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PURPOSE: Applications of deep learning to histopathology have proven capable of expert-level performance, but approaches have largely focused on supervised classification tasks requiring context-specific training and deployment. More generalizable workflows that can be easily shared across subspecialties could help accelerate and broaden adoption. Here, we hypothesized that histology-optimized feature representations, generated by a convolutional neural network (CNN) during supervised learning, are transferable and can resolve meaningful differences in large-scale, discovery-type unsupervised analyses. METHODS: We used a CNN, previously trained to recognize brain tumor histomorphologies, to extract 512 feature representations from > 550 digital whole-slide images (WSIs) of renal cell carcinomas (RCCs) from The Cancer Genome Atlas and other previously unencountered tumors. We use these extracted feature vectors to conduct unsupervised image-set clustering and analyze the clinical and biologic relevance of the intra- and interpatient subgroups generated. RESULTS: Within individual WSIs, feature-based clustering could reliably segment tumor regions and other relevant histopathologic subpatterns (eg, adenosquamous and poorly differentiated regions). Across the larger RCC cohorts, clustering extracted features generated subgroups enriched for clinically relevant subtypes (eg, papillary RCC) and outcomes (eg, survival). Importantly, individual feature activation mapping highlighted salient subtype-specific patterns and features of malignancies (eg, nuclear grade, sarcomatous change) contributing to subgroupings. Moreover, some proposed clusters were enriched for recurring, human-based RCC-subtype misclassifications. CONCLUSION: Our data support that CNNs, pretrained on large histologic datasets, can extend learned representations to novel scenarios and resolve clinically relevant intra- and interpatient tissue-pattern differences without explicit instruction or additional optimization. Repositioning of existing histology-educated networks could provide scalable approaches for image classification, quality assurance, and discovery of unappreciated patterns and subgroups of disease. [ABSTRACT FROM AUTHOR]

Most reports of active surveillance (AS) of small renal masses (SRMs) lack biopsy confirmation, and therefore include benign tumors and different subtypes of renal cell carcinoma (RCC). We compared the growth rates and progression of different histologic subtypes of RCC SRMs (SRMRCC) in the largest cohort of patients with biopsy-characterized SRMs on AS. Data from patients in a multicenter Canadian trial and a Princess Margaret cohort were combined to include 136 biopsy-proven SRMRCC lesions managed by AS, with treatment deferred until progression or patient/surgeon decision. Growth curves were estimated from serial tumor size measures. Tumor progression was defined by sustained size ≥4 cm or volume doubling within 1 yr. Median follow-up for patients who remained on AS was 5.8 yr (interquartile range 3.4–7.5 yr). Clear cell RCC SRMs (SRMccRCC) grew faster than papillary type 1 SRMs (0.25 and 0.02 cm/yr on average, respectively, p = 0.0003). Overall, 60 SRMRCC lesions progressed: 49 (82%) by rapid growth (volume doubling), seven (12%) increasing to ≥4 cm, and four (6.7%) by both criteria. Six patients developed metastases, and all were of clear cell RCC histology. Limitations include the use of different imaging modalities and a lack of central imaging review. Tumor growth varies between histologic subtypes of SRMRCC and among SRMccRCC, which likely reflects individual host and tumor biology. Without validated biomarkers that predict this variation, initial follow-up of histologically characterized SRMs can inform personalized treatment for patients on AS. Many small kidney cancers are suitable for surveillance and can be monitored over time for change. We demonstrate that different types of kidney cancers grow at different rates and are at different risks of progression. These results may guide better personalized treatment. Tumor growth varies within and between histological subtypes of small renal masses (renal cell carcinomas), which likely reflects individual host and tumor biology. Histology-specific growth rates and initial monitoring of small renal masses can inform personalized treatment for patients on active surveillance. [ABSTRACT FROM AUTHOR]

