Thyroid-stimulating hormone receptor (TSHR) as a target for imaging differentiated thyroid cancer.

BACKGROUND: Of the half a million cases of thyroid cancer diagnosed annually, 95% are differentiated thyroid cancers. Although clinical guidelines recommend surgical resection followed by radioactive iodine ablation, loss of sodium-iodine symporter expression causes up to 20% of differentiated thyroid cancers to become radioactive iodine refractory. For patients with radioactive iodine refractory disease, there is an urgent need for new diagnostic and therapeutic approaches. We evaluated the thyroid-stimulating hormone receptor as a potential target for imaging of differentiated thyroid cancer. METHODS: We immunostained tissue microarrays containing 52 Hurthle cell carcinomas to confirm thyroid-stimulating hormone receptor expression. We radiolabeled chelator deferoxamine conjugated to recombinant human thyroid-stimulating hormone analog superagonist TR1402 with 89Zr (t1/2 = 78.4 h, ß+ =22.7%) to produce [89Zr]Zr-TR1402. We performed in vitro uptake assays in high-thyroid-stimulating hormone receptor and low-thyroid-stimulating hormone receptor-expressing THJ529T and FTC133 thyroid cancer cell lines. We performed in vivo positron emission tomography/computed tomography and biodistribution studies in male athymic nude mice bearing thyroid-stimulating hormone receptor-positive THJ529T tumors. RESULTS: Immunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were thyroid-stimulating hormone receptor membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 was 38 ± 17% bound/mg in thyroid-stimulating hormone receptor-positive THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (P < .01), with a similar difference seen in FTC133 cell lines (P < .0001). In vivo and biodistribution studies showed uptake of [89Zr]Zr-TR1402 in thyroid-stimulating hormone receptor-expressing tumors, with a mean percentage of injected dose/g of 1.9 ± 0.4 at 3 days post-injection. CONCLUSION: Our observation of thyroid-stimulating hormone receptor expression in tissue microarrays and [89Zr]Zr-TR1402 accumulation in thyroid-stimulating hormone receptor-positive thyroid cancer cells and tumors suggests thyroid-stimulating hormone receptor is a promising target for imaging of differentiated thyroid cancer.

Renal oncocytoma in a 13-year-old girl: A case report and literature review.

Renal oncocytoma is a benign renal neoplasm which has mostly been reported in adults. Occurrence in children is infrequent. To date, there are only six pediatric cases of renal oncocytoma reported previously. Herein, we report a 13-year-old girl presented with hematuria for a week. Abdominal computed tomography showed a well-defined heterogeneous solid mass with a stellate central scar in the left kidney. The patient underwent a nephron sparing surgery. Histopathological and immunohistochemical findings confirmed the diagnosis of renal oncocytoma. Though uncommon, renal oncocytoma should be considered as the differential diagnosis of renal tumor in children. In addition, intranuclear inclusions were firstly described in this pediatric patient with unclear significance, which need a large cohort to summarize and analyze.

99m Tc-MIBI SPECT/CT Evaluation of a Renal Collision Tumor.

ABSTRACT: Preoperative differentiation of oncocytomas from renal cell carcinoma (RCC) is often challenging. 99m Tc-MIBI imaging could play a potential role in differentiating oncocytoma from RCC, which in turn could guide surgical decision-making. We present the use of 99m Tc-MIBI SPECT/CT to characterize a renal mass in a 66-year-old man with a complex medical history, including history of bilateral oncocytomas. 99m Tc-MIBI SPECT/CT showed features suspicious of a malignant tumor, which was confirmed postnephrectomy as a chromophobe and papillary RCC collision tumor. This case supports 99m Tc-MIBI imaging for preoperative differentiation of benign versus malignant renal tumors.

Clinical Performance of Technetium-99m-Sestamibi SPECT/CT Imaging in Differentiating Oncocytic Tumors From Renal Cell Carcinoma in Routine Clinical Practice.

