Background: Small renal masses (SRMs) are defined as contrast-enhanced renal lesions less than or equal to 4 cm in maximal diameter, which can be compatible with stage T1a renal cell carcinomas (RCCs). Currently, 50-61% of all renal tumors are found incidentally. Methods: The characteristics of the lesion influence the choice of the type of management, which include several methods SRM of management, including nephrectomy, partial nephrectomy, ablation, observation, and also stereotactic body radiotherapy. Typical imaging methods available for differentiating benign from malignant renal lesions include ultrasound (US), contrast-enhanced ultrasound (CEUS), computed tomography (CT), and magnetic resonance imaging (MRI). Results: Although ultrasound is the first imaging technique used to detect small renal lesions, it has several limitations. CT is the main and most widely used imaging technique for SRM characterization. The main advantages of MRI compared to CT are the better contrast resolution and tissue characterization, the use of functional imaging sequences, the possibility of performing the examination in patients allergic to iodine-containing contrast medium, and the absence of exposure to ionizing radiation. For a correct evaluation during imaging follow-up, it is necessary to use a reliable method for the assessment of renal lesions, represented by the Bosniak classification system. This classification was initially developed based on contrast-enhanced CT imaging findings, and the 2019 revision proposed the inclusion of MRI features; however, the latest classification has not yet received widespread validation. Conclusions: The use of radiomics in the evaluation of renal masses is an emerging and increasingly central field with several applications such as characterizing renal masses, distinguishing RCC subtypes, monitoring response to targeted therapeutic agents, and prognosis in a metastatic context.

Radiomics, the extraction and analysis of quantitative features from medical images, has emerged as a promising field in radiology with the potential to revolutionize the diagnosis and management of renal lesions. This comprehensive review explores the radiomics workflow, including image acquisition, feature extraction, selection, and classification, and highlights its application in differentiating between benign and malignant renal lesions. The integration of radiomics with artificial intelligence (AI) techniques, such as machine learning and deep learning, can help patients' management and allow the planning of the appropriate treatments. AI models have shown remarkable accuracy in predicting tumor aggressiveness, treatment response, and patient outcomes. This review provides insights into the current state of radiomics and AI in renal lesion assessment and outlines future directions for research in this rapidly evolving field.

Radiomics is a type of quantitative analysis that provides a more objective approach to detecting tumor subtypes using medical imaging. The goal of this paper is to conduct a comprehensive assessment of the literature on computed tomography (CT) radiomics for distinguishing renal cell carcinomas (RCCs) from oncocytoma.

From February 15th 2012 to 2022, we conducted a broad search of the current literature using the PubMed/MEDLINE, Google scholar, Cochrane Library, Embase, and Web of Science. A meta-analysis of radiomics studies concentrating on discriminating between oncocytoma and RCCs was performed, and the risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies method. The pooled sensitivity, specificity, and diagnostic odds ratio were evaluated via a random-effects model, which was applied for the meta-analysis. This study is registered with PROSPERO (CRD42022311575).

After screening the search results, we identified 6 studies that utilized radiomics to distinguish oncocytoma from other renal tumors; there were a total of 1064 lesions in 1049 patients (288 oncocytoma lesions vs 776 RCCs lesions). The meta-analysis found substantial heterogeneity among the included studies, with pooled sensitivity and specificity of 0.818 [0.619-0.926] and 0.808 [0.537-0.938], for detecting different subtypes of RCCs (clear cell RCC, chromophobe RCC, and papillary RCC) from oncocytoma. Also, a pooled sensitivity and specificity of 0.83 [0.498-0.960] and 0.92 [0.825-0.965], respectively, was found in detecting oncocytoma from chromophobe RCC specifically.

According to this study, CT radiomics has a high degree of accuracy in distinguishing RCCs from RO, including chromophobe RCCs from RO. Radiomics algorithms have the potential to improve diagnosis in scenarios that have traditionally been ambiguous. However, in order for this modality to be implemented in the clinical setting, standardization of image acquisition and segmentation protocols as well as inter-institutional sharing of software is warranted.

To assess the ability to discriminate oncocytoma from RCC based on a model using whole tumor ADC histogram parameters with additional use of tumor volume and patient characteristics.

