Yield of second-round MRI targeted ultrasound-guided fusion prostate biopsy after initial first-round targeted biopsy.

INTRODUCTION: We aimed to determine the yield of second-round magnetic resonance imaging-ultrasound (MRI-US) fusion biopsy and factors that may predict eventual clinically significant (CS) prostate cancer (PCa) diagnosis. METHODS: From 2013 to 2021, 85 men underwent second-round MRI-US fusion biopsy of 92 lesions (47.8% [44/92] peripheral zone and 52.2% [48/92] transition zone). Patient age, prostate-specific antigen (PSA), PSA density (PSAD), size/location of lesions, ADC value, Prostate Imaging-Reporting and Data System (PI-RADS), and PRECISE scores were recorded and compared to histopathological diagnosis (International Society of Urological Pathology [ISUP] grade-group 1 PCa, CS PCa=ISUP grade group ≥2 PCa) using logistic regression. RESULTS: Mean patient age, PSA, and PSAD were 64±7 years, 8.5±7.0 ng/ml, and 0.17±0.11, respectively. Results from first-round targeted biopsy were 63% (58/92) negative and 37% (34/92) clinically insignificant (grade group 1) PCa. Overall, second-round targeted biopsy identified 25% (23/92) CS PCa (grade group 2, n=19; grade group 3, n=4). Considering only lesions with initial negative targeted-biopsy results (n=58), 21% (12/58; grade group 2, n=8; grade group 3, n=4) CS PCa and 13 grade group 1 PCa were diagnosed at second-round biopsy. There was no difference in PSA (p=0.564), size (p=0.595), location (p=0.293), or PI-RADS score (p=0.342) of lesions by eventual CS PCa diagnosis. PSAD (0.2±1.4 vs. 0.16±0.10, p=0.167), ADC (0.748±0.199 vs. 0.833±0.257, p=0.151), and PRECISE score (p<0.01) showed a trend towards association or association with eventual CS PCa diagnosis. CONCLUSIONS: Repeat second-round targeted MRI-US fusion biopsy yielded CS PCa diagnosis in the targeted biopsy specimen in approximately 20% of patients in our study. PRECISE score may be a useful marker to help predict which patients require second-round biopsy.

Diagnostic Accuracy of MRI for Solid Renal Masses: A Systematic Review and Meta-analysis.

BACKGROUND: Biparametric (bp)-MRI and multiparametric (mp)-MRI may improve the diagnostic accuracy of renal mass histology. PURPOSE: To evaluate the available evidence on the diagnostic accuracy of bp-MRI and mp-MRI for solid renal masses in differentiating malignant from benign, aggressive from indolent, and clear cell renal cell carcinoma (ccRCC) from other histology. STUDY TYPE: Systematic review. POPULATION: MEDLINE, EMBASE, and CENTRAL up to January 11, 2022 were searched. FIELD STRENGTH/SEQUENCE: 1.5 or 3 Tesla. ASSESSMENT: Eligible studies evaluated the accuracy of MRI (with at least two sequences: T2, T1, dynamic contrast and diffusion-weighted imaging) for diagnosis of solid renal masses in adult patients, using histology as reference standard. Risk of bias and applicability were assessed using QUADAS-2. STATISTICAL TESTS: Meta-analysis using a bivariate logitnormal random effects model. RESULTS: We included 10 studies (1239 masses from approximately 1200 patients). The risk of bias was high in three studies, unclear in five studies and low in two studies. The diagnostic accuracy of malignant (vs. benign) masses was assessed in five studies (64% [179/281] malignant). The summary estimate of sensitivity was 95% (95% confidence interval [CI]: 77%-99%), and specificity was 63% (95% CI: 46%-77%). No study assessed aggressive (vs. indolent) masses. The diagnostic accuracy of ccRCC (vs. other subtypes) was evaluated in six studies (47% [455/971] ccRCC): the summary estimate of sensitivity was 85% (95% CI: 77%-90%) and specificity was 77% (95% CI: 73%-81%). DATA CONCLUSION: Our study reveals deficits in the available evidence on MRI for diagnosis of renal mass histology. The number of studies was limited, at unclear/high risk of bias, with heterogeneous definitions of solid masses, imaging techniques, diagnostic criteria, and outcome measures. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Molecular Pathogenesis of Penile Squamous Cell Carcinoma: Current Understanding and Potential Treatment Implications.