PURPOSE: Technetium-99m-sestamibi single-photon emission CT/x-ray CT is an emerging clinical tool to differentiate oncocytic tumors from renal cell carcinomas. We report data from a large institutional cohort of patients who underwent technetium-99m-sestamibi scans during evaluation of renal masses. MATERIALS AND METHODS: Patients who underwent technetium-99m-sestamibi single-photon emission CT/x-ray CT between February 2020 and December 2021 were included in the analysis. Scans were defined as "hot" for oncocytic tumor when technetium-99m-sestamibi uptake was qualitatively equivalent or higher between the mass of interest and normal renal parenchyma, suggesting oncocytoma, hybrid oncocytic/chromophobe tumor, or chromophobe renal cell carcinoma. Demographic, pathological, and management strategy data were compared between "hot" and "cold" scans. For individuals who underwent diagnostic biopsy or extirpative procedures, the concordance between radiological findings and pathology was indexed. RESULTS: A total of 71 patients (with 88 masses) underwent technetium-99m-sestamibi imaging with 60 (84.5%) patients having at least 1 "cold" mass on imaging and 11 (15.5%) patients exhibiting only "hot" masses. Pathology was available for 7 "hot" masses, with 1 biopsy specimen (14.3%) being discordant (clear cell renal cell carcinoma). Five patients with "cold" masses underwent biopsy. Out of 5 biopsied masses, 4 (80%) were discordant oncocytomas. Of the extirpated specimens, 35/40 (87.5%) harbored renal cell carcinoma and 5/40 (12.5%) yielded discordant oncocytomas. In sum, 20% of pathologically sampled masses that were "cold" on technetium-99m-sestamibi imaging still harbored oncocytoma/hybrid oncocytic/chromophobe tumor/chromophobe renal cell carcinoma. CONCLUSIONS: Further work is needed to define utility of technetium-99m-sestamibi in real-world clinical practice. Our data suggest this imaging strategy is not yet ready to replace biopsy.

MR texture analysis in the differentiation of renal oncocytoma with localized renal cell carcinoma subtypes.

OBJECTIVES: We aimed to explore the diagnostic efficacy of MR texture analysis and imaging signs in the differentiation of renal oncocytoma from renal cell carcinoma (RCC). METHODS: From January 2015 to March 2019, a total of 168 localized solid renal masses (37 oncocytomas, 131 RCCs) were retrospectively included. Two radiologists reviewed complete MR images and recorded imaging presentation. Texture parameters were extracted from 3D ROIs on axial FSE-T2WI. Univariate and multivariate logistic regressions were used for feature selection and nomogram construction. The diagnostic performances were assessed by receiver operating characteristic (ROC) curves. RESULTS: Cystic change, hemorrhage, SEI and four texture parameters significantly correlated with oncocytoma in the training cohort. For differentiating oncocytoma from RCC, the nomogram yielded an AUC of 0.874 in the training cohort and 0.830 in the testing cohort. For differentiating oncocytoma from chRCC, the nomogram had an AUC of 0.889 in the training cohort and 0.861 in the testing cohort. For differentiating oncocytoma from pRCC, the nomogram had an AUC of 0.932 in the training cohort and 0.792 in the testing cohort. For differentiating oncocytoma from ccRCC, the nomogram had an AUC of 0.829 in the training cohort and 0.813 in the testing cohort. CONCLUSION: The diagnostic nomogram combining MR texture parameters with imaging signs performed well in differentiating oncocytomas with localized RCC and its subtypes. ADVANCES IN KNOWLEDGE: Few articles reported using the combination of MR texture analysis with imaging signs in differentiating RCC from oncocytoma. Our study established a useful nomogram in subtype characterization.

Quantitative differentiation of minimal-fat angiomyolipomas from renal cell carcinomas using grating-based x-ray phase-contrast computed tomography: An ex vivo study.

BACKGROUND: The differentiation of minimal-fat-or low-fat-angiomyolipomas from other renal lesions is clinically challenging in conventional computed tomography. In this work, we have assessed the potential of grating-based x-ray phase-contrast computed tomography (GBPC-CT) for visualization and quantitative differentiation of minimal-fat angiomyolipomas (mfAMLs) and oncocytomas from renal cell carcinomas (RCCs) on ex vivo renal samples. MATERIALS AND METHODS: Laboratory GBPC-CT was performed at 40 kVp on 28 ex vivo kidney specimens including five angiomyolipomas with three minimal-fat (mfAMLs) and two high-fat (hfAMLs) subtypes as well as three oncocytomas and 20 RCCs with eight clear cell (ccRCCs), seven papillary (pRCCs) and five chromophobe RCC (chrRCC) subtypes. Quantitative values of conventional Hounsfield units (HU) and phase-contrast Hounsfield units (HUp) were determined and histogram analysis was performed on GBPC-CT and grating-based attenuation-contrast computed tomography (GBAC-CT) slices for each specimen. For comparison, the same specimens were imaged at a 3T magnetic resonance imaging (MRI) scanner. RESULTS: We have successfully matched GBPC-CT images with clinical MRI and histology, as GBPC-CT presented with increased soft tissue contrast compared to absorption-based images. GBPC-CT images revealed a qualitative and quantitative difference between mfAML samples (58±4 HUp) and oncocytomas (44±10 HUp, p = 0.057) and RCCs (ccRCCs: 40±12 HUp, p = 0.012; pRCCs: 43±9 HUp, p = 0.017; chrRCCs: 40±7 HUp, p = 0.057) in contrast to corresponding laboratory attenuation-contrast CT and clinical MRI, although not all differences were statistically significant. Due to the heterogeneity and lower signal of oncocytomas, quantitative differentiation of the samples based on HUp or in combination with HUs was not possible. CONCLUSIONS: GBPC-CT allows quantitative differentiation of minimal-fat angiomyolipomas from pRCCs and ccRCCs in contrast to absorption-based imaging and clinical MRI.