In this prospective study, 39 patients (mean age 65 years, range 28-79; 9/39 (23%) female) with 39 renal tumors (32/39 (82%) RCC and 7/39 (18%) oncocytoma) underwent multiparametric MRI between November 2014 and June 2018. Two regions of interest (ROIs) were drawn to cover both the entire tumor volume and a part of healthy renal cortex. ROI ADC maps were calculated using a mono-exponential model and ADC histogram distribution parameters were calculated. A logistic regression model was created using ADC histogram parameters, radiographic and patient characteristics that were significantly different between oncocytoma and RCC. A ROC curve of the model was constructed and the AUC, sensitivity and specificity were calculated. Furthermore, differences in intra-patient ADC histogram parameters between renal tumor and healthy cortex were calculated. A separate ROC curve was constructed to differentiate oncocytoma from RCC using statistically significant intra-patient parameter differences.

ADC standard deviation (p = 0.008), entropy (p = 0.010), tumor volume (p = 0.012), and patient sex (p = 0.018) were significantly different between RCC and oncocytoma. The regression model of these parameters combined had an ROC-AUC of 0.91 with a sensitivity of 86% and specificity of 84%. Intra-patient difference in ADC 25th percentile (p < 0.01) and entropy (p = 0.030) combined had a ROC-AUC of 0.86 with a sensitivity and specificity of 86%, and 81%, respectively.

A model combining ADC standard deviation and entropy with tumor volume and patient sex has the highest diagnostic value for discrimination of oncocytoma. Although less accurate, intra-patient difference in ADC 25th percentile and entropy between renal tumor and healthy cortex can also be used. Although the results of this preliminary study do not yet justify clinical use of the model, it does stimulate further research using whole tumor ADC histogram parameters.

Radiomics is a specific field of medical research that uses programmable recognition tools to extract objective information from standard images to combine with clinical data, with the aim of improving diagnostic, prognostic, and predictive accuracy beyond standard visual interpretation. We performed a narrative review of radiomic applications that may support improved characterization of small renal masses (SRM). The main focus of the review was to identify and discuss methods which may accurately differentiate benign from malignant renal masses, specifically between renal cell carcinoma (RCC) subtypes and from angiomyolipoma without visible fat (fat-poor AML) and oncocytoma. Furthermore, prediction of grade, sarcomatoid features, and gene mutations would be of importance in terms of potential clinical utility in prognostic stratification and selecting personalised patient management strategies.

A detailed search of original articles was performed using the PubMed-MEDLINE database until 20 September 2020 to identify the English literature relevant to radiomics applications in renal tumour assessment. In total, 42 articles were included in the analysis in 3 main categories related to SRM: prediction of benign versus malignant SRM, subtypes, and nuclear grade, and other features of aggressiveness.

Overall, studies reported the superiority of radiomics over expert radiological assessment, but were mainly of retrospective design and therefore of low-quality evidence. However, it is clear that radiomics is an attractive modality that has the potential to improve the non-invasive diagnostic accuracy of SRM imaging and prediction of its natural behaviour. Further prospective validation studies of radiomics are needed to augment management algorithms of SRM.

Low-grade oncocytic tumour (LOT) has recently been introduced as a potential distinct entity.

At the Indiana University department of pathology, primary renal epithelial neoplasms between 2005 and 2020 were searched after appropriate institutional review board permissions.

Twenty-three cases (male/female ratio 14/9) with a median age of 66 (23-84 years) were identified. The majority of patients underwent partial nephrectomy (15/23, 65%), with a median tumour size of 4.0 cm (2.2-10.5 cm). Only one case had infiltration beyond the kidney (perinephric fat). Solid/diffuse proliferation of tightly packed oncocytic tumour cells and occasional tubule formations, with an abrupt edematous change in the stroma with loosely connected small clusters of tumour cells. Along with diffuse CK7 expression with lack of CD117 in all cases, vimentin was positive in 8/23 cases (35%, 5 focal). CD10 was expressed in 6/13 (46%, 4 focal). Alpha-Methylacyl-CoA Racemase (AMACR) was positive in 5/8 (63%) cases. Focal but intense cytoplasmic colloidal iron stain was present in 3/20 (15%) cases. Luminal or cytoplasmic/perinuclear precipitation was observed in 8/20 (40%) cases. Succinate Dehydrogenase B (SDHB) was performed in 6 cases, with all retained expression.

