Search

So-called oncocytic papillary renal cell carcinoma (OPRCC) is a poorly defined variant of papillary renal cell carcinoma. Since its first description, several studies were published with conflicting results, and thus precise definition is lacking. A cohort of 39 PRCCs composed of oncocytic cells were analyzed. Cases were divided into 3 groups based on copy number variation (CNV) pattern. The first group consisted of 23 cases with CNV equal to renal oncocytoma. The second group consisted of 7 cases with polysomy of chromosomes 7 and 17 and the last group of 9 cases included those with variable CNV. Epidemiologic, morphologic and immunohistochemical features varied among the groups. There were not any particular histomorphologic features correlating with any of the genetic subgroups. Further, a combination of morphologic, immunohistochemical, and molecular-genetic features did not allow to precisely predict biologic behavior. Owing to variable CNV pattern in OPRCC, strict adherence to morphology and immunohistochemical profile is recommended, particularly in limited samples (i.e., core biopsy). Applying CNV pattern as a part of a diagnostic algorithm can be potentially misleading. OPRCC is a highly variable group of tumors, which might be misdiagnosed as renal oncocytoma. Using the term OPRCC as a distinct diagnostic entity is, thanks to its high heterogeneity, questionable.

Renal oncocytoma and chromophobe renal cell carcinoma have been long recognized as distinct tumors; however, it remains unknown if uniform diagnostic criteria are used to distinguish these tumor types in practice. A survey was distributed to urologic pathologists regarding oncocytic tumors. Responses were received from 17 of 26 invitees. Histologically, more than 1 mitotic figure was regarded as most worrisome (n=10) or incompatible (n=6) with oncocytoma diagnosis. Interpretation of focal nuclear wrinkling, focal perinuclear clearing, and multinucleation depended on extent and did not necessarily exclude oncocytoma if minor. Staining techniques most commonly used included the following: cytokeratin 7 (94%), KIT (71%), vimentin (65%), colloidal iron (59%), CD10 (53%), and AMACR (41%). Rare cytokeratin 7-positive cells (≤5%) were regarded as most supportive of oncocytoma, although an extent excluding oncocytoma was not universal. Multiple chromosomal losses were most strongly supportive for chromophobe renal cell carcinoma diagnosis (65%). Less certainty was reported for chromosomal gain or a single loss. For tumors with mixed or inconclusive features, many participants use an intermediate diagnostic category (82%) that does not label the tumor as unequivocally benign or malignant, typically "oncocytic neoplasm" or "tumor" with comment. The term "hybrid tumor" was used variably in several scenarios. A slight majority (65%) report outright diagnosis of oncocytoma in needle biopsies. The morphologic, immunohistochemical, and genetic characteristics that define oncocytic renal tumors remain incompletely understood. Further studies correlating genetics, behavior, and histology are needed to define which tumors truly warrant classification as carcinomas for patient counseling and follow-up strategies.

Objective To report a contemporary series of surgically treated patients with tumors involving kidneys with fusion anomalies. Materials and Methods We retrospectively reviewed the medical records of all 10 patients treated at a single tertiary care institution for tumors involving kidneys with fusion anomalies between the years 2000 and 2015. One patient, diagnosed with lymphoma, did not undergo surgical treatment and was therefore excluded. Data regarding patient, tumor, and treatment characteristics were collected and described. Results The study cohort included 7 male and 2 female patients, at a median age of 52 years. Seven patients underwent open partial nephrectomy. Nephroureterectomy was performed on 2 patients; 1 open and 1 laparoscopic. All patients had localized disease at diagnosis. Tumor histologies were renal cell carcinoma in 5 patients, renal oncocytoma in 1 patient, urothelial carcinoma in 2 patients, and a well-differentiated liposarcoma involving the kidney in 1 patient. Accessory blood vessels were identified in 8 of 9 patients. Median estimated blood loss was 300 mL (interquartile range: 150-1000). Four patients had postoperative complications, including 3 major (Clavien grade ≥ 3) and 3 minor (Clavien grade ≤ 2) complications. During a median follow-up of 19.2 months (interquartile range: 3-34.8), 1 patient with urothelial carcinoma developed a bladder recurrence. None of the patients developed new-onset chronic kidney disease during the early postoperative period. Conclusion Localized renal cortical tumors in kidneys with fusion anomalies may be treated with partial nephrectomy; however, complication rates are relatively high. Preoperative imaging of the blood vessels is necessary, as most patients have an accessory blood supply.

