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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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MESH Headings
- Humans
- Kidney Neoplasms/pathology
- Kidney Neoplasms/classification
- Kidney Neoplasms/diagnosis
- Carcinoma, Renal Cell/pathology
- Carcinoma, Renal Cell/classification
- Carcinoma, Renal Cell/diagnosis
- Biomarkers, Tumor/genetics
- Diagnosis, Differential
- Adenoma, Oxyphilic/pathology
- Adenoma, Oxyphilic/diagnosis
- Adenoma, Oxyphilic/classification
- Carcinoma, Papillary/pathology
- Carcinoma, Papillary/classification
- Carcinoma, Papillary/diagnosis
- Tumor Suppressor Proteins
- Ubiquitin Thiolesterase
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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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Yang X, Liu Y, Wang H, Xu Y, Zhang H, Zhao M, Luo X, Jin H, Xiong J, Tao L, Xu J, Zhou L, Li X, Xu H, Dong L, Wang C. Fumarate Hydratase-Deficient Renal Cell Carcinoma With Predominant Tubulocystic Features Mimics Tubulocystic Renal Cell Carcinoma. Arch Pathol Lab Med 2024; 148:1358-1364. [PMID: 38390749 DOI: 10.5858/arpa.2023-0330-oa] [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: 12/11/2023] [Indexed: 02/24/2024]
Abstract
CONTEXT.— Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) rarely exhibits a predominant tubulocystic architecture with few other components. RCC with pure tubules and cysts lined by eosinophilic tumor cells with prominent nucleoli would raise the diagnosis of tubulocystic RCC. It is important to differentiate the 2 entities because they lead to different outcomes. OBJECTIVE.— To address this concern, a multicenter study was implemented to explore useful clinicopathologic features in differentiation between tubulocystic FH-deficient RCC and tubulocystic RCC. DESIGN.— Clinical factors included age, sex, tumor size, and outcome. Morphologic factors included cell morphology, presence or absence of a nontubulocystic component, and stromal findings. Immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing were performed to explore the protein expression and molecular profiles of the 2 entities. RESULTS.— We evaluated 6 patients with tubulocystic RCC and 10 patients with tubulocystic FH-deficient RCC. Tubulocystic RCC exhibited a small size (<4.0 cm, pT1a), low Ki-67 index (<5%), retained FH, and negative 2SC expression. Tubulocystic FH-deficient RCC had a relatively large size and a high Ki-67 index. Perinucleolar haloes, loss of FH, and 2SC positivity were always observed. Pure tubulocystic architecture was not observed in FH-deficient RCC, because focal nontubulocystic components can always be seen. CONCLUSIONS.— We emphasized multiple sectioning to identify a nontubulocystic architecture to exclude tubulocystic RCC. Moreover, tumor size, FH/2SC staining, and the Ki-67 index can differentiate tubulocystic FH-deficient RCC from tubulocystic RCC. The diagnosis of tubulocystic RCC was not recommended in renal mass biopsy because of the limited tissues sampled.
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Affiliation(s)
- Xiaoqun Yang
- From the Department of Pathology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China (Yang, Liu, H. Wang, J. Xu, L Zhou, Li, H. Xu, Dong, C. Wang)
| | - Yang Liu
- From the Department of Pathology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China (Yang, Liu, H. Wang, J. Xu, L Zhou, Li, H. Xu, Dong, C. Wang)
| | - Huafeng Wang
- From the Department of Pathology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China (Yang, Liu, H. Wang, J. Xu, L Zhou, Li, H. Xu, Dong, C. Wang)
| | - Yunze Xu
- the Department of Urology, Shanghai Jiao Tong University Medical School Affiliated Renji Hospital, Shanghai, China (Y. Xu)
| | - Huizhi Zhang
- the Department of Pathology, Ningbo Clinical Pathology Diagnosis Center, Zhejiang, China (Zhang)
| | - Ming Zhao
- the Department of Pathology, Zhejiang Provincial People's Hospital, Zhejiang, China (Zhao)
| | - Xiaoqing Luo
- the Department of Pathology, Xiangyang No. 1 People's Hospital, Hubei, China (Luo)
| | - Hongtao Jin
- the Department of Pathology, Shenzhen People's Hospital, Shenzhen, China (Jin)
| | - Ji Xiong
- the Department of Pathology, Huashan Hospital Fudan University, Shanghai, China (Xiong)
| | - Lili Tao
- the Department of Pathology, Peking University Shenzhen Hospital, Shenzhen, China (Tao)
| | - Jiankun Xu
- From the Department of Pathology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China (Yang, Liu, H. Wang, J. Xu, L Zhou, Li, H. Xu, Dong, C. Wang)
| | - Luting Zhou
- From the Department of Pathology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China (Yang, Liu, H. Wang, J. Xu, L Zhou, Li, H. Xu, Dong, C. Wang)
| | - Xiangyun Li
- From the Department of Pathology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China (Yang, Liu, H. Wang, J. Xu, L Zhou, Li, H. Xu, Dong, C. Wang)
| | - Haimin Xu
- From the Department of Pathology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China (Yang, Liu, H. Wang, J. Xu, L Zhou, Li, H. Xu, Dong, C. Wang)
| | - Lei Dong
- From the Department of Pathology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China (Yang, Liu, H. Wang, J. Xu, L Zhou, Li, H. Xu, Dong, C. Wang)
| | - Chaofu Wang
- From the Department of Pathology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China (Yang, Liu, H. Wang, J. Xu, L Zhou, Li, H. Xu, Dong, C. Wang)
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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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5
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Cai Q, Gagan J, Koduru P, Cadeddu J, Shah RB, Kapur P, Palsgrove DN. Multicystic Clear Cell Renal Tumors With Low-grade Nuclear Features: Time to Include TFE3 Translocation-associated Carcinomas. Adv Anat Pathol 2024; 31:34-42. [PMID: 37937590 DOI: 10.1097/pap.0000000000000420] [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: 11/09/2023]
Abstract
TFE3 -rearranged renal cell carcinoma (RCC) is a distinct, uncommon entity with more than 20 different fusion partners identified; however, histomorphology may be suggestive of specific fusion partners in select TFE3 -rearranged RCCs. For example, most MED15 :: TFE3 fusion associated RCCs exhibit multilocular cystic morphology, mimicking multilocular cystic renal neoplasm of low malignant potential. Here we present a case of MED15 :: TFE3 RCC in an older adult and review the literature with an emphasis on practical diagnostic approaches for predominantly cystic, low-grade, clear cell renal tumors.