Four-phase computed tomography helps differentiation of renal oncocytoma with central hypodense areas from clear cell renal cell carcinoma

PURPOSE: To explore the utility of four-phase computed tomography (CT) in distinguishing renal oncocytoma with central hypodense areas from clear cell renal cell carcinoma (ccRCC). METHODS: Eighteen patients with oncocytoma and 63 patients with ccRCC presenting with central hypodense areas were included in this study. All patients underwent four-phase CT imaging including the excretory phases later than 20 min after contrast injection. Two blinded experienced radiologists visually reviewed the enhancement features of the central hypodense areas in the excretory phase images and selected the area demonstrating the greatest degree of enhancement of the tumor in the corticomedullary phase images. Regions of interest (ROIs) were placed in the same location in each of the three contrast-enhanced imaging phases. Additionally, ROIs were placed in the adjacent normal renal cortex for normalization. The ratio of the lesion to cortex attenuation (L/C) for the three contrast-enhanced imaging phases and absolute de-enhancement were calculated. The receiver operating characteristic curve was used to obtain the cut-off values. RESULTS: Complete enhancement inversion of the central areas was observed in 12 oncocytomas (66.67%) and 16 ccRCCs (25.40%) (P = 0.003). Complete enhancement inversion combined with L/C in the corticomedullary phase lower than 1.0 (P < 0.001) or absolute de-enhancement lower than 42.5 HU (P < 0.001) provided 86.42% and 85.19% accuracy, 61.11% and 55.56% sensitivity, 93.65% and 93.65% specificity, 73.33% and 71.43% positive predictive value (PPV), and 89.39% and 88.06% negative predictive value (NPV), respectively, for the diagnosis of oncocytomas. Combined with complete enhancement inversion, L/C in the corticomedullary phase lower than 1.0 and absolute de-enhancement lower than 42.5 HU provided 87.65%, 55.56%, 96.83%, 83.33%, and 88.41% of accuracy, sensitivity, specificity, PPV, and NPV, respectively, for the diagnosis of oncocytomas. CONCLUSION: The combination of enhancement features of the central hypodense areas and the peripheral tumor parenchyma can help distinguish oncocytoma with central hypodense areas from ccRCC.

Reliability and Management Outcomes Following a Percutaneous Biopsy Diagnosis of Oncocytoma: A 15-year Retrospective Analysis.

Background There is uncertainty in the management of renal masses diagnosed as oncocytomas with image-guided percutaneous biopsy. Purpose To assess the reliability of a diagnosis of oncocytoma based on image-guided percutaneous renal mass biopsy and evaluate patient outcomes following different management strategies. Materials and Methods In this retrospective study, image-guided percutaneous biopsy pathology reports from April 2004 to April 2019 were searched for keywords "oncocytoma" and "oncocytic neoplasm" and compared with surgical pathology or repeat biopsy results. Patients with at least 12 months of clinical follow-up and known cause of death were grouped according to management strategies, and disease-specific survival and metastatic renal cell carcinoma (RCC)-free survival were compared. Mass growth rates were calculated with use of a normal linear mixed model. Results The database yielded 160 biopsy reports of 149 renal masses in 139 patients; 149 masses were categorized as oncocytoma (n = 107), likely oncocytoma (n = 12), oncocytic neoplasm (n = 28), and indeterminate with oncocytoma in differential (n = 2). Biopsied masses categorized as oncocytoma or likely oncocytoma were oncocytomas in 16 of 17 masses (94%) based on surgical pathology or repeat biopsy; four of eight masses (50%) categorized as oncocytic neoplasms were low-grade RCCs. Outcome analysis included 121 patients (mean age ± SD, 68 years ± 9.1; 82 men); 80 patients initially underwent active surveillance (11 were later treated), 33 underwent ablation, and eight underwent surgery. Disease-specific survival and metastatic-free survival were 100% after each management strategy (median follow-up, 86.6 months; range, 14.2-207.9 months). Mass growth rate (mean, 1.7 mm per year) showed no evidence of a significant difference among biopsy result categories (P = .37) or initial (P = .84) or final management strategies (P = .11). Conclusion Image-guided percutaneous biopsy diagnosis of renal oncocytoma was reliable. Although some masses diagnosed as oncocytic neoplasms were low-grade renal cell carcinomas (RCCs) at final diagnosis, no patients died of RCC, including those managed with active surveillance. © RSNA, 2023 See also the editorial by Lockhart in this issue.