The simultaneous presence of renal angiomyolipoma and oncocytoma is a rare occurrence. Extrarenal retroperitoneal angiomyolipoma is an even more rare neoplasm, and its simultaneous presence with renal oncocytoma has not been documented. We present herein the first case to be reported in English literature.

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

Rationale: Hybrid oncocytic/chromophobe tumor (HOCT) is defined as tumor composed of renal oncocytoma (RO) and chromophobe renal cell carcinoma (CHRCC). Sporadic HOCT is extremely rare, the preoperative diagnosis is difficult, and no guidelines for clinical therapy. We report a case who is the youngest male patient of sporadic HOCT in the world, review the previously reported cases, and share the clinical features, diagnosis, treatment, and prognosis of HOCT. Patient concerns: A 30-year-old man was admitted with the complaints of incidental right renal tumor detected by abdominal ultrasound. He had no complaints of urological symptoms, abdominal pain, osphyalgia, and hematuria. Abdominal contrast-enhanced computed tomography revealed an 85 mm × 80 mm × 80 mm unilateral and solid renal mass, and no findings of metastases. Diagnosis: The preoperative diagnosis was right renal tumor. Interventions: Laparoscopic right radical nephrectomy was performed. Outcomes: Histopathology demonstrated a mixture of cells with the morphologic features of those seen in CHRCC and RO. The patient was final diagnosed as sporadic HOCT. After follow-up of 14 months, the patient had no complaints and evidence of disease recurrence. Lessons: Sporadic HOCT is extremely rare. It is possible that core biopsy could improve diagnostic accuracy. Laparoscopic radical nephrectomy or nephron sparing surgery should be considered the clinical therapy of the sporadic HOCT patients. The clinical behavior of HOCT is still entirely uncertain and should be proved by studies with available long follow-up.

Precise diagnosis and subtyping of kidney tumors are imperative to optimize and personalize treatment decision for patients. Patients with the most common benign renal tumor, renal oncocytomas, may be overtreated with surgical resection because of limited preoperative diagnostic methods that can accurately identify the benign condition with certainty. In this study, desorption electrospray ionization (DESI)-mass spectrometry (MS) imaging was applied to study the metabolic and lipid profiles of various types of renal tissues, including normal kidney, renal oncocytoma, and renal cell carcinomas (RCC). A total of 73,992 mass spectra from 71 patient samples were obtained and used to build predictive models using the least absolute shrinkage and selection operator (Lasso). Overall accuracies of 99.47% per pixel and 100% per patient for prediction of the three tissue types were achieved. In particular, renal oncocytoma and chromophobe RCC, which present the most significant morphologic overlap and are sometimes indistinguishable using histology alone, were also investigated and the predictive models built yielded 100% accuracy in discriminating these tumor types. Discrimination of three subtypes of RCC was also achieved on the basis of DESI-MS imaging data. Importantly, several small metabolites and lipids species were identified as characteristic of individual tissue types and chemically characterized using tandem MS and high mass accuracy measurements. Collectively, our study shows that the metabolic data acquired by DESI-MS imaging in conjunction with statistical modeling allows discrimination of renal tumors and thus has the potential to be used in the clinical setting to improve treatment of patients with kidney tumor. Significance: Metabolic data acquired by mass spectrometry imaging in conjunction with statistical modeling allows discrimination of renal tumors and has the potential to be used in the clinic to improve treatment of patients.

