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Renal oncocytomas are asymptomatic, benign tumors often encountered incidentally on various imaging modalities. Renal oncocytomas comprise 5–7% of primary renal neoplasms and are derived from cells of the distal renal tubule. We present a case report of renal oncocytoma in a 22-year-old male having right-sided flank pain and symptomatic gross hematuria with a giant urinary bladder clot retention. The tumor was excised, and the patient underwent laparoscopic partial nephrectomy. Typical features of renal oncocytoma were observed upon histopathological examination of the resected specimen. The patient was catheterized, and bladder irrigation with clot retraction was performed.

Renal oncocytoma is the most common benign epithelial renal neoplasm. Several adverse features that would typically increase the stage of renal cell carcinomas are not uncommon in renal oncocytoma, including perinephric, sinus fat, or renal vein invasion. Herein, we report the largest single institutional series of renal oncocytoma with adverse pathologic features. The cohort comprised 50 patients, 38 were men (76%) and 12 were women (24%), with a mean age of 68 years (range, 50-87 years). All cases were diagnosed on nephrectomy specimens. No laterality predilection was noted. The tumors ranged in size from 1.5-15.7 cm (mean, 5.3 cm). Adverse pathologic features included perinephric fat invasion (n = 25; 50%), renal sinus fat invasion (n = 9; 18%), and renal vein invasion (n = 5; 10%). More than one adverse feature was seen in 11 tumors (22%). All tumors showed diffuse reactions to KIT (n = 40; 100%) and cyclin D1 (n = 27; 100%). Keratin 7 highlighted rare (

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.

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.

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. 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. 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. 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.

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.

Recent advances in molecular genetics have expanded our knowledge of renal tumors and enabled better classification. These studies have revealed that renal tumors with predominantly “eosinophilic/ oncocytic” cytoplasm include a number of novel biologic subtypes beyond the traditionally well recognized renal oncocytoma (RO) and eosinophilic variant of chromophobe renal cell carcinoma (ChRCC). Herein, we present a comprehensive review of Eosinophilic Vacuolated Tumor (EVT), a recently described novel renal epithelial tumor subtype. Leveraging the comprehensive study of radiology, histopathology, electron microscopy and next generation sequencing of a patient with EVT with sporadic MTOR mutation, we shed insight on the pathogenesis of EVT. These data allows us to postulate that loss of chromosome 1 loss observed in EVT with MTOR mutation may be related to mTORC1 being a dimer since a heterodimer of wild-type and mTOR p.L2427R proteins may not confer sufficient mTORC1 activation. mTORC1 is best known for its role in promoting protein translation. Consistently, dilated cisterns of rough endoplasmic reticulum (ER) were noted on electron microscopic examination that likely corresponded to the cytoplasmic vacuoles seen by light microscopy. This ER expansion may contribute to the increase in phospho-S6 observed in these tumors, as S6 is a ribosomal protein and ribosomes may be increased with the ER expansion. We further discuss the evolving concepts in the classification of this emerging entity.

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 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.

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.

Objective: To discuss the imaging features of renal oncocytoma, and to improve the preoperative diagnostic accuracy. Methods: Radiology data of 16 renal oncocytoma patients were analyzed retrospectively. All the cases were confirmed by pathology. All patients underwent pre-contrast and multiple phase contrast scanning on multi-slice CT. The patients also underwent MRI examination. Results: All patients had solitary lesion, the location of oncocytoma were in right kidney (n = 9) and left kidney (n = 7). Round or round-like shape, clear boundary, protruding mass. Isodense or slightly higher density on CT pre-contrast scanning, among them, 2 cases developed into the renal sinus, 2 cases with calcification. 13 lesions showed obvious enhancement on the cortical phase, and on the medullary phase showed continuous enhancement. 4 lesions showed segmental enhancement inversion and central stellate scar was found in 8 lesions. Bleeding, necrosis, cystic change or fatty change was rare. 9 lesions showed tortuous expansion of the support vessel on the cortical phase, 6 lesions with invasion to the perirenal fat tissue. In our study, 3 samples of lesions underwent MR examination, which showed iso/hypo-intensity on T1WI. On T2WI, 1 lesion showed slightly lower signal, 2 lesion showed mixed signal. Clear pseudocapsule was revealed in MR imaging. Enhanced scan showed mild continuous enhancement. Conclusion: Most of the oncocytomas showed certain characteristic imaging, multiple phase contrast scanning are helpful in the accurate preoperative diagnosis.

Pathology differentiation of renal cancer types is challenging due to tissue similarities or overlapping histological features of various tumor (sub)types. As assessment is often manually conducted outcomes can be prone to human error and therefore require high-level expertise and experience. Mass spectrometry can provide detailed histo-molecular information on tissue and is becoming increasingly popular in clinical settings. Spatially resolving technologies such as mass spectrometry imaging and quantitative microproteomics profiling in combination with machine learning approaches provide promising tools for automated tumor classification of clinical tissue sections.In this proof of concept study we used MALDI-MS imaging (MSI) and rapid LC-MS/MS-based microproteomics technologies (15 min/sample) to analyze formalin-fixed paraffin embedded (FFPE) tissue sections and classify renal oncocytoma (RO, n=11), clear cell renal cell carcinoma (ccRCC, n=12) and chromophobe renal cell carcinoma (ChRCC, n=5). Both methods were able to distinguish ccRCC, RO and ChRCC in cross-validation experiments. MSI correctly classified 87% of the patients whereas the rapid LC-MS/MS-based microproteomics approach correctly classified 100% of the patients.This strategy involving MSI and rapid proteome profiling by LC-MS/MS reveals molecular features of tumor sections and enables cancer subtype classification. Mass spectrometry provides a promising complementary approach to current pathological technologies for precise digitized diagnosis of diseases.