LOT is a clinically indolent and potentially benign entity with distinguishable morphology and immunohistochemical profile that can be performed and be easily interpreted in most of surgical pathology settings. Additional studies with larger cohorts, comprehensive molecular evaluation and longer follow-up are needed to definitively recognise these tumours as a separate entity and to further address the possibility of active surveillance options in eligible patients.

Radiomics allows for high throughput extraction of quantitative data from images. This is an area of active research as groups try to capture and quantify imaging parameters and convert these into descriptive phenotypes of organs or tumors. Texture analysis is one radiomics tool that extracts information about heterogeneity within a given region of interest. This is used with or without associated machine learning classifiers or a deep learning approach is applied to similar types of data. These tools have shown utility in characterizing renal masses, renal cell carcinoma, and assessing response to targeted therapeutic agents in metastatic renal cell carcinoma.

To perform a systematic review on apparent diffusion coefficient (ADC) values of renal tumor subtypes and meta-analysis on the diagnostic performance of ADC for differentiation of localized clear cell renal cell carcinoma (ccRCC) from other renal tumor types.

Medline, Embase, and the Cochrane Library databases were searched for studies published until May 1, 2019, that reported ADC values of renal tumors. Methodological quality was evaluated. For the meta-analysis on diagnostic test accuracy of ADC for differentiation of ccRCC from other renal lesions, we applied a bivariate random-effects model and compared two subgroups of ADC measurement with vs. without cystic and necrotic areas.

We included 48 studies (2588 lesions) in the systematic review and 13 studies (1126 lesions) in the meta-analysis. There was no significant difference in ADC of renal parenchyma using b values of 0-800 vs. 0-1000 (p = 0.08). ADC measured on selected portions (sADC) excluding cystic and necrotic areas differed significantly from whole-lesion ADC (wADC) (p = 0.002). Compared to ccRCC, minimal-fat angiomyolipoma, papillary RCC, and chromophobe RCC showed significantly lower sADC while oncocytoma exhibited higher sADC. Summary estimates of sensitivity and specificity to differentiate ccRCC from other tumors were 80% (95% CI, 0.76-0.88) and 78% (95% CI, 0.64-0.89), respectively, for sADC and 77% (95% CI, 0.59-0.90) and 77% (95% CI, 0.69-0.86) for wADC. sADC offered a higher area under the receiver operating characteristic curve than wADC (0.852 vs. 0.785, p = 0.02).

ADC values of kidney tumors that exclude cystic or necrotic areas more accurately differentiate ccRCC from other renal tumor types than whole-lesion ADC values.

• Selective ADC of renal tumors, excluding cystic and necrotic areas, provides better discriminatory ability than whole-lesion ADC to differentiate clear cell RCC from other renal lesions, with area under the receiver operating characteristic curve (AUC) of 0.852 vs. 0.785, respectively (p = 0.02). • Selective ADC of renal masses provides moderate sensitivity and specificity of 80% and 78%, respectively, for differentiation of clear cell renal cell carcinoma (RCC) from papillary RCC, chromophobe RCC, oncocytoma, and minimal-fat angiomyolipoma. • Selective ADC excluding cystic and necrotic areas are preferable to whole-lesion ADC as an additional tool to multiphasic MRI to differentiate clear cell RCC from other renal lesions whether the highest b value is 800 or 1000.

Renal cell carcinoma (RCC) is a relatively rare malignancy of the urinary tract system. RCC is a heterogenous disease in terms of underlying histology and its associated underlying pathobiology, prognosis and treatment schedule. The most prevalent histological RCC subtype is clear-cell renal cell carcinoma (ccRCC), accounting for about 70-80% of all RCCs. Though the pathobiology and treatment schedule for ccRCC are well-established, non-ccRCC subtypes account for 20%-30% of RCC altogether, and their underlying molecular biology and treatment options are poorly defined. The class of non-coding RNAs-molecules that are generally not translated into proteins-are new cancer drivers and suppressors in all types of cancer. Of these, small non-coding microRNAs (miRNAs) contribute to carcinogenesis by regulating posttranscriptional gene silencing. Additionally, a growing body of evidence supports the role of long non-coding RNAs (lncRNAs) in cancer development and progression. Most studies on non-coding RNAs in RCC focus on clear-cell histology, and there is a relatively limited number of studies on non-ccRCC subtypes. The aim of this review is to give an overview of the current knowledge regarding the role of non-coding RNAs (including short and long non-coding RNAs) in non-ccRCC and to highlight possible implications as diagnostic, prognostic and predictive biomarkers.