Renal cell carcinoma (RCC) is often diagnosed incidentally as a small renal mass (SRM; pT1a, ≤4 cm). Increasing concerns surrounding the overtreatment of patients with benign or clinically silent SRMs has resulted in a recent shift in treatment recommendations, especially in elderly and infirm patients. There are currently no biomarkers that can predict progression. We used a quantitative label-free liquid chromatography–tandem mass spectrometry peptidomics approach and targeted parallel-reaction monitoring to identify early, noninvasive diagnostic and prognostic biomarkers for early-stage RCC-SRMs. In total, 115 urine samples, including 33 renal oncocytoma (≤4 cm) cases, 30 progressive and 26 nonprogressive clear cell RCC-SRM cases, and 26 healthy controls were evaluated. Nine endogenous peptides that displayed significantly elevated expression in clear cell RCC-SRMs relative to healthy controls were identified. Peptides NVINGGSHAGNKLAMQEF, VNVDEVGGEALGRL, and VVAGVANALAHKYH showed significantly elevated expression in clear cell RCC-SRMs relative to renal oncocytoma. Additionally, peptides SHTSDSDVPSGVTEVVVKL and IVDNNILFLGKVNRP displayed significantly elevated expression in progressive relative to nonprogressive clear cell RCC-SRMs. Peptide SHTSDSDVPSGVTEVVVKL showed the most significant discriminatory utility (area under the curve, 0.76; 95% CI, 0.62–0.90; P = 0.0027). Patients with elevated SHTSDSDVPSGVTEVVVKL expression had significantly shorter overall survival (hazard ratio, 4.13; 95% CI, 1.09–15.65; P = 0.024) compared to patients with low expression. Pretreatment characterization of urinary peptides can provide insight into early RCC progression and may aid clinical decision-making and improve disease management.

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.

INTRODUCTION AND OBJECTIVES:Among the >65,000 new kidney cancer cases in the U.S., about 10% of these patients turn out to have benign renal cell oncocytomas (Onco). They face a 30% risk of complic...

Convolutional neural networks (CNN) are a class of machine learning model that are especially well suited for imagebased tasks. In this study, we design and train a CNN on tissue samples imaged using Multi-Photon Microscopy (MPM) and show that the model can distinguish between chromophobe renal cell carcinoma (chRCC) and oncocytoma. We demonstrate the method to train a model using simple max-pooling vote fusion, and use the model to highlight regions of the input that cause a positive classification. The model can be tuned for higher sensitivity at the cost of specificity with a constant threshold and little impact to accuracy overall. Several numerical experiments were run to measure the model’s accuracy on both image and patient level analysis. Our models were designed with a dropout parameter that biases the model towards higher sensitivity or specificity. Our best performance model, as measured by area under the receiver operating characteristic curve (AUC of ROC, or AUROC) on patient level classification, is measured with a 94% AUROC and 88% accuracy, along with 100% sensitivity and 75% specificity.

The cytogenetic alterations in renal oncocytoma (RO) are poorly understood. We analyzed 130 consecutive RO for karyotypic alterations. Clonal chromosome abnormalities were identified in 63 (49%) cases, which could be categorized into three classes of mutually exclusive cytogenetic categories. Class 1 (N = 20) RO had diploid karyotypes with characteristic 11q13 rearrangement in balanced translocations with 10 or more different chromosome partners in all cases. We identified recurrent translocation partners at 5q35, 6p21, 9p24, 11p13-14, and 11q23, and confirmed that CCND1 gene rearrangement at 11q13 utilizing fluorescence in situ hybridization (FISH). Class 2 RO (N = 25) exhibited hypodiploid karyotypes with loss of chromosome 1 and/or losses of Y in males and X in females in all cases. The class 3 tumors comprising of 18 cases showed diverse types of abnormalities with the involvement of two or more chromosomes exclusive of abnormalities seen in classes 1 and 2 tumors. Furthermore, karyotypically uninformative cases were subjected to FISH analysis to identify classes 1 and 2 abnormalities. In this group, we found similar frequencies of CCND1 rearrangement, loss of chromosome 1 or Y as with karyotypically abnormal cases. We validated our results against 91 tumors from the Mitelman database. Correlation of clinical data with all the three classes of ROs showed no clear evidence of overall patient survival. Our findings support the hypothesis that RO exhibit three principal cytogenetic categories, which may have different roles in initiation and/or progression. These cytogenetic markers provide a key tool in the diagnostic evaluation of RO.