CONTEXT.­: Penile squamous cell carcinomas (PSCCs) are divided into tumors that are human papillomavirus (HPV) associated and those that are non-HPV associated. HPV and non-HPV PSCCs each display unique pathogenic mechanisms, histologic subtypes, and clinical behaviors. Treatment of localized PSCC tumors is linked to significant physical and psychological morbidity, and management of advanced disease is often treatment refractory. The identification of novel actionable mutations is of critical importance so that translational scientists and clinicians alike can pursue additional therapeutic options. OBJECTIVE.­: To provide an update on the molecular pathogenesis associated with PSCC. A special emphasis is placed on next-generation sequencing data and its role in identifying potential therapeutic targets. DATA SOURCES.­: A literature review using the PubMed search engine to access peer-reviewed literature published on PSCC. CONCLUSIONS.­: Our understanding of the genetic and molecular mechanisms that underlie PSCC pathogenesis continues to evolve. PSCC tumorigenesis is mediated by multiple pathways, and mutations of oncogenic significance have been identified that may represent targets for personalized therapy. Preliminary results of treatment with immune checkpoint inhibition and tyrosine kinase inhibitors have produced variable clinical results. Further insight into the pathogenesis of PSCC will help guide clinical trials and develop additional precision medicine approaches.

Renal organoid modeling of tuberous sclerosis complex reveals lesion features arise from diverse developmental processes.

Tuberous sclerosis complex (TSC) is a multisystem tumor-forming disorder caused by loss of TSC1 or TSC2. Renal manifestations predominately include cysts and angiomyolipomas. Despite a well-described monogenic etiology, the cellular pathogenesis remains elusive. We report a genetically engineered human renal organoid model that recapitulates pleiotropic features of TSC kidney disease in vitro and upon orthotopic xenotransplantation. Time course single-cell RNA sequencing demonstrates that loss of TSC1 or TSC2 affects multiple developmental processes in the renal epithelial, stromal, and glial compartments. First, TSC1 or TSC2 ablation induces transitional upregulation of stromal-associated genes. Second, epithelial cells in the TSC1-/- and TSC2-/- organoids exhibit a rapamycin-insensitive epithelial-to-mesenchymal transition. Third, a melanocytic population forms exclusively in TSC1-/- and TSC2-/- organoids, branching from MITF+ Schwann cell precursors. Together, these results illustrate the pleiotropic developmental consequences of biallelic inactivation of TSC1 or TSC2 and offer insight into TSC kidney lesion pathogenesis.

Development of a Multiparametric Renal CT Algorithm for Diagnosis of Clear Cell Renal Cell Carcinoma Among Small (≤ 4 cm) Solid Renal Masses.