Aims: The International Collaboration on Cancer Reporting (ICCR) has provided detailed data sets based upon the published reporting protocols of the Royal College of Pathologists, the Royal College of Pathologists of Australasia and the College of American Pathologists. Methods and results: The data set for carcinomas of renal tubular origin treated by nephrectomy was developed to provide a minimum structured reporting template suitable for international use, and incorporated recommendations from the 2012 Vancouver Consensus Conference of the International Society of Urological Pathology (ISUP) and the fourth edition of the World Health Organisation Bluebook on tumours of the urinary and male genital systems published in 2016. Reporting elements were divided into those, which are required and recommended components of the report. Required elements are: specimen laterality, operative procedure, attached structures, tumour focality, tumour dimension, tumour type, WHO/ISUP grade, sarcomatoid/rhabdoid morphology, tumour necrosis, extent of invasion, lymph node status, surgical margin status, AJCC TNM staging and co-existing pathology. Recommended reporting elements are: preoperative treatment, details of tissue removed for experimental purposes prior to submission, site of tumour(s) block identification key, extent of sarcomatoid and/or rhabdoid component, extent of necrosis, presence of tumour in renal vein wall, lymphovascular invasion and lymph node status (size of largest focus and extranodal extension). Conclusions: It is anticipated that the implementation of this data set in routine clinical practice will inform patient treatment as well as provide standardised information relating to outcome prediction. The harmonisation of data reporting should also facilitate international research collaborations. [ABSTRACT FROM AUTHOR]

Introduction: Renal tumour biopsies (RTBs) can provide the histology of small renal masses (SRMs) prior to treatment decisionmaking. However, many urologists are reluctant to use RTB as a standard of care. This study characterizes the current use of RTB in the management of SRMs and identifies barriers to a more widespread adoption. Methods: A web-based survey was sent to members of the Canadian and Quebec Urological Associations who had registered email address (n=767) in June 2016. The survey examined physicians' practice patterns, RTB use, and potential barriers to RTB. Chi-squared tests were used to assess for differences between respondents. Results: The response rate was 29% (n=223), of which 188 respondents were eligible. A minority of respondents (12%) perform RTB in >75% of cases, while 53% never perform or perform RTB in <25% of cases. Respondents with urological oncology fellowship training were more likely to request a biopsy than their colleagues without such training. The most frequent management-related reason for not using routine RTB was a belief that biopsy won't alter management, while the most frequent pathology-related reason was the risk of obtaining a false-negative or a non-diagnostic biopsy. Conclusions: Adoption of RTBs remains low in Canada. Concerns about the accuracy of RTB and its ability to change clinical practice are the largest barriers to adoption. A knowledge translation strategy is needed to address these concerns. Future studies are also required in order to define where RTB is most valuable and how to best to implement it. [ABSTRACT FROM AUTHOR]

MiT family translocation tumors are a group of neoplasms characterized by translocations involving MiT family transcription factors. The translocation renal cell carcinomas, TFE3 (Xp11.2) and TFEB (t6;11) are known members of this family. Melanotic Xp11 translocation renal cancer is a more recently described entity. To date only 14 cases have been described. It is characterized by a distinct set of features including a nested epithelioid morphology, melanin pigmentation, labeling for markers of melanocytic differentiation, lack of labeling for markers of renal tubular differentiation, predominance in a younger age population and association with aggressive clinical behavior. There are noted similarities between that entity and TFE3 associated PEComas. There are no cases reported of equivalent melanotic TFEB translocation renal cancer. We report 2 rare cases of melanotic translocation renal neoplasms. The first is a melanotic TFE3 translocation renal cancer with an indolent clinical course, occurring in a patient more than 3-decades older than the usual average age in which such tumors have been described. The other case is, to our knowledge, the first reported melanotic TFEB translocation cancer of the kidney. Both cases exhibit the same H&E morphology as previously reported in melanotic translocation renal cancers and label accordingly with HMB45 and Melan-A. While the TFE3 melanotic tumor lacked any evidence of renal tubular differentiation, the TFEB melanotic cancer exhibited some staining for renal tubular markers. Based on the unique features noted above, these two cases expand the clinical and molecular spectrum of the melanotic translocation renal cancers. [ABSTRACT FROM AUTHOR]

