Skeletal involvement in Erdheim-Chester disease: Multimodality imaging features and association with the BRAFV600E mutation.

OBJECTIVE: The aim of this study was to characterize the distribution of skeletal involvement in Erdheim-Chester disease (ECD) by using radiography, computed tomography (CT), 18F-FDG positron emission tomography/computed tomography (PET/CT), and bone scans, as well as looking for associations with the BRAFV600E mutation. MATERIAL AND METHODS: Prospective study of 50 consecutive patients with biopsy-confirmed ECD who had radiographs, CT, 18F-FDG PET/CT, and Tc-99m MDP bone scans. At least two experienced radiologists with expertise in the relevant imaging studies analyzed the images. Summary statistics were expressed as the frequency with percentages for categorical data. Fisher's exact test, as well as odds ratios (OR) with 95 % confidence intervals (CI), were used to link imaging findings to BRAFV600E mutation. The probability for co-occurrence of bone involvement at different locations was calculated and graphed as a heat map. RESULTS: All 50 cases revealed skeletal involvement at different regions of the skeleton. The BRAFV600E mutation, which was found in 24 patients, was correlated with femoral and tibial involvement on 18F-FDG PET/CT and bone scan. The appearance of changes on the femoral, tibial, fibular, and humeral involvement showed correlation with each other based on heat maps of skeletal involvement on CT. CONCLUSION: This study reports the distribution of skeletal involvement in a cohort of patients with ECD. CT is able to detect the majority of ECD skeletal involvement. Considering the complementary nature of information from different modalities, imaging of ECD skeletal involvement is optimized by using a multi-modality strategy.

18Fluorodeoxyglucose-positron emission tomography/computed tomography for differentiation of renal tumors in hereditary kidney cancer syndromes.

PURPOSE: To assess differences in FDG-PET/CT uptake among four subtypes of renal tumors: clear cell RCC (ccRCC), papillary type I and II RCC (pRCC), and oncocytoma. METHODS: This retrospective study investigated 33 patients with 98 hereditary renal tumors. Lesions greater than 1 cm and patients with a timeframe of less than 18 months between preoperative imaging and surgery were considered. FDG-PET/CT images were independently reviewed by two nuclear medicine physicians, blinded to clinical information. Volumetric lesion SUVmean was measured and used to calculate a target-to-background ratio respective to liver (TBR). The Shrout-Fleiss intra-class correlation coefficient was used to assess reliability between readers. A linear mixed effects model, accounting for within-patient correlations, was used to compare TBR values of primary renal lesions with and without distant metastasis. RESULTS: The time interval between imaging and surgery for all tumors had a median of 77 (Mean: 139; Range: 1-512) days. Intra-class reliability of mean TBR resulted in a mean κ score of 0.93, indicating strong agreement between the readers. The mixed model showed a significant difference in mean TBR among the subtypes (p < 0.0001). Pairwise comparison showed significant differences between pRCC type II and ccRCC (p < 0.0001), pRCC type II and pRCC type I (p = 0.0001), and pRCC type II and oncocytoma (p = 0.0016). Furthermore, a significant difference in FDG uptake was present between primary pRCC type II renal lesions with and without distant metastasis (p = 0.023). CONCLUSION: pRCC type II lesions demonstrated significantly higher FDG activity than ccRCC, pRCC type I, or oncocytoma. These findings indicate that FDG may prove useful in studying the metabolic activity of renal neoplasms, identifying lesions of highest clinical concern, and ultimately optimizing active surveillance, and personalizing management plans.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome: Spectrum of imaging findings.

PURPOSE: To retrospectively investigate the radiological presentations of HLRCC-associated renal tumors to facilitate accurate lesion characterization and compare these presentations with simple cysts and characteristics of other subtypes of renal cell carcinoma (RCC) as reported in the literature. METHODS: The MRI and CT imaging characteristics of 39 pathologically confirmed lesions from 30 patients (20 male, 10 female) with HLRCC syndrome were evaluated by two radiologists. Patients had an average age at diagnosis of 43.8 ± 13.1 years. Lesion characteristics including laterality, homogeneity, diameter (cm), nodularity, septations, T1 and T2 signal intensity, enhancement, and restricted diffusion were recorded. Imaging characteristics of the lesions were further compared to characteristics of benign simple cysts surgically removed at the same time point. RESULTS: The examined lesions had a mean diameter of 5.06 ± 3.80 cm, an average growth rate of 2.91 × 10-3 cm/day and an estimated annual growth rate of 1.06 cm/year. 50% of lesions demonstrated nodularity, 65% were mostly T2-hyperintense, 83% demonstrated restricted diffusion in solid portions of the lesions, and 65% had well-defined margins. 76% of patients demonstrated extra-renal manifestations, 53% lymphadenopathy, and 43% distant metastasis. CONCLUSIONS: Our analysis confirmed that while HLRCC-associated renal lesions demonstrate diversity in imaging presentations, the majority are unilateral and solitary, T2-hyperintense, heterogeneous with well-defined margins, and frequently demonstrate restricted diffusion and nodularity.

