 0.5 to 6.5 cm). During follow-up (range 12-121 months, median 50 months), no recurrence or metastasis was observed. Histopathologically, all cases of ccpRCC exhibited a tubular and papillary architecture, covered by tumor cells with clear cytoplasm. Immunohistochemistry showed intermediate (5/26, 19%) to diffuse (21/26, 81%) and moderate (2/26, 8%) to strong (24/26, 92%) membranous staining for VDR in each case. All cases (26/26, 100%) were diffuse and strong cytoplasmic and fibrillar staining for cytokeratin 7 (CK7), but negative forα-methylacyl-CoA-racemase (AMACR). Each case showed diffuse (26/26, 100%) and moderate (4/26, 15%) to strong (22/26, 85%) membranous staining for carbonic anhydrase IX (CA IX). In addition, the majority of cases showed negative for cluster of differentiation 10 (CD10) (20/26, 77%) and renal cell carcinoma maker (RCC-Ma) (24/26, 92%). This unique staining pattern is helpful for distinguishing ccpRCC from its mimics. Furthermore, VDR positive expression suggests that ccpRCC originates from the precursor epithelium of distal nephron.
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Affiliation(s)
- Yiqiu Wang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Surgical Oncology, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, China
| | - Ying Ding
- Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chao Qin
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Min Gu
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
| | - Zengjun Wang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Conghui Han
- Department of Urology, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, China
| | - Xia Liu
- Department of Pathology, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, China
| | - Hongxia Li
- Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hongjin Hua
- Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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47
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Wang Y, Ding Y, Wang J, Gu M, Wang Z, Qin C, Han C, Li H, Liu X, Wu P, Li G. Clinical features and survival analysis of clear cell papillary renal cell carcinoma: A 10-year retrospective study from two institutions. Oncol Lett 2018; 16:1010-1022. [PMID: 29963177 PMCID: PMC6019899 DOI: 10.3892/ol.2018.8752] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Accepted: 05/15/2018] [Indexed: 12/16/2022] Open
Abstract
Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized subtype of renal cell carcinoma entity, however, little is known about its clinical features. In the present study, 26 cases of CCPRCC were screened out from two institutions. The patient data, tissue pathology, immunohistochemical phenotype, computed tomographic images and survival analysis were studied. The mean age was 53.3 years and the average tumor size was 2.5 cm. A total of 17 patients' body mass indexes were higher than the normal level. A total of 11 patients had hypertension and 6 patients had a smoking history. Histopathologically, all cases of CCPRCC exhibited a tubular and papillary architecture, small to medium-sized cuboidal tumor cells with clear cytoplasms, and a low Fuhrman nuclear grade. All tumors were encapsulated by variably thick fibrous capsules. Immunohistochemistry showed diffuse and moderate to strong cytoplasmic staining for CK7, CA IX and vimentin, but negative for AMACR and CD10 (sometimes focally positive) in all cases. According to the results of Ki67 labeling index, the expression of Ki67 in CCPRCC was much lower than that in clear cell renal cell carcinoma (CCRCC) (2.19 vs. 7.07%, P<0.001) and that in papillary renal cell carcinoma (PRCC) (2.19 vs. 6.65%, P<0.001). Radiographically, the tumors were shown as small masses with smooth contour and mixed enhancement pattern. The multiphasic attenuation curve for CCPRCC, like that for CCRCC, increased in the corticomedullary phase markedly and decreased in the nephrographic phase and excretory phase gradually. At a median follow-up period of 50 months, no cancer-specific death or tumor recurrence was observed. Considering the favorable prognosis of CCPRCC, preoperative biopsy in order to make clear the diagnosis is particularly important. In light of the present findings, partial nephrectomy for patients with CCPRCC is recommended. If the patients cannot tolerate surgery, closed monitoring or radiofrequency ablation may be considered.