Background: Patients with clear cell renal cell carcinoma (ccRCC) have few therapeutic options, as ccRCC is unresponsive to chemotherapy and is highly resistant to radiation. Recently targeted therapies have extended progression-free survival, but responses are variable and no significant overall survival benefit has been achieved. Commercial ccRCC cell lines are often used as model systems to develop novel therapeutic approaches, but these do not accurately recapitulate primary ccRCC tumors at the genomic and transcriptional levels. Furthermore, ccRCC exhibits significant intertumor genetic heterogeneity, and the limited cell lines available fail to represent this aspect of ccRCC. Our objective was to generate accurate preclinical in vitro models of ccRCC using tumor tissues from ccRCC patients.Methods: ccRCC primary single cell suspensions were cultured in fetal bovine serum (FBS)-containing media or defined serum-free media. Established cultures were characterized by genomic verification of mutations present in the primary tumors, expression of renal epithelial markers, and transcriptional profiling.Results: The apparent efficiency of primary cell culture establishment was high in both culture conditions, but genotyping revealed that the majority of cultures contained normal, not cancer cells. ccRCC characteristically shows biallelic loss of the von Hippel Lindau (VHL) gene, leading to accumulation of hypoxia-inducible factor (HIF) and expression of HIF target genes. Purification of cells based on expression of carbonic anhydrase IX (CA9), a cell surface HIF target, followed by culture in FBS enabled establishment of ccRCC cell cultures with an efficiency of >80 %. Culture in serum-free conditions selected for growth of normal renal proximal tubule epithelial cells. Transcriptional profiling of ccRCC and matched normal cell cultures identified up- and down-regulated networks in ccRCC and comparison to The Cancer Genome Atlas confirmed the clinical validity of our cell cultures.Conclusions: The ability to establish primary cultures of ccRCC cells and matched normal kidney epithelial cells from almost every patient provides a resource for future development of novel therapies and personalized medicine for ccRCC patients. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (cc RCC) is the most prevalent adult kidney cancer. Prognostic markers are needed to guide patient management toward aggressive versus more conservative approaches, especially for small tumors ≤4 cm. miR-194 was reported to be downregulated in several cancers and is involved in epithelial to mesenchymal transition. We evaluated miR-194 as a prognostic marker in cc RCC. In a cohort of 234 patients with primary cc RCC, we correlated miR-194 expression level with multiple clinicopathological features including disease-free and overall survival, tumor size, clinical stage, and histological grade. Our results shows a stepwise decrease in miR-194 expression from normal kidney to primary cc RCC ( P = 0.0032) and a subsequent decrease from primary to metastatic lesions. Additionally, patients with higher miR-194 expression has significantly longer disease-free survival ( P = 0.041) and overall survival ( P = 0.031) compared to those with lower expression. In multivariate analysis, miR-194-positive tumors retain significance in disease-free survival and overall survival, suggesting miR-194 is an independent marker for good prognosis in cc RCC. Moreover, miR-194 is a marker for good prognosis for patients with small renal masses ( P = 0.014). These findings were validated on an independent data set from The Cancer Genome Atlas. We also compared miR-194 expression between RCC subtypes. cc RCC had the highest levels, whereas chromophobe RCC and oncocytoma had comparable lower levels. Target prediction coupled with pathway analysis show that miR-194 is predicted to target key molecules and pathways involved in RCC progression. miR-194 represents a prognostic biomarker in cc RCC. [ABSTRACT FROM AUTHOR]

Background Renal tumor biopsy (RTB) for the characterization of small renal masses (SRMs) has not been widely adopted despite reported safety and accuracy. Without pretreatment biopsy, patients with benign tumors are frequently overtreated. Objective To assess the diagnostic rate of RTBs, to determine their concordance with surgical pathology, and to assess their impact on management. Design, setting, and participants This is a single-institution retrospective study of 529 patients with biopsied solid SRMs ≤4 cm in diameter. RTBs were performed to aid in clinical management. Outcome measurements and statistical analysis Diagnostic and concordance rates were presented using proportions. Factors that contributed to a diagnostic biopsy were identified using a multivariable logistic regression. Results and limitations The first biopsy was diagnostic in 90% ( n = 476) of cases. Of the nondiagnostic biopsies, 24 patients underwent a second biopsy of which 83% were diagnostic. When both were combined, RTBs yielded an overall diagnostic rate of 94%. Following RTB, treatment could have been avoided in at least 26% of cases because the lesion was benign. Tumor size and exophytic location were significantly associated with biopsy outcome. RTB histology and nuclear grade were highly concordant with final pathology (93% and 94%, respectively). Adverse events were low (8.5%) and were all self-limited with the exception of one. Although excellent concordance between RTB and final pathology was observed, only a subset of patients underwent surgery following biopsy. Thus it is possible that some patients were misdiagnosed. Conclusions RTB of SRMs provided a high rate of diagnostic accuracy, and more than a quarter were benign. Routine RTB for SRMs informs treatment decisions and diminishes unnecessary intervention. Our results support its systematic use and suggest that a change in clinical paradigm should be considered. Patient summary Renal tumor biopsy (RTB) for pretreatment identification of the pathology of small renal masses (SRMs) is safe and reliable and decreases unnecessary treatment. Routine RTB should be considered in all patients with an indeterminate SRM for which treatment is being considered. [ABSTRACT FROM AUTHOR]

