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Objectives: To investigate different radiomics models based on single phase and the different phase combinations of radiomics features from 3D tri-phasic CT to distinguish RO from chRCC., Methods: A total of 96 patients (30 RO and 66 chRCC) were enrolled in this study. Radiomics features were extracted from unenhanced phase (UP), corticomedullary phase (CMP), and nephrographic phase (NP) CT images. Feature selection was based on the least absolute shrinkage and selection operator regression (LASSO) method. The selected features were used to develop different radiomics models using logistic regression (LR) analysis, including model 1 (UP), model 2(CMP), model 3(NP), model 4(UP+CMP), model 5(UP+NP), model 6(CMP+NP), and model 7(UP+CMP+NP). The radiomics model demonstrating the highest discrimination performance was utilized to construct the combined model (model 8) with clinical factors. A nomogram based on the model 8 was established. To evaluate the diagnostic performance of the different models, the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used. Delong's test was utilized to assess the statistical significance of the AUC improvement across the models., Results: Among the seven radiomics models, model 7 exhibited the highest AUC of 0.84 (95% CI 0.69, 0.99), and model 7 demonstrated a significantly superior AUC compared to the other radiomics models (all P < 0.05). The AUC values of radiomics models based on two phases (model4, mode5, mode6) were greater than the models based on single phase (model1, mode2, mode3) (all P < 0.05). Model 3 illustrated the best performance of the three radiomics models based on single phase with an AUC of 0.76 (95% CI 0.57, 099). Model 6 illustrated the best performance of the three radiomics models based on two-phases combination with an AUC of 0.83 (0.66, 0.99). Model 8 achieved an AUC of 0.93 (95% CI 0.83, 1.00) which is higher than those all radiomics models., Conclusion: Radiomics models based on combination of radiomics features from UP, CMP, and NP can be a useful and promising technique to differentiate RO from chRCC. Moreover, the model combining clinical factors and radiomics features showed better classification performance to distinguish them., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction and Objective: To evaluate whether significant loss in ipsilateral renal parenchymal volume (IRPV) and renal function occurs during active surveillance (AS) of renal oncocytoma (RO) patients., Methods: Renal function (estimated glomerular filtration rate, eGFR) dynamics were retrospectively analyzed in 32 consecutive biopsy-diagnosed RO patients managed with AS at a National Comprehensive Cancer Network institute. Three-dimensional kidney and tumor reconstructions were generated and IRPV was calculated using volumetry software (Myrian®) for all patients with manually estimated RO growth >+10 cm 3 . GFR and IRPV were compared at AS initiation vs. the last follow-up using 2-sided paired t-tests. The correlation between change in IRPV and change in RO size or GFR was tested using a Spearman coefficient., Results: With median follow-up of 37 months, there was no significant change between initial vs. last eGFR (median 71.0 vs. 70.5 ml/min/1.73 m 2 , P = 0.50; median change -3.0 ml/min/1.73 m 2 ). Among patients (n = 17) with RO growth >+10 cm 3 during AS (median growth +28.6 cm 3 , IQR +16.9- + 46.5 cm 3 ), IRPV generally remained stable (median change +0.5%, IQR -1.2%- + 1.2%), with only 2 cases surpassing 5% loss. No IRPV loss was detected among any patient within the top tertile of RO growth magnitude. RO growth magnitude did not correlate with loss of either IRPV (ρ = -0.30, P = 0.24) or eGFR (ρ = -0.16, P = 0.40), including among patient subsets with lower initial eGFR. Study limitations include a lack of long-term follow-up., Conclusions: Volumetry is a promising novel tool to measure kidney and tumor tissue changes during AS. Our study using volumetry indicates that clinically significant loss of IRPV or eGFR is uncommon and unrelated to tumor growth among untreated RO patients with intermediate follow-up. These findings support that AS is in general functionally safe for RO patients, however longer study is needed to determine safety durability, particularly among uncommon ≥cT2 RO variants., Competing Interests: Conflict of interest The authors report no potential conflicts of interest relevant to this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Correct tumor subtyping of primary renal tumors is essential for treatment decision in daily routine. Most of the tumors can be classified based on morphology alone. Nevertheless, some diagnoses are difficult, and further investigations are needed for correct tumor subtyping. Besides histochemical investigations, high-mass-resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can detect new diagnostic biomarkers and hence improve the diagnostic., Patients and Methods: Formalin-fixed paraffin embedded tissue specimens from clear cell renal cell carcinoma (ccRCC, n = 552), papillary renal cell carcinoma (pRCC, n = 122), chromophobe renal cell carcinoma (chRCC, n = 108), and renal oncocytoma (rO, n = 71) were analyzed by high-mass-resolution MALDI fourier-transform ion cyclotron resonance (FT-ICR) MSI. The SPACiAL pipeline was executed for automated co-registration of histological and molecular features. Pathway enrichment and pathway topology analysis were performed to determine significant differences between RCC subtypes., Results: We discriminated the four histological subtypes (ccRCC, pRCC, chRCC, and rO) and established the subtype-specific pathways and metabolic profiles. rO showed an enrichment of pentose phosphate, taurine and hypotaurine, glycerophospholipid, amino sugar and nucleotide sugar, fructose and mannose, glycine, serine, and threonine pathways. ChRCC is defined by enriched pathways including the amino sugar and nucleotide sugar, fructose and mannose, glycerophospholipid, taurine and hypotaurine, glycine, serine, and threonine pathways. Pyrimidine, amino sugar and nucleotide sugar, glycerophospholipids, and glutathione pathways are enriched in ccRCC. Furthermore, we detected enriched phosphatidylinositol and glycerophospholipid pathways in pRCC., Conclusion: In summary, we performed a classification system with a mean accuracy in tumor discrimination of 85.13%. Furthermore, we detected tumor-specific biomarkers for the four most common primary renal tumors by MALDI-MSI. This method is a useful tool in differential diagnosis and biomarker detection., (© 2022 S. Karger AG, Basel.)

Background: 99m Tc-Sestamibi Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) contributes to the non-invasive differentiation of renal oncocytoma (RO) from renal cell carcinoma (RCC) by characterising renal tumours as Sestamibi positive or Sestamibi negative regarding their 99m Tc-Sestamibi uptake compared to the non-tumoral renal parenchyma., Purpose: To determine whether 99m Tc- Sestamibi uptake in renal tumour and the non-tumoral renal parenchyma measured using Standard Uptake Value (SUV) SPECT, has a beneficial role in differentiating RO from RCC., Material and Methods: Fifty-seven renal tumours from 52 patients were evaluated. In addition to visual evaluation of 99m Tc-Sestamibi uptake, SUV max measurements were performed in the renal tumour and the ipsilateral non-tumoral renal parenchyma. Analysis of the area under the receiver operating characteristic curve identified an optimal cut-off value for detecting RO, based on the relative ratio of 99m Tc- Sestamibi uptake., Results: Semiquantitative evaluation of 99m Tc-Sestamibi uptake did not improve the performance of 99m Tc- Sestamibi SPECT/CT in detecting RO. 99m Tc- Sestamibi SPECT/CT identifies a group of mostly indolent Sestamibi-positive tumours with low malignant potential containing RO, Low-Grade Oncocytic Tumours, Hybrid Oncocytic Tumours, and a subset of chromophobe RCCs., Conclusion: The imaging limitations for accurate differentiation of Sestamibi-positive renal tumours mirror the recognised diagnostic complexities of the histopathologic evaluation of oncocytic neoplasia. Patients with Sestamibi-positive renal tumours could be better suited for biopsy and follow-up, according to the current active surveillance protocols.

