Proteomic analysis of chromophobe renal cell carcinoma and benign renal oncocytoma biopsies reveals shared metabolic dysregulation.

BACKGROUND: This study investigates the proteomic landscapes of chromophobe renal cell carcinoma (chRCC) and renal oncocytomas (RO), two subtypes of renal cell carcinoma that together account for approximately 10% of all renal tumors. Despite their histological similarities and shared origins, chRCC is a malignant tumor necessitating aggressive intervention, while RO, a benign growth, is often subject to overtreatment due to difficulties in accurate differentiation. METHODS: We conducted a label-free quantitative proteomic analysis on solid biopsies of chRCC (n = 5), RO (n = 5), and normal adjacent tissue (NAT, n = 5). The quantitative analysis was carried out by comparing protein abundances between tumor and NAT specimens. Our analysis identified a total of 1610 proteins across all samples, with 1379 (85.7%) of these proteins quantified in at least seven out of ten LC‒MS/MS runs for one renal tissue type (chRCC, RO, or NAT). RESULTS: Our findings revealed significant similarities in the dysregulation of key metabolic pathways, including carbohydrate, lipid, and amino acid metabolism, in both chRCC and RO. Compared to NAT, both chRCC and RO showed a marked downregulation in gluconeogenesis proteins, but a significant upregulation of proteins integral to the citrate cycle. Interestingly, we observed a distinct divergence in the oxidative phosphorylation pathway, with RO showing a significant increase in the number and degree of alterations in proteins, surpassing that observed in chRCC. CONCLUSIONS: This study underscores the value of integrating high-resolution mass spectrometry protein quantification to effectively characterize and differentiate the proteomic landscapes of solid tumor biopsies diagnosed as chRCC and RO. The insights gained from this research offer valuable information for enhancing our understanding of these conditions and may aid in the development of improved diagnostic and therapeutic strategies.

Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging: Diagnostic Pathways and Metabolites for Renal Tumor Entities.

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.

A triple-classification for differentiating renal oncocytoma from renal cell carcinoma subtypes and CK7 expression evaluation: a radiomics analysis.

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

Differential diagnosis of renal oncocytoma and chromophobe renal cell carcinoma using CT features: a central scar-matched retrospective study.

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

Growth and renal function dynamics of renal oncocytomas in patients on active surveillance.

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.

Cytogenetic analysis of 130 renal oncocytomas identify three distinct and mutually exclusive diagnostic classes of chromosome aberrations.

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.

Small renal masses (≤ 4 cm): differentiation of oncocytoma from renal clear cell carcinoma using ratio of lesion to cortex attenuation and aorta-lesion attenuation difference (ALAD) on contrast-enhanced CT.

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

Diagnostic Performance of Contrast-Enhanced Ultrasound (CEUS) in the Evaluation of Solid Renal Masses.

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

Immunohistochemistry and renal neoplasias.

Tento přehledový článek stručně shrnuje možnosti využití imunohistochemie při vyšetřování především renálních karcinomů a základní molekulárně genetické znaky vybraných neoplázií. Článek však v žádném případě nelze brát jako univerzální návod pro diagnostiku renálních tumorů. Renální karcinomy dokážou mít velmi variabilní morfologický vzhled a to i v rámci jedné léze (nádorová heterogenita) a často velmi nepředvídatelný a neuniformní imunohistochemický profil. Některé renální neoplázie jsou diagnostikovány striktně na podkladě molekulárně-genetických vlastností, bez ohledu na morfologický vzhled.

Development of a Robust Ultrasonic-Based Sample Treatment To Unravel the Proteome of OCT-Embedded Solid Tumor Biopsies.