Clear Cell Renal Cell Carcinoma Growth Correlates with Baseline Diffusion-weighted MRI in Von Hippel-Lindau Disease.

Background Identification of markers to aid in understanding the growth kinetics of Von Hippel-Lindau (VHL)-associated clear cell renal cell carcinoma (ccRCC) has the potential to allow individualization of patient care, thereby helping prevent unnecessary screening and optimizing intervention. Purpose To determine whether the degree of restricted diffusion at baseline MRI holds predictive potential for the growth rate of VHL-associated ccRCC. Materials and Methods Patients with VHL disease who underwent surgical resection of tumors between November 2014 and October 2017 were analyzed retrospectively in this HIPAA-compliant study. The change in ccRCC volume between two time points and apparent diffusion coefficient (ADC) at baseline was calculated by using segmentations by two readers at nephrographic-phase CT and diffusion-weighted MRI, respectively. Intraclass correlation coefficient was used to assess agreement between readers. Repeated-measures correlation was used to investigate relationships between ADC (histogram parameters) and tumor size at baseline with growth rate and volume doubling time (VDT). Predictive performance of the ADC parameter with highest correlation and tumor size at baseline was reviewed to differentiate tumors based on their VDT (≤1 year or >1 year). Results Forty-six patients (mean age, 46 years ± 7 [standard deviation]; 25 women) with 100 ccRCCs were evaluated. Interreader agreement resulted in mean κ scores of 0.89, 0.82, and 0.93 for mean ADC, baseline tumor volume, and follow-up tumor volume, respectively. ADC percentiles correlated negatively with tumor growth rate but correlated positively with VDT. Lower ADC values demonstrated stronger correlations. The 25th percentile ADC had the strongest correlation with growth rate (ρ = -0.52, P < .001) and VDT (ρ = 0.60, P < .001) and enabled prediction of VDT (≤1 year or >1 year) with an area under the receiver operating characteristic curve of 0.86 (sensitivity, 67%; specificity, 89%) (P < .001). Conclusion Apparent diffusion coefficient at baseline was negatively correlated with tumor growth rate. Diffusion-weighted MRI may be useful to identify clear cell renal cell carcinomas with higher growth rates. © RSNA, 2020See also the editorial by Goh and Prezzi in this issue.

Assessing lymph node status in patients with kidney cancer.

Accurate detection of lymph node involvement on pre-operative imaging in patients diagnosed with renal cell carcinoma (RCC) is critical for determination of disease stage, one of the most significant prognostic factors in RCC. The presence of lymph node involvement in RCC doubles a patient's risk of distant metastasis and significantly reduces their 5-year survival. Currently, lymph node involvement in patients with RCC is evaluated with numerous modalities, with rapid advancements occurring across these modalities. The purpose of this study was to evaluate the advantages and disadvantages of each modality and utilize sensitivities and specificities to determine the highest performing modalities for accurate lymph node involvement in renal cancer. A comprehensive computer-based literature search of full-length original research English language studies of human subjects with biopsy-proven RCC was performed to evaluate publications on the diagnostic performance of color Doppler sonography (CDS), magnetic resonance imaging (MRI), lymphotrophic nanoparticle enhanced MRI (LNMRI), multidetector-row computed tomography (MDCT), F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET), and PET/CT for evaluation of lymph node status in kidney cancers in articles that were published prior to May 2018. Limited studies were available for evaluating CDS performance for determination of lymph node involvement in renal cancer. While CT is the most common modality for nodal staging, due to its availability and relatively low expense, it did not demonstrate the highest performance of the modalities examined for determination of lymph node status in patients with RCC. Of the modalities examined, MRI demonstrated the highest sensitivity (92-95.7%) for detection of lymph node involvement in RCC. Studies of lymph node involvement in RCC using both MRI and CT indicated that using the current diameter criteria (greater than 1 cm) for determination of positive lymph nodes should be re-evaluated as micro-metastases are frequently overlooked. Studies evaluating lymph node involvement with FDG-PET had the highest specificity (100%), indicating FDG-PET is the preferred modality for confirming lymph node involvement and extent of involvement. However, due to the low sensitivity of FDG-PET, clinicians should be skeptical of negative reports of lymph node involvement in RCC patients. Further studies examining determination of lymph node involvement in renal cancer across modalities are greatly needed, current literature suggests utilizing a combination of MRI and FDG-PET may offer the highest accuracy.