BACKGROUND. The MRI clear cell likelihood score predicts the likelihood that a renal mass is clear cell renal cell carcinoma (ccRCC). A CT-based algorithm has not yet been established. OBJECTIVE. The purpose of our study was to develop and evaluate a CT-based algorithm for diagnosing ccRCC among small (≤ 4 cm) solid renal masses. METHODS. This retrospective study included 148 patients (73 men, 75 women; mean age, 58 ± 12 [SD] years) with 148 small (≤ 4 cm) solid (> 25% enhancing tissue) renal masses that underwent renal mass CT (unenhanced, corticomedullary, and nephrographic phases) before resection between January 2016 and December 2019. Two radiologists independently evaluated CT examinations and recorded calcification, mass attenuation in all phases, mass-to-cortex corticomedullary attenuation ratio, and heterogeneity score (score on a 5-point Likert scale, assessed in corticomedullary phase). Features associated with ccRCC were identified by multivariable logistic regression analysis and then used to create a five-tiered CT score for diagnosing ccRCC. RESULTS. The masses comprised 53% (78/148) ccRCC and 47% (70/148) other histologic diagnoses. The mass-to-cortex corticomedullary attenuation ratio was higher for ccRCC than for other diagnoses (reader 1: 0.84 ± 0.68 vs 0.68 ± 0.65, p = .02; reader 2: 0.75 ± 0.29 vs 0.59 ± 0.25, p = .02). The heterogeneity score was higher for ccRCC than other diagnoses (reader 1: 4.0 ± 1.1 vs 1.5 ± 1.6, p < .001; reader 2: 4.4 ± 0.9 vs 3.3 ± 1.5, p < .001). Other features showed no difference. A five-tiered diagnostic algorithm including the mass-to-cortex corticomedullary attenuation ratio and heterogeneity score had interobserver agreement of 0.71 (weighted κ) and achieved an AUC for diagnosing ccRCC of 0.75 (95% CI, 0.68-0.82) for reader 1 and 0.72 (95% CI, 0.66-0.82) for reader 2. A CT score of 4 or greater achieved sensitivity, specificity, and PPV of 71% (95% CI, 59-80%), 79% (95% CI, 67-87%), and 79% (95% CI, 67-87%) for reader 1 and 42% (95% CI, 31-54%), 81% (95% CI, 70-90%), and 72% (95% CI, 56-84%) for reader 2. A CT score of 2 or less had NPV of 85% (95% CI, 69-95%) for reader 1 and 88% (95% CI, 69-97%) for reader 2. CONCLUSION. A five-tiered renal CT algorithm, including the mass-to-cortex corticomedullary attenuation ratio and heterogeneity score, had substantial interobserver agreement, moderate AUC and PPV, and high NPV for diagnosing ccRCC. CLINICAL IMPACT. The CT algorithm, if validated, may represent a useful clinical tool for diagnosing ccRCC.

Utility of Quantitative T2-Mapping Compared to Conventional and Advanced Diffusion Weighted Imaging Techniques for Multiparametric Prostate MRI in Men with Hip Prosthesis.

BACKGROUND: Diffusion weighted imaging (DWI) is fundamental for prostate cancer (PCa) detection with MRI; however, limited by susceptibility artifact from hip prosthesis. PURPOSE: To evaluate image quality and ability to detect PCa with quantitative T2-mapping and DWI in men with hip prosthesis undergoing prostate MRI. STUDY TYPE: Prospective, cross-sectional study. POPULATION: Thirty consecutive men with hip replacement (18 unilateral, 12 bilateral) undergoing prostate MRI from 2019 to 2021. FIELD STRENGTH/SEQUENCE: 3-T; multiparametric MRI (T2W, DCE-MRI, echo-planar [EPI]-DWI), T2-mapping (Carr-Purcell-Meiboom-Gill), FOCUS-EPI-DWI, PROPELLER-DWI. ASSESSMENT: Five blinded radiologists independently evaluated MRI image quality using a 5-point Likert scale. PI-RADS v2.1 scores were applied in four interpretation strategies: 1) T2W-FSE+DCE-MRI+EPI-DWI, 2) T2W-FSE+DCE-MRI+EPI-DWI+FOCUS-EPI-DWI, 3) T2W-FSE+DCE-MRI+EPI-DWI+PROPELLER-DWI, 4) T2W-FSE+DCE-MRI+EPI-DWI+T2-maps. Five-point confidence scores were recorded. STATISTICAL ANALYSIS: ANOVA, Kruskal-Wallis with pair-wise comparisons by Wilcoxon sign-rank, and paired t-tests, P < 0.05 was considered significant. Cohen's Kappa (k) for PI-RADSv2.1 scoring and proportion of correctly classified lesions tabulated for pathology-confirmed cases with 95% confidence intervals (CIs). RESULTS: For all radiologists, T2-map image quality was significantly higher than EPI-DWI, FOCUS-EPI-DWI, and PROPELLER-DWI and similar (P = 0.146-0.706) or significantly better (for two readers) than T2W-FSE and DCE-MRI. PI-RADS v2.1 agreement improved comparing strategy A (k = 0.46) to strategy B (k = 0.58) to strategy C (k = 0.58) and was highest with strategy D which included T2-maps (k = 1.00). Radiologists' confidence was significantly highest with strategy D. Strategies B and C had similar confidence (P = 0.051-0.063) both significantly outperforming strategy A. Twelve men with 17 lesions had pathology confirmed diagnoses (13 PCa, 4 benign). Strategy D had the highest proportion of correctly classified lesions (76.5-82.4%) with overlapping 95% confidence intervals. DATA CONCLUSION: T2-mapping may be a valuable adjunct to prostate MRI in men with hip replacement resulting in improved image quality, higher reader confidence, interobserver agreement, and accuracy in PI-RADS scoring. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Bosniak Classification version 2019: validation and comparison to original classification in pathologically confirmed cystic masses.