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Affiliation(s)
| | | | | | - Jeffrey Cadeddu
- Urology
- Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX
| | | | - Payal Kapur
- Departments of Pathology
- Urology
- Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX
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Li H, Argani P, Halper-Stromberg E, Lotan TL, Merino MJ, Reuter VE, Matoso A. Positive GPNMB Immunostaining Differentiates Renal Cell Carcinoma With Fibromyomatous Stroma Associated With TSC1/2/MTOR Alterations From Others. Am J Surg Pathol 2023; 47:1267-1273. [PMID: 37661807 PMCID: PMC10592185 DOI: 10.1097/pas.0000000000002117] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
Renal cell carcinoma with fibromyomatous stroma (RCCFMS) include ELOC/TCEB1 -mutated renal cell carcinoma (RCC) and those with TSC1/2 / MTOR alterations. Besides morphologic similarity, most of these tumors is known to be diffusely positive for carbonic anhydrase IX and cytokeratin 7 by immunohistochemistry. We previously showed strong and diffuse expression of GPNMB (glycoprotein nonmetastatic B) in translocation RCC and eosinophilic renal neoplasms with known TSC1/2/MTOR alterations. We retrospectively identified molecularly confirmed cases of TCEB1/ELOC -mutated RCC (7 tumors from 7 patients), and RCCFMS with alterations in TSC1/2/MTOR (6 tumors from 5 patients, 1 patient with tuberous sclerosis syndrome). In addition, we included 7 clear cell papillary renal cell tumors (CCPRCTs) and 8 clear cell RCC, as they can also present morphologic overlap with RCCFMS. Morphologically, RCCs with TSC1/2/MTOR alterations and those with TCEB1/ELOC mutations were indistinguishable and characterized by papillary, nested, or tubular architecture, with tumor cells with clear cytoplasm and low nuclear grade. By immunohistochemistry, cytokeratin 7 was positive in 5/7 (71%) of TCEB1/ELOC -mutated RCCs, 6/6 (100%) of RCCs with TSC1/2/mTOR alterations, and 7/7 (100%) of CCPRCTs ( P =not significant). Carbonic anhydrase IX was positive in 7/7 TCEB1/ELOC -mutated RCCs, 6/6 (100%) of RCCs with TSC1/2/MTOR alterations, and 7/7 (100%) of CCPRCTs ( P =NS). GPNMB was strongly and diffusely positive in all tumors with TSC1/2/MTOR alterations (6/6), while negative in all TCEB1/ELOC -mutated RCCs (0/6), or CCPRCTs (0/7) ( P =0.002). Two of 8 clear cell RCC showed focal weak staining, while 6/8 were negative. In conclusion, the results support the use of GPNMB to distinguish RCCFMS with TSC1/2/MTOR alterations from others with similar morphology.
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Affiliation(s)
- Huili Li
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, 21231
| | - Pedram Argani
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, 21231
- Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, 21231
| | | | - Tamara L. Lotan
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, 21231
- Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, 21231
| | - Maria J. Merino
- Translational Surgical Pathology, Laboratory of Pathology, National Institutes of health, Bethesda, MD 20892
| | - Victor E. Reuter
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10021
| | - Andres Matoso
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, 21231
- Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, 21231
- Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, 21231
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Maughan BL, Sirohi D. Papillary Renal Cell Carcinoma: A Review of Prospective Clinical Trials. Curr Treat Options Oncol 2023; 24:1199-1212. [PMID: 37407886 DOI: 10.1007/s11864-023-01107-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/12/2023] [Indexed: 07/07/2023]
Abstract
OPINION STATEMENT PRCC is a unique histologic entity compared to other forms of renal cell carcinoma, harboring distinct molecular drivers. The WHO 2022 classification is further emphasizing the molecular biology by making molecular classifications of PRCC subclassifications and discontinuing the morphologic type 1 and type 2 classification system. We agree with this functional classification system and encourage all future clinical trials to only include patients with similar diagnosis instead of conducting basket trials (including all nccRCC together) which limits the scientific value of those conclusions. Based on recent disease-specific clinical trial (S1500, PAPMET), the current standard of care for patients with treatment naïve PRCC is cabozantinib. Prospective clinical trials clearly establish that immune checkpoint inhibitor therapy has meaningful activity in PRCC. The data to date include only single-arm clinical trials of combination immune therapy. Despite the positive and encouraging results, we need validation through randomized studies because of the overestimation of effect size seen in single-arm trials. These randomized trials are currently underway and enrolling. We strongly encourage all physicians to support these studies and enroll patients with PRCC to these trials in order to continue improving the standard of care.
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Affiliation(s)
- Benjamin L Maughan
- Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Drive, Salt Lake City, UT, 84112, USA.
| | - Deepika Sirohi
- University of Utah School of Medicine, Salt Lake City, UT, USA
- Molecular Oncology, ARUP Laboratories, 2000 Circle of Hope Drive, Salt Lake City, UT, 84112, USA
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da Paz AR, de Souza MF, Santana CMDM, Athanazio DA. Clear Cell Papillary Renal Cell Tumors: A Study of 42 Tumors with Emphasis on the Fibrous Capsule, Cystic Component, and GATA3 Immunohistochemistry. Int J Surg Pathol 2023; 31:38-45. [PMID: 35503256 DOI: 10.1177/10668969221091583] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Clear cell papillary renal cell tumor is a common and sometimes underdiagnosed renal cell neoplasm. Its proper recognition is important because its diagnosis implies a remarkably high probability of indolent behavior. This study aimed to evaluate the frequency of a fibrous capsule, a cystic component, and a GATA3 expression in clear cell papillary renal cell tumors. We assessed 419 renal cell neoplasms from three institutions located in northeastern Brazil and identified 42 clear cell papillary renal cell tumors (from 39 patients), which were the fourth most common renal cell neoplasm. These tumors commonly exhibited fibrous capsules (all showed complete or partial capsules) and cystic component (93%). Eighteen out of 42 tumors (43%) showed some expression of GATA3, and weak and focal staining was common among the positive tumors. Clear cell papillary renal cell tumor must always be included in the differential diagnosis of predominantly cystic renal cell neoplasms. As GATA3 is inconsistently expressed in clear cell papillary renal cell tumors, it is not useful in this diagnosis.