Chromophobe renal cell carcinoma (ChRCC) accounts for 5% to 7% of all renal cell carcinomas. It was thought for many years that ChRCC exhibits a hypodiploid genome. Recent studies using advanced molecular genetics techniques have shown more complex and heterogenous pattern with frequent chromosomal gains. Historically, multiple losses of chromosomes 1, 2, 6, 10, 13, 17, and 21 have been considered a genetic hallmark of ChRCC, both for classic and eosinophilic ChRCC variants. In the last 2 decades, multiple chromosomal gains in ChRCCs have also been documented, depicting a considerably broader genetic spectrum than previously thought. Studies of rare morphologic variants including ChRCC with pigmented microcystic adenomatoid/multicystic growth, ChRCC with neuroendocrine differentiation, ChRCC with papillary architecture, and renal oncocytoma-like variants also showed variable chromosomal numerical aberrations, including multiple losses (common), gains (less common), or chromosomal changes overlapping with renal oncocytoma. Although not the focus of the review, The Cancer Genome Atlas (TCGA) data in ChRCC show TP53, PTEN, and CDKN2A to be the most mutated genes. Given the complexity of molecular genetic alterations in ChRCC, this review analyzed the existing published data, aiming to present a comprehensive up-to-date survey of the chromosomal abnormalities in classic ChRCC and its variants. The potential role of chromosomal numerical aberrations in the differential diagnostic evaluation may be limited, potentially owing to its high variability.

International audience; Renal oncocytoma is an uncommon tumor that exhibits numerous features which are characteristic but not necessarily unique. Percutaneous biopsy is a safe method of diagnosis. However, differentiation from other tumor subtypes often requires sophisticated analysis and is not universally feasible. This is why, surgical management can be considered as a first-line treatment or after surveillance. Potential triggers for change in management are: tumor size >3 cm, stage progression, kinetics of size progression (>5 mm/y), and clinical change in patient or tumor factors. Long-term follow-up data are lacking and greater centralization should be considered to reach adequate management.

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.

Purpose DNA ploidy measurement has earlier been suggested as a potentially powerful prognostic tool in many cancer types, but the role in renal tumors is still unclear. Methods To clarify its prognostic impact, we analyzed the DNA content of 1320 kidney tumors, including clear cell, papillary and chromophobe renal cell carcinoma (RCC) as well as renal oncocytoma and compared these data with clinico-pathological parameters and patient prognosis. Results A non-diploid DNA content was seen in 37% of 1276 analyzable renal tumors with a striking predominance in chromophobe carcinoma (74.3% of 70 cases). In clear cell carcinoma, a non-diploid DNA content was significantly linked to high-grade (ISUP, Fuhrman, Thoenes; p p = 0.0011), distant metastasis (p p = 0.0010), and earlier recurrence (p p = 0.0063), distant metastasis (p = 0.0138), shortened overall survival (p = 0.0010), and earlier recurrence (p = 0.0003). Conclusion In summary, the results of our study identify a non-diploid DNA content as a predictor of an unfavorable prognosis in clear cell and papillary carcinoma.

Introduction: Renal oncocytomas are benign tumours arising from the intercalated cells of the collecting ducts and account for 3% to 7% of primary renal tumours. It was first described by Zippel in 1942. Oncocytomas are mostly asymptomatic and often discovered incidentally. They are often diagnosed postoperatively due to clinical and radiographic challenges in differentiating them from renal cell carcinoma. Presentation of Case: The present study reports two cases of renal oncocytoma in a 61‑year‑old man who was asymptomatic and a 73‑year‑old woman who was symptomatic. Relevant clinical and imaging data on the two patients were reviewed. Both patients underwent nephrectomy via flank incisions. Discussion: The typical morphologic features of oncocytoma were observed on histological examination of the excised kidney speci­mens. The postoperative course of each patient was uneventful and they were discharged 14 and 6-days post‑surgery, respec­tively. In addition, the present study reviews the literature regarding the clinical, radiological and pathological characteristics of renal oncocytoma. Conclusion: Renal oncocytoma though is benign and has an excellent prognosis, the preoperative diagnostic challenges invariable warranted radical nephrectomy.

The primary objectives of this systematic review and meta-analysis were to evaluate the diagnostic accuracy of 99mTc-sestamibi SPECT/CT for detecting renal oncocytoma versus (1) all other renal lesions and (2) chromophobe renal cell carcinoma (ChrRCC) alone. A systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and the Gray Literature was performed. Original articles with > 5 patients evaluating oncocytomas versus other renal lesions with SPECT/CT using a pathological reference standard were included. Patient, clinical, imaging, and performance parameters were independently acquired by two reviewers. Meta-analysis was performed using a bivariate mixed-effects regression model. Four articles with a total of 117 renal lesions were included in analysis. The pooled and weighted sensitivity and specificity values of 99mTc-sestamibi SPECT/CT for detecting (1) renal oncocytoma versus other renal lesions were 92% (95% CI 72–98%) and 88% (95% CI 79–94%), respectively, and (2) 89% and 67%, respectively, for renal oncocytoma versus ChrRCC. The specificity for the detecting the oncocytoma-ChrRCC spectrum was 96% (95% CI 84–99%). The sensitivity and specificity for detecting benign versus malignant renal lesions were 86% (95% CI 66–95%) and 90% (95% CI 80–95%), and 88% and 95% when HOCTs were characterized as benign. All reporting studies used a cut-off tumor-to-background renal parenchyma radiotracer uptake ratio of > 0.6 for positive studies. 99mTc-sestamibi SPECT/CT demonstrates a high sensitivity and specificity for characterizing benign and low-grade renal lesions. This test can help improve the diagnostic confidence for patients with indeterminate renal masses being considered for active surveillance.