An effective three-step proteomics workflow is proposed to overcome the pitfalls caused by polymers present in optimum cutting temperature (OCT)-embedded tissue during its preparation for mass spectrometry analysis. First, the OCT-embedded tissue biopsies are cleaned using ethanol and water in a sequential series of ultrasonic washes in an ultrasound bath (35 kHz ultrasonic frequency, 100% ultrasonic amplitude, 2 min of ultrasonic duty time). Second, a fast ultrasonic-assisted extraction of proteins is done using an ultrasonic probe (30 kHz ultrasonic frequency, 50% ultrasonic amplitude, 2 min of ultrasonic duty time, 1 mm diameter tip). Third, a rapid ultrasonic digestion of complex proteomes is performed using a microplate horn assembly device (20 kHz ultrasonic frequency, 25% ultrasonic amplitude, 4 min of ultrasonic duty time). As a proof of concept, the new workflow was applied to human normal and tumor kidney biopsies including chromophobe renal cell carcinomas (chRCCs) and renal oncocytomas (ROs). A successful cluster of proteomics profiles was obtained comprising 511 and 172 unique proteins found in chRCC and RO samples, respectively. The new method provides high sample throughput and comprehensive protein recovery from OCT samples.

Contemporary surgical management of renal oncocytoma: a nation's outcome.

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

[Low-grade eosinophilic unclassified renal cell carcinoma, a recently proposed entity in the spectrum of eosinophilic renal cells tumors: Report of one case and discussion]. / Le carcinome rénal inclassé de bas grade à cellules éosinophiles, une entité récemment proposée dans le spectre des tumeurs rénales à cellules éosinophiles : étude d'un cas et discussion.

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

Diffusion-weighted imaging versus contrast-enhanced MR imaging for the differentiation of renal oncocytomas and chromophobe renal cell carcinomas.

OBJECTIVES: To compare the performance of diffusion-weighted imaging (DWI) with that of contrast-enhanced MRI in differentiating renal oncocytomas from chromophobe renal cell carcinomas (RCCs). METHODS: We recruited 48 patients with histopathologically confirmed renal oncocytomas (n=16) and chromophobe RCCs (n=32). All patients underwent preoperative DWI and contrast-enhanced MRI. Apparent diffusion coefficient (ADC) and signal intensity were measured in each patient. ADC ratio and percentage of signal intensity change were calculated. RESULTS: Mean ADC values for renal oncoctytomas were significantly higher than those for chromophobe RCCs (1.59±0.21 vs. 1.09±0.29× 10-3 mm2/s, p < 0.001). Area under the ROC curve, sensitivity and specificity were 0.931, 87.5% and 84.4%, respectively, for ADC measurement of DW imaging; 0.825, 87.5% and 75%, respectively, for enhancement ratio (p > 0.05). Adding ADC values to the enhancement ratios in the ROC, analysis to differentiate renal oncocytoma from chromophobe RCCs increased specificity from 75 to 87.5% at 87.5% sensitivity without significantly increasing the AUC (0.930). CONCLUSIONS: Both DWI and contrast-enhanced MRI may assist in differentiating renal oncocytomas from chromophobe RCCs, with DWI showing higher diagnostic value. The combination of the two parameters could potentially provide better performance in distinguishing these two tumours. KEY POINTS: • ADC values can assist in differentiating renal oncocytomas from chromophobe RCCs. • DW imaging possesses better specificity than does contrast-enhanced MR imaging. • Combining the two parameters provides higher specificity regarding the differential diagnosis.

Can the multiphasic computed tomography be useful in the clinical management of small renal masses?

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

Active surveillance is suitable for intermediate term follow-up of renal oncocytoma diagnosed by percutaneous core biopsy.

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.

Comparative study of CT appearances in renal oncocytoma and chromophobe renal cell carcinoma.

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

Small (< 4 cm) Renal Mass: Differentiation of Oncocytoma From Renal Cell Carcinoma on Biphasic Contrast-Enhanced CT.

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

Coexisting hybrid malignancy in a solitary sporadic solid benign renal mass: implications for treating patients following renal biopsy.

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

Ultrasonographic features of renal oncocytoma with histopathologic correlation.

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

Radiomics analysis based on single phase and different phase combinations of radiomics features from tri-phasic CT to distinguish renal oncocytoma from chromophobe renal cell carcinoma.

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