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Affiliation(s)
- Alexandre Rolim da Paz
- Hospital Napoleão Laureano, João Pessoa, Brazil.,Universidade Federal da Paraíba, João Pessoa, Brazil
| | - Maiara Ferreira de Souza
- Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil.,Imagepat, Laboratory of Pathology, Brazil
| | | | - Daniel Abensur Athanazio
- Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil.,Imagepat, Laboratory of Pathology, Brazil.,Hospital Universitário Professor Edgard Santos / Federal University of Bahia, Brazil
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Semjén D, Dénes B, Somorácz Á, Fintha A, Forika G, Jenei A, Dobi D, Micsik T, Eizler KV, Giba N, Sánta F, Sejben A, Iványi B, Kuthi L. Renal Cell Carcinoma in End-Stage Renal Disease: A Retrospective Study in Patients from Hungary. Pathobiology 2023; 90:322-332. [PMID: 36696889 PMCID: PMC10614572 DOI: 10.1159/000529276] [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: 09/28/2022] [Accepted: 01/14/2023] [Indexed: 01/27/2023] Open
Abstract
INTRODUCTION End-stage renal disease (ESRD) and acquired cystic kidney disease (ACKD) are known risk factors for renal cell carcinoma (RCC). Hereby, the clinicopathological features of RCCs developed in ESRD were investigated. METHODS A database consisting of 34 tumors from 31 patients with ESRD among 2,566 nephrectomy samples of RCC was built. The demographic, clinical, and follow-up data along with pathological parameters were analyzed. The RCCs were diagnosed according to the current WHO Classification of Urinary and Male Genital Tumors. RESULTS Twenty-two tumors developed in men and 12 in women, with a median age of 56 years (range: 27-75 years). The causes of ESRD were glomerulonephritis (n = 7), hypertensive kidney disease (n = 6), autosomal dominant polycystic kidney disease (n = 6), chronic pyelonephritis (n = 4), diabetic nephropathy (n = 3), chemotherapy-induced nephropathy (n = 1), and undetermined (n = 4). ACKD complicated ESRD in 12 patients. The following histological subtypes were identified: clear cell RCC (n = 19), papillary RCC (n = 5), clear cell papillary tumor (n = 5), ACKD RCC (n = 3), and eosinophilic solid and cystic RCC (n = 2). The median tumor size was 31 mm (range: 10-80 mm), and 32 tumors were confined to the kidney (pT1-pT2). There was no tumor-specific death during the period of this study. Progression was registered in 1 patient. CONCLUSION In our cohort, the most common RCC subtype was clear cell RCC (55%), with a frequency that exceeded international data appreciably (14-25%). The incidence of clear cell papillary tumor and ACKD RCC (14.7% and 8.5%) was lower than data reported in the literature (30% and 40%). Our results indicate a favorable prognosis of RCC in ESRD.
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Affiliation(s)
- Dávid Semjén
- Department of Pathology, Medical School and Clinical Centre, University of Pécs, Pécs, Hungary
| | | | | | - Attila Fintha
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Gertrúd Forika
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Alex Jenei
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Deján Dobi
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Tamás Micsik
- Pathology Unit, Fejér County Szent György University Teaching Hospital, Székesfehérvár, Hungary
| | | | - Nándor Giba
- Pathology Unit, Fejér County Szent György University Teaching Hospital, Székesfehérvár, Hungary
| | - Fanni Sánta
- Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Anita Sejben
- Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Béla Iványi
- Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Levente Kuthi
- Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
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10
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Demko N, Glennon KI, Arseneault M, Lach K, Nishimura T, Tanguay S, Riazalhosseini Y, Brimo F. A Sarcomatoid Renal Cell Carcinoma with Clear Cell Papillary-Like Primary Tumor and Lymph Node Metastasis: A Diagnostic Conundrum. Int J Surg Pathol 2022:10668969221145011. [PMID: 36562104 DOI: 10.1177/10668969221145011] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Clear cell papillary renal cell tumor (CCPRCT) is a distinct clinical entity with characteristic pathological features and non-aggressive clinical behavior. Diagnostically challenging cases present when there are immunomorphological findings of CCPRCT associated with heterogeneous morphologies, aggressive histological features, and advanced pathological stages-so-called CCPRCT-like tumors. In this report, we describe a heterogeneous, multifocal renal tumor with immunomorphological characteristics of CCPRCT but with associated aggressive features such as sarcomatoid and necrotic areas, perirenal and sinus fat involvement, and most notably, lymph node metastasis composed entirely of classic CCPRCT morphology and immunophenotype. Immunohistochemical and fluorescence in situ hybridization studies did not support a translocation renal cell carcinoma. Molecular analyses did not identify common mutations or chromosomal abnormalities seen in clear cell renal cell carcinoma or ELOC-mutated renal cell carcinoma. This case highlights that rare renal cell tumors remain difficult to classify and the distinction between CCPRCT and CCPRCT-like tumors remains to be better defined.