The present techniques of clinical and histopathological diagnosis hardly distinguish chromophobe renal cell carcinoma (ChRCC) from renal oncocytoma (RO). To identify differentially expressed genes (DEGs) as effective biomarkers for diagnosis and prognosis of ChRCC and RO, three mRNA microarray datasets (GSE12090, GSE19982, and GSE8271) were downloaded from the GEO database. Functional enrichment analysis of DEGs was performed by DAVID. STRING and Cytoscape were applied to construct the protein-protein interaction (PPI) network and key modules of DEGs. Visualized plots were conducted by the R language. We downloaded clinical data from the TCGA database and the influence of key genes on the overall survival of ChRCC was performed by Kaplan–Meier and Cox analyses. Gene set enrichment analysis (GSEA) was utilized in exploring the function of key genes. A total of 79 DEGs were identified. Enrichment analyses revealed that the DEGs are closely related to tissue invasion and metastasis of cancer. Subsequently, 14 hub genes including ESRP1, AP1M2, CLDN4, and CLDN7 were detected. Kaplan–Meier analysis indicated that the low expression of CLDN7 and GNAS was related to the worse overall survival in patients with ChRCC. Univariate Cox analysis showed that CLDN7 might be a helpful biomarker for ChRCC prognosis. Subgroup analysis revealed that the expression of CLDN7 showed a downtrend with the development of the clinical stage, topography, and distant metastasis of ChRCC. GSEA analysis identified that cell adhesion molecules cams, B cell receptor signaling pathway, T cell receptor signaling pathway, RIG-I like receptor signaling pathway, Toll-like receptor signaling pathway, and apoptosis pathway were associated with the expression of CLDN7. In conclusion, ESRP1, AP1M2, CLDN4, PRSS8, and CLDN7 were found to distinguish ChRCC from RO. Besides, the low expression of CLDN7 was closely related to ChRCC progression and could serve as an independent risk factor for the overall survival in patients with ChRCC.

Background Renal cell carcinoma (RCC) is often detected incidentally as a small renal mass (SRM; pT1a, ≤4 cm). It is clinically challenging to predict progression in patients with SRMs. This is largely due to the recent recognition of clinically progressive and non-progressive RCC-SRMs. It is critical to accurately stratify SRM patients according to risk to avoid unnecessary treatment. This is especially significant for elderly and infirm patients, where the risk of surgery outweighs mortality from SRMs. Methods We employed a qRT-PCR array-based approach and targeted qRT-PCR to identify and validate early, non-invasive diagnostic and prognostic biomarkers of RCC-SRMs. In total, we evaluated eighty urine samples, including 30 renal oncocytoma (≤4 cm) cases, 26 progressive and 24 non-progressive clear cell RCC-SRM (ccRCC-SRM) cases. Results We identified nine urinary miRNAs which displayed significantly elevated expression in ccRCC-SRMs (pT1a; ≤4 cm) relative to renal oncocytoma (≤4 cm). Additionally, miR-328-3p displayed significantly down-regulated expression in progressive relative to non-progressive ccRCC-SRMs. Patients with elevated miR-328-3p expression had significantly longer overall survival (HR = 0.29, 95% CI = 0.08–1.03, p = 0.042) compared to patients with low miR-328-3p expression. We also found no significant association between miR-328-3p expression levels and gender, age, laterality, tumor size, or grade, suggesting that miR-328-3p is an independent prognostic biomarker. Conclusions Our in-depth miRNA profiling approach identified novel biomarkers for early-stage ccRCC-SRMs. Pretreatment characterization of urinary miRNAs may provide insight into early RCC progression and could potentially aid clinical decision-making, improving patient management and reducing overtreatment.

Introduction. Renal neoplasms are a common disease. Differential diagnostics of different tumor subtypes for prognosis and treatment is necessary given that some of them, like renal cell oncocytomas, are benign, and others, like chromophobe renal cell carcinomas, are malignant. Unfortunately, the histological similarity between these tumors makes accurate diagnostics difficult. In some cases, additional diagnostic methods such as immunohistochemistry should be used. The aim of our study is to analyze the histological characteristics of chromophobe renal cell carcinomas and renal oncocytomas, in order to specify their pathognomonic features, allowing for the confirmation of the diagnosis. Materials and methods. We used data from histories of disease and histological postoperative material of 198 patients with chromophobe renal cell carcinoma and renal oncocytoma. After the diagnosis was confirmed, we described the histological features of the tumors and calculated their relative prevalence amongst the renal oncocytoma and chromophobe renal cell carcinoma tissues. To conclude, we identified the histological features that are more likely to be present in the case of chromophobe renal cell carcinoma. Conclusions. Chromophobe renal cell carcinomas are present in 31 % of our samples. Tumors are more prevalent in patients in their sixth and seventh decade. Most chromophobe renal cell carcinomas are unilateral. Chromophobe renal cell carcinomas have a polymorphic histological structure. The classic variant of chromophobe renal cell carcinoma is more common than the eosinophilic one. A mixed variant of chromophobe renal cell carcinoma is present in a minority of cases. The most common features of ChRCC are solid and alveolar growth patterns, clear and reticular cytoplasm, raisinoid nuclei. After comparing the relative prevalence of various histological features in renal oncocytomas to those present in chromophobe renal cell carcinomas, we are able to ascertain that chromophobe renal cell carcinomas tend to exhibit the following features significantly more often than renal oncocytomas: differing nuclear size, raisinoid nuclei, reticular cytoplasm, clear cytoplasm. The particular features mentioned in the preceding paragraph, can be present on a small subset of the tumor tissue, and are thus, often missed during analysis, which can lead to misdiagnosis. In order to mitigate this risk, we recommend analyzing a big sample of tumor tissue and using additive methods such as immunohistochemistry with biomarkers CD 10 (56C6), CD 68 (KP1), Cytokeratin 7 (OV-TL 12/30), CD117/c-kit, Vimentin (Vim3B4), S-100 (4C4.9).