Renal tumors with oncocytic or chromophobe-like morphology can be a common source of diagnostic difficulty. In some series, they constitute the largest group of unclassified renal cell carcinomas, a term used for neoplasms that do not fit the current classification of renal tumors. We describe the histological, immunohistochemical, and molecular findings of an eosinophilic renal neoplasm which presented with rib and liver metastases, and provide a review of the literature. The possibility of a renal oncocytoma with metastases was initially considered but excluded on the basis of several morphological and immunohistochemical features. Additionally, the tumor did not correspond with other traditional or newly emerging categories of renal neoplasms. It was therefore regarded as an unclassified oncocytic renal neoplasm which demonstrated evidence of malignant potential due to the presence of multiple metastases.

Background: To investigate the value of computed tomography (CT)-based radiomics model analysis in differentiating renal oncocytoma (RO) from renal cell carcinoma subtypes (chromophobe renal cell carcinoma, clear cell carcinoma) and predicting the expression of Cytokeratin 7 (CK7)., Methods: In this retrospective study, radiomics was applied for patients with RO, chRCC and ccRCC who underwent surgery between January 2013 and December 2019 comprised the training cohort, and the testing cohort was collected between January and October 2020. The corticomedullary (CMP) and nephrographic phases (NP) were manually segmented, and radiomics texture parameters were extracted. Support vector machine was generated from CMP and NP after feature selection. Shapley additive explanations were applied to interpret the radiomics features. A radiomics signature was built using the selected features from the two phases, and the radiomics nomogram was constructed by incorporating the radiomics features and clinical factors. Receiver operating characteristic curve was calculated to evaluate the above models in the two sets. Furthermore, Rad-score was used for correlation analysis with CK7., Results: A total of 123 patients with RO, chRCC and ccRCC were analyzed in the training cohort and 57 patients in the testing cohort. Subsequently, 396 radiomics features were selected from each phase. The radiomics features combining two phases yielded the highest area under the curve values of 0.941 and 0.935 in the training and testing sets, respectively. The Pearson's correlation coefficient was statistically significant between Rad-score and CK7., Conclusion: We proposed a non-invasive and individualized CT-based radiomics nomogram to differentiation among RO, chRCC and ccRCC preoperatively and predict the immunohistochemical protein expression for accurate clinical diagnosis and treatment decision., (© 2022. The Author(s).)

Here we report a case of renal oncocytoma in a 68 year-old male. The diagnosis was initially made on a needle biopsy 6 years prior to the partial nephrectomy. The case is unique that in addition to the gross and microscopic features commonly seen in renal oncocytomas, both lymphovascular invasion and prominent intracytoplasmic vacuole-like spaces are also present in this tumor. Although vascular invasion is increasingly recognized as compatible with renal oncocytoma, intracytoplasmic vacuoles are a rare and unusual finding that may lead to diagnostic difficulty. The diagnosis of renal oncocytoma was confirmed after immunohistochemistry was performed to argue against succinate dehydrogenase deficient renal cell carcinoma (RCC) and chromophobe RCC. This case highlights the importance for practicing pathologists to recognize the rare co-occurrence of lymphovascular invasion and large intracytoplasmic vacuole-like spaces in renal oncocytoma. Other differential diagnoses may include emerging renal tumor entities, such as the recently-proposed eosinophilic vacuolated tumor.

Renal oncocytomas are rare benign epithelial tumors of the kidney. However, they are easily misdiagnosed as renal cancers, resulting in unnecessary radical nephrectomy. This review summarizes the use of ultrasound for the diagnosis of renal oncocytomas. On two-dimensional grayscale ultrasound, renal oncocytomas appear as solid, well-defined, round or oval, and relatively isoechoic or slightly hyperechoic masses. On color Doppler flow imaging, the "spoke-wheel" sign is evident. On power Doppler flow imaging, renal oncocytomas show mixed penetrating and peripheral patterns. Renal oncocytomas usually appear as highly enhanced on contrast-enhanced ultrasound images, and irregular nonenhanced areas in larger tumors. This review will help sonographers recognize renal oncocytomas., (© 2021. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Objective: Differentiation between renal oncocytoma (RON) and chromophobe renal cell carcinoma (chRCC) remains challenging. We aimed to assess the accurate apparent diffusion coefficient (ADC) radiomics features in differentiating these tumors., Materials and Methods: This single-center retrospective study included 14 patients with histopathologically proven RON (n = 6) and chRCC (n = 8) who underwent magnetic resonance imaging. Features were extracted from ADC maps. Features with an intraclass correlation coefficient >0.90, an intergroup p < 0.01 and interrater differences with normal distribution underwent agreement and receiver operating characteristic curve analyses., Results: Overall, 6 features qualified for further analysis and Bland-Altman plots revealed acceptable agreement for all. Only 1 first order feature and 5 high order texture features successfully predicted RON with more than 90% sensitivities and specificities more than 80%., Conclusion: Squared mean ADC and certain gray level run length matrix features extracted by radiomics of ADC mapping provide quite high diagnostic precision in terms of distinguishing between RON and chRCC., (Copyright © 2021 AEU. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC) have a common cellular origin and different clinical management and prognosis., Purpose: To explore the utility of computed tomography (CT) in the differentiation of RO and chRCC., Material and Methods: Twenty-five patients with RO and 73 patients with chRCC presenting with the central scar were included retrospectively. Two experienced radiologists independently reviewed the CT imaging features, including location, tumor size, relative density ratio, segmental enhancement inversion (SEI), necrosis, and perirenal fascia thickening, among others. Interclass correlation coefficient (ICC, for continuous variables) or Kappa coefficient test (for categorical variables) was used to determine intra-observer and inter-observer bias between the two radiologists., Results: The inter- and intra-reader reproducibility of the other CT imaging parameters were nearly perfect (>0.81) except for the measurements of fat (0.662). RO differed from chRCC in the cortical or medullary side ( P  = 0.005), relative density ratio ( P  = 0.020), SEI ( P  < 0.001), and necrosis ( P  = 0.045). The logistic regression model showed that location (right kidney), hypo-density on non-enhanced CT, SEI, and perirenal fascia thickening were highly predictive of RO. The combined indicators from logistic regression model were used for ROC analysis. The area under the ROC curve was 0.923 ( P  < 0.001). The sensitivity and specificity of the four factors combined for diagnosing RO were 88% and 86.3%, respectively. The correlation coefficient between necrosis and tumor size in all tumors including both of RO and chRCC was 0.584, indicating a positive correlation ( P  < 0.001)., Conclusion: The CT imaging features of location (right kidney), hypo-density on non-enhanced CT, SEI, and perirenal fascia thickening were valuable indicators in distinguishing RO from chRCC.