OBJECTIVE: To evaluate Bosniak Classification v2019 definitions in pathologically confirmed cystic renal masses. MATERIALS AND METHODS: Seventy-three cystic (≤ 25% solid) masses with histological confirmation (57 malignant, 16 benign) imaged by CT (N = 28) or CT+MRI (N = 56) between 2009 and 2019 were independently evaluated by three blinded radiologists using Bosniak v2019 and original classifications. Discrepancies were resolved by consensus with a fourth blinded radiologist. Overall class and v2019 features were compared to pathology. RESULTS: Inter-observer agreement was slightly improved comparing v2019 to Original Bosniak Classification (kappa = 0.26-0.47 versus 0.24-0.34 respectively). v2019 proportion of IIF and III masses (20.5% [15/73, 95% confidence interval (CI) 12.0-31.6%], 38.6% [28/73, 95% CI 27.2-50.5%]) differed from the original classification (6.8% [5/73, 95% CI 2.3-15.3%], 61.6% [45/73, 95% CI 49.5-72.8%]) with overlapping proportion of malignancy in each class. Mean septa number (7 ± 4 [range 1-10]) was not associated with malignancy (p = 0.89). Mean wall and septa thicknesses were 3 ± 3 (1-14) and 3 ± 2 (1-10) mm and higher in malignancies (p = 0.03 and 0.20 respectively). Areas under the receiver-operator-characteristic curve for wall and septa thickness were 0.66 (95% CI 0.54-0.79) and 0.61 (95% CI 0.45-0.78) with an optimal cut point of ≥ 3 mm (sensitivity 33.3%, specificity 86.7% and sensitivity 53%, specificity 73% respectively). Proportion of malignancy occurring in masses with the v2019 features "irregularity" (76.9% [10/13], 95% CI 46.2-94.9%) and "nodule" (89.7% [26/29], 95% CI 72.7-97.8%) overlapped. Angle of "nodule" (p = 0.27) was not associated with malignancy. CONCLUSION: Bosniak v2019 definitions for wall/septa thickness and protrusions are associated with malignancy. Overall, Bosniak v2019 categorizes a higher proportion of malignant masses in Class IIF with slight improvement in inter-observer agreement. KEY POINTS: • Considering Bosniak v2019 Class IIF cystic masses with many (≥ 4) smooth and thin septa, there was no association between the number of septa and malignancy (p = 0.89) in this study. • Increased cyst wall and septa thickness are associated with malignancy and a lower threshold of ≥ 3 mm maximized overall diagnostic accuracy compared to ≥ 4 mm threshold proposed for Bosniak v2019 Class 3. • An overlapping proportion of malignant masses is noted in Bosniak v2019 Class 3 masses with "irregularity" (76.9% [10/13], 95% CI 46.2-94.9%) compared to Bosniak v2019 Class 4 masses with "nodule" (89.7% [26/29], 95% CI 72.7-97.8%).

Prevalence of prostate cancer in PI-RADS version 2.1 T2-weighted transition zone 'nodule in nodule' and 'homogeneous mildly hypointense area between nodules' criteria: MRI-radical prostatectomy histopathological evaluation.