Tumours of the distal nephron are uncommon but can create diagnostic difficulties. They may be divided into three groups-tumours of intercalated cell phenotype, those of principal cell phenotype and others with an unconfirmed distal nephron origin. Oncocytomas, chromophobe carcinoma and hybrid oncocytoma chromophobe carcinoma, all show features of intercalated cells and the distinction amongst these is one of the most common areas of diagnostic dilemma. Collecting duct carcinoma and renal medullary carcinoma are the most aggressive forms of renal cancer but recent evidence suggests they may respond to targeted therapy so their recognition becomes crucial to the management of these patients. There remains debate over the precise phenotype of both tubulocystic carcinoma and mucinous tubular and spindle cell carcinoma.

Thymic neuroendocrine carcinomas are the most common mediastinal neuroendocrine tumor. These malignancies are not often diagnosed by fine-needle aspiration (FNA), as they are more commonly diagnosed by biopsy or excision. We describe a case of a FNA of a paratracheal mass from a 38-year-old man who presented with Cushing syndrome. A low-grade neuroendocrine carcinoma with oncocytic features was diagnosed, which was later confirmed by excision of the thymus, anterior mediastinal and paratracheal soft tissue, and lymph nodes. Oncocytic features in these tumors are a rare finding and bring metastatic medullary thyroid carcinomas as well as other metastases into the differential diagnosis. The prognosis of neuroendocrine carcinomas in this location is worse than neuroendocrine carcinomas in other areas, and close follow-up is recommended.

The spectrum of primary renal tumors in which clear cells may appear is revisited in this review. The pathologist's viewpoint of this topic is pertinent because not all the tumors with clear cells are carcinomas and not all renal cell carcinomas with clear cells are clear cell renal cell carcinomas. In fact, some of them are distinct entities according to the new WHO classification. The morphological approach is combined with genetics. Renal cell carcinoma related to von Hippel-Lindau disease is reviewed first because many of the genetic disorders underlying this disease are also present in sporadic, conventional renal cell clear cell carcinomas. Subsequently, conventional renal cell clear cell carcinomas, familial, non von Hippel-Lindau-associated renal cell carcinomas, translocation carcinomas, hereditary papillary renal cell carcinomas, carcinomas associated to tuberous sclerosis and to Birt-Hogg-Dubé syndrome, chromophobe renal cell carcinomas, carcinomas associated with end-stage renal disease, and clear cell tubulopapillary carcinomas are reviewed. Finally, epithelioid angiomyolipoma is also considered in this review.

To determine whether enhancement at multiphasic multidetector computed tomography (CT) can help differentiate clear cell renal cell carcinoma (RCC) from oncocytoma, papillary RCC, and chromophobe RCC.

With institutional review board approval for this HIPAA-compliant retrospective study, the pathology database was queried to derive a cohort of 298 cases of RCC and oncocytoma with preoperative multiphasic multidetector CT with as many as four phases (unenhanced, corticomedullary, nephrographic, and excretory). A total of 170 clear cell RCCs, 57 papillary RCCs, 49 oncocytomas, and 22 chromophobe RCCs were evaluated for multiphasic enhancement and compared by using t tests. Cutoff analysis was performed to determine optimal threshold levels to discriminate among the four groups.