Objective:Pre-operative differentiation between renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC) is critical due to their different clinical behavior and different clinical treatment decisions. The aim of this study was to develop and validate a CT-based radiomics nomogram for the pre-operative differentiation of RO from chRCC.Methods:A total of 141 patients (84 in training data set and 57 in external validation data set) with ROs (n = 47) or chRCCs (n = 94) were included. Radiomics features were extracted from tri-phasic enhanced-CT images. A clinical model was developed based on significant patient characteristics and CT imaging features. A radiomics signature model was developed and a radiomics score (Rad-score) was calculated. A radiomics nomogram model incorporating the Rad-score and independent clinical factors was developed by multivariate logistic regression analysis. The diagnostic performance was evaluated and validated in three models using ROC curves.Results:Twelve features from CT images were selected to develop the radiomics signature. The radiomics nomogram combining a clinical factor (segmental enhancement inversion) and radiomics signature showed an AUC value of 0.988 in the validation set. Decision curve analysis revealed that the diagnostic performance of the radiomics nomogram was better than the clinical model and the radiomics signature.Conclusions:The radiomics nomogram combining clinical factors and radiomics signature performed well for distinguishing RO from chRCC.Advances in knowledge:Differential diagnosis between renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC) is rather difficult by conventional imaging modalities when a central scar was present. A radiomics nomogram integrated with the radiomics signature, demographics, and CT findings facilitates differentiation of RO from chRCC with improved diagnostic efficacy. The CT-based radiomics nomogram might spare unnecessary surgery for RO.

Renal cell carcinoma (RCC) is frequently diagnosed incidentally as an early-stage small renal mass (SRM; pT1a, ≤4 cm). Overtreatment of patients with benign or clinically indolent SRMs is increasingly common and has resulted in a recent shift in treatment recommendations. There are currently no available biomarkers that can accurately predict clinical behavior. Therefore, we set out to identify early biomarkers of RCC progression. We employed a quantitative label-free liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) proteomics approach and targeted parallel-reaction monitoring to identify and validate early, noninvasive urinary biomarkers for RCC-SRMs. In total, we evaluated 115 urine samples, including 33 renal oncocytoma (≤4 cm) cases, 30 progressive and 26 nonprogressive clear cell RCC (ccRCC)-SRM cases, in addition to 26 healthy controls. We identified six proteins, which displayed significantly elevated expression in clear cell RCC-SRMs (ccRCC-SRMs) relative to healthy controls. Proteins C12ORF49 and EHD4 showed significantly elevated expression in ccRCC-SRMs compared to renal oncocytoma (≤4 cm). Additionally, proteins EPS8L2, CHMP2A, PDCD6IP, CNDP2 and CEACAM1 displayed significantly elevated expression in progressive relative to nonprogressive ccRCC-SRMs. A two-protein signature (EPS8L2 and CCT6A) showed significant discriminatory ability (areas under the curve: 0.81, 95% CI: 0.70-0.93) in distinguishing progressive from nonprogressive ccRCC-SRMs. Patients (Stage I-IV) with EPS8L2 and CCT6A mRNA alterations showed significantly shorter overall survival (p = 1.407 × 10-6 ) compared to patients with no alterations. Our in-depth proteomic analysis identified novel biomarkers for early-stage RCC-SRMs. Pretreatment characterization of urinary proteins may provide insight into early RCC progression and could potentially help assign patients to appropriate management strategies.

Hybrid oncocytic/chromophobe tumor (HOCT) of the kidney represents a poorly understood clinicopathologic entity with pathologic features that overlap between benign renal oncocytoma (RO) and malignant chromophobe renal cell carcinoma (ChRCC). Consequently, characterization of HOCT and its separation from the foregoing entities are clinically important. The aim of this study was to describe the pathologic and molecular features of HOCT and to compare them with those of RO and ChRCC. We retrospectively identified a cohort of 73 cases with renal oncocytic tumors (19 RO, 27 HOCT, and 27 ChRCC) for whom clinical follow-up data were available by 2 tertiary care hospitals. All cases were sporadic except for 2 HOCTs that were associated with Birt–Hogg–Dube syndrome. Lesional tissues were retrieved for molecular analysis. We performed targeted gene sequencing of all exons of 261 cancer related genes on a subset of HOCT samples (n = 16). Gene expression profiling of a customized codeset was conducted on 19 RO, 24 HOCT, and 27 ChRCC samples. Clinicopathologic characteristics as well as DNA copy number alterations, mutational and transcriptional features of HOCT derived from sequencing and expression profiling data are described and compared to those in RO and ChRCC. HOCTs were more frequently multifocal and did not exhibit mutations in genes that are recurrently mutated in RO or ChRCC but showed copy number alterations primarily involving losses in chromosomes 1 and X/Y. The mRNA transcript data show that HOCT can be separated from RO and ChRCC. Hence, HOCT appears to represent a distinct renal tumor entity with genomic features that are intermediate between those of RO and ChRCC.

Immunohistochemical and molecular studies to differentiate eosinophilic kidney tumors are gradually increasing. The present study investigated the role of transient receptor potential cation channel subfamily M member 4 (TRPM4), a non-selective cation channel associated with migration, proliferation and invasion in cancer cells, in this differentiation. The aim was to investigate the effectiveness of TRPM4 in differentiation of eosinophilic kidney tumors. The study included a total of 112 patients, including 97 eosinophilic kidney tumors with the diagnoses of 33 eosinophilic clear cell renal cell carcinoma (CCRCC), 35 eosinophilic chromophobe renal cell carcinoma (ChRCC), 8 papillary renal cell carcinoma type 2 (P2RCC), 21 renal oncocytoma (RO), as well as 15 papillary renal cell carcinoma type 1 to differentiate from P2RCC. For TRPM4, diffuse staining (>10%) was observed in 2 CCRCC, 15 ChRCC, 20 RO and 4 P2RCC cases. There was a significant difference between eosinophilic CCRCC and other eosinophilic tumors (P