OBJECTIVES: To evaluate the prevalence of prostate cancer (PCa) of two PI-RADS version (v) 2.1 transition zone (TZ) features (PI-RADS 1 ['nodule in nodule'] and 2 ['homogeneous mildly hypointense area between nodules']). METHODS: With an institutional review board approval, from a 5-year cohort between 2012 and 2017, we retrospectively identified 53 consecutive men with radical prostatectomy (RP) confirmed TZ tumors and MRI. Three blinded radiologists (R1/2/3) independently evaluated T2-weighted and diffusion-weighted imaging (DWI) using PI-RADS v2.1 for the presence of (1) 'nodule in nodule' (recording 'cystic change', inner nodule encapsulation, size, and DWI score) and (2) 'homogeneous mildly hypointense area between nodules' (also recording size and DWI score). MRI-RP maps established ground truth. Primary tumor was evaluated assessing PI-RADS v2.1 category, size, and presence of imaging variants. RESULTS: R1/2/3 identified 26/18/22 'nodule in nodule' respectively with 7.7% (2/26; 95% confidence interval [95% CI]: 0.1-17.9%), 5.6% (1/18; 95% CI: 0.01-16.1%), and 4.5% (1/22; 95% CI: 0.01-13.3%) PCa (both Gleason score 3 + 4 = 7). Agreement was fair-to-substantial, kappa = 0.222-0.696. 'Cystic change', inner nodule absent/incomplete encapsulation and DWI score ≥ 4 for R1/R2/R2 were present in 80.8% (21/26), 46.2% (12/26), 7.7% (2/26); 94.4% (17/18), 33.3% (6/18), 5.6% (1/18); and 59.1% (13/22), 63.6% (14/22), 9.1% (2/22). Both PCa had inner nodule absent/incomplete encapsulation and DWI score ≥ 4. No other TZ tumors demonstrated 'nodule in nodule', nodule 'cystic change', or 'homogeneous mildly hypointense area between nodules'. R1/2/3 identified 5/6/13 'homogeneous mildly hypointense area between nodules' with zero PCa for any reader (upper bound 95% CI: 24.7-52.2%). Interobserver agreement was fair-to-substantial, kappa = 0.104-0.779. CONCLUSION: The proportion of cancers in PI-RADS v2.1 'nodule in nodule' was low (~5-8%) with zero cancers detected in 'homogeneous mildly hypointense area between nodules'. When 'nodule in nodule' inner nodule shows absent or incomplete encapsulation with marked restricted diffusion, PCa may be considered; however, this warrants further studies. KEY POINTS: • The prevalence of clinically significant prostate cancers in PI-RADS v2.1 'nodule in nodule' was low (5-8%, 95% CI: 0.1-17.9%). • Clinically significant prostate cancer was only detected in the 'nodule in nodule' variant when the inner nodule showed absent or incomplete encapsulation ('atypical nodule') with marked restricted diffusion. • 'Homogeneous mildly hypointense area between nodules' is likely benign with no cancers identified in the current study, however, with a wide 95% CI due to low prevalence.

Carbonic anhydrase IX (CA9) expression in multiple renal epithelial tumour subtypes.

AIMS: Renal epithelial neoplasms (RENs) can be difficult to subclassify, owing to overlapping morphological features. Carbonic anhydrase 9 (CA9) is a common biomarker for clear cell renal cell carcinoma (CCRCC); however, the sensitivity and specificity across REN subtypes are less clear. The aim of this study was to investigate CA9 expression in RENs, especially those in the differential diagnosis with CCRCC and less common entities, to determine its reliability as a diagnostic biomarker. METHODS AND RESULTS: CA9 immunostaining was performed on 262 RENs, including 119 CCRCCs and 143 non-CCRCC. Immunostaining was evaluated as negative (0%), rare (1+, 1-10%), focal (2+, 11-50%), or diffuse (3+, >50%). CCRCCs were 3+ CA9-positive in 93% of cases; 4% were CA9-negative. Sixty-seven percent of papillary renal cell carcinomas (RCCs) were 1+/2+ CA9-positive, whereas 33% were CA9-negative. Chromophobe RCCs were nearly always CA9-negative (93%), with 7% showing rare cell reactivity. Clear cell tubulopapillary RCCs (CCTPRCCs) were consistently 3+ CA9-positive, but with a cup-like staining pattern. Fifty-three percent of Xp11.2 RCCs were CA9-negative; however, 6% were 3+ CA9-positive and 12% were 2+ CA9-positive. Two of eight fumarate hydratase-deficient RCCs were 3+ CA9-positive. A small subset of the remaining RCCs showed rare to focal CA9 expression. All oncocytomas and eosinophilic solid and cystic RCCs were CA9-negative. CONCLUSIONS: Overall, diffuse CA9 expression was identified in nearly all CCRCCs and in all CCTPRCCs (high sensitivity); however, CA9 was not entirely specific. At least focal CA9 expression can been seen in a subset of many RCCs, and such findings should be taken into consideration with other morphological, immunophenotypic and clinical findings.