Objectives: To study the natural history of renal oncocytomas and address indications for intervention by determining how growth is associated with renal function over time, the reasons for surgery and ablation, and disease-specific survival., Patients and Methods: The study was conducted in a retrospective cohort of consecutive patients with renal oncocytoma on active surveillance reviewed at the Specialist Centre for Kidney Cancer at the Royal Free London NHS Foundation Trust (2012 to 2019). Comparison between groups was performed using Mann-Whitney U-tests and chi-squared tests. A mixed-effects model with a random intercept for patient was used to study the longitudinal association between tumour size and estimated glomerular filtration rate (eGFR)., Results: Longitudinal data from 98 patients with 101 lesions were analysed. Most patients were men (68.3%) and the median (interquartile range [IQR]) age was 69 (13) years. The median (IQR) follow-up was 29 (26) months. Most lesions were small renal masses, and 24% measured over 4 cm. Over half (64.4%) grew at a median (IQR) rate of 2 (4) mm per year. No association was observed between tumour size and eGFR over time (P = 0.871). Nine lesions (8.9%) were subsequently treated. Two deaths were reported, neither were related to the diagnosis of renal oncocytoma., Conclusion: Natural history data from the largest active surveillance cohort of renal oncocytomas to date show that renal function does not seem to be negatively impacted by growing oncocytomas, and confirms clinical outcomes are excellent after a median follow-up of over 2 years. Active surveillance should be considered the 'gold standard' management of renal oncocytomas up to 7cm., (© 2021 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Purpose: Renal oncocytoma (RO) is the most commonly resected benign renal tumor because of misdiagnosis as renal cell carcinoma. This misdiagnosis is generally owing to overlapping imaging features. This study describes the building of a radiomics nomogram based on clinical data and radiomics signature for the preoperative differentiation of RO from clear cell renal cell carcinoma (ccRCC) on tri-phasic contrast-enhanced CT., Methods: A total of 122 patients (85 in training set and 37 in external validation set) with ROs (n = 46) or ccRCCs (n = 76) were enrolled. Patient characteristics and tri-phasic contrast-enhanced CT imaging features were evaluated to build a clinical factors model. A radiomics signature was constructed by extracting radiomics features from tri-phasic contrast-enhanced CT images and a radiomics score (Rad-score) was calculated. A radiomics nomogram was then built by incorporating the Rad-score and significant clinical factors according to a multivariate logistic regression analysis. The diagnostic performance of the above three models was evaluated in training and validation sets., Results: Central stellate area and perirenal fascia thickening were selected to build the clinical factors model. Eleven radiomics features were combined to construct the radiomics signature. The AUCs of the radiomics nomogram, which was based on the selected clinical factors and Rad-score, were 0.960 and 0.898 in the training and validation sets, respectively. The decision curves of the radiomics nomogram and radiomics signature in the validation set indicated an overall net benefit over the clinical factors model., Conclusion: Our radiomics nomogram can effectively predict the preoperative diagnosis of ROs and may therefore be of assistance in sparing unnecessary surgery and tailoring precise therapy. The ROC curves of the clinical model, the radiomics signature and the radiomics nomogram for the validation set. RO = Renal oncocytoma; ccRCC = Clear cell renal cell carcinoma., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate the ability of inferior vena cava-lesion-attenuation-difference (ILAD) and lesion-cortex-attenuation-ratio (LCAR) to differentiate renal oncocytomas (RO) from chromophobe renal cell carcinomas (chRCC)., Methods: Retrospective study with analysis of 84 cases of chRCC and 30 cases of RO confirmed by surgical pathology. ILAD was calculated by measuring the difference in Hounsfield units (HU) between the inferior vena cava and the lesion of interest on the same image slice on preoperative CT scan. Calculating LCAR using the CT attenuation ratio of lesion to renal cortex at the same image slice. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic values of ILAD and LCAR for disease activity., Results: There were no statistically significant differences in demographic and lesion characteristics between patients with chRCC and RO (p > 0.05). ILAD has significant statistical differences in the identification of RO and chRCC in the arterial (p = 0.031), venous (p = 0.047), and delayed phase (p = 0.002). And LCAR showed a statistically significant difference between two lesions during the arterial (p = 0.043), venous (p = 0.026), and delayed phase (p = 0.008). When all significant variables were used in combination to build a predicting model (Mix), the AUC was 0.871 (95% CI 0.759-0.984) with 67.9% sensitivity and 100% specificity., Conclusion: ILAD and LCAR at the arterial phase, venous phase and delayed phase were shown to be useful CT attenuation parameter in discriminating RO from chRCC when histologic evaluation on biopsy is indeterminate.

FOXI1 is a forkhead family transcription factor that plays a key role in differentiation and functional maintenance for the renal intercalated cell (IC). The diagnostic utility of FOXI1 is rarely studied thus far. Comparative analyses of FOXI1 mRNA expression in normal kidney tissue and different renal neoplasms including chromophobe renal cell carcinoma (chRCC), renal oncocytoma (RO), and other renal cell carcinomas were conducted using transcriptomic data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and single-cell RNA-seq datasets, in combination with integrative analyses using mutant data, karyotype data, and digital slides for cases with anomalous FOXI1 expression in TCGA. Formalin-fixed, paraffin-embedded whole-tissue slides of varied primary renal neoplasms (n = 367) were subjected to FOXI1 staining for validating FOXI1 transcription levels. We confirmed that FOXI1 was significantly upregulated at mRNA levels in ICs, chRCCs, and ROs compared with other renal tubule cell and renal cell carcinoma subtypes. Furthermore, most of the cases with FOXI1 expression outliers were misclassified in the TCGA kidney cancer project. An underlying novel entity with frequent mutations involved in the mTOR pathway was also found. FOXI1 immunoreactivity was consistently noted in ICs of the distal nephron. FOXI1 staining was positive in 85 of 93 chRCCs and 13 of 18 ROs, respectively. FOXI1 staining was not seen in renal neoplasms (n = 254) derived from non-ICs. In conclusion, FOXI1 expression in normal kidney tissue is restricted to ICs. This cell type-specific expression is retained during neoplastic transformation from ICs to chRCCs or ROs. FOXI1 is thereby a potential biomarker of IC-related tumors.

The histologic features of renal oncocytoma (RO) are similar to those for the more aggressive chromophobe renal cell carcinoma (ChRCC). To assess immunohistochemical markers of the two, the sensitivity and specificity of cytokeratin 7 (CK7) and C-kit, as well as hepatocyte nuclear factor-1β (HNF-1β), were analyzed. Typical cases of ChRCC and RO at Severance Hospital between July 2014 and July 2018 were selected retrospectively. Among 44 cases, 17 were unanimously compatible with ChRCC, 16 were RO, and 11 cases were indeterminate. Samples from all selected cases were used for immunostaining with antibodies against CK7, C-kit, HNF-1β, and CD10. Immunostaining demonstrated complete loss of HNF-1β expression in 11 out of 17 (64.7%) ChRCC cases and a partial, but significant loss in > 50% of tumor cells in the remaining 6 cases (35.3%). In contrast, HNF-1β expression was preserved in tumor cells of RO cases. Fourteen of 17 ChRCC cases (82.4%) were diffusely positive for CK7, whereas cases of RO were focal positive or negative. C-kit staining did not show a significant difference between ChRCC and RO. Two of five ChRCC cases showing diffuse immunoreactivity for CD10 had poor prognoses of local invasion, distant metastasis, or death. Loss of HNF-1β expression is a useful marker with which to diagnose ChRCC, especially in cases with confusing histologic findings or equivocal CK7 staining. Additionally, CD10 staining in high-grade ChRCC aids in diagnosis and prediction of the clinical prognosis.