The use of percutaneous renal tumour biopsy (RTB) as a diagnostic tool for the histological characterization of renal masses has increased dramatically within the last 30 years. This increased utilization has paralleled advances in imaging techniques and an evolving knowledge of the clinical value of nephron sparing surgery. Improved biopsy techniques using image guidance, coupled with the use of smaller gauge needles has led to a decrease in complication rates. Reports from series containing a large number of cases have shown the non-diagnostic rate of RTB to range from 4% to 21%. Re-biopsy has been shown to reduce this rate, while the use of molecular markers further improves diagnostic sensitivity. In parallel with refinements of the biopsy procedure, there has been a rapid expansion in our understanding of the complexity of renal cell neoplasia. The 2013 Vancouver Classification is the current classification for renal tumours, and contains five additional entities recognized as novel forms of renal malignancy. The diagnosis of tumour morphotype on RTB is usually achievable on routine histology; however, immunohistochemical studies may be of assistance in difficult cases. The morphology of the main tumour subtypes, based upon the Vancouver Classification, is described and differentiating features are discussed. [ABSTRACT FROM AUTHOR]

Background Over 90% of cancer-related deaths in clear cell renal cell carcinoma (RCC) are caused by tumor relapse and metastasis. Thus, there is an urgent need for new molecular markers that can potentiate the efficacy of the current clinical-based models of prognosis assessment. The objective of this study is to evaluate the potential significance of lactate dehydrogenase A (LDHA), assessed by immunohistochemical staining, as a prognostic marker in clear cell renal cell carcinoma in relation to clinicopathological features and clinical outcome. Methods We assessed the expression of LDHA at the protein level, by immunohistochemistry, and correlated its expression with multiple clinicopathological features including tumor size, clinical stage, histological grade, disease-free and overall survival in 385 patients with primary clear cell renal cell carcinoma. We also correlated the LDHA expression with overall survival, at mRNA level, in an independent data set of 170 clear cell renal cell carcinoma cases from The Cancer Genome Atlas databases. Cox proportional hazards models adjusted for the potential clinicopathological factors were used to test for associations between the LDHA expression and both disease-free survival and overall survival. Results There is statistically significant positive correlation between LDHA level of expression and tumor size, clinical stage and histological grade. Moreover, LDHA expression shows significantly inverse correlation with both disease-free survival and overall survival in patients with clear cell renal cell carcinoma. Our results are validated by examining LDHA expression, at the mRNA level, in the independent data set of clear cell renal cell carcinoma cases from The Cancer Genome Atlas databases which also shows that higher lactate dehydrogenase A expression is associated with significantly shorter overall survival. Conclusion Our results indicate that LDHA up-regulation can be a predictor of poor prognosis in clear cell renal cell carcinoma. Thus, it represents a potential prognostic biomarker that can boost the accuracy of other prognostic models in patients with clear cell renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Most small renal masses (SRMs) are diagnosed inci-dentally and have a low malignant potential. As more elderly patients and infirm patients are diagnosed with SRMs, there is an increased interest in active surveillance (AS) with delayed inter-vention. Patient and tumour characteristics relating to aggressive disease have not been well-studied. The objective was to determine predictors of growth of SRMs treated with AS. Methods: A multicentre prospective phase 2 clinical trial was con-ducted on 207 SRMs in 169 patients in 8 institutions in Canada from 2004 to 2009; in these patients treatment was delayed until disease progression. Patient and tumour characteristics were evalu-ated to determine predictors of growth of SRMs by measuring rates of change in growth (on imaging) overtime. All patients underwent AS for presumed renal cell carcinoma (RCC) based on diagnostic imaging. We used the following factors to develop a predictive model of tumour growth with binary recursive partitioning analysis: patient characteristics (age, symptoms at diagnosis) and tumour characteristics (consistency [solid vs. cystic] and maximum diam-eter at diagnosis. Results: With a median follow-up of 603 days, 169 patients (with 207 SRMs) were followed prospectively. Age, symptoms at diagno-sis, tumour consistency and maximum diameter of the renal mass were not predictors of growth. This cohort was limited by lack of availability of patient and tumour characteristics, such as sex, degree of endophytic component and tumour location. Conclusion: Slow growth rates and the low malignant potential of SRMs have led to AS as a treatment option in the elderly and infirm population. In a large prospective cohort, we have shown that age, symptoms, tumour consistency and maximum diameter of the mass at diagnosis are not predictors of growth of T1 a lesions. More knowledge on predictors of growth of SRMs is needed. [ABSTRACT FROM AUTHOR]