CT differentiation of the oncocytoma and renal cell carcinoma based on peripheral tumor parenchyma and central hypodense area characterisation.

BACKGROUND: Although the central scar is an essential imaging characteristic of renal oncocytoma (RO), its utility in distinguishing RO from renal cell carcinoma (RCC) has not been well explored. The study aimed to evaluate whether the combination of CT characteristics of the peripheral tumor parenchyma (PTP) and central hypodense area (CHA) can differentiate typical RO with CHA from RCC. METHODS: A total of 132 tumors on the initial dataset were retrospectively evaluated using four-phase CT. The excretory phases were performed more than 20 min after the contrast injection. In corticomedullary phase (CMP) images, all tumors had CHAs. These tumors were categorized into RO (n = 23), clear cell RCC (ccRCC) (n = 85), and non-ccRCC (n = 24) groups. The differences in these qualitative and quantitative CT features of CHA and PTP between ROs and ccRCCs/non-ccRCCs were statistically examined. Logistic regression filters the main factors for separating ROs from ccRCCs/non-ccRCCs. The prediction models omitting and incorporating CHA features were constructed and evaluated, respectively. The effectiveness of the prediction models including CHA characteristics was then confirmed through a validation dataset (8 ROs, 35 ccRCCs, and 10 non-ccRCCs). RESULTS: The findings indicate that for differentiating ROs from ccRCCs and non-ccRCCs, prediction models with CHA characteristics surpassed models without CHA, with the corresponding areas under the curve (AUC) being 0.962 and 0.914 versus 0.952 and 0.839 respectively. In the prediction models that included CHA parameters, the relative enhancement ratio (RER) in CMP and enhancement inversion, as well as RER in nephrographic phase and enhancement inversion were the primary drivers for differentiating ROs from ccRCCs and non-ccRCCs, respectively. The prediction models with CHA characteristics had the comparable diagnostic ability on the validation dataset, with respective AUC values of 0.936 and 0.938 for differentiating ROs from ccRCCs and non-ccRCCs. CONCLUSION: The prediction models with CHA characteristics can help better differentiate typical ROs from RCCs. When a mass with CHA is discovered, particularly if RO is suspected, EP images with longer delay scanning periods should be acquired to evaluate the enhancement inversion characteristics of CHA.

CT radiomics for differentiating oncocytoma from renal cell carcinomas: Systematic review and meta-analysis.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Parotid gland oncocytoma mimicking local malignancy of Warthin's tumour on contrast-enhanced ultrasound.

Not required for Clinical Vignette.

Giant asymptomatic left renal oncocytoma in a 40-year-old man: a case report.

Renal oncocytoma is a benign tumor that arises from epithelial cells of the distal renal tubules. It is naturally presented with a small-sized mass, and giant oncocytoma is uncommon. Renal oncocytoma is frequently asymptomatic and challenging to distinguish preoperatively from renal cell carcinoma (RCC). We present a 40-year-old man who presented with intermittent abdominal pain in the last two years. Abdominal computed tomography (CT) scan showed a large, heterogenous left renal mass measured 15 x 16 x 19.5 cm and associated with central calcifications suspected of RCC. The patient underwent a left radical nephrectomy without complication. The histopathological study revealed typical oncocytoma features. There was no detected recurrence or distant metastasis on six months follow-up. In conclusion, it is challenging to distinguish renal oncocytoma from RCC via preoperative radiology images, especially when a giant mass is present. The only histopathology examination of the removed specimen can provide a definitive diagnosis.

The value of CT features and demographic data in the differential diagnosis of type 2 papillary renal cell carcinoma from fat-poor angiomyolipoma and oncocytoma.