Renal oncocytoma (RO) accounts for 5% of renal cancers and generally behaves as a benign tumor with favorable long-term prognosis. It is difficult to confidently distinguish between benign RO and other renal malignancies, particularly chromophobe renal cell carcinoma (chRCC). Therefore, RO is often managed aggressively with surgery. We sought to identify molecular biomarkers to distinguish RO from chRCC and other malignant renal cancer mimics. In a 44-patient discovery cohort, we identified a significant differential abundance of nine genes in RO relative to chRCC. These genes were used to train a classifier to distinguish RO from chRCC in an independent 57-patient cohort. The trained classifier was then validated in five independent cohorts comprising 89 total patients. This nine-gene classifier trained on the basis of differential gene expression showed 93% sensitivity and 98% specificity for distinguishing RO from chRCC across the pooled validation cohorts, with a c-statistic of 0.978. This tool may be a useful adjunct to other diagnostic modalities to decrease the diagnostic and management uncertainty associated with small renal masses and to enable clinicians to recommend more confidently less aggressive management for some tumors. PATIENT SUMMARY: Renal oncocytoma is generally a benign form of kidney cancer that does not necessarily require surgical removal. However, it is difficult to distinguish renal oncocytoma from other more aggressive forms of kidney cancer, so it is treated most commonly with surgery. We built a classification tool based on the RNA levels of nine genes that may help avoid these surgeries by reliably distinguishing renal oncocytoma from other forms of kidney cancer., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: We investigate the use of ratio of lesion to cortex (L/C) attenuation and aorta-lesion attenuation difference (ALAD) on multiphase contrast-enhanced CT to help distinguish oncocytoma from clear cell RCC in small renal masses (diameter < 4 cm)., Methods: We retrospectively identified 76 patients that undergo CT before surgery for a suspicious small renal mass between January 2014 and December 2018 with pathological diagnosis of 21 oncocytomas (ROs), 25 clear cell RCCs, 7 chromophobe RCCs, 7 papillary RCCs, 7 multilocular cystic RCCs, 7 angiomyolipomas and 2 leiomyomas. CT attenuation values were obtained for the tumor, the normal renal cortex and the aorta, placing a circular region of interest (ROI) in the same slice by two radiologists, independently., Results: In the corticomedullary phase, ROs showed isodense enhancement to the renal cortex (ratio L/C 0.92 ± 0.12), while clear cell RCCs appeared hypodense to the renal cortex (ratio L/C 0.69 ± 0.20; p < 0.01) with an accuracy of 80% for diagnosing RO. In nephrographic phase, the ratio L/C attenuation was lower than the corticomedullary phase in ROs (0.78 ± 0.11) showing an early washout pattern, while the ratio L/C was similar to the corticomedullary phase in clear cell RCCs (0.69 ± 0.13; p = 0.025, with an accuracy of 65% for diagnosing RO). The ratio L/C attenuation showed considerable overlap between ROs and clear cell RCCs in the excretory phase (p = 0.27). Mean ALAD values in the nephrographic phase were 21.95 ± 16.24 for ROs and 36.96 ± 30.53 for clear cell RCCs (p = 0.049)., Conclusion: The ratio L/C attenuation in corticomedullary phase may be useful to differentiate RO from clear cell RCC.

Background: The present study aims to evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) for discriminating between benign and malignant solid renal masses., Methods: 18 patients with histopathologically confirmed benign solid renal masses (11 oncocytomas, seven angiomyolipomas) as well as 96 patients with confirmed renal cell carcinoma (RCC) who underwent CEUS followed by radical or partial nephrectomy were included in this single-center study. CEUS examinations were performed by an experienced radiologist (EFSUMB Level 3) and included the application of a second-generation contrast agent., Results: Renal angiomyolipomas, oncocytomas, and renal cell carcinomas showed varying sonomorphological characteristics in CEUS. Angiomyolipomas showed heterogeneous echogenicity (57% hypo-, 43% hyperechoic), while all lesions showed rapid contrast-enhancement with two lesions also showing venous wash-out (29%). Notably, 9/11 oncocytomas could be detected in conventional ultrasound (64% hypo-, 9% hyper-, 9% isoechoic) and 2/11 only demarcated upon intravenous application of contrast agent (18%). All oncocytomas showed hyperenhancement in CEUS, venous wash-out was registered in 7/11 lesions (64%)., Conclusions: In line with the current state of knowledge, no specific sonomorphological characteristics allowing for accurate distinction between benign and malignant solid renal masses in CEUS could be detected in our study.

Objective: Renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC) originate from the same cell origin, that is, the intercalated cells of the collecting duct. [1] In most cases, there are clear morphologic differences between RO and ChRCC; however, in some instances, overlapping features may be encountered and the differentiation between the two entities becomes difficult. [2] Several immunohistochemical markers with different expression patterns in ChRCC and RO have been described to rule out this dilemma., Materials and Methods: About 47 primary renal neoplasms that had been diagnosed as RO or ChRCC were submitted for immunohistochemical staining of amylase α-1A (AMY1A), MOC 31, and CD 82. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy have been analyzed., Results: AMY1A positivity was observed in all RO cases in our work with 91.7% sensitivity and 100% specificity in the diagnosis of RO. The PPV of its expression was (100%) and NPV (97.2%) with a diagnostic accuracy of 97.9%. A significant high expression of MOC 31 was observed in ChRCC compared to its expression in RO with a statistical significance (P < 0.001). In addition, we obtained 82.9% sensitivity and 91.7% specificity of MOC 31 expression in the diagnosis of ChRCC. The positive predictive value (PPV) was (96.7%), negative predictive value (NPV) (64.7%) with diagnostic accuracy (85.1%). In our studied cases, we detected positive immunoexpression of CD 82 in 10 cases (83.3%) of ChRCC. However, it was lost in all RO cases (100%). CD 82 sensitivity and specificity in differentiating ChRCC from RO were 100% and 83.3%, respectively., Conclusion: We propose MOC 31 and CD 82 as negative immunostains for RO, as these markers are commonly expressed in ChRCC. In conjunction with AMY1A strong immunopositivity in RO cases, we provide a triple panel of biomarkers (AMY1A, MOC 31, and CD 82) for the distinction between RO and ChRCC.