Abstract: The use of needle biopsies in basic research is increasing, and our study provides a comprehensive analysis of their adequacy in genomic and proteomic studies of kidney cancer. Frozen clear cell renal cell carcinoma (ccRCC) needle core biopsies and sections from core biopsies embedded in optimal cutting temperature (OCT) compound were used to extract DNA, RNA and protein. Their integrity was determined using genomic and proteomic analyses. VHL mutation testing was performed on ccRCC biopsies and corresponding tumors using bulk and laser capture microdissection (LCM) extractions for comparison. Adequate amounts of good quality DNA (5.8–13.3μg/whole core, 0.6–2.7μg/20 sections), RNA (2.9–11.9μg/whole core, 0.5–1.3μg/20 sections) and protein (137.4–444μg/whole core, 39.9–74.1μg/20 sections) were obtained from whole core and frozen sections of ccRCC needle biopsies, respectively. We observed VHL sequence mutations in 75% of ccRCC tumors and, in most cases, the same mutations were detected in both tumors and corresponding biopsies. Mutations observed by bulk extractions from tumors and biopsies were also detected by LCM without significant differences between both methodologies. ccRCC needle biopsies provide ample material for genomic and proteomic studies of kidney cancer. They are good representatives of their corresponding tumors for VHL mutation detection using both bulk and LCM extractions. LCM does not increase sensitivity of VHL mutation detection. [Copyright &y& Elsevier]

Abstract: Background: Percutaneous needle core biopsy has become established in the management of small renal masses ≤4cm (SRMs). Recent series have reported success rates of ≥80%. Nondiagnostic results continue to be problematic. Objective: To determine the results of SRM biopsy and the outcomes of nondiagnostic biopsy and repeat biopsy. Design, setting, and participants: Patients undergoing renal tumor biopsy (RTB) for suspected renal cell carcinoma (RCC) were included in a prospectively maintained database. Measurements: The database was analyzed retrospectively to determine the pathology and outcomes of SRM biopsy. Outcomes of patients with nondiagnostic biopsy were determined. Patients undergoing repeat biopsy were identified and their outcomes analyzed. Results and limitations: Three hundred forty-five biopsies were performed (mean diameter: 2.5cm). Biopsy was diagnostic in 278 cases (80.6%) and nondiagnostic in 67 cases (19.4%). Among diagnostic biopsies, 221 (79.4%) were malignant, 94.1% of which were RCC. Histologic subtyping and grading of RCC was possible in 88.0% and 63.5% of cases, respectively. Repeat biopsy was performed in 12 of the 67 nondiagnostic cases, and a diagnosis was possible in 10 (83.3%). Eight lesions were malignant and two were oncocytic neoplasms. Pathology was available for 15 masses after initial nondiagnostic biopsy; 11 (73%) were malignant. Larger tumor size and a solid nature on imaging predicted a successful biopsy on multivariate analysis. Grade 1 complications were experienced in 10.1% of cases, with no major bleeding and no seeding of the biopsy tract. There was one grade 3a complication (0.3%). This is a retrospective study and some data are unavailable on factors that may affect biopsy success rates. Repeat biopsy was not standard practice prior to this analysis. Conclusions: RTB can be performed safely and accurately in the investigation of renal masses ≤4cm. A nondiagnostic biopsy should not be considered a surrogate for the absence of malignancy. Repeat biopsy can be performed with similar accuracy, providing a diagnosis for most patients. [Copyright &y& Elsevier]