Renal oncocytomas and retroperitoneal schwannomas are rare and typically benign tumors with characteristic histopathologic features. Ideal management of both renal oncocytoma and retroperitoneal schwannoma is surgical resection. We present a rare case of a 63-year-old man with multifocal renal oncocytoma and retroperitoneal ancient schwannoma which, preoperatively, masqueraded as metastatic renal cell carcinoma. Both tumors were successfully resected surgically. Immunochemistry and histopathology confirmed each diagnosis.

A 59-year-old woman presented with abdominal pain and a palpable abdominal mass. Initial imaging revealed a 14cm solid, enhancing renal mass and suspicion for liver and bone metastases. Family history included a brother with clear cell renal cell carcinoma and mother with glioblastoma multiforme. After liver biopsy was inconclusive, she underwent radical nephrectomy with final pathologic diagnosis of oncocytoma. Renal oncocytoma is the most common benign renal tumor but remains difficult to distinguish clinically and radiographically from renal cell carcinoma. Should urologists use renal mass biopsy even more frequently prior to surgical intervention?

Background. There is a morphological overlap among renal epithelial tumors, particularly chromophobe renal cell carcinoma (CHRCC), clear cell renal cell carcinoma (CCRCC), renal oncocytoma (RO), and papillary renal cell carcinoma (PRCC). Discriminating between these tumors is important but sometimes challenging. This study is aimed at evaluating the clinical usefulness of the combined immunochemistry for the “three 7” markers (CK7, CD117, and Claudin-7) to distinguish chromophobe renal cell carcinoma from these mimics.Methods. Immunochemical staining for CK7, CD117, and Claudin-7 was performed in 68 CHRCCs, 199 CCRCCs, 32 ROs, and 30 PRCCs. Fluorescence in situ hybridization (FISH) was performed in some cases to exclude CCRCC and PRCC. The sensitivity (SE) and specificity (SP) for CHRCC as well as the immunoreactivity of each marker and their combinations were statistically evaluated.Results. High positive rates for CK7 (94%), CD117 (87%), Claudin-7 (94%), and their combinations (CK7+CD117, 79%; CK7+Claudin-7, 88%; CD117+Claudin-7, 82%; CK7+CD117+Claudin-7, 76%) were observed in CHRCC compared to those in CCRCC, RO, and PRCC, with increasingly higher SP when combinations of the “three 7” markers were applied (CK7, 0.80; CD117, 0.82; Claudin-7, 0.78; CK7+CD117, 0.95; CK7+Claudin-7, 0.97; CD117+Claudin-7, 0.97; CK7+CD117+Claudin-7, 1).Conclusion. CK7, CD117, and Claudin-7 are frequently expressed in CHRCC with high specificity. We recommend the routine use of these 3 markers as a routine panel when making a differential diagnosis of CHRCC and excluding other mimics.

The 2016 World Health Organization Renal Tumor Classification defines renal oncocytoma (RO) as a benign epithelial tumor; however, malignant histopathologic features have been documented. Rare cases with metastases have been reported. We describe the case of a 62-year-old woman who was referred to the Urology Clinic for a routine work-up. Magnetic resonance imaging and computerized tomography showed a 7-cm mass in the middle and lower portions of the left kidney and 2 suspected liver metastases. The patient underwent surgery. Microscopically both renal and liver lesions presented solid, solid-nested, and microcystic architecture, composed predominantly of large eosinophilic cells without any worrisome pattern except the vascular extension. The cells were positive for S100A1, CD117, and PAX-8 and negative for CAIX, CK7, and AMACR. Fluorescence in situ hybridization showed a disomic profile for the chromosomes 1, 2, 6, 7, 10, 17. No mutation of coding sequence of the SDHB, SDHC, SDHD, VHL, and BHD genes and no loss of heterozygosity at 3p were found. The final diagnosis was "RO" according to the 2016 World Health Organization Renal Tumor Classification with "liver metastases." This report provides a wide clinical-pathologic, immunophenotypical and molecular documentation of a RO with liver metastases.