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Objectives . Differentiating renal oncocytoma (RO) from chromophobe renal cell carcinoma (ChRCC) can occasionally be challenging. We evaluated the expression of RB1 and ERBB4 in RO and ChRCC, and compared the immunohistochemistry (IHC) results to RB1 and ERBB4 gene abnormalities detected by fluorescence in situ hybridization (FISH). Materials and Methods. Fifty-three kidney resections (ChRCC, n=28; RO, n=25) were stained for RB1 and ERBB4 IHC and FISH was performed to evaluate gene copy number analysis. Results. A loss of RB1 staining was identified in 64% (18/28) of ChRCCs, which was not found in any ROs (0/25; P <.001). FISH analysis revealed 36% (10/28) of ChRCCs contained a RB1 hemizygous deletion with a concordance of 56% (10/18) between the IHC and FISH findings. No RB1 gene copy number variations were detected in any of the ROs (0/25; P <.001) and retained expression of RB1 by IHC. ERBB4 showed cytoplasmic/membranous staining in all ROs and ChRCCs. However, 75% (21/28) of ChRCCs also contained nuclear positivity for ERBB4, which was uncommonly seen in ROs (3/25, 12%; P < .001). A hemizygous ERBB4 gene deletion was detected in 46% of ChRCCs (13/28), but none of the ROs (0/25; 0%). Loss of labeling by RB1 or nuclear staining for ERBB4 IHC identified 25 of 28 (89%) of ChRCCs. Conclusion. In summary, the loss of RB1 expression is a highly specific diagnostic biomarker in distinguishing ChRCC from RO. Nuclear ERBB4 expression also appears to be a sensitive diagnostic biomarker for ChRCC, albeit the mechanism is unknown.

Purpose: The aim of the present retrospective single-center study is to evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in the evaluation of renal oncocytoma. Method: Thirteen patients with histopathologically confirmed renal oncocytoma and 26 patients with histopathologically confirmed renal cell carcinoma were included in this retrospective single-center study on whom CEUS was performed between 2005 and 2015. The applied contrast agent was a second-generation blood pool agent. CEUS examinations were performed and interpreted by a single radiologist with more than 15 years of experience (EFSUMB Level 3). Results: CEUS examinations were successfully performed in all included patients without any adverse effects. Renal oncocytomas showed varying echogenicity (46% hypoechoic, 23% hyperechoic, 8% iso-/hyperechoic, 8% isoechoic). In two cases renal oncocytoma only demarcated upon i.v. application of contrast medium. In bilateral oncocytosis, lesions presented as hyperechoic. Only 23% of renal oncocytomas showed slight vascularization using Color Doppler. No oncocytoma-specific pattern of microperfusion could be elucidated: 85% of the oncocytomas presented hyperenhancing, of whom 50% also showed delayed venous wash-out; 8% of renal oncocytomas showed venous wash-out without early arterial hyperenhancement. Conclusions: Within the frame of the present study and in line with the recent state of knowledge, no specific sonomorphological feature - including CEUS - could be detected allowing for adequate discrimination between oncocytoma and renal cell carcinoma.

A novel analytical approach is proposed to discriminate between solid biopsies of chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). The method comprises the following steps: (i) ultrasonic extraction of proteins from solid biopsies, (ii) protein depletion with acetonitrile, (iii) ultrasonic assisted in-solution digestion using magnetic nanoparticle with immobilized trypsin, (iv) C18 tip-based preconcentration of peptides, (v) sequential extraction of the peptides with ACN, (vi) MALDI-snapshot of the extracts and (vii) investigation of the extract containing the most discriminating features using high resolution mass spectrometry. With this approach we have been able to differentially cluster renal oncocytoma and chromophobe renal cell carcinoma and identified 18 proteins specific to chromophobe and seven unique to renal oncocytoma. Chromophobes express proteins associated with ATP function (ATP5I & 5E; VATE1 & G2; ADT2), glycolysis (PGK1) and neuromedin whilst oncocytomas express ATP5H, ATPA, DEPD7 and TRIPB thyroid receptor interacting protein., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Renal oncocytoma is generally regarded as a benign renal tumor. We herein report a case of large renal oncocytoma with renal venous tumor thrombus. The patient may need to be carefully followed up because hematogenous metastasis may occur.

Background/aim: Renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC) are suggested to develop from α- and β-intercalated (IC) cells of the collecting duct expressing solute carrier family 4 member 1 (SLC4A1) and SLC26A4 under control of forkhead box 1 (FOXI1) transcription factor. The aim of this study was to clarify the possible cellular origin and of RO and chRCC., Materials and Methods: Immunohistochemistry for aquaporin 2 (AQP2), FOXI1, SLC4A1 and SLC16A4 was applied to distinct types of renal cell tumors., Results: Nuclear FOXI1 staining occurred in 96% of 83 ROs, in 3% of 90 chRCCs and none of the other tumor types. The α-IC cell marker SLC4A1 was seen in 60% of RO and 11% of chRCC, whereas staining for the β-IC cell marker SLC26A4 was negative in all but one tumor., Conclusion: Although the origin of RO remains unclear, our findings suggest that FOXI1 immunohistochemistry is useful in differential diagnosis of RO from chRCC with overlapping histology., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Low-grade eosinophilic unclassified renal cell carcinoma is a rare kidney tumor recently described, not included in the WHO classification, which is very close to oncocytoma. It is unknown to most pathologists and clinicians. From a histopathological point of view, this tumor is composed of oncocytic cells arranged in a diffuse and solid pattern, without cell nests, that makes it possible to differentiate it from oncocytoma, and expresses cytokeratin 7 (CK7) heterogeneously. We report a case with a cranial vault metastasis, and present the features to differentiate this entity from oncocytoma. Furthemore, we discuss about unclassified renal cell carcinomas with oncocytic cells., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The increase in serendipitous detection of solid renal masses on imaging has not resulted in a reduction in mortality from renal cell carcinoma. Consequently, efforts for improved lesion characterization have been pursued and incorporated into management algorithms for distinguishing clinically significant tumors from those with favorable histology or benign conditions. Although diagnostic imaging strategies have evolved for optimized lesion detection, distinction between benign tumors and both indolent and aggressive malignant neoplasms remain an important diagnostic challenge. Recent advances in cross-sectional imaging have expanded the role of these tests in the noninvasive characterization of solid renal tumors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To report on the contemporary UK experience of surgical management of renal oncocytomas., Patients and Methods: Descriptive analysis of practice and postoperative outcomes of patients with a final histological diagnosis of oncocytoma included in The British Association of Urological Surgeons (BAUS) nephrectomy registry from 01/01/2013 to 31/12/2016. Short-term outcomes were assessed over a follow-up of 60 days., Results: Over 4 years, 32 130 renal surgical cases were recorded in the UK, of which 1202 were oncocytomas (3.7%). Most patients were male (756; 62.9%), the median (interquartile range [IQR]) age was 66.8 (13) years. The median (IQR; range) lesion size was 4.1 (3; 1-25) cm, 43.5% were ≤4 cm and 30.3% were 4-7 cm lesions. In all, 35 patients (2.9%) had preoperative renal tumour biopsy. Most patients had minimally invasive surgery, either radical nephrectomy (683 patients; 56.8%), partial nephrectomy (483; 40.2%) or other procedures (36; 3%). One in five patients (243 patients; 20.2%) had in-hospital complications: 48 were Clavien-Dindo classification grade ≥III (4% of the total cohort), including three deaths. Two additional deaths occurred within 60 days of surgery. The analysis is limited by the study's observational nature, not capturing lesions on surveillance or ablated after biopsy, possible underreporting, short follow-up, and lack of central histology review., Conclusion: We report on the largest surgical series of renal oncocytomas. In the UK, the complication rate associated with surgical removal of a renal oncocytoma was not negligible. Centralisation of specialist services and increased utilisation of biopsy may inform management, reduce overtreatment, and change patient outcomes for this benign tumour., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Background: Renal oncocytoma is the most common benign renal tumor, and papillary renal cell carcinoma is the second most common histologic subtype of renal cell carcinoma. Renal tumors containing different components such as papillary renal cell carcinoma and oncocytoma are extremely rare., Case Presentation: A renal mass was incidentally detected in a 52-year-old Korean woman, and a computed tomographic scan showed a 32-mm multicystic mass with some calcifications in the lower pole of the right kidney. She underwent laparoscopic partial nephrectomy without any perioperative complications. We found a papillary renal cell carcinoma and an oncocytoma in a tumor mass., Conclusions: The possibility of a mixed malignant tumor should be considered while treating benign tumors such as oncocytoma.