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Affiliation(s)
- Yiqiu Wang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.,Department of Surgical Oncology, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P.R. China
| | - Ying Ding
- Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Jian Wang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Min Gu
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Zengjun Wang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Chao Qin
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Conghui Han
- Department of Urology, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P.R. China
| | - Hongxia Li
- Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Xia Liu
- Department of Pathology, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P.R. China
| | - Pengfei Wu
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Guangchao Li
- Department of Radiology, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P.R. China
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48
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Nouhaud FX, Bernhard JC, Bigot P, Khene ZE, Audenet F, Lang H, Bergerat S, Fraisse G, Grenier N, Cornelis F, Nedelcu C, Béjar S, Fromont-Hankard G, Allory Y, Lindner V, Verkarre V, Daniel L, Yacoub M, Correas JM, Méjean A, Rioux-Leclercq N, Bensalah K. Contemporary assessment of the correlation between Bosniak classification and histological characteristics of surgically removed atypical renal cysts (UroCCR-12 study). World J Urol 2018; 36:1643-1649. [PMID: 29730837 DOI: 10.1007/s00345-018-2307-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 04/24/2018] [Indexed: 12/30/2022] Open
Abstract
PURPOSE To evaluate and compare pathological characteristics of renal cysts Bosniak IIF, III and IV in light of recent histological classification. PATIENTS AND METHODS The French research network for kidney cancer UroCCR conducted a multicentre study on patients treated surgically for a renal cyst between 2007 and 2016. Independent radiological and centralized pathological reviews were performed for every patient. Pathological characteristics were compared to the Bosniak classification. RESULTS Of a total 216 patients included, 175 (81.0%) tumours (90.9% of Bosniak IV, 69.8% of Bosniak III) were malignant or had a low malignant potential, with 60% of clear cell renal cell carcinoma (CCRCC), 24% of papillary RCC (PRCC) and 6.9% of multilocular cystic renal tumour of low malignant potential (MCRTLMP). Malignancies were mostly of low pT stage (86.4% of pT1-2), and low ISUP grade (68.0% of 1-2). Bosniak III cysts had a lower rate of CCRCC (46.7 vs. 67.3%), higher rate of PRCC (30 vs. 20.9%) and MCRTLMP (18.3 vs. 0.9%) compared to Bosniak IV (p < 0.001). Low-malignant potential lesions were less likely Bosniak IV and pT3-4 stage was more frequent in Bosniak IV vs. III (15.7 vs. 3.5%; p = 0.04). There were two recurrences (1.1%) and no cancer-related death occurred during follow-up. CONCLUSION These results confirmed that cystic renal malignancies have excellent prognosis. Bosniak III cysts had a low malignant potential, which suggests surveillance could be an option for these lesions.
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Affiliation(s)
| | | | - Pierre Bigot
- Department of Urology, Angers University Hospital, Angers, France
| | | | - François Audenet
- Department of Urology, European Georges Pompidou Hospital, APHP, Paris, France
| | - Herve Lang
- Department of Urology, Strasbourg University Hospital, Strasbourg, France
| | - Sebastien Bergerat
- Department of Urology, Strasbourg University Hospital, Strasbourg, France
| | - Guillaume Fraisse
- Department of Urology, European Georges Pompidou Hospital, APHP, Paris, France
| | - Nicolas Grenier
- Department of Radiology, Bordeaux University Hospital, Bordeaux, France
| | - François Cornelis
- Department of Radiology, Bordeaux University Hospital, Bordeaux, France
| | - Cosmina Nedelcu
- Department of Radiology, Angers Urology Hospital, Angers, France
| | - Sofiane Béjar
- Department of Radiology, Rouen University Hospital, Rouen, France
| | | | - Yves Allory
- Department of Pathology, Henry Mondor University Hospital, APHP, Créteil, France
| | - Véronique Lindner
- Department of Pathology, Strasbourg University Hospital, Strasbourg, France
| | - Virginie Verkarre
- Department of Pathology, European Georges Pompidou Hospital, APHP, Paris, France
| | - Laurent Daniel
- Department of Pathology, Timone University Hospital, APHM, Marseille, France
| | - Mokrane Yacoub
- Department of Pathology, Bordeaux University Hospital, Bordeaux, France
| | - Jean-Michel Correas
- Department of Radiology, European Georges Pompidou Hospital, APHP, Paris, France
| | - Arnaud Méjean
- Department of Urology, European Georges Pompidou Hospital, APHP, Paris, France
| | | | - Karim Bensalah
- Department of Urology, Rennes University Hospital, Rennes, France
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49