Thoracic involvement in Erdheim-Chester disease: computed tomography imaging findings and their association with the BRAFV600E mutation.

OBJECTIVES: To investigate the computed tomography (CT) thoracic findings in Erdheim-Chester disease (ECD) and evaluate the association of these findings with the BRAFV600E mutation. METHODS: This was a prospective study of patients with ECD (n=61, men=46) who underwent thoracic CT imaging. CT examinations were independently interpreted by two experienced radiologists. Association of imaging findings with BRAFV600E was achieved via the Chi-square or Fisher's exact test and odds ratios (OR) with 95% confidence intervals (CI), as appropriate. RESULTS: Fifty-five ECD patients (90%) showed pulmonary findings, which included interlobular septal thickening (69%), pulmonary nodules (62%), airway thickening (13%) and ground glass opacities (36%). Pulmonary nodules were classified by the pattern of distribution: subpleural regions (36%), lung parenchyma (13%) and both regions (13%). Pleural and mediastinal involvement were present in 15% and 62% of cases, respectively. The most common mediastinal finding was sheathing of the right coronary artery (34%), followed by sheathing of the thoracic aorta (30%). The BRAFV600E mutation, positive in 31 patients, was associated with the frequency of sheathing of the coronary arteries (p = 0.01). CONCLUSIONS: Of the thoracic findings reported in this study, we found a statistically significant positive association between the BRAFV600E mutation and presence of coronary artery sheathing. KEY POINTS: • To assess the degree of thoracic involvement in ECD with CT. • BRAF V600E mutation has a high association with right coronary artery sheathing. • BRAF V600E genetic testing detects patients at high risk of developing RCA sheathing.

Differentiating papillary type I RCC from clear cell RCC and oncocytoma: application of whole-lesion volumetric ADC measurement.

PURPOSE: To determine whether objective volumetric whole-lesion apparent diffusion coefficient (ADC) distribution analysis improves upon the capabilities of conventional subjective small region-of-interest (ROI) ADC measurements for prediction of renal cell carcinoma (RCC) subtype. METHODS: This IRB-approved study retrospectively enrolled 55 patients (152 tumors). Diffusion-weighted imaging DWI was acquired at b values of 0, 250, and 800 s/mm2 on a 1.5T system (Aera, Siemens Healthcare). Whole-lesion measurements were performed by a research fellow and reviewed by a fellowship-trained radiologist. Mean, median, skewness, kurtosis, and every 5th percentile ADCs were determined from the whole-lesion histogram. Linear mixed models that accounted for within-subject correlation of lesions were used to compare ADCs among RCC subtypes. Receiver-operating characteristic (ROC) curve analysis with optimal cutoff points from the Youden index was used to test the ability of ADCs to differentiate clear cell RCC (ccRCC), papillary RCC (pRCC), and oncocytoma subtypes. RESULTS: Whole-lesion ADC values were significantly different between pRCC and ccRCC, and between pRCC and oncocytoma, demonstrating strong ability to differentiate subtypes across the quantiles (both P < 0.001). Best percentile ROC analysis demonstrated AUC values of 95.2 for ccRCC vs. pRCC; 67.6 for oncocytoma vs. ccRCC; and 95.8 for oncocytoma vs. pRCC. Best percentile ROC analysis further indicated model sensitivities/specificities of 84.5%/93.1% for ccRCC vs. pRCC; 100.0%/10.3% for oncocytoma vs. ccRCC; and 88.5%/93.1% for oncocytoma vs. pRCC. CONCLUSION: The objective methodology of whole-lesion volumetric ADC measurements maintains the sensitivity/specificity of conventional expert-based ROI analysis, provides information on lesion heterogeneity, and reduces observer bias.