Objectives: To compare the performance of diffusion-weighted imaging (DWI) with that of contrast-enhanced MRI in differentiating renal oncocytomas from chromophobe renal cell carcinomas (RCCs)., Methods: We recruited 48 patients with histopathologically confirmed renal oncocytomas (n=16) and chromophobe RCCs (n=32). All patients underwent preoperative DWI and contrast-enhanced MRI. Apparent diffusion coefficient (ADC) and signal intensity were measured in each patient. ADC ratio and percentage of signal intensity change were calculated., Results: Mean ADC values for renal oncoctytomas were significantly higher than those for chromophobe RCCs (1.59±0.21 vs. 1.09±0.29× 10 -3 mm 2 /s, p < 0.001). Area under the ROC curve, sensitivity and specificity were 0.931, 87.5% and 84.4%, respectively, for ADC measurement of DW imaging; 0.825, 87.5% and 75%, respectively, for enhancement ratio (p > 0.05). Adding ADC values to the enhancement ratios in the ROC, analysis to differentiate renal oncocytoma from chromophobe RCCs increased specificity from 75 to 87.5% at 87.5% sensitivity without significantly increasing the AUC (0.930)., Conclusions: Both DWI and contrast-enhanced MRI may assist in differentiating renal oncocytomas from chromophobe RCCs, with DWI showing higher diagnostic value. The combination of the two parameters could potentially provide better performance in distinguishing these two tumours., Key Points: • ADC values can assist in differentiating renal oncocytomas from chromophobe RCCs. • DW imaging possesses better specificity than does contrast-enhanced MR imaging. • Combining the two parameters provides higher specificity regarding the differential diagnosis.

Background Small renal masses (SRMs; ≤4 cm) represent a challenging issue. Computed tomography (CT) is widely used for investigating renal tumors even if its ability to differentiate among the different subtypes has not yet been definitively established. Purpose To assess the potential role of the morphological features and angiodynamic behavior on multiphasic CT in the preoperative evaluation of SRMs. Material and Methods The CT images of 80 patients with SRMs who underwent surgical resection at our institution were retrospectively reviewed. The morphological features, the pattern, and the quantitative analysis of enhancement were assessed for each lesion and were correlated with the histological subtypes. Results Overall, 81 SRMs were evaluated. Final pathological examination showed 30 (37%) oncocytomas, 22 (27.2%) clear cell renal cell carcinomas (ccRCCs), 16 (19.8%) papillary RCCs (pRCCs), and 13 (16%) chromophobe RCCs (chRCCs). Of the morphological features, only necrosis was significantly associated with ccRCC ( P = 0.047). The analysis of enhancement allowed the identification of two groups of lesions, based on arterial behavior: hypervascular (oncocytomas/ccRCC) and hypovascular (chRCC/pRCC) lesions. A significant difference between the two groups in terms of degree of enhancement on CT phases was found ( P < 0.05); this was also confirmed by the receiver operating characteristic (ROC) analysis. Conclusion Except for necrosis, the morphological features are not useful in making a correct diagnosis in the case of SRMs. The angiodynamic behavior on multiphasic CT showed high accuracy in differentiating between hypovascular and hypervascular tumors; this differentiation could be useful for deciding on the most appropriate clinical management of SRMs.

Detection of solid renal masses has increased, although it has not resulted in significant mortality reduction from renal cell carcinoma. Efforts for improved lesion characterization have been pursued and incorporated in management algorithms, in order to distinguish clinically significant tumors from favorable or benign conditions. Concurrently, imaging methods have produced evidence supporting their role as useful tools not only in lesion detection but also characterization. In addition, newer modalities, such as contrast-enhanced ultrasonography, and advanced applications of MR imaging, are being investigated. This article reviews the current role of different imaging methods in the characterization of solid renal masses., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the intermediate outcome of conservative management in patients with biopsy-proven oncocytoma., Patients and Methods: Patients with oncocytoma diagnosed on percutaneous core biopsy between January 2000 to December 2014 were identified from the renal biopsy database of a large specialist urologic pathology laboratory. After review of patient clinical records, the study cohort comprised only of patients enrolled in active surveillance. Clinicopathological and follow-up details were reviewed for each case, in particular: type and interval of surveillance imaging, tumour growth, definitive intervention and reason for intervention. Where possible, correlation was made between the final surgical and the initial biopsy specimens., Results: Fifty three patients diagnosed with oncocytoma on core biopsy were initially placed on active surveillance with median follow-up of 34 months (range 6-109). The median age at diagnosis was 65 years (range 20-85) and median tumour size was 30 mm (range 13-87). Mean average tumour growth was 1.4 mm per annum (median 0 mm/year) with the majority (36 of 53, 68%) exhibiting minimal growth (less than 2 mm per annum) or partial regression. Forty seven of the 53 patients remained on active surveillance with no significant progression. Six patients elected to undergo definitive intervention (five surgical excision, one ablation). Renal oncocytoma was confirmed in all five patients who underwent surgical excision of their lesions., Conclusions: The majority of oncocytomas in this study showed minimal growth rate or regression. Patients with biopsy proven oncocytoma can be conservatively managed with active surveillance., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Background: Renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC) share histologic and some imaging features., Purpose: To investigate the multidetector computed tomography (MDCT) characteristics of these two tumor types., Material and Methods: Fifty-six patients with RO and 54 patients with ChRCC were studied retrospectively. MDCT was undertaken to investigate differences in tumor characteristics., Results: Calcifications were visible in 24 (42.8%) patients with RO and in 11 (20.4%) patients with ChRCC (P = 0.011). 26 patients with RO had stellate scars as did 14 patients with ChRCC (P = 0.025). Spoken-wheel-like enhancement was visible in 41 patients with RO and in 11 with ChRCC (P < 0.001). Thirty-nine (69.6%) patients with RO and nine (16.7%) patients with ChRCC showed segmental inversion (P < 0.001). Two patients with RO had retroperitoneal lymph node enlargement as did 13 patients with ChRCC (P = 0.002). Combined evaluation of stellate scar, spoken-wheel-like enhancement, and segmental enhancement inversion features were found to have a sensitivity of 99.1% (106 of 107), a specificity of 100% (3 of 3), a positive predictive value of 100% (106 of 106), and a negative predictive value of 75% (3 of 4). The attenuation of RO tumors was greater than that of ChRCC tumors, normal renal parenchyma on unenhanced CT (P = 0.031). Enhancement was higher with RO than with ChRCC tumors in all phases (P = 0.021, < 0.001, and 0.007, respectively)., Conclusion: CT imaging features such as stellate scar, spoken-wheel-like enhancement, and segmental enhancement inversion were more common in RO and they may help in differentiating RO from ChRCC., (© The Foundation Acta Radiologica 2015.)