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Favazza L, Chitale DA, Barod R, Rogers CG, Kalyana-Sundaram S, Palanisamy N, Gupta NS, Williamson SR. Renal cell tumors with clear cell histology and intact VHL and chromosome 3p: a histological review of tumors from the Cancer Genome Atlas database. Mod Pathol 2017; 30:1603-1612. [PMID: 28731045 DOI: 10.1038/modpathol.2017.72] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Revised: 05/17/2017] [Accepted: 05/20/2017] [Indexed: 02/07/2023]
Abstract
Clear cell renal cell carcinoma is by far the most common form of kidney cancer; however, a number of histologically similar tumors are now recognized and considered distinct entities. The Cancer Genome Atlas published data set was queried (http://cbioportal.org) for clear cell renal cell carcinoma tumors lacking VHL gene mutation and chromosome 3p loss, for which whole-slide images were reviewed. Of the 418 tumors in the published Cancer Genome Atlas clear cell renal cell carcinoma database, 387 had VHL mutation, copy number loss for chromosome 3p, or both (93%). Of the remaining, 27/31 had whole-slide images for review. One had 3p loss based on karyotype but not sequencing, and three demonstrated VHL promoter hypermethylation. Nine could be reclassified as distinct or emerging entities: translocation renal cell carcinoma (n=3), TCEB1 mutant renal cell carcinoma (n=3), papillary renal cell carcinoma (n=2), and clear cell papillary renal cell carcinoma (n=1). Of the remaining, 6 had other clear cell renal cell carcinoma-associated gene alterations (PBRM1, SMARCA4, BAP1, SETD2), leaving 11 specimens, including 2 high-grade or sarcomatoid renal cell carcinomas and 2 with prominent fibromuscular stroma (not TCEB1 mutant). One of the remaining tumors exhibited gain of chromosome 7 but lacked histological features of papillary renal cell carcinoma. Two tumors previously reported to harbor TFE3 gene fusions also exhibited VHL mutation, chromosome 3p loss, and morphology indistinguishable from clear cell renal cell carcinoma, the significance of which is uncertain. In summary, almost all clear cell renal cell carcinomas harbor VHL mutation, 3p copy number loss, or both. Of tumors with clear cell histology that lack these alterations, a subset can now be reclassified as other entities. Further study will determine whether additional entities exist, based on distinct genetic pathways that may have implications for treatment.
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Affiliation(s)
- Laura Favazza
- Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, MI, USA
| | - Dhananjay A Chitale
- Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, MI, USA.,Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA.,Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Ravi Barod
- Vattikutti Urology Institute, Henry Ford Health System, Detroit, MI, USA
| | - Craig G Rogers
- Vattikutti Urology Institute, Henry Ford Health System, Detroit, MI, USA
| | | | - Nallasivam Palanisamy
- Vattikutti Urology Institute, Henry Ford Health System, Detroit, MI, USA.,Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Nilesh S Gupta
- Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, MI, USA
| | - Sean R Williamson
- Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, MI, USA.,Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA.,Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA
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50
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Inamura K. Renal Cell Tumors: Understanding Their Molecular Pathological Epidemiology and the 2016 WHO Classification. Int J Mol Sci 2017; 18:E2195. [PMID: 29053609 PMCID: PMC5666876 DOI: 10.3390/ijms18102195] [Citation(s) in RCA: 108] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 10/14/2017] [Accepted: 10/17/2017] [Indexed: 02/06/2023] Open
Abstract
Accumulating evidence suggests that renal cell tumors represent a group of histologically and molecularly heterogeneous diseases, even within the same histological subtype. In accordance with the increased understanding of the morphological, immunohistochemical, molecular, and epidemiological characteristics of renal cell tumors, the World Health Organization (WHO) classification of renal cell tumors has been modified. This review provides perspectives on both new and current subtypes of renal cell tumors, as well as on the emerging/provisional renal cell carcinomas in the new 2016 WHO classification, which focuses on features of their molecular pathological epidemiology. The WHO classification will require additional revisions to enable the classification of renal cell tumors as clinically meaningful subtypes and provide a better understanding of the unique characteristics of renal cell tumors.
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Affiliation(s)
- Kentaro Inamura
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
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