Mean enhancement of clear cell RCCs and oncocytomas peaked in the corticomedullary phase; mean enhancement of papillary and chromophobe RCCs peaked in the nephrographic phase. Enhancement of clear cell RCCs was greater than that of oncocytomas in the corticomedullary (125 HU vs 106 HU, P = .045) and excretory (80 HU vs 67 HU, P = .034) phases. Enhancement of clear cell RCCs was greater than that of papillary RCCs in the corticomedullary (125 HU vs 54 HU, P < .001), nephrographic (103 HU vs 64 HU, P < .001), and excretory (80 HU vs 54 HU, P < .001) phases. Enhancement of clear cell RCCs was greater than that of chromophobe RCCs in the corticomedullary (125 HU vs 74 HU, P < .001) and excretory (80 HU vs 60 HU, P = .008) phases. Thresholding of enhancement helped to discriminate clear cell RCC from oncocytoma, papillary RCC, and chromophobe RCC with accuracies of 77% (83 of 108 cases), 85% (101 of 119 cases), and 84% (81 of 97 cases).

Enhancement at multiphasic multidetector CT, if prospectively validated, may assist in the discrimination of clear cell RCC from oncocytoma, papillary RCC, and chromophobe RCC.

Kidney and upper urinary tract cancers account for approximately 54,000 cases every year in the United States, and represent about 3.7% of adult malignancies, with more than 13,000 annual deaths. Classification of renal tumors is typically based on histomorphologic characteristics but, on occasion, morphologic characteristics are not sufficient. Each of the most common histologic subtypes harbors specific recurrent genetic abnormalities, such as deletion of 3p in conventional clear cell carcinoma, trisomy 7 and 17 in papillary renal cell carcinoma, multiple monosomies in chromophobe renal cell carcinoma, and a nearly diploid genome in benign oncocytomas. Knowledge of this information can provide diagnostic support and prognostic refinement in renal epithelial tumors. Identification of the specific subtype of a renal tumor is critical in guiding surveillance for recurrence and the appropriate use of targeted therapies. Cytogenomic arrays are increasingly being used as a clinical tool for genome-wide assessment of copy number and loss of heterozygosity in renal tumors. In addition, the improved understanding of the hereditary causes of renal tumors and their role in sporadic malignancies has led to the development of more effective targeted therapies. This review summarizes the genetic and genomic changes in the most common types of renal epithelial tumors and highlights the clinical implications of these aberrations.

Renal oncocytoma and chromophobe renal cell carcinoma (CRCC) are closely related tumors. They are considered the extremes of a spectrum with several variants. Ultrastructural examination of the mitochondria is a helpful procedure in the diagnosis of these neoplasms. Renal oncocytomas show mitochondria with piled lamellar cristae, and CRCC exhibited mitochondria with tubulovesicular cristae. In a series of 23 histologically diagnosed renal oncocytomas examined by electron microscopy, the authors found 5 tumors exhibiting more cells with mitochondria showing tubulovesicular cristae. The authors believe these 5 cases present a submicroscopic appearance intermediate between renal oncocytoma and CRCC, although with benign clinical behavior.

Renal oncocytosis is a rare pathological condition in which renal parenchyma is diffusely involved by numerous oncocytic nodules in addition to showing a spectrum of other oncocytic changes. We describe our experience with renal oncocytosis, focusing on management and outcomes.

A total of 20 patients with a final pathological diagnosis of renal oncocytosis from July 1995 through June 2009 were included in the analysis. Patient demographics, intraoperative variables and postoperative outcomes are reported.

Median age at nephrectomy was 71 years (IQR 59-75). Of the patients 15 (75%) had bilateral disease. There were 23 operations (9 right side, 14 left side) performed on 20 patients, and of these procedures 13 (57%) were partial nephrectomies and 10 (43%) were radical nephrectomies. Median dominant tumor mass diameter was 4.1 cm (IQR 3-6.4, range 1 to 14.6). The most common dominant tumor histology was hybrid tumor between oncocytoma and chromophobe renal cell carcinoma in 13 of 23 specimens (57%), followed by chromophobe renal cell carcinoma in 6 (26%), oncocytoma in 3 (13%) and conventional renal cell carcinoma in 1 (4%). Ten patients (50%) had preexisting chronic kidney disease before nephrectomy and chronic kidney disease developed in 5 more after surgery. After a median followup of 35 months no patients had metastatic disease.