WOS: 000462163200001, PubMed ID: 30644365, PURPOSE We aimed to evaluate magnetic resonance imaging (MRI) features, including signal intensities, enhancement patterns and T2 signal intensity ratios to differentiate oncocytoma from chromophobe renal cell carcinoma (RCC). METHODS This retrospective study included 17 patients with oncocytoma and 33 patients with chromophobe RCC who underwent dynamic MRI. Two radiologists independently reviewed images blinded to pathology. Morphologic characteristics, T1 and T2 signal intensities were reviewed. T2 signal intensities, wash-in, wash-out values, T2 signal intensity ratios were calculated. Sensitivity and specificity analyses were performed. RESULTS Mean ages of patients with oncocytoma and chromophobe RCC were 61.0 +/- 11.6 and 58.5 +/- 14.0 years, respectively. Mean tumor size was 60.6 +/- 47.3 mm for oncocytoma, 61.7 +/- 45.9 mm for chromophobe RCC. Qualitative imaging findings in conventional MRI have no distinctive feature in discrimination of two tumors. Regarding signal intensity ratios, oncocytomas were higher than chromophobe RCCs. Renal oncocytomas showed higher signal intensity ratios and wash-in values than chromophobe RCCs in all phases. Fast spin-echo T2 signal intensities were higher in oncocytomas than chromophobe RCCs. CONCLUSION Signal intensity ratios, fast spin-echo T2 signal intensities and wash-in values constitute diagnostic parameters for discriminating between oncoytomas and chromophobes. In the excretory phase of dynamic enhanced images, oncocytomas have higher signal intensity ratio than chromophobe RCC and high wash-in values strongly imply a diagnosis of renal oncocytoma.

The Von Hippel-Lindau (VHL) syndrome has been rarely associated with renal oncocytomas, and tumors usually show HIF1α chronic stabilization. By contrast, oncocytomas mainly associated with respiratory chain (RC) defects due to severe mitochondrial DNA (mtDNA) mutations are incapable of stabilizing HIF1α, since oxygen consumption by the RC is dramatically diminished and prolylhydroxylase activity is increased by α-ketoglutarate accumulation following Krebs cycle slowdown. Here, we investigate the cooccurrence of a pseudohypoxic condition with oncocytic transformation in a case of VHL-associated renal oncocytoma. While HIF1α was abundant in nuclei concordantly with defects in VHL, negative staining of its targets carbonic anhydrase IX (CAIX) and glucose transporter GLUT1, usually overexpressed in VHL-associated neoplasms, suggested HIF1α to be present in its inactive (hydroxylated) form. MtDNA sequencing and immunohistochemistry analyses revealed a MT-CO1 stop-gain mutation and cytochrome c oxidase loss. We suggest that a mitochondrial respiration impairment may lead to hyperhydroxylation of the transcription factor, which we confirmed by specific staining of hydroxylated HIF1α. Such inactive form hence accumulated in the VHL-deficient tumor, where it may contribute to the benign nature of the neoplasm. We propose that the protumorigenic role of HIF1α in VHL cancers may be blunted through drugs inhibiting mitochondrial respiratory complexes, such as metformin.

Tubulocystic renal cell carcinoma is an uncommon subtype of renal cell carcinoma that was only recently acknowledged by the World Health Organization. There is a relatively small collection of literature dedicated to the features and clinical course of this lesion. Despite its rarity, this diagnosis should remain in the differential for all cystic renal masses. We present a case report of tubulocystic renal cell carcinoma (TC-RCC) with remarkable similarity to cystic renal oncocytoma, highlighting the diagnostic challenges associated with this unusual renal malignancy.

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.

The urinary tract encompasses the kidney and the urinary collecting system, ureter, bladder and urethra. Benign lesions of the kidney include angiomyolipoma and renal oncocytoma. The main subtypes of renal cell carcinoma include clear cell, papillary and chromophobe variants. Prognostic factors reported by pathologists are reviewed, including the current grading and staging systems. Urothelial tumours include urothelial carcinoma in situ, papillary urothelial carcinoma, and invasive urothelial carcinoma. Aspects of their grading and staging are covered, and several less common variants and benign urothelial lesions are mentioned. General aspects of core biopsy and resection specimens for renal disease are examined, including indications for frozen section examination.