Abstract: Background: Most early stage kidney cancers are renal cell carcinomas (RCCs), and most are diagnosed incidentally by imaging as small renal masses (SRMs). Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize. Objective: To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology. Design, setting, and participants: A multicenter prospective phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and/or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression. Intervention: Patients underwent serial imaging and needle core biopsies. Measurements: We measured rates of change in tumor diameter (growth measured by imaging) and progression to ≥4cm, doubling of tumor volume, or metastasis with histology on biopsy. Results and limitations: Local progression occurred in 25 patients (12%), plus 2 progressed with metastases (1.1%). Of the 178 subjects with 209 SRMs, 127 with 151 SRMs had>12 mo of follow-up with two or more images, with a mean follow-up of 28 mo. Their tumor diameters increased by an average of 0.13cm/yr. Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate. Limitations included no central review of imaging and pathology and a short follow-up. Conclusions: This is the first SRM active surveillance study to correlate growth with histology prospectively. In the first 2 yr, the rate of local progression to higher stage is low, and metastases are rare. SRMs appear to grow very slowly, even if biopsy proven to be RCC. Many patients with SRMs can therefore be initially managed conservatively with serial imaging, avoiding the morbidity of surgical or ablative treatment. [Copyright &y& Elsevier]

Abstract: Background: Renal cell carcinoma (RCC) encompasses different histologic subtypes. Distinguishing between the subtypes is usually made by morphologic assessment, which is not always accurate. Objective: Our aim was to identify microRNA (miRNA) signatures that can distinguish the different RCC subtypes accurately. Design, setting, and participants: A total of 94 different subtype cases were analysed. miRNA microarray analysis was performed on fresh frozen tissues of three common RCC subtypes (clear cell, chromophobe, and papillary) and on oncocytoma. Results were validated on the original as well as on an independent set of tumours, using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis with miRNA-specific primers. Measurements: Microarray data were analysed by standard approaches. Relative expression for qRT-PCR was determined using the ΔΔCT method, and expression values were normalised to small nucleolar RNA, C/D box 44 (SNORD44, formerly RNU44). Experiments were done in triplicate, and an average was calculated. Fold change was expressed as a log2 value. The top-scoring pairs classifier identified operational decision rules for distinguishing between different RCC subtypes and was robust under cross-validation. Results and limitations: We developed a classification system that can distinguish the different RCC subtypes using unique miRNA signatures in a maximum of four steps. The system has a sensitivity of 97% in distinguishing normal from RCC, 100% for clear cell RCC (ccRCC) subtype, 97% for papillary RCC (pRCC) subtype, and 100% accuracy in distinguishing oncocytoma from chromophobe RCC (chRCC) subtype. This system was cross-validated and showed an accuracy of about 90%. The oncogenesis of ccRCC is more closely related to pRCC, whereas chRCC is comparable with oncocytoma. We also developed a binary classification system that can distinguish between two individual subtypes. Conclusions: MiRNA expression patterns can distinguish between RCC subtypes. [Copyright &y& Elsevier]

The most common renal tumours are clear cell, papillary, chromophobe and collecting duct renal cell carcinomas (RCCs), and benign oncocytomas and angiomyolipomas. Tumours with hybrid features between some of these entities have been recognised; in particular, tumours with features of both chromophobe RCC and oncocytoma. Case reports describing one distinct type of primary renal tumour actually within another are very rare. The incidental finding of a papillary RCC located in an oncocytoma in a nephrectomy specimen from a 75-year-old man is described. Morphological criteria for each tumour type were completely satisfied and fluorescence in situ hybridisation detected the expected number of copies of chromosome 7 in the cells of each tumour type. The cells in the papillary tumour contained three copies, whereas the oncocytoma cells contained only two per nucleus. To our knowledge, this is the first report of a papillary RCC being identified within an oncocytoma. [ABSTRACT FROM AUTHOR]