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Affiliation(s)
- Nadine Demko
- Department of Anatomical Pathology, 5620McGill University, Montréal, Québec, Canada
| | - Kate I Glennon
- Department of Human Genetics, 5620McGill University, Montréal, Québec, Canada.,McGill Genome Centre, 5620McGill University, Montréal, Québec, Canada
| | - Madeleine Arseneault
- Department of Human Genetics, 5620McGill University, Montréal, Québec, Canada.,McGill Genome Centre, 5620McGill University, Montréal, Québec, Canada
| | - Katherine Lach
- Department of Anatomical Pathology, 5620McGill University, Montréal, Québec, Canada
| | - Tamiko Nishimura
- Department of Human Genetics, 5620McGill University, Montréal, Québec, Canada.,McGill Genome Centre, 5620McGill University, Montréal, Québec, Canada
| | - Simon Tanguay
- Division of Urology, 5620McGill University, Montréal, Québec, Canada
| | - Yasser Riazalhosseini
- Department of Human Genetics, 5620McGill University, Montréal, Québec, Canada.,McGill Genome Centre, 5620McGill University, Montréal, Québec, Canada
| | - Fadi Brimo
- Department of Anatomical Pathology, 5620McGill University, Montréal, Québec, Canada
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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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Nayak B, Phulware RH, Dhamija E, Barwad A. Renal angiomyoadenomatous tumor in young man a rare entity. Indian J Cancer 2022; 59:433-435. [PMID: 36412320 DOI: 10.4103/ijc.ijc_327_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Brusabhanu Nayak
- Department of Urology, All India Institute of Medical Sciences, New Delhi, India
| | - Ravi H Phulware
- Department of Pathology, PGIMER, ABVIMS, RML Hospital, New Delhi, India
| | - Ekta Dhamija
- Department of Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Adarsh Barwad
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
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13
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Abstract
Renal cell carcinoma (RCC) with fibromyomatous stroma (FMS) was included as an "emerging/provisional" entity in the 2016 World Health Organization (WHO) classification as a "RCC with (angio) leiomyomatous stroma." It has been debated whether RCCFMS represents a separate entity or a group of RCCs with overlapping morphologies. Accordingly, various names have been used to refer to the RCCs that exhibited clear cells and prominent smooth muscle and fibromatous stroma. Recent studies have demonstrated that RCCFMS indeed represents a distinct entity with subtle but distinguishable features that can be separated from other RCCs that exhibit clear cells, as well as tubulopapillary morphology and smooth muscle/fibromatous stroma, such as clear cell RCC and clear cell papillary RCC. Microscopically, the epithelial component forms tumor nodules composed of elongated and frequently branching tubules, lined by clear or mildly eosinophilic cells containing voluminous cytoplasm. Focal papillary morphology is also frequently present. Diffuse CK7 positivity is typical and is required for the diagnosis. Molecular analysis of these tumors demonstrated recurrent mutations involving the TSC/mTOR pathway. A subset of tumors with similar morphology has shown mutations involving ELOC (previously referred to as TCEB1), typically associated with monosomy 8. Finally, in addition to the more common RCCFMS that are sporadic, essentially identical tumors have been found in patients with tuberous sclerosis complex, suggesting the existence of hereditary and sporadic counterparts of this tumor. It is currently debated whether TSC/mTOR and ELOC mutated RCCFMS should be grouped together, based on their shared and overlapping morphology and common CK7 reactivity, despite the differing molecular alterations. This review outlines evidence supporting the recognition of RCCFMS as a novel subtype of RCC with morphologic, immunohistochemical, and molecular characteristics distinct from clear cell RCC and clear cell papillary RCC.
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Affiliation(s)
- Rajal B Shah
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX
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14
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Paner GP, Chumbalkar V, Montironi R, Moch H, Amin MB. Updates in Grading of Renal Cell Carcinomas Beyond Clear Cell Renal Cell Carcinoma and Papillary Renal Cell Carcinoma. Adv Anat Pathol 2022; 29:117-130. [PMID: 35275846 DOI: 10.1097/pap.0000000000000341] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The World Health Organization (WHO) recommends grading of clear cell renal cell carcinoma (RCC) and papillary RCC using the WHO/International Society of Urological Pathology (ISUP) grade, which is primarily based on nuclear features. As the spectrum of RCC continues to evolve, with more recently described subtypes in the past decade, literature evidence on grading these subtypes is limited or not available for some tumor types. Herein, we outline a pragmatic approach to the topic of grading RCC, dividing the contemporarily described RCC subtypes into 7 categories based on the potential clinical applicability of grading as a useful prognostic parameter: (1) RCC subtypes that are reasonably validated and recommended for WHO/ISUP grading; (2) RCC subtypes where WHO/ISUP is not applicable; (3) RCC subtypes where WHO/ISUP grading is potentially clinically useful; (4) inherently aggressive RCC subtypes where histologic classification itself confers an aggressive biologic potential; (5) renal epithelial tumors where WHO/ISUP grading provides potentially misleading prognostic implication; (6) renal epithelial neoplasms where low WHO/ISUP grade features are a prerequisite for accurate histologic classification; and (7) renal epithelial neoplasms with no or limited data on grading or incomplete understanding of the biologic potential. Our aim in outlining this approach is 2-fold: (a) identify the gaps in understanding and application of grading in RCC subtypes so that researchers in the field may perform additional studies on the basis of which the important pathologic function of assignment of grade may be recommended to be performed as a meaningful exercise across a wider spectrum of RCC; and (b) to provide guidance in the interim to surgical pathologists in terms of providing clinically useful grading information in RCC based on currently available clinicopathologic information.
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Affiliation(s)
- Gladell P Paner
- Department of Pathology, University of Chicago
- Department of Surgery, Section of Urology, University of Chicago, Chicago, IL
| | | | - Rodolfo Montironi
- Molecular Medicine and Cell Therapy Foundation, Department of Clinical and Molecular Sciences, Polytechnic University of the Marche Region, Ancona, Italy
| | - Holger Moch
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland
| | - Mahul B Amin
- Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN
- Department of Urology, USC Keck School of Medicine, Los Angeles, CA
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15
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Lim EJ, Fong KY, Li J, Huang HH, Chen K, Tay KJ, Cheng CWS, Ho HSS, Ngo NT, Yuen JSP. Clinicopathological features of non-conventional renal cell carcinoma histological subtypes: Learning points from a large contemporary series spanning over three decades. Investig Clin Urol 2022; 63:151-158. [PMID: 35244988 PMCID: PMC8902431 DOI: 10.4111/icu.20210373] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 11/20/2021] [Accepted: 01/03/2022] [Indexed: 11/18/2022] Open
Abstract
Purpose To perform a retrospective review of the clinicopathological features of patients with conventional and non-conventional renal cell carcinoma (cRCC and ncRCC). Materials and Methods A large prospectively maintained uro-oncological registry was accessed to extract clinicopathological data of patients diagnosed with renal tumors who subsequently underwent nephrectomy from 1990–2019. Demographics and operative parameters were extracted. Analyses of overall survival (OS) and cancer-specific survival (CSS) were performed using the Kaplan–Meier method. Cox proportional-hazards analysis was used to identify risk factors which influenced survival. Results There were a total of 1,686 consecutive nephrectomies which was retrieved, with 1,286 cRCC and 400 ncRCC. The commonest ncRCC subtypes were papillary (n=198, 11.7%), clear cell papillary (n=50, 3.0%) and chromophobe (n=49, 2.9%) RCC. Kaplan–Meier estimates of OS were higher in cRCC (0.74; 95% confidence interval [CI], 0.71–0.78) than ncRCC (hazard ratio, 1.47; 95% CI, 1.16–1.87). Among individual subtypes, chromophobe RCC had the highest 5-year OS (0.90; 95% CI, 0.79–1.0). Among ncRCC subtypes, acquired cystic RCC demonstrated the highest association with end-stage renal failure and hypertension, with the highest CSS. MiT family translocation RCC had the youngest mean age at presentation (45.6±12.8 y) and excellent CSS. Factors associated with increased OS in the entire cohort included shorter operative time, partial nephrectomy and lower tumor stages. Conclusions This study provides a comprehensive contemporary overview of ncRCCs which are yet poorly characterized, in comparison to cRCCs. Data from this study would contribute towards tailored patient counseling and healthcare resource planning.