Patients with renal oncocytosis usually present with multiple and bilateral renal nodules. Half of the patients had chronic kidney disease at diagnosis and 25% had new onset of chronic kidney disease. No patient had distant metastatic disease during followup. Our management approach is to perform partial nephrectomy when possible and then use careful surveillance of the remaining renal masses.

The purpose of this study was to retrospectively describe the MRI features of the pathologically related entities renal oncocytoma and chromophobe renal cell carcinoma (RCC).

Twenty-eight cases of histologically proven renal oncocytoma and 15 of chromophobe RCC evaluated with preoperative MRI from January 2003 through June 2009 at our institution were independently reviewed for an array of MRI features by two radiologists blinded to the final histopathologic diagnosis. These features were tabulated and compared between chromophobe RCC and renal oncocytoma by use of the Mann-Whitney test and binary logistic regression.

Renal oncocytoma and chromophobe RCC showed no significant difference in size or any of 16 qualitative imaging features (p = 0.0842-1.0, reader 1; p = 0.0611-1.0, reader 2). Microscopic fat, hemorrhage, cysts, infiltrative margins, perinephric fat invasion, renal vein invasion, enhancement homogeneity, and hypervascularity were each observed in less than 20% of cases by both readers. A central scar and segmental enhancement inversion (a recently described finding in which early contrast-enhanced images show relatively more enhanced and less enhanced intralesional components with inversion of their relative enhancement on later images) were observed by both readers in at least 10% of cases of both renal oncocytoma and of chromophobe RCC with no significant difference between the two entities (p = 0.2092-0.2960).

We have presented the largest series to date of the MRI features of both renal oncocytoma and chromophobe RCC. These related entities exhibited similar findings, and no MRI features were reliable in distinguishing between them.

Salivary gland tumours usually show great variability both in their morphopathology as well as their clinical behaviour. In the present study, the usefulness of antimitochondrial monoclonal antibody 113-1 in the diagnosis and categorization of salivary tumours was studied.

A series of 22 benign and malignant salivary tumours and 5 non-tumoral salivary gland specimens were immunohistochemically analysed using an antimitochondrial monoclonal antibody (Ab Mo 113-1), which recognises a non-glycosylated mitochondrial protein of 60 Kd.

The use of this antibody allowed us to recognize all salivary tumours with oncocytic differentiation. Two salivary tumours (1 papillary cystadenoma and 1 epithelial-myoepithelial carcinoma) (2/22; 10%) were also reclassified as oncocytic tumoral subtypes, in principle unidentified.

Our study highlights the usefulness of this antibody to facilitate the classification of salivary tumours, an aspect that may sometimes have not only diagnostic implications, but also prognostic.

Metastatic renal cell carcinoma (mRCC) patients treated with anti-vascular endothelial growth factor (VEGF) therapies demonstrate promising outcomes but not all patients benefit. Factors that predict response remain to be elucidated.

Nephrectomy material from 37 patients with mRCC receiving bevacizumab +/- erlotinib was used for protein and gene expression assessment. Protein lysates were subjected to reverse-phase protein array profiling. RNA extracts were used to carry out gene expression microarray-based profiling. Normalized protein and gene expression data were correlated with overall survival (OS) and progression-free survival (PFS) using univariate Cox hazard model and linear regression. Immunoblotting was carried out to validate the results.

High protein levels of AMP-activated protein kinase and low levels of cyclin B1 (CCNB1) were associated with longer OS and PFS. Further validation revealed reduced expression and activation of phosphoinositide 3-kinase (PI3K) pathway components and cell cycle factors in patients with prolonged survival after therapy. Gene expression analysis revealed up-regulation of PI3K- and cell cycle-related pathways in patients with shorter PFS.

The OS and PFS of bevacizumab +/- erlotinib-treated patients with renal cell carcinoma were associated with changes in expression of protein and gene expression markers related to PI3K pathway and cell cycle signaling.