Purpose To explore the value of CT-enhanced quantitative features combined with machine learning for differential diagnosis of renal chromophobe cell carcinoma (chRCC) and renal oncocytoma (RO). Methods Sixty-one cases of renal tumors (chRCC = 44; RO = 17) that were pathologically confirmed at our hospital between 2008 and 2018 were retrospectively analyzed. All patients had undergone preoperative enhanced CT scans including the corticomedullary (CMP), nephrographic (NP), and excretory phases (EP) of contrast enhancement. Volumes of interest (VOIs), including lesions on the images, were manually delineated using the RadCloud platform. A LASSO regression algorithm was used to screen the image features extracted from all VOIs. Five machine learning classifications were trained to distinguish chRCC from RO by using a fivefold cross-validation strategy. The performance of the classifier was mainly evaluated by areas under the receiver operating characteristic (ROC) curve and accuracy. Results In total, 1029 features were extracted from CMP, NP, and EP. The LASSO regression algorithm was used to screen out the four, four, and six best features, respectively, and eight features were selected when CMP and NP were combined. All five classifiers had good diagnostic performance, with area under the curve (AUC) values greater than 0.850, and support vector machine (SVM) classifier showed a diagnostic accuracy of 0.945 (AUC 0.964 ± 0.054; sensitivity 0.999; specificity 0.800), showing the best performance. Conclusions Accurate preoperative differential diagnosis of chRCC and RO can be facilitated by a combination of CT-enhanced quantitative features and machine learning.

CONTEXT: 9p loss appears a reliable and promising marker able to differentiate specific categories of patients with renal cell carcinoma associated with a worse prognosis. OBJECTIVE: The aim was to systematically evaluate relative risk of death, cancer-specific survival (CSS) and disease-free survival (DFS) among patients harboring 9p loss. EVIDENCE SYNTHESIS: We found a total of 92 potentially relevant articles focused on the detection of 9p loss in patients with renal cell carcinoma and clinical outcomes of this population. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were employed to carry out this work. Fourteen studies resulted to be eligible for this analysis; 11 of these reported data on 5-year overall survival, six on CSS and four on DFS. An increased risk of death has been observed in patients harboring 9p loss (pooled relative risk of 3.965; 95% confidence interval [CI] 2.647-5.940, p

Background: Differentiation of chromophobe renal cell carcinoma (chRCC) from benign renal oncocytoma (RO) can be challenging especially when there are overlapping histological and morphological features. In this study we have investigated immunohistochemical biomarkers (cytokeratin 7/CK7, Caveolin-1/Cav-1 and S100 calcium-binding protein A1/S100A1) to aid in this difficult differentiation and attempted to validate their use in human renal tumour tissue to assess their discriminatory ability, particularly for chRCC and RO, in an Australian cohort of patients. Methods: Retrospective study was carried out of archived formalin-fixed paraffin-embedded renal tumours from tumour nephrectomy specimens of 75 patients: 30 chRCC, 15 RO and 30 clear cell RCC (ccRCC). Sections were cut and immunostained with specific polyclonal antibodies of CK7, Cav-1 and S100A1. Morphometry was used to determine expression patterns of the biomarkers using Aperio ImageScope. Results were assessed with student t -test and ANOVA with significance at P

Renal cell carcinoma (RCC) is the second-most common uronephrological cancer. In the absence of specific symptoms, early diagnosis of RCC is challenging. Monitoring of the aberrant expression of tumour-associated antigens (TAAs) and related autoantibody response is considered as a novel approach of RCC diagnostics. The aim of this study was to examine the aberrant expression of arrestin-1 in renal tumours, to investigate the possible epigenetic mechanism underlying arrestin-1 expression, and to assess the frequency of anti-arrestin-1 autoantibody response. Immunohistochemistry was used to assess the presence of arrestin-1 in primary tumours and metastases of 39 patients with RCC and renal oncocytoma. Bisulfite sequencing was employed to analyse the methylation status of the promoter of the SAG gene encoding arrestin-1. Western blot analysis was performed to detect autoantibodies against arrestin-1 in serum samples of 36 RCC and oncocytoma patients. Arrestin-1 was found to be expressed in RCC (58.7% of cases) and renal oncocytoma (90% of cases) cells, while being absent in healthy kidney. The expression of arrestin-1 in RCC metastases was more prominent than in primary tumours. Hypomethylation of the SAG gene promoter is unlikely to be the mechanism for the aberrant expression of arrestin-1. Autoantibodies against arrestin-1 were detected in sera of 75% of RCC patients. Taken together, our findings suggest employment of autoantibody against arrestin-1 as biomarker of RCC.

Introduction Hybrid oncocytic/chromophobe tumor (HOCT) is a renal cell neoplasm displaying overlapping cellular and architectural features of both renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC). It has been described in the context of oncocytosis, Birt-Hogg-Dube syndrome, and also sporadically. Thus far, HOCT immunohischemical profile and cytogenetic alterations have been reported, but not epigenetic alterations. Herein, we characterize a HOCT case, including microRNA expression, comparing it to sporadic RO and chRCC. Methods An HOCT was entirely submitted. Representative paraffin blocks were selected for histochemical, immunohistochemical and FISH analyses. MicroRNAs were extracted from the two components separately and selected microRNA expression was performed. Results This 4 cm HOCT, from a 69 year-old female, was composed mainly by oncocytic cells with an insular distribution (RO-like) and areas of larger clarified cells (chRCC-like). The two areas displayed different features: RO-like areas showed negative colloidal iron staining, multifocal CD15, negative CK7, focal multiple tetrasomies, and higher miR21 expression; chRCC-like areas showed colloidal iron diffuse staining with moderate intensity, focal CD15 and CK7, no numeric chromosomic alterations, and higher miR141 and miR200b expression. Conclusion microRNA expression in the two HOCT components is similar to its sporadic tumors counterparts. Morphologic, immunohistochemical, cytogenetic and epigenetic data on this case suggest either two independent pathogenic pathways or an early pathogenic divergence for RO-like and chRCC-like components of HOCT.