Objective: The purpose of this study was to evaluate whether small (< 4 cm) oncocytomas can be differentiated from renal cell carcinomas (RCCs) on biphasic contrast-enhanced CT., Materials and Methods: Forty-three patients with 53 oncocytomas and 123 patients with 128 RCCs (24 papillary subtype and 104 clear cell and other subtypes) who underwent biphasic contrast-enhanced CT were included in the study. Patient demographics and CT tumor characteristics were evaluated in each case. A multinomial logistic regression model was then constructed for differentiating oncocytoma from clear cell and other subtype RCCs, oncocytoma from papillary RCCs, and clear cell and other subtype RCCs from papillary RCCs. The probability of each group was calculated from the model. Diagnostic performance among three pairwise diagnoses and between oncocytoma and any RCC (clear cell and other subtypes and papillary) were assessed by AUC values., Results: Patient age, tumor CT attenuation values and skewness (i.e., histogram analysis of CT values) in both the corticomedullary and nephrographic phases, and subjective tumor heterogeneity were statistically significant variables in the multinomial logistic regression analysis. The logistic regression model using the variables yielded AUCs of 0.82, 0.95, 0.91, and 0.84 for differentiating oncocytomas from clear cell and other subtype RCCs, oncocytomas from papillary RCCs, clear cell and other subtype RCCs from papillary RCCs, and oncocytomas from any RCC (clear cell and other subtypes and papillary), respectively., Conclusion: A combination of imaging features on biphasic CT, including tumor CT attenuation values and tumor texture (heterogeneity and skewness), can help differentiate oncocytoma from RCC.

Purpose: To investigate and distinguish the computed tomography (CT) characteristics of chromophobe renal cell carcinoma (chRCC) and renal oncocytoma., Materials and Methods: Fifty-one patients with renal oncocytoma and 120 patients with chRCC, diagnosed by surgery between November 2005 and June 2015, were studied retrospectively. Two observers, who were urologists and unaware of the pathological results, reviewed the preoperative CT images. The tumors were evaluated for size, laterality, tumor type (ball or bean pattern), central stellate scar, segmental enhancement inversion, and angular interface pattern and tumor complexity. To accurately analyze the mass-enhancing pattern of renal mass, we measured Hounsfield units (HUs) in each phase and analyzed the mean, maximum, and minimum HU values and standard deviations., Results: There were 51 renal oncocytomas and 120 chRCCs in the study cohort. No differences in clinical and demographic characteristics were observed between the two groups. A central stellate scar and segmental enhancement inversion were more likely in oncocytomas. However, there were no differences in ball-/bean-type categorization, enhancement pattern, and the shape of the interface between the groups. Higher HU values tended to be present in the corticomedullary and nephrogenic phases in oncocytomas than in chRCC. Receiver-operating characteristic curve analysis showed that the presence of a central stellate scar and higher mean HU values in the nephrogenic phase were highly predictive of renal oncocytoma (area under the curve=0.817, p<0.001)., Conclusions: The appearance of a central stellate scar and higher mean HU values in the nephrogenic phase could be useful to distinguish renal oncocytomas from chRCCs.

The distinction between chromophobe renal cell carcinoma (ChRCC), clear cell renal cell carcinoma (CRCC) and renal oncocytoma may cause a diagnostic dilemma. The usefulness of DOG1, cyclin D1, CK7, CD117 and vimentin in the differential diagnosis of these renal epithelial tumors was investigated. DOG1 was positive in ChRCC (32 of 32, 100%) and in renal oncocytoma (21 of 21, 100%). In contrast, DOG1 was absent in all CRCC (0 of 30). Cyclin D1 was positive in renal oncocytomas (17 of 21, 81%) but negative in the ChRCC (0/23) and CRCC (0 of 30). CK7 was positive in ChRCC (30 of 32, 94%), but was negative in oncocytoma (only scattered single positive cells), and was only focal positive in two cases of CRCC. CD117 was expressed in 88% of ChRCC (28 of 32), 86% of renal oncocytoma (18 of 21), and was negative in all CRCC (0 of 30). Twenty-six of the 30 cases of CRCC were positive (87%) for vimentin with prominent membrane staining patterns. All 23 chromophobe carcinomas were negative for vimentin and 15 of 21 oncocytomas demonstrated focal vimentin positivity, but less than 10%. The above results demonstrate that: (1) DOG1 was very sensitive and specific marker for distinguish ChRCC from CRCC; (2) Cyclin D1 was a useful marker to discriminate between ChRCC and renal oncocytoma; (3) CK7 and CD117 were useful markers to distinguish ChRCC from renal oncocytoma and CRCC. (4) Vimentin was helpful for distinguishing clear cell RCC from chromophobe and oncocytoma (87% of clear cell RCC positive, negative in chromophobe, only focally positive in oncocytoma). (5) CK8/18, CK19, CD10, β-catenin and E-cadherin could not be used to distinguish ChRCC from renal oncocytoma and CRCC., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Introduction: C-kit overexpression has previously been described in chromophobe renal cell carcinoma (cpRCC) and renal oncocytoma (RO). However, so far no KIT mutations have been found. The objective of our study was to analyse c-kit in a large cohort of renal tumors and to perform KIT mutation analysis in a subset cpRCC and RO cases with overexpression of c-kit., Materials and Methods: We studied the immunohistochemical expression of c-kit on tissue microarrays containing formalin-fixed, paraffin-embedded samples of 948 patients with renal tumors. CpRCC and RO cases with c-kit overexpression (n=23) were analyzed for KIT mutations in exons 9, 11, 13, 14, 15, and 17., Results: Expression of c-kit was found in 6/642 (0.9%) clear cell RCC, 3/154 (1.9%) papillary RCC, 54/69 (78.3%) cpRCC, 37/45 (82.2%) RO and 2/30 (6.7%) of other unclassified tumor types. In none of the RO and cpRCC cases analyzed, a KIT gene mutation was found., Conclusion: C-kit expression is found in the majority of cpRCC and RO, but these tumors do not harbor the usual c-kit activating mutations. This may have implications for the use of tyrosine kinase inhibitors in patients with advanced cpRCC and c-kit expression., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Background: To analyze the sonographic (US) features of renal oncocytoma and correlate them with histopathologic findings., Methods: The medical records of 12 patients with a histologic diagnosis of renal oncocytomas were reviewed. The location, size, shape, margin, echogenicity, homogeneity, and blood flow distribution of the lesions were analyzed, and the US features were compared with histopathologic findings., Results: Oncocytomas appeared as solid, solitary, well-marginated, unencapsulated, fairly homogeneous renal cortical masses (n = 10), with regular shape, relatively isoechoic (n = 5) or slightly hyperechoic (n = 7) to the adjacent renal parenchyma, and an exophytic growth pattern was exhibited in most cases (n = 9). Two larger masses (≥9 cm) demonstrated a central stellate scar and a characteristic of spoke-wheel vascular pattern. The tumors with a low percentage of stroma (<20%) were associated with an echotexture isoechoic to renal parenchyma, whereas oncocytomas with a higher percentage of stroma (>20%) were slightly hyperechoic., Conclusions: Although the US features are not pathognomonic, their presence should alert to the possible diagnosis of renal oncocytoma., (Copyright © 2014 Wiley Periodicals, Inc.)