The purpose of this study was to compare whole-lesion (WL) enhancement parameters to single region of interest (ROI)-based enhancement in discriminating clear cell renal cell carcinoma (ccRCC) from renal oncocytoma. In this IRB-approved retrospective study, the surgical database was queried to derive a cohort of 94 postnephrectomy patients with ccRCC or oncocytoma (68 ccRCC, 26 oncocytoma), who underwent preoperative multiphase contrast-enhanced computed tomography (CECT) between June 2009 and August 2013. CT acquisitions were transferred to a three-dimensional workstation, and WL ROIs were manually segmented. WL enhancement and histogram distribution parameters skewness, kurtosis, standard deviation (SD), and interquartile range (IQR) were calculated. WL enhancement parameters were compared to single ROI-based enhancement using receiver operating characteristic (ROC) analysis. Oncocytoma had significantly higher WL enhancement than ccRCC in nephrographic (mean, p = 0.02; median, p = 0.03) and excretory phases (mean, p = 0.03; median p

ResumoIntroduçãoAo longo dos últimos anos, a crescente utilização de exames imagiológicos, nomeadamente ecografia e tomografia computorizada (TC), traduziu‐se num aumento do diagnóstico incidental de tumores renais, sobretudo pequenas massas renais (

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.

Background Numerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). A systematic review and meta-analysis of the published literature was carried out to summarise and analyse the evidence for discriminatory IHC biomarkers to differentiate the two entities. Methods PubMed database was used to identify relevant literature. Primary end point was comparison of positive immunostaining of the biomarkers in chRCC and RO, with extracted data used to calculate OR and 95% CI and statistical I 2 test of heterogeneity for multiple studies. Results One hundred and nine manuscripts were available for review. Data extracted were subjected to quantitative meta-analysis. Ten most effective biomarkers (OR of chRCC/RO and CI) are: amylase α1A (n=129, OR=0.001, 95% CI 0.0001 to 0.019); Wnt-5a (n=38, OR=0.0076, 95% CI 0.0004 to 0.015); FXYD2 (n=57, OR=130, 95% CI 14.2 to 1192.3); ankyrin-repeated protein with a proline-rich region (ARPP) (n=25, OR=0.0054, 95% CI 0.0002 to 0.12); cluster of differentiation 63 (CD63) (n=62, diffuse (chRCC) vs apical/polar (RO) stain pattern); transforming growth factor β 1 (TGFβ1) (n=34, membranous (chRCC) vs cytoplasmic (RO)); cytokeratin 7 (CK7) (11 studies, n=448, pooled OR=44.22, 95% CI 22.52 to 86.64, I 2 =15%); S100A1 (4 studies, n=124, pooled OR=0.01, 95% CI 0 to 0.03, I 2 =0%); caveolin-1 (2 studies, n=102, pooled OR=32.95, 95% CI 3.67 to 296.1, I 2 =70%) and claudin-7 (3 studies, n=89, pooled OR=24.7, 95% CI 6.28 to 97.1, I 2 =0%). Conclusions We recommend a panel of IHC biomarkers of amylase α1A, Wnt-5a, FXYD2, ARPP, CD63, TGFβ1, CK7, S100A1, caveolin-1 and claudin-7 to aid in the differentiation of chRCC and RO.