Despite advances in our understanding of the biology of chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO), the differential diagnosis among these tumors remains one of the most problematic in renal pathology. Today, CK7 is the most recommended marker to distinguish these entities, however it appears insufficiently accurate by itself. This study aimed to find an easily accessible IHC stain that might out-compete CK7 in this field. Expressions of CK7, cyclin D1, p16, survivin, CD138, Ki-67 and caspase 3 (CASP3) were analyzed in a total of 27 cases (20 ROs and 7 ChRCCs). Immunoreactivity was assessed based on a combined score of the extent and intensity of staining. Compared to RO, a higher percentage of the total ChRCCs stained positive for CK7 (67% vs. 22%, respectively) and CASP3 (86% vs. 25%) (P

Background: 99mTc-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). We investigated whether standard uptake value (SUV) SPECT, has a beneficial role in differentiating renal oncocytoma (RO) from renal cell carcinoma (RCC) besides visual assessment. As a secondary aim, we evaluated the mitochondrial content of 19 oncocytic tumours arranged in a tissue microarray, by immunohistochemistry, using succinate dehydrogenase complex subunit B (SDHB) protein expression. In addition to visual evaluation of 99mTc-Sestamibi uptake by characterizing renal tumours as Sestamibi positive or Sestamibi negative regarding their uptake compared to the non-tumoral renal parenchyma, SUVmean and SUVmax measurements were performed in the renal tumour and the non-tumoral renal parenchyma. Intra Class Correlation calculated to assess the intra-reader reliability of SUV measurements. ROC-analysis demonstrated an optimal cut off SUV value that differentiates RO from RCC. SDHB score was analysed using Cochran–Armitage test for trend.Results: 57 renal tumours from 52 patients were evaluated. Visual evaluation of 99mTc-Sestamibi SPECT/CT examination resulted in a sensitivity of 83%, whereas quantitative evaluation showed a sensitivity of 64% regarding the differential of RO from RCC. A significant trend (p=0,0328) of increased SDHB score found in the Sestamibi positive group.Conclusion: Quantitative evaluation with SUV SPECT measurements did not improve the performance of 99mTc-Sestamibi SPECT/CT in differentiating RO from RCC. 99mTc- Sestamibi SPECT/CT identified a larger Sestamibi-positive tumour group containing RO, Hybrid Oncocytic Chromophobe Tumours and the majority of chromophobe RCCs. Thus, Sestamibi-negative renal tumours, that are possibly malignant, should be considered for surgery. Patients with Sestamibi-positive tumours can be suited for biopsy and follow up according to active surveillance protocols. Low Grade Oncoytic Tumour, a provisional renal entity with no proven recurrence or metastatic potential, appears to be positive on 99mTc- Sestamibi SPECT/CT examination.

Renal oncocytoma represents between 6-12% of T1 renal tumours in surgical series (1-2). Contemporary imaging cannot differentiate oncocytoma from malignant renal cell carcinoma (RCC). Uptake of renal tumour biopsy in clinical practice has been variable (3) and surgery with partial or radical nephrectomy is the first-line in the management of RCC (4,5). Therefore, many patients with renal masses undergo empirical surgery for presumed RCC with post-operative histologic diagnosis of benign oncocytoma.

Introduction. Cathepsin K is overexpressed in several tumors associated with microphthalmia transcription factor (MiTF) family or mechanistic target of rapamycin (mTOR) upregulation. Among renal neoplasms, MiTF translocation renal cell carcinoma (RCC), perivascular epithelioid cell neoplasms (PEComa), and eosinophilic solid and cystic RCC have demonstrated Cathepsin K immunoreactivity. In this study, we demonstrate a uniform Cathepsin K expression in oncocytoma, chromophobe RCC (CHRCC), and distal tubules. Design. We stained 13 oncocytomas, 13 CHRCC, 14 clear cell RCC (CCRCC), 9 papillary RCC (PRCC), 9 PEComas, and 5 MiTF RCC. Additionally, we assessed immunoreactivity for Cathepsin K in non-neoplastic renal parenchyma. Immunolabeling was performed on regularly charged slides from formalin-fixed paraffin-embedded tissue with monoclonal anti-rabbit antibodies to human Cathepsin K (clone EPR19992, Abcam). Results. All oncocytomas demonstrated diffuse strong cytoplasmic immunolabeling. CHRCC demonstrated uniform less intense immunolabeling in all cases with membranous accentuation. The assessment of the non-neoplastic renal parenchyma in all cases showed strong cytoplasmic immunoreaction in distal tubules and proximal tubules stained faintly. Mesangial cells were not immunoreactive. All MiTF RCC and PEComas were immunoreactive for Cathepsin K, whereas CCRCC and PRCC were negative in all cases. Conclusions. In this study, we expand the spectrum of renal neoplasms reactive with a particular clone of Cathepsin K (EPR19992). Distal tubules are strongly immunoreactive for Cathepsin K. Our conclusions need to be taken into consideration when differential diagnosis includes MiTF RCC or PEComa and this Cathepsin K clone is included in the immunohistochemical panel. This newer antibody clone was not tested in prior publications, potentially explaining the difference in conclusions.

Background Benign and malignant renal tumors share similar some imaging findings. Methods Sixty-six patients with clear cell renal cell carcinoma (CCRCC), 13 patients with renal angiomyolipoma with minimal fat (RAMF) and 7 patients with renal oncocytoma (RO) were examined. For diffusion kurtosis imaging (DKI), respiratory triggered echo-planar imaging sequences were acquired in axial plane (3 b-values: 0, 500, 1000s/mm2). Mean Diffusivity (MD), fractional Anisotropy (FA), mean kurtosis (MK), kurtosis anisotropy (KA) and radial kurtosis (RK) were performed. Results For MD, a significant higher value was shown in CCRCC (3.08 ± 0.23) than the rest renal tumors (2.93 ± 0.30 for RO, 1.52 ± 0.24 for AML, P P P > 0.05). For MK, KA and RK, a significant higher value was shown in AML (1.32 ± 0.16, 1.42 ± 0.23, 1.41 ± 0.29) than CCRCC (0.43 ± 0.08, 0.57 ± 0.16, 0.37 ± 0.11) and RO (0.81 ± 0.08, 0.86 ± 0.16, 0.69 ± 0.08) (P P Conclusion DKI can be used as another noninvasive biomarker for benign and malignant renal tumors’ differential diagnosis.