The most important differential diagnosis of chromophobe renal cell carcinoma (CRCC) is renal oncocytoma. Due to overlapping morphological characteristics of renal oncocytoma and CRCC, particularly its eosinophilic variant, making a correct diagnosis can be challenging. To date, no data are available on the presence of the tumor fibrous capsule as a diagnostic feature in differentiating these tumors. The main purpose of this study was to establish the presence and compare the thickness of the tumor fibrous capsule between two tumor groups. A total of 37 tumors--18 cases of CRCC (three eosinophilic and 15 classic) and 19 cases of renal oncocytoma--were analyzed. Four slides of each tumor stained with hematoxylin and eosin were first scanned at low-power magnification (x40) to assess the presence of the capsule. If present, the capsule was measured in three different thickest areas at higher magnification (x200). The mean value of capsule thickness was calculated and taken into consideration. The capsule was present in 12 (66.7%) cases of CRCCs and in only two (10.5%) cases of renal oncocytomas. Statistical analysis showed significant difference between the presence of fibrous capsule in these two observed tumor groups (P = 0.001). Average thickness of capsule in CRCCs was 337.7 microm, and 115.4 microm in renal oncocytomas, but the median was not statistically significant (P = 0.198). Studies with a larger number of cases are needed to conclude if this characteristic could be a low-cost, reliable microscopic feature in differentiating between CRCC and renal oncocytoma.

To retrospectively determine the usefulness of segmental enhancement inversion during the corticomedullary phase (CMP) and early excretory phase (EEP) of biphasic multidetector computed tomography (CT) in differentiating small renal oncocytoma from renal cell carcinoma (RCC).

This retrospective study was institutional review board approved; informed consent was waived. Between January 2004 and December 2006, 98 patients with pathologically confirmed renal masses smaller than 4 cm (10 renal oncocytomas and 88 RCCs) were included in this study. Segmental enhancement inversion was defined as follows: In a mass with two segments showing different degrees of enhancement during CMP, the relatively highly enhanced segment became less enhanced during EEP, whereas the less-enhanced segment during CMP became highly enhanced during EEP. Two experienced radiologists retrospectively assessed the presence of segmental inversion in all masses and measured attenuation with consensus. The Fisher exact test was used to determine the significance of segmental enhancement inversion in differentiating small renal oncocytoma from RCC.

Eight of 10 renal oncocytomas and only one of 88 RCCs showed segmental inversion during CMP and EEP, which significantly differentiated small renal oncocytomas and RCCs (P < .0001). For differentiating oncocytoma from RCC, segmental inversion was found to have a sensitivity of 80% (eight of 10), a specificity of 99% (87 of 88), a positive predictive value of 89% (eight of nine), and a negative predictive value of 98% (87 of 89). The mean values of the attenuation differences shown by two segments during CMP and EEP were 62.75 HU +/- 36.96 (standard deviation) and -36.88 HU +/- 20.02, respectively.

Segmental enhancement inversion during CMP and EEP was found to be a characteristic enhancement pattern of small renal oncocytoma at biphasic multidetector CT and it may help in differentiating small oncocytoma from RCC.

http://radiology.rsnajnls.org/cgi/content/full/2522081180/DC1.

Claudin-7 and claudin-8 code for tight junction proteins expressed in distal nephron epithelium. In a recent oligonucleotide microarray study, we identified claudin-7 and claudin-8 as candidate markers to distinguish chromophobe renal cell carcinoma from other renal tumors, including oncocytoma. Distinction of these lesions can be difficult by light microscopy but is clinically important because chromophobe renal cell carcinoma has malignant biological potential, whereas renal oncocytoma is benign. Claudin-7 and claudin-8 expression was studied by immunohistochemistry in 11 chromophobe renal cell carcinomas and 17 oncocytomas using formalin-fixed paraffin-embedded tissue sections of tumor with adjacent nonneoplastic kidney. Steam antigen retrieval was performed before immunohistochemistry. Specificity was verified by negative control reactions without primary antibody and appropriate membranous staining patterns in positive control tissues (colon carcinoma and adjacent nonneoplastic kidney). Claudin-7 protein was expressed in a membranous pattern in 10 of 11 chromophobe renal cell carcinomas and 4 of 17 oncocytomas (P < .01). Claudin-8 was expressed in multiple patterns: In oncocytoma, 11 of 17 cases showed cytoplasmic, 4 of 17 membranous, and 2 of 17 negative reactions. In chromophobe renal cell carcinoma, 0 of 11 cases showed cytoplasmic, 3 of 11 membranous, and 8 of 11 negative reactions (P < .01). The immunohistochemical pattern of membranous claudin-7 and negative claudin-8 was seen in 7 of 11 chromophobe renal cell carcinomas and 1 of 17 oncocytomas (63% sensitivity, 84% specificity, 88% positive predictive value for chromophobe renal cell carcinoma). Negative claudin-7 and cytoplasmic claudin-8 were observed in 10 of 17 oncocytomas and 0 of 11 chromophobe renal cell carcinomas (59% sensitivity, 100% specificity and positive predictive value for oncocytoma). The distal nephron proteins claudin-7 and claudin-8 have potential use as immunohistochemical biomarkers in the differential diagnosis of chromophobe renal cell carcinoma and oncocytoma. Expression of claudin-7 and claudin-8 may reflect the relationship of chromophobe renal cell carcinoma and oncocytoma to intercalated cells of the cortical collecting duct. It may be necessary to identify additional biomarkers to include with claudin-7 and claudin-8 in a larger immunohistochemical panel to improve diagnostic sensitivity and specificity.