PURPOSES: To determine the CT features and demographic data predictive of type 2 papillary renal cell carcinoma (PRCC) that can help distinguish this neoplasm from fat-poor angiomyolipoma (fpAML) and oncocytoma. METHODS: Fifty-four patients with type 2 PRCC, 48 with fpAML, and 47 with oncocytoma in the kidney from multiple centers were retrospectively reviewed. The demographic data and CT features of type 2 PRCC were analyzed and compared with those of fpAML and oncocytoma by univariate analysis and multiple logistic regression analysis to determine the predictive factors for differential diagnosis. Then, receiver operating characteristic (ROC) curve analysis was performed to further assess the logistic regression model and set the threshold level values of the numerical parameters. RESULTS: Older age (≥ 46.5 years), unenhanced lesion-to-renal cortex attenuation (RLRCA) < 1.21, corticomedullary ratio of lesion to renal cortex net enhancement (RLRCNE) < 0.32, and size ≥ 30.1 mm were independent predictors for distinguishing type 2 PRCC from fpAML (OR 14.155, 8.332, and 57.745, respectively, P < 0.05 for all). The area under the curve (AUC) of the multiple logistic regression model in the ROC curve analysis was 0.970. In the combined evaluation, the four independent predictors had a sensitivity and specificity of 0.896 and 0.889, respectively. A corticomedullary RLRCNE < 0.61, irregular shape, and male sex were independent predictors for the differential diagnosis of type 2 PRCC from oncocytoma (OR 15.714, 12.158, and 6.175, respectively, P < 0.05 for all). In the combined evaluation, the three independent predictors had a sensitivity and specificity of 0.889 and 0.979, respectively. The AUC of the multiple logistic regression model in the ROC curve analysis was 0.964. CONCLUSION: The combined application of CT features and demographic data had good ability in distinguishing type 2 PRCC from fpAML and oncocytoma, respectively.

Central Stellated Scar Sign: Classic Imaging Finding of Renal Oncocytoma with Radiopathological Correlation.

Oncocytomas are benign tumors, with the classic stellate scar found in up to a third of cases, mainly in large ones. We present the case of a 69-year-old man with a palpable, mobile, and painless mass on the right flank, where abdominal ultrasound and abdominal computed tomography detected the presence of a solid right kidney lesion with a central stellate area in the sinus. Postoperative histological analysis confirmed the presence of oncocytoma with a central stellate scar. Biopsy may not be useful to distinguish this entity from renal carcinoma, surgery being necessary for definitive confirmation of the diagnosis of oncocytoma.

Renal oncocytoma: a challenging diagnosis.

PURPOSE OF REVIEW: The aim of the review is to provide an update on the current and evolving approaches to diagnosing the challenging clinical entity of renal oncocytoma. RECENT FINDINGS: Renal oncocytoma is being increasingly recognized among patients with renal masses, and it can be found in up to 50% of benign small renal masses (SRMs) less than 4 cm. Renal oncocytomas have benign clinical biology but distinguishing them from some of the other renal masses with more malignant potential can be challenging due to overlapping imaging, histologic, and immunophenotypic characteristics. Increasing integration of various imaging modalities, histologic characteristics, cytogenetics, and molecular and metabolic signatures is helping better define and characterize renal masses. SUMMARY: Evolving and complementary diagnostic approaches, including at the molecular level, are continuing to help refine the classification of renal tumors, with implications on their clinical behavior and ultimately clinical management.

Nomogram predictive model for differentiation between renal oncocytoma and chromophobe renal cell carcinoma at multi-phasic CT: a retrospective study.

AIM: To develop a predictive model to discriminate renal oncocytoma (RO) from chromophobe renal carcinoma (chRCC) using multiphase computed tomography (CT). MATERIALS AND METHODS: Two hundred and five cases of renal tumours were analysed retrospectively regarding attenuation values during four CT phases, in addition to age, size, and sex. Then, logistic analysis was applied and a nomogram model developed to predict the most significant variables that can be used to differentiate between both tumour types. The cases were histopathologically proven as 81 cases of RO and 124 cases of chRCC. RESULTS: There was no association between the sex of the patient and the tumour types (p=0.41); however, there was a significant positive association between RO and the age of the patient (odds ratio 1.05; 95% confidence interval 1.02-1.08; p=0.001)) and a significant negative association between tumour size and RO (odds ratio 0.81; 95% confidence interval 73-90; p<0.001). There was a significant difference between tumour types in the contrast-enhanced phases. Logistic regression showed that absolute arterial enhancement (AAE) and absolute venous enhancement (AVE) are the most significant predictors for discriminating between tumour types. Combining these variables, size, AAE, and AVE were the best classifiers to discriminate between tumour types with an area under the curve of 0.90. A nomogram model was developed using these variables to predict RO probability in different case scenarios. CONCLUSION: The nomogram can predict the probability of RO from chRCC by using the best predictors, size, AAE, and AVE, with high accuracy.