Low-grade Oncocytic Tumor (LOT) of kidney is an emerging neoplasm that forms an important differential diagnosis in a spectrum of entities with oncocytic morphology. It has overlapping features with renal oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma, but with distinct clinical, histomorphological and immunohistochemical features. LOT exhibits characteristic low grade oncocytic morphology with a CD117 negative/CK7 positive immunophenotype. Herein, we describe two cases of this emerging entity, LOT, with emphasis on the diagnostic aspects, including the histomorphology, immunoprofile and discussion on the close differentials.

Background: Renal cancer is one of the most frequent malignancies in Western countries, with an unpredictable clinical outcome, partly due to its high heterogeneity and the scarcity of reliable biomarkers of tumour progression. (Pro)renin receptor (PRR) is a novel receptor of the renin-angiotensin system (RAS) that has been associated with the development and progression of some solid tumours by RAS-dependent and -independent mechanisms. (2) Methods: In this study, we analysed the immunohistochemical expression of PRR at the centre and border in a series of 83 clear-cell renal cell (CCRCCs), 19 papillary (PRCC) and 7 chromophobe (ChRCC) renal cell carcinomas, and the benign tumour renal oncocytoma (RO, n = 11). (3) Results: PRR is expressed in all the tumour subtypes, with higher mean staining intensity in ChRCCs and ROs. A high expression of PRR at the tumour centre and at the infiltrative front of CCRCC tissues is significantly associated with high grade, tumour diameter, local invasion and stage, and with high mortality risk by UCLA integrated staging system (UISS) scale. (4) Conclusions: These findings indicate that PRR is associated with the development and progression of renal tumours. Its potential as a novel biomarker for RCC diagnosis/prognosis and as a promising therapeutic target should be taken into account in the future. Basque Government (ELKARTEK KK2018-00090 and KK-2020/00069) 3.992 JCR (2021) Q2, 60/172 Medicine, General & Internal 0.658 SJR (2021) Q2, 56/119 Clinical Biochemistry No data IDR 2021 UEM

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). 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. 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. 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.

Fine needle aspiration cytology (FNAC) helps diagnose space-occupying lesions of the kidney with indeterminate diagnosis in radiology. FNAC also provides a diagnosis in the metastatic tumours in the kidney and unresectable mass lesions. Similarly, FNAC of adrenal space-occupying lesions helps significantly in the management. This chapter describes the detailed cytological features of neoplastic and non-neoplastic renal and adrenal lesions.

Background The morbidity rate of kidney cancer has been increasing. Management of patients and their prognosis depend on the specific histological type of tumor. Unfortunately, different renal tumors can have similar histological features, making differential diagnostics challenging. Among the most challenging tasks is differential diagnosis of renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC). Aim To analyze different histological features of renal oncocytomas and specify their pathognomonic characteristics that may be advantageous for the confirmation of the diagnosis. Materials and methods The medical records and histopathological reports of 197 patients with diagnosis of either RO or ChRCC were analyzed. 37 histological parameters were then evaluated and their prevalence in RO or ChRCC was compared by performing a contingency table analysis. Odds ratio was also calculated. Results The most common growth patterns of ROs were solid (53%), nested (47%), cystic (29%), and alveolar (28%). A combination of two or more growth patterns was seen in 82% of cases mostly composing of nested, cystic, alveolar or solid structures. Most tumors exhibited granular inclusions (70%) and dense cytoplasm (58%). Conclusion With more than 95% confidence, the nested pattern, myxoid stroma, granular cytoplasm and round nuclei are likely indicative of RO, whereas the varying nuclear size, raisinoid nuclei and reticular cytoplasm indicate higher likelihood of ChRCC. Therefore, these features should be analyzed for RO confirmation.

Renal oncocytoma is a benign renal tumor originated from intercalated cells of collecting ducts like chromophobe renal cell carcinoma (RCC). The differential diagnosis of these 2 tumors is important because while they are histologically and cytologically similar, they show different biological behavior. For the differential diagnosis, several immunohistochemical markers have been investigated. But, differential diagnostic challenges remain and the identification of additional markers is needed. Cytokeratin 7 (CK7) is one of ductal-type keratins, which is expressed in tumors of breast, pancreas, lung, thyroid, ovary, endometrium, urinary bladder, and the kidney. S100A1 is the first defined member of the calcium-binding S100 protein family and it organizes several cellular functions including cell cycle progression and cell differentiation.CD82 is a tetraspanin membrane protein, which functions as a metastasis supressor. In this study, we immunohistochemically investigated the expressions of CK7, S100A1, and CD82 in 30 chromophobe RCC (23 classic and 7 eosinophilic variant) and 19 oncocytomas. When these markers were evaluated separately and together, their expressions in chromophobe RCC and renal oncocytoma show statistically significant difference (P