Renal cell carcinomas (RCCs) are neoplasias with high prevalence and mortality. We previously reported that several peptidases may be involved in the pathophysiology of clear cell renal cell carcinoma (CCRCC). Now, to gain insight into the reasons that lead the various RCC types to behave very differently with regard to aggressiveness and response to anticancer treatments, we analyzed subsets of chromophobe renal cell carcinoma (ChRCC), and renal oncocytoma (RO), a benign tumor; as well as different grades and stages of CCRCCs. Particulate APN, APB, and APA activities were decreased in both ChRCC and RO (tumor vs. nontumor tissues). Interestingly, activities were downregulated in a tumor-type specific way and the intensities of the decreases were stronger in the benign tumor than in the malignant type. Moreover, when two key histopathological parameters for tumor prognosis (high vs. low stage and grade) were analyzed, increases of activity were also observed in several of these cell surface peptidases (APN, APB). Some soluble activities (APB, Asp-AP) were also downregulated in the RCCs. With respect to genetic expression, PSA and APN were in a positive correlation related to their activities in both ChRCC and RO; but not APB, Asp-AP, APA, and PGI. These results may suggest an involvement of several peptidases in the pathophysiology of renal cancer, since they presented different patterns of activity and expression in tumors with different behaviors.

The differential diagnosis of eosinophilic renal tumors can be difficult by light microscopy. In particular, chromophobe renal cell carcinoma (RCC) is difficult to distinguish from oncocytoma. This differential diagnosis is important because chromophobe RCC is malignant, whereas oncocytoma is benign. Furthermore, chromophobe RCC has distinct malignant potential and prognosis compared with eosinophilic variants of other RCC subtypes. Immunohistochemistry is useful for distinguishing chromophobe RCC from other subtypes of renal carcinoma, but no expression marker reliably separates chromophobe RCC from oncocytoma.

In a previous gene expression microarray analysis of renal tumor subtypes, we found the distal nephron markers claudin-7 and claudin-8 to be overexpressed in chromophobe RCC versus oncocytoma and other tumor subtypes. We have confirmed similar findings in independent microarray data and validated differential claudin-7 protein expression by immunohistochemistry.

Immunohistochemical analysis of claudin-7 in 36 chromophobe RCCs, 43 oncocytomas, 42 clear cell RCCs, and 29 papillary RCCs.

Membranous claudin-7 expression was detected in 67% chromophobe RCCs, compared with 0% clear cell RCCs, 28% papillary RCCs, and 26% oncocytomas (P < .001).

Based on microarray and immunohistochemical data, we propose claudin-7 to be a candidate expression marker for distinguishing chromophobe RCC from other renal tumor subtypes, including the morphologically similar oncocytoma. The clinical utility of claudin-7 should be validated in independent studies of renal tumors, possibly in combination with additional targets in a multiplex immunohistochemical panel.

Systemic syndromes with cutaneous manifestations represent a continually evolving entity. New syndromes are described, while improved understanding of others, with new features of disease or enhanced genetic understanding of the disease are discovered. This review highlights the latest information on syndromes with cutaneous manifestations and presents several newly described dermatologic diagnoses.