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Affiliation(s)
- Ee Jean Lim
- Department of Urology, Singapore General Hospital, Singapore
| | - Khi Yung Fong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jingqiu Li
- Department of Urology, Singapore General Hospital, Singapore
| | - Hong Hong Huang
- Department of Urology, Singapore General Hospital, Singapore
| | - Kenneth Chen
- Department of Urology, Singapore General Hospital, Singapore
| | - Kae Jack Tay
- Department of Urology, Singapore General Hospital, Singapore
| | | | | | - Nye Thane Ngo
- Department of Pathology, Singapore General Hospital, Singapore
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16
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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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17
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Smith SC, Wobker SE. Precision for the Conventional. Am J Clin Pathol 2021; 156:495-496. [PMID: 33942844 DOI: 10.1093/ajcp/aqab007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Steven Christopher Smith
- Departments of Pathology and Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Sara E Wobker
- Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA
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18
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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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19
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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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20
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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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21
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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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22
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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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23
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Baniak N, Flood TA, Buchanan M, Dal Cin P, Hirsch MS. Carbonic anhydrase IX (CA9) expression in multiple renal epithelial tumour subtypes. Histopathology 2020; 77:659-666. [PMID: 32639054 DOI: 10.1111/his.14204] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 07/02/2020] [Indexed: 12/21/2022]
Abstract
AIMS Renal epithelial neoplasms (RENs) can be difficult to subclassify, owing to overlapping morphological features. Carbonic anhydrase 9 (CA9) is a common biomarker for clear cell renal cell carcinoma (CCRCC); however, the sensitivity and specificity across REN subtypes are less clear. The aim of this study was to investigate CA9 expression in RENs, especially those in the differential diagnosis with CCRCC and less common entities, to determine its reliability as a diagnostic biomarker. METHODS AND RESULTS CA9 immunostaining was performed on 262 RENs, including 119 CCRCCs and 143 non-CCRCC. Immunostaining was evaluated as negative (0%), rare (1+, 1-10%), focal (2+, 11-50%), or diffuse (3+, >50%). CCRCCs were 3+ CA9-positive in 93% of cases; 4% were CA9-negative. Sixty-seven percent of papillary renal cell carcinomas (RCCs) were 1+/2+ CA9-positive, whereas 33% were CA9-negative. Chromophobe RCCs were nearly always CA9-negative (93%), with 7% showing rare cell reactivity. Clear cell tubulopapillary RCCs (CCTPRCCs) were consistently 3+ CA9-positive, but with a cup-like staining pattern. Fifty-three percent of Xp11.2 RCCs were CA9-negative; however, 6% were 3+ CA9-positive and 12% were 2+ CA9-positive. Two of eight fumarate hydratase-deficient RCCs were 3+ CA9-positive. A small subset of the remaining RCCs showed rare to focal CA9 expression. All oncocytomas and eosinophilic solid and cystic RCCs were CA9-negative. CONCLUSIONS Overall, diffuse CA9 expression was identified in nearly all CCRCCs and in all CCTPRCCs (high sensitivity); however, CA9 was not entirely specific. At least focal CA9 expression can been seen in a subset of many RCCs, and such findings should be taken into consideration with other morphological, immunophenotypic and clinical findings.
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Affiliation(s)
- Nicholas Baniak
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Trevor A Flood
- Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, ON, Canada
| | - Mark Buchanan
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Paola Dal Cin
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Michelle S Hirsch
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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24
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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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25
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"Renal Cell Carcinoma With Leiomyomatous Stroma" Harbor Somatic Mutations of TSC1, TSC2, MTOR, and/or ELOC (TCEB1): Clinicopathologic and Molecular Characterization of 18 Sporadic Tumors Supports a Distinct Entity. Am J Surg Pathol 2020; 44:571-581. [PMID: 31850909 DOI: 10.1097/pas.0000000000001422] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Renal cell carcinoma with (angio) leiomyomatous stroma (RCCLMS) is included as a provisional entity in the 2016 World Health Organization (WHO) classification of renal epithelial neoplasia; however, debate remains whether it represents a distinct entity or a heterogenous group of renal cell carcinomas (RCCs) with overlapping morphology. Also, its relationship to similar tumors occurring in the setting of tuberous sclerosis complex (TSC) is not fully addressed. We analyzed the clinicopathologic, immunohistochemical, and molecular characteristics of 23 sporadic RCCs associated with smooth muscle stroma and classified them into 2 groups, independent of molecular results: (1) RCCLMS (n=18) and (2) clear cell renal cell carcinoma (CCRCC) (n=5). The classification of a case as "RCCLMS" was based on morphologic comparison with 5 "index" RCCs from 3 patients with TSC showing similar features and the presence of diffuse CK7 expression. To investigate mutational and copy number alterations, a 170-gene solid tumor panel was utilized to sequence 14 RCCLMSs and control of 5 CCRCCs. Also, 4 RCCLMSs, suspicious for chromosome 8 monosomy, were further evaluated by a broader 479 gene sequencing panel that included ELOC (also referred to as TCEB1). Clinical information and follow-up data were obtained from electronic medical records. The mean age of patients with RCCLMS was 52 years (range, 33 to 69) with male:female ratio of 1:2. Macroscopically, all tumors were solitary and predominantly (82%) tan/red, circumscribed, and solid. The average tumor size was 2.3 cm (range, 1.1 to 4.5). Microscopically, the distinctive feature included tumor nodules of elongated and frequently branching tubules lined by cells with voluminous clear to mildly eosinophilic cytoplasm (100%), separated by focal to prominent smooth muscle stroma. Additional frequently identified features included: biphasic pattern of collapsed acini surrounding tubules with voluminous cytoplasm (50%), focal papillary architecture (39%), peritumoral lymphoid aggregates (39%), and hemosiderin-laden macrophages (33%). All 11 (100%) RCCLMSs with available staging information were pT1; 78% were WHO/International Society of Urologic Pathology (ISUP) grade 2 and 22% grade 3. Immunophenotypically, RCCLMSs were characterized by diffuse CK7, CAM5.2 and CD10 reactivity (100%). All patients with available follow-up (n=10) were alive and without disease progression after a mean and median follow-up of 25.2 (range: 1 to 58) and 25 months, respectively. The molecular results showed recurrent mutations in all RCCLMS: TSC1 (4), TSC2 (4), MTOR (6), and/or ELOC (2). Five control CCRCCs demonstrated primary alterations in VHL gene, while all 14 RCCLMS cases tested had intact VHL gene. Of 2 RCCLMSs with confirmed monosomy 8, 1 showed a hotspot ELOC mutation without TSC/MTOR mutations, and 1 showed a previously undescribed 3-bp in-frame ELOC deletion, along with a truncating TSC1 mutation. In conclusion, RCCLMS, as defined herein, harbors recurrent mutations of TSC1/TSC2, MTOR, and/or ELOC, consistent with hyperactive MTOR complex. Our findings argue that these tumors represent the sporadic counterpart to morphologically identical tumors occurring in TSC patients. Finally, the data support that RCCLMS is a novel subtype of RCC with unique morphologic, immunohistochemical, and molecular characteristics that is distinct from CCRCC and clear cell-papillary RCC.