The differentiation of oncocytic tumors of the kidneys is often difficult, particularly in renal biopsies. Differential diagnoses are chromophobe renal cell carcinoma (ChRCC), renal oncocytoma (RO), the oncocytic variant of papillary renal cell carcinoma (OPRCC), the eosinophilic variant of clear cell renal cell carcinoma (CCRCC) and hybrid oncocytic chromophobe tumors (HOCT). In difficult cases that cannot be resolved by morphology alone, immunohistochemistry is usually helpful. The RO and ChRCC show positive reactions for CD117, they are negative for vimentin and alpha-methylacyl-CoA racemase (AMACR), while CCRCC are positive for vimentin and OPRCC are positive for AMACR. To distinguish between RO and ChRCC, CK7, claudin-7 (both strongly positive in ChRCC and negative or patchy positive in RO) and epithelial cell adhesion molecule (EpCAM) can be used (positive in ChRCC, negative in RO); however, a diagnosis may remain difficult in some cases even with the use of immunohistochemistry. Thus, numerous new methods are being developed in the field of molecular pathology and computer-based morphometric tumor analysis; however, these new methods have not yet been applied in routine diagnostics.

Renal oncocytoma (RO) may present with a tubulocystic growth in 3% to 7% of cases, and in such cases its morphology may significantly overlap with tubulocystic renal cell carcinoma (TCRCC). We compared the morphologic and immunohistochemical characteristics of these tumors, aiming to clarify the differential diagnostic criteria, which facilitate the discrimination of RO from TCRCC. Twenty-four cystic ROs and 15 TCRCCs were selected and analyzed for: architectural growth patterns, stromal features, cytomorphology, ISUP nucleolar grade, necrosis, and mitotic activity. Immunohistochemical panel included various cytokeratins (AE1-AE3, OSCAR, CAM5.2, CK7), vimentin, CD10, CD117, AMACR, CA-IX, antimitochondrial antigen (MIA), EMA, and Ki-67. The presence of at least focal solid growth and islands of tumor cells interspersed with loose stroma, lower ISUP nucleolar grade, absence of necrosis, and absence of mitotic figures were strongly suggestive of a cystic RO. In contrast, the absence of solid and island growth patterns and presence of more compact, fibrous stroma, accompanied by higher ISUP nucleolar grade, focal necrosis, and mitotic figures were all associated with TCRCC. TCRCC marked more frequently for vimentin, CD10, AMACR, and CK7 and had a higher proliferative index by Ki-67 (>15%). CD117 was negative in 14/15 cases. One case was weakly CD117 reactive with cytoplasmic positivity. All cystic RO cases were strongly positive for CD117. The remaining markers (AE1-AE3, CAM5.2, OSCAR, CA-IX, MIA, EMA) were of limited utility. Presence of tumor cell islands and solid growth areas and the type of stroma may be major morphologic criteria in differentiating cystic RO from TCRCC. In difficult cases, or when a limited tissue precludes full morphologic assessment, immunohistochemical pattern of vimentin, CD10, CD117, AMACR, CK7, and Ki-67 could help in establishing the correct diagnosis.

Renal oncocytosis is a rare pathological condition characterised by the presence of multiple oncocytic tumours with a spectrum of histological features ranging from renal oncocytoma, hybrid oncocytic tumour and rarely chromophobe renal cell carcinoma, sometimes overlapping. Here we retrospectively analysed histological, immunohistochemical (IHC), and cytogenetic features of 42 lesions in 11 patients with renal oncocytosis, not associated with Birt-Hogg-Dubé syndrome. The histology of all the lesions was blindly reviewed by three dedicated genitourinary pathologists. IHC for cytokeratin 7 (CK7) and fluorescence in situ hybridisation (FISH) for copy number variation of chromosomes 1, 6, 7 and 17 were performed in all 42 nodules. Among the 42 lesions 36 (85.7%) were histologically renal oncocytomas, two (4.76%) 'hybrid oncocytic tumours' (HOT), one (2.4%) clear cell renal cell carcinoma (ccRCC), one (2.4%) papillary renal cell carcinoma (pRCC), one typical angiomyolipoma (2.4%), and one mixed epithelial/stromal tumour of the kidney (2.4%). FISH analysis confirmed the histological diagnosis of all the lesions. We show that most patients with renal oncocytosis harbour benign or low malignant potential tumours that can be treated conservatively.