Purpose: Concern regarding coexisting malignant pathology in benign renal tumors deters renal biopsy and questions its validity. We examined the rates of coexisting malignant and high grade pathology in resected benign solid solitary renal tumors., Materials and Methods: Using our prospectively maintained database we identified 1,829 patients with a solitary solid renal tumor who underwent surgical resection between 1994 and 2012. Lesions containing elements of renal oncocytoma, angiomyolipoma or another benign pathology formed the basis for this analysis. Patients with an oncocytic malignancy without classic oncocytoma and those with known hereditary syndromes were excluded from study., Results: We identified 147 patients with pathologically proven elements of renal oncocytoma (96), angiomyolipoma (44) or another solid benign pathology (7). Median tumor size was 3.0 cm (IQR 2.2-4.5). As quantified by the R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior and location relative to polar lines) nephrometry score, tumor anatomical complexity was low in 28% of cases, moderate in 56% and high in 16%. Only 4 patients (2.7%) were documented as having hybrid malignant pathology, all involving chromophobe renal cell carcinoma in the setting of renal oncocytoma. At a median followup of 44 months (IQR 33-55) no patient with a hybrid tumor experienced regional or metastatic progression., Conclusions: In our cohort of patients with a solitary, sporadic, solid benign renal mass fewer than 3% of tumors showed coexisting hybrid malignancy. Importantly, no patient harbored coexisting high grade pathology. These data suggest that uncertainty regarding hybrid malignant pathology coexisting with benign pathological components should not deter renal biopsy, especially in the elderly and comorbid populations., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Renal cell carcinoma (RCC) accounts for around 3% of cancers in the UK, and both incidence and mortality are increasing with the aging population. RCC can be divided into several subtypes: conventional RCC (the most common, comprising 75% of all cases), papillary RCC (15%) and chromophobe RCC (5%). Renal oncocytoma is a benign tumor and accounts for 5% of RCC. Cancer and epigenetics are closely associated, with DNA hypermethylation being widely accepted as a feature of many cancers. In this study the DNA methylation profiles of chromophobe RCC and renal oncocytomas were investigated by utilizing the Infinium HumanMethylation450 BeadChips. Cancer-specific hypermethylation was identified in 9.4% and 5.2% of loci in chromophobe RCC and renal oncocytoma samples, respectively, while the majority of the genome was hypomethylated. Thirty (hypermethylated) and 41 (hypomethylated) genes were identified as differentially methylated between chromophobe RCC and renal oncocytomas (p < 0.05). Pathway analysis identified some of the differentially hypermethylated genes to be involved in Wnt (EN2), MAPK (CACNG7) and TGFβ (AMH) signaling, Hippo pathway (NPHP4), and cell death and apoptosis (SPG20, NKX6-2, PAX3 and BAG2). In addition, we analyzed ccRCC and papillary RCC data available from The Cancer Genome Atlas portal to identify differentially methylated loci in chromophobe RCC and renal oncocytoma in relation to the other histological subtypes, providing insight into the pathology of RCC subtypes and classification of renal tumors.

Renal oncocytoma is a rare and benign renal tumor. Only few cases have been reported in Moroccan populations. In the present study, we report our experiences in the diagnosis, management and follow-up of this disease. We report on six cases of renal oncocytoma indentified between 1990 and 2008 in the urology department of "CHU Ibn Sina" in Rabat. These six cases are listed among 130 kidney tumors reported during the study period. We assess the clinical, radiological and therapeutic features of the patients and we review literature. Six cases of renal oncocytoma, representing 4.6% of all primitive kidney tumors treated in our institution during the study period. The mean age was 53 ±9.7 years (range 34 to 61 years). One patient was asymptomatic at presentation, five patients (83%) had flank pain and two (33%) had macroscopic hematuria. The tumor was right sided in 4 cases (66%) and left sided in 2 cases (33%). All patients underwent CT scan which showed, in three cases, a centrally located stellate area of low attenuation. The clinical suspicion of oncocytoma was made preoperatively in only 3 patients by imaging studies, but the suspicion of renal cell carcinoma persist and all patients were treated with radical nephrectomy. Definitive diagnosis was made in all cases postoperatively. All the tumors were well circumscribed but unencapsulated. The mean tumor size was 8,75±2,04 cm. Four patients were classified at stage pT2 and two at stage p T1. Most of the pathological features in our patients were typical of this entity. Predominant cell type was a typical oncocytoma with general low mitotic activity. No extension to peri-nephric fat tissue or lymphovascular invasion was observed. After a mean follow-up of 36 months (range 26-62 months), there was neither recurrence nor death from oncocytoma. Accordingly, the disease-specific survival was 100%. Renal oncocytoma has a benign clinical course with excellent long-term outcomes. In our series, it happened mostly in females and is more frequently symptomatic. Although radical nephrectomy is the usual treatment, a conservative approach should be considered whenever there are signs of clinical and radiological presumptions.

Renal oncocytomas (RO) and chromophobe renal cell carcinomas (RCC) display morphological and functional alterations of the mitochondria. Previous studies showed that accumulation of mitochondria in ROs is associated with somatic mutations of mitochondrial DNA (mtDNA) resulting in decreased activity of the respiratory chain complex I, whereas in chromophobe RCC only heteroplasmic mtDNA mutations were found. To identify proteins associated with these changes, for the first time we have compared the mitochondrial proteomes of mitochondria isolated from ROs and chromophobe RCCs as well as from normal kidney tissues by two-dimensional polyacrylamide gel electrophoresis. The proteome profiles were reproducible within the same group of tissues in subsequent experiments. The expression patterns within each group of samples were compared and 81 in-gel digested spots were subjected to nanoLC-MS/MS-based identification of proteins. Although the list of mitochondrial proteins identified in this study is incomplete, we identified the downregulation of NDUFS3 from complex I of the respiratory chain and upregulation of COX5A, COX5B, and ATP5H from complex IV and V in ROs. In chromophobe RCCs downregulation of ATP5A1, the alpha subunit of complex V, has been observed, but no changes in expression of other complexes of the respiratory chain were detected. To confirm the role of respiratory chain complex alterations in the morphological and/or functional changes in chromophobe RCCs and ROs, further studies will be necessary.

Introduction “Other oncocytic renal tumors of the kidney” is a new category constituted by 2022 WHO classification and different in the point of morphology and immunohistochemistory from typical oncocytic/eosinophilic renal tumors including chromophobe renal cell carcinoma and oncocytoma. Case presentation The patient was an 84‐year‐old woman in whom a left renal tumor was incidentally discovered. She underwent left nephrectomy, and the pathological specimens showed a borderline eosinophilic renal tumor between chromophobe renal cell carcinoma and renal oncocytoma. After all recognized oncocytic tumors were excluded, we diagnosed the tumor as other oncocytic renal tumor of the kidney. Conclusion Other oncocytic renal tumor of the kidney is a provisional category. Therefore, further research and accumulation of similar cases are necessary.