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26
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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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27
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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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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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29
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Pan CC, Yeh YC, Wang YC, Chang YH. Differential expression analysis of clear cell renal cell carcinomas in The Cancer Genome Atlas distinguishes an aggressive subset enriched with chromosomes 7 and 12 gains. Histopathology 2020; 76:950-958. [PMID: 32170764 DOI: 10.1111/his.14104] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 02/11/2020] [Accepted: 03/09/2020] [Indexed: 11/30/2022]
Abstract
AIMS The Cancer Genome Atlas (TCGA) provides an integrated resource for investigating the genetic, phenotypical and clinical characteristics of cancer. In this study, we aimed to define distinct subsets of clear cell renal cell carcinoma (ccRCC) through differential expression and principal component analyses. METHODS AND RESULTS We used DESeq2 to examine the expression profiles of 472 cases in TCGA. After a process of segregation and regrouping, we compared the mutation and copy number variation landscapes to discern two major clusters: cluster 1, composed mainly of classic ccRCC, and cluster 2, which was associated with gains at chromosomes 7 and 12. Gene set enrichment analysis disclosed that cluster 2 tumours were enriched in genes involving epithelial-mesenchymal transition. Histologically, cluster 2 tumours frequently exhibited cell elongation or spindling. Patients with cluster 2 tumours or tumours harbouring chromosomes 7 or 12 gains had a significantly greater cumulative incidence of mortality. We then employed fluorescence in-situ hybridisation with probes against chromosomes 7 and 12 in a cohort of 119 cases of ccRCC from our institute for validation. Chromosomes 7 and 12 gains were associated with lower survival rates in both univariate and multivariate analyses. CONCLUSIONS Our study demonstrates that genetic data obtained through appropriate molecular methodologies can be a useful adjunct to help predict prognosis. It also provides an example of exploring TCGA to extract meaningful information that can eventually contribute to precision medicine.
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Affiliation(s)
- Chin-Chen Pan
- Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei.,School of Medicine, National Yang-Ming University, Taipei
| | - Yi-Chen Yeh
- Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei.,School of Medicine, National Yang-Ming University, Taipei.,Institute of Biomedical Informatics, National Yang-Ming University, Taipei
| | - Yu-Chao Wang
- Institute of Biomedical Informatics, National Yang-Ming University, Taipei.,Preventive Medicine Research Center, National Yang-Ming University, Taipei
| | - Yen-Hwa Chang
- Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan
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30
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An Algorithmic Immunohistochemical Approach to Define Tumor Type and Assign Site of Origin. Adv Anat Pathol 2020; 27:114-163. [PMID: 32205473 DOI: 10.1097/pap.0000000000000256] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Immunohistochemistry represents an indispensable complement to an epidemiology and morphology-driven approach to tumor diagnosis and site of origin assignment. This review reflects the state of my current practice, based on 15-years' experience in Pathology and a deep-dive into the literature, always striving to be better equipped to answer the age old questions, "What is it, and where is it from?" The tables and figures in this manuscript are the ones I "pull up on the computer" when I am teaching at the microscope and turn to myself when I am (frequently) stuck. This field is so exciting because I firmly believe that, through the application of next-generation immunohistochemistry, we can provide better answers than ever before. Specific topics covered in this review include (1) broad tumor classification and associated screening markers; (2) the role of cancer epidemiology in determining pretest probability; (3) broad-spectrum epithelial markers; (4) noncanonical expression of broad tumor class screening markers; (5) a morphologic pattern-based approach to poorly to undifferentiated malignant neoplasms; (6) a morphologic and immunohistochemical approach to define 4 main carcinoma types; (7) CK7/CK20 coordinate expression; (8) added value of semiquantitative immunohistochemical stain assessment; algorithmic immunohistochemical approaches to (9) "garden variety" adenocarcinomas presenting in the liver, (10) large polygonal cell adenocarcinomas, (11) the distinction of primary surface ovarian epithelial tumors with mucinous features from metastasis, (12) tumors presenting at alternative anatomic sites, (13) squamous cell carcinoma versus urothelial carcinoma, and neuroendocrine neoplasms, including (14) the distinction of pheochromocytoma/paraganglioma from well-differentiated neuroendocrine tumor, site of origin assignment in (15) well-differentiated neuroendocrine tumor and (16) poorly differentiated neuroendocrine carcinoma, and (17) the distinction of well-differentiated neuroendocrine tumor G3 from poorly differentiated neuroendocrine carcinoma; it concludes with (18) a discussion of diagnostic considerations in the broad-spectrum keratin/CD45/S-100-"triple-negative" neoplasm.