SummaryOncocytomas are predominantly benign neoplasms possessing pathogenic mitochondrial mutations and accumulation of respiration-defective mitochondria, characteristics of unknown significance. Using exome and transcriptome sequencing, we identified two main subtypes of renal oncocytoma. Type 1 is diploid with CCND1 rearrangements, whereas type 2 is aneuploid with recurrent loss of chromosome 1, X or Y, and/or 14 and 21, which may proceed to more aggressive eosinophilic chromophobe renal cell carcinoma (ChRCC). Oncocytomas activate 5′ adenosine monophosphate-activated protein kinase (AMPK) and Tp53 (p53) and display disruption of Golgi and autophagy/lysosome trafficking, events attributed to defective mitochondrial function. This suggests that the genetic defects in mitochondria activate a metabolic checkpoint, producing autophagy impairment and mitochondrial accumulation that limit tumor progression, revealing a novel tumor-suppressive mechanism for mitochondrial inhibition with metformin. Alleviation of this metabolic checkpoint in type 2 by p53 mutations may allow progression to eosinophilic ChRCC, indicating that they represent higher risk.

Introduction Small-cell variant of RO is a rare subtype of renal tumor that can be easily misdiagnosed. To date, only 20 cases had been reported, with its genetic alterations largely unknown due to insufficient information. Materials and methods We report a case of the tumor with genetic characterization using exome sequencing chip. We also reviewed literature on this lesion to summarize clinicopathological presentation and differential diagnosis of the tumor. Discussion Grossly, the tumor is yellow to grayish brown, with clear boundary, central scar, or cystic degeneration. Microscopically, small-cell variant RO show scant eosinophilic cytoplasm with small-round nuclei, arranged in small acini and tubules. Nucleoli and necrosis are rarely observed. Immunohistochemically, the tumor is positive for EMA, cytokeratin 18, CD117 and E-cadherin. Genetically, 4745 differentially expressed genes in this tumor, which encode tricarboxylic acid cycle enzymes and are involved in mitochondrial respiratory chain. This result strongly supports the diagnosis of small cell variant of RO. Findings from the molecular genetic analysis of our case suggests that metabolic pathway-related genes (PIK3R5, PI3KCB, PLA2G4E, PLA2G2A, PLA2G6, PLCB4, PLCG2) may be exploited as potential targets for diagnosis and treatment when necessary. These genes may provide new clues for future research. Conclusion Small-cell variant of RO is considered benign renal neoplasms with good prognosis. A histochemical and immunohistochemical stains assist in diagnosis of this tumor. Definitive diagnosis can help avoid unnecessary total renal nephrectomy. The exact mechanism of Small-cell variant of RO remains to be further investigated.

Background The discrimination between chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO) has been a topic of concern in medicine. Because ChRCC is a malignant tumor, whereas RO is a tumor with benign behavior, it is important to distinguish these two entities. We aimed to study the possible differentiation concepts between ChRCC and RO. Aim We attempted to study the pathological features of RO and ChRCC and correlate them focusing on the reliability of leptin immunostain use as a tool in differentiation. Materials and methods A total of 25 cases of renal tumors (17 RO cases and eight ChRCC ones) were studied for clinicopathological features’ correlation and leptin immunohistochemical expression. Results The included cases’ mean±SD age was 53.1±12.7 years, with range of 28–72 years. The male sex slightly exceeded the female one in prevalence of studied renal neoplasms (52 vs. 48%, respectively). Regarding the size of oncocytoma tumors in gross examination, it had a mean±SD of 5±2 cm, whereas that of ChRCC was 7±4 cm. The central scar is present in only four (23.5%) cases of oncocytoma, being absent in most cases (13 cases, 76.5%). In ChRCC, the nuclear grade 2 is the most common in the studied group (62.5%). Regarding leptin immunostaining scores, positive score was found in 13/17 oncocytoma cases, and only 2/8 cases of ChRCC showed nuclear leptin stain, with significant P value of 0.028. Oncocytoma leptin-positive cases represented 86.70%, whereas those of ChRCC represented 13.30% of total cases. Leptin sensitivity was estimated to be 76.5%, specificity 75.0%, positive predictive value 86.7%, negative predictive value 60.0%, with overall accuracy of 76%. Conclusion Leptin immunostain can be of an extreme help in differentiating ChRCC and RO.

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.