BackgroundMorphology, clinical behavior, and genomic profiles of renal oncocytoma (RO) and its malignant counterpart chromophobe renal cell carcinoma (ChRCC) are distinctly different. However, there is a substantial group of sporadic oncocytic tumors with peculiar hybrid phenotypes as well as a perplexing degree of morphologic and immunohistochemical overlap between classic RO and ChRCC with eosinophilic cytoplasm. The aim of this study is to provide detailed characterization of these hybrid tumors.DesignThirty eight sporadic oncocytic neoplasms with ambiguous morphology from two institutions were reviewed by 4 pathologists. CKIT positivity was used as a selection criterion. We correlated CK7 and S100A1 immunostaining and detailed morphologic features with cytogenetic profiles. DNA from the FFPE tissues was extracted and analyzed using Cytogenomic Microarray Analysis (CMA) to evaluate copy number alterations and ploidy.ResultsCMA categorized cases into 3 groups: RO (N=21), RO variant (N=7) and ChRCC (N=10). Cytogenetic RO had either no CNA (48%) or loss of chromosome 1p, X or Y (52%). RO-variant had additional chromosomal losses [-9q, –14 (n=2), –13] and chromosomal gains [+1q (n=2), +4, +7 (n=2), +13, +19, +20, and +22]. ChRCC were either hypodiploid with numerous monosomies (40%) or hypotetraploid with multiple relative losses (60%). RO, RO-variant and ChRCC groups differed significantly in tumor architecture (p5% cells (pConclusionsGenomic profile allows classification of oncocytic tumors with ambiguous morphology into RO, RO-variant and ChRCC. Several architectural and cytologic features combined with CK7 expression are significantly associated with cytogenetic RO, RO-variant or ChRCC tumors. Doubled hypodiploidy by whole genome endoduplication is a common phenomenon in eosinophilic ChRCC.Parts of this study were presented in an abstract form at the 104th annual meeting of the United Stated and Canadian Academy of Pathology, Boston, March 21–27, 2015

Background The goal of this study was to evaluate the morphology, immunoprofile, and management of renal oncocytoma (RO), hybrid oncocytic tumor (HOT), and chromophobe renal cell carcinoma (ChRCC). Methods Forty-seven cases of RO, 7 cases of HOT, and 25 cases of ChRCC were included in the study. Tissue microarrays were prepared for immunohistochemical evaluation. Results Large sheets of cells with transverse vessels, and higher nuclear grade were seen more often in ChRCC than in RO or HOT. Tumor cells of RO were more uniform in size and shape relative to HOT and ChRCC. The cytoplasmic features of RO were more uniformly granular relative to HOT and ChRCC, which exhibited variable cytoplasmic features. CK7 and MUC1 were expressed more frequently and diffusely in ChRCC (54% and 94%, respectively) than RO (4% and 52%, respectively) and HOT (0% and 71%, respectively). AMACR and PAX8 were more frequently expressed diffusely in RO (67% and 42%, respectively) than in HOT (0% and 0%, respectively) or ChRCC (14% and 11%, respectively). Most HOT (57%) and CHRCC (60%) patients underwent nephrectomy. Cryoablation was the treatment of choice for 24% of patients with ChRCC, 2% of patients with RO, and 0% of patients with HOT. The majority of patients with RO (88%) opted for active surveillance-a much higher rate than that for patients with HOT (29%) or ChRCC (12%). Conclusion Some cytologic features and immunomarkers are useful in differentiating RO, HOT, and ChRCC. Because no immunomarker or morphologic finding is specific by itself, a combination of morphologic features with immunohistochemistry appears to be the most reliable way to distinguish ChRCC, HOT, and RO on biopsy samples. Subclassification of renal oncocytic tumors into specific categories impacts clinical management and downstream treatment selection.

INTRODUCTION AND OBJECTIVE:The oncologic safety of active surveillance in renal oncocytoma is well reported. However concern remains at the hypothetical possibility of renal functional deterioratio...

INTRODUCTION AND OBJECTIVE:The available data on long term outcomes of surgically treated renal oncocytoma (RO) are scant and largely outdated. Herein we describe our institutional outcomes of surg...

The development of steroid diabetes was studied in a consecutive series of 114 patients receiving a cadaveric renal graft. All were first-time transplantations. For acceptance in the series the graft should have functioned for at least 2 weeks after the transplant operation. The median age of the patients was 52 years. The follow-up period was at least one year. The criterion for a diagnosis of steroid diabetes was an elevated fasting blood glucose concentration of more than 8 mmoles/l. Fifty-two of the patients (46 per cent) developed steroid diabetes. Thirty-four (65 per cent) of them required insulin therapy or peroral anti-diabetic drugs. The mean age of these patients was higher than for those not afflicted by this complication. The first-year mortality was significantly higher, 42 against 13 per cent, respectively (p less than 0.01). The level of significance was not notably affected by correction for age at transplantation. Severe infection was the cause of a large proportion of the deaths in the diabetes group. The findings suggest that the development of steroid diabetes can serve as a warning signal for excessive dosage of corticosteroids, and help to identify patients that are particularly sensitive to immunosuppressive therapy with large doses of steroids.

Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are closely related, rare kidney tumors. Mutations in complex I (CI)-encoding genes play an important role in dysfunction of the oxidative phosphorylation (OXPHOS) system in renal oncocytoma, but are less frequently observed in chRCC. As such, the relevance of OXPHOS status and role of CI mutations in chRCC remain unknown. To address this issue, we performed proteome and metabolome profiling as well as mitochondrial whole-exome sequencing to detect mitochondrial alterations in chRCC tissue specimens. Multiomic analysis revealed downregulation of electron transport chain (ETC) components in chRCC that differed from the expression profile in renal oncocytoma. A decrease in mitochondrial (mt)DNA content, rather than CI mutations, was the main cause for reduced OXPHOS in chRCC. There was a negative correlation between protein and transcript levels of nuclear DNA- but not mtDNA-encoded ETC complex subunits in chRCC. In addition, the reactive oxygen species scavenger glutathione (GSH) was upregulated in chRCC due to decreased expression of proteins involved in GSH degradation. These results demonstrate that distinct mechanisms of OXPHOS exist in chRCC and renal oncocytoma and that expression levels of ETC complex subunits can serve as a diagnostic marker for this rare malignancy. Significance: These findings establish potential diagnostic markers to distinguish malignant chRCC from its highly similar but benign counterpart, renal oncocytoma.