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31
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Banno T, Takagi T, Kondo T, Yoshida K, Iizuka J, Okumi M, Ishida H, Morita S, Nagashima Y, Tanabe K. Computed tomography imaging characteristics of clear cell papillary renal cell carcinoma. Int Braz J Urol 2020; 46:26-33. [PMID: 31851455 PMCID: PMC6968899 DOI: 10.1590/s1677-5538.ibju.2018.0716] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 08/30/2019] [Indexed: 12/04/2022] Open
Abstract
Purpose: Clear cell papillary (CCP) renal cell carcinoma (RCC) is a new subtype of RCC that was formally recognized by the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia in 2013. Subsequently, CCP RCC was added to the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. In this study, we retrospectively investigated the computed tomography (CT) findings of pathologically diagnosed CCP RCC. Materials and Methods: This study included 12 patients pathologically diagnosed with CCP RCC at our institution between 2015 and 2017. We reviewed the patient's CT data and analyzed the characteristics. Results: Nine solid masses and 3 cystic masses with a mean tumor size of 22.7±9.2mm were included. Solid masses exhibited slight hyper-density on unenhanced CT with a mean value of 34±6 Hounsfield units (HU), good enhancement in the corticomedullary phase with a mean of 195±34HU, and washout in the nephrogenic phase with a mean of 133±29HU. The walls of cystic masses enhanced gradually during the corticomedullary and nephrogenic phases. Solid and cystic masses were preoperatively diagnosed as clear cell RCC and cystic RCC, respectively. Conclusions: The CT imaging characteristics of CCP RCCs could be categorized into either the solid or cystic type. These masses were diagnosed radiologically as clear cell RCC and cystic RCC, respectively.
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Affiliation(s)
- Taro Banno
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Toshio Takagi
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Tsunenori Kondo
- Department of Urology, Tokyo Women's Medical University, Medical Center East, Tokyo, Japan
| | - Kazuhiko Yoshida
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Junpei Iizuka
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Masayoshi Okumi
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hideki Ishida
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Satoru Morita
- Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Yoji Nagashima
- Department of Surgical Pathology, Tokyo Women's Medical University, Tokyo, Japan
| | - Kazunari Tanabe
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
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32
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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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MacLennan GT, Cheng L. Five decades of urologic pathology: the accelerating expansion of knowledge in renal cell neoplasia. Hum Pathol 2019; 95:24-45. [PMID: 31655169 DOI: 10.1016/j.humpath.2019.09.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 09/06/2019] [Indexed: 02/07/2023]
Abstract
Those who are knowledgeable in cosmology inform us that the expansion of the universe is such that the velocity at which a distant galaxy is receding from the observer is continually increasing with time. We humbly paraphrase that as "The bigger the universe gets, the faster it gets bigger." This is an interesting analogy for the expansion of knowledge in the field of renal tumor pathology over the past 30 to 50 years. It is clear that a multitude of dedicated investigators have devoted incalculable amounts of time and effort to the pursuit of knowledge about renal epithelial neoplasms. As a consequence of the contributions of numerous investigators over many decades, the most recent World Health Organization classification of renal neoplasms includes about 50 well defined and distinctive renal tumors, as well as various miscellaneous and metastatic tumors. In addition, a number of emerging or provisional new entities are under active investigation and may be included in future classifications. In this review, we will focus on a number of these tumors, tracing as accurately as we can the origins of their discovery, relating relevant additions to the overall knowledge base surrounding them, and in some instances addressing changes in nomenclature.
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Affiliation(s)
- Gregory T MacLennan
- Department of Pathology and Laboratory Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH.
| | - Liang Cheng
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
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35
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Morlote DM, Harada S, Batista D, Gordetsky J, Rais-Bahrami S. Clear cell papillary renal cell carcinoma: molecular profile and virtual karyotype. Hum Pathol 2019; 91:52-60. [DOI: 10.1016/j.humpath.2019.05.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 05/26/2019] [Accepted: 05/31/2019] [Indexed: 02/01/2023]
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36
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Diagnostic role of kidney injury molecule-1 in renal cell carcinoma. Int Urol Nephrol 2019; 51:1893-1902. [DOI: 10.1007/s11255-019-02231-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 07/10/2019] [Indexed: 10/26/2022]
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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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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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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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40
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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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41
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Kondo T, Sasa N, Yamada H, Takagi T, Iizuka J, Kobayashi H, Yoshida K, Fukuda H, Ishihara H, Tanabe K, Tsuzuki T. Acquired cystic disease-associated renal cell carcinoma is the most common subtype in long-term dialyzed patients: Central pathology results according to the 2016 WHO classification in a multi-institutional study. Pathol Int 2018; 68:543-549. [PMID: 30187581 DOI: 10.1111/pin.12718] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Accepted: 08/09/2018] [Indexed: 01/20/2023]
Abstract
New pathological subtypes of renal cell carcinoma (RCC) were designated in the 2016 World Health Organization (WHO) classification corresponding to the features commonly seen in patients with end-stage renal disease (ESRD). To determine the clinicopathological findings of new subtypes, we reanalyzed all sections from 315 kidneys in 291 ESRD patients bearing RCC tumors surgically resected in three Japanese institutes by the central pathologist. Clear cell RCC was diagnosed in 144 kidneys (45.7%), acquired cystic disease (ACD)-associated RCC in 100 (31.7%), papillary RCC in 41 (13.0%), and other minor subtypes in 30 (9.52%). Multivariate analysis showed that longer duration of dialysis, young age, and male sex were independent prognostic clinical factors for the occurrence of ACD-associated RCC. ACD-associated RCC included more WHO/International Society of Urologic Pathology (ISUP) grade 3/4 cases compared to other RCCs. In contrast, other unfavorable findings were less frequent in ACD-associated RCC, including the presence of a sarcomatoid component, lymphovascular invasion, and necrosis. In conclusion, ACD-associated RCC is a common histology in Japanese patients with ESRD. In addition, ACD-associated RCC showed more cases with a higher WHO/ISUP grade, but fewer cases with other unfavorable pathological features, suggesting a favorable prognosis of ACD-associated RCC.
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Affiliation(s)
- Tsunenori Kondo
- Department of Urology, Tokyo Women's Medical University.,Department of Urology, Tokyo Women's Medical University Medical Center East, Tokyo
| | - Naoto Sasa
- Department of Urology, Nagoya University
| | - Hiroshi Yamada
- Department of Urology, Japanese Red Cross Nagoya Daini Hospital
| | - Toshio Takagi
- Department of Urology, Tokyo Women's Medical University
| | - Junpei Iizuka
- Department of Urology, Tokyo Women's Medical University
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42
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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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43
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Pan CC, Tsuzuki T, Morii E, Fushimi H, Chen PCH, Epstein JI. Whole-exome sequencing demonstrates recurrent somatic copy number alterations and sporadic mutations in specialized stromal tumors of the prostate. Hum Pathol 2018; 76:9-16. [DOI: 10.1016/j.humpath.2017.12.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/23/2017] [Accepted: 12/07/2017] [Indexed: 12/30/2022]
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44
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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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45
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Williamson SR, Hornick JL, Eble JN, Gupta NS, Rogers CG, True L, Grignon DJ, Cheng L. Renal cell carcinoma with angioleiomyoma-like stroma and clear cell papillary renal cell carcinoma: exploring SDHB protein immunohistochemistry and the relationship to tuberous sclerosis complex. Hum Pathol 2018; 75:10-15. [DOI: 10.1016/j.humpath.2017.11.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Revised: 11/04/2017] [Accepted: 11/14/2017] [Indexed: 12/31/2022]
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46
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Kurkov AV, Shekhter AB, Paukov VS. [Costal cartilage structural and functional changes in children with a funnel or keeled chest]. Arkh Patol 2018; 79:57-62. [PMID: 29027531 DOI: 10.17116/patol201779557-62] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Congenital chest wall deformities (CCWDs) in children are severe diseases leading to cosmetic defects and diseases of the respiratory and cardiovascular systems. The most common of these deformities are funnel-shaped (pectus excavatum, FD) and keeled (pectus carinatum, KD) ones. The pathogenesis of CCWDs and the role of costal cartilage structural and functional changes in their pathogenesis have now been not well studied, which makes it difficult to elaborate pathogenetic approaches to correcting these diseases. Analysis of the literature has shown that structural and functional changes occur in the matrix and chondrocytes from the costal cartilage in FD. Similar costal cartilage changes are observed in KD. It is still unknown exactly which pathological processes are present in the costal cartilage and how they result in the development of one or other type of CCWDs. The role of amianthoid transformation (AT) of costal cartilages in these processes is also unknown. It is not improbable that it is AT drastically changing the native cartilage matrix, which is one of the key mechanisms leading to changes in its properties and to the subsequent development of FD or KD.
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Affiliation(s)
- A V Kurkov
- Institute for Regenerative Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia; Acad. A.I. Strukov Department of Pathological Anatomy, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia; Institute of Photonic Technologies, Federal Research Center of Crystallography and Photonics, Russian Academy of Sciences, Moscow, Russia
| | - A B Shekhter
- Institute for Regenerative Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia; Institute of Photonic Technologies, Federal Research Center of Crystallography and Photonics, Russian Academy of Sciences, Moscow, Russia
| | - V S Paukov
- Acad. A.I. Strukov Department of Pathological Anatomy, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia
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47
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Evaluating prognosis by CK7 differentiating renal cell carcinomas from oncocytomas can be used as a promising tool for optimizing diagnosis strategies. Oncotarget 2018; 7:46528-46535. [PMID: 27341023 PMCID: PMC5216814 DOI: 10.18632/oncotarget.10225] [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: 10/16/2015] [Accepted: 05/13/2016] [Indexed: 11/25/2022] Open
Abstract
Renal Oncocytomas and renal cell carcinomas (RCCs) share a common phenotype. This makes it very difficult to differentiate between the two tumors. Here, this study was to confirmed and expanded the findings that CK7 as a promising tool differentiate RCC from Oncocytomas across various geographic regions. A systematic search of databases was carried out and other relevant articles were also identified. Then the meta-analyses were conducted for 1,711 participants according to the standard guidelines. A total of 21 studies were included on the basis of inclusion criteria. CK7 by IHC was significantly associated with increased diagnosis of RCC (OR=10.64; 95% CI, 7.44-15.23; P=0.0001). Subgroup-analysis showed that findings didn't substantially change when only Caucasians or Asians (OR=10.58; 95% CI, 6.97-16.07; P<0.01 or OR=10.83; 95% CI, 5.39-21.74; P=0.004) were considered. There was also no significant publication bias observed. Our findings provide further evidences that the expression of CK7 contribute to differentiate RCC from Oncocytomas. CK7 protein overexpression was found in RCC, low expression in any of Oncocytomas. CK7 is potentially an important renal tumor marker.
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48
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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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49
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Gomez G, Althaus A, Gruessner CE, Hirsch MS, Steele GS. Clear cell tubopapillary renal cell carcinoma mimicking polycystic kidney disease: A case report. Urol Case Rep 2017; 16:35-37. [PMID: 29062716 PMCID: PMC5645085 DOI: 10.1016/j.eucr.2017.10.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 10/05/2017] [Indexed: 12/01/2022] Open
Abstract
Clear cell tubopapillary renal cell carcinoma (CCTP-RCC) is a distinct histologic subtype of RCC recognized for its unique clinicopathologic and immunohistochemical features. A 72-year-old man with presumed polycystic kidney disease (PKD) and bilateral clear cell RCC (CC-RCC) underwent left radical nephrectomy and right partial nephrectomy 20 years ago at an outside hospital. On surveillance imaging, RCC recurrence was suspected and right radical nephrectomy was performed. Histologic and gross examination of the right remaining kidney was consistent with CCTP-RCC. Review of his original pathology report revealed both kidneys in fact represented CCTP-RCC, mimicking PKD.
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Affiliation(s)
- Gricelda Gomez
- Brigham and Women's Hospital, 75 Francis St. Boston, MA 02115, USA
| | - Adam Althaus
- Brigham and Women's Hospital, 75 Francis St. Boston, MA 02115, USA
| | | | | | - Graeme S Steele
- Brigham and Women's Hospital, 75 Francis St. Boston, MA 02115, USA
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50
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Mantilla JG, Antic T, Tretiakova M. GATA3 as a valuable marker to distinguish clear cell papillary renal cell carcinomas from morphologic mimics. Hum Pathol 2017; 66:152-158. [DOI: 10.1016/j.humpath.2017.06.016] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 06/07/2017] [Accepted: 06/29/2017] [Indexed: 02/07/2023]
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