Shape Analysis of Peripheral Zone Observations on Prostate DWI: Correlation to Histopathology Outcomes After Radical Prostatectomy.

OBJECTIVE. The objective of our study was to subjectively and quantitatively assess shape features of peripheral zone (PZ) tumors at DWI compared with pathologic outcomes. MATERIALS AND METHODS. During the study period, 241 consecutive men with PZ dominant prostate tumors underwent 3-T MRI including DWI before undergoing radical prostatectomy. DW images of these patients were retrospectively assessed by two blinded radiologists. The reviewers assigned Prostate Imaging Reporting and Data System (PI-RADS) shape categories (round or oval, crescentic [i.e., conforming to PZ], linear or wedge-shaped) and segmented tumors for quantitative shape analysis. Discrepancies were resolved by consensus. Comparisons were performed with Gleason score (GS) and pathologic stage. RESULTS. Consensus review results were as follows: 63.9% (154/241) of tumors were round or oval; 22.8% (55/241), crescentic; and 13.3% (32/241), linear or wedge-shaped. Agreement for shape assessment was moderate (κ = 0.41). Round or oval tumors were higher grade (GS 6 = 1.3%, GS 7 = 78.0%, GS ≥ 8 = 20.7%) than crescentic tumors (GS 6 = 9.1%, GS 7 = 74.6%, GS ≥ 8 = 16.3%) and linear or wedge-shaped tumors (GS 6 = 6.3%, GS 7 = 78.1%, GS ≥ 8 = 15.6%) (p = 0.011). In addition, round or oval tumors had higher rates of extraprostatic extension (EPE) and seminal vesicle invasion (SVI) (EPE and SVI: 70.1% and 26.0%) than crescentic tumors (67.3% and 9.1%; p = 0.003) and linear or wedge-shaped tumors (40.6% and 9.4%; p = 0.008). Quantitatively, the shape features termed "circularity" and "roundness" were associated with EPE (p < 0.001 and p = 0.003), SVI (p < 0.001 and p = 0.029), and increasing GS (p = 0.009 and p = 0.021), but there was overlap between groups. CONCLUSION. In this study, approximately 10% of resected PZ tumors were linear or wedge-shaped on DWI. PZ tumors that were judged subjectively and evaluated quantitatively to be round or oval were associated with increased prostate cancer aggressiveness.

Effect of observation size and apparent diffusion coefficient (ADC) value in PI-RADS v2.1 assessment category 4 and 5 observations compared to adverse pathological outcomes.

OBJECTIVE: To compare observation size and apparent diffusion coefficient (ADC) values in Prostate Imaging Reporting and Data System (PI-RADS) v2.1 category 4 and 5 observations to adverse pathological features. MATERIALS AND METHODS: With institutional review board approval, 267 consecutive men with 3-T MRI before radical prostatectomy (RP) between 2012 and 2018 were evaluated by two blinded radiologists who assigned PI-RADS v2.1 scores. Discrepancies were resolved by consensus. A third blinded radiologist measured observation size and ADC (ADC.mean, ADC.min [lowest ADC within an observation], ADC.ratio [ADC.mean/ADC.peripheral zone {PZ}]). Size and ADC were compared to pathological stage and Gleason score (GS) using t tests, ANOVA, Pearson correlation, and receiver operating characteristic (ROC) analysis. RESULTS: Consensus review identified 267 true positive category 4 and 5 observations representing 83.1% (222/267) PZ and 16.9% (45/267) transition zone (TZ) tumors. Inter-observer agreement for PI-RADS v2.1 scoring was moderate (K = 0.45). Size was associated with extra-prostatic extension (EPE) (19 ± 8 versus 14 ± 6 mm, p < 0.001) and seminal vesicle invasion (SVI) (24 ± 9 versus 16 ± 7 mm, p < 0.001). Size ≥ 15 mm optimized the accuracy for EPE with area under the ROC curve (AUC) and sensitivity/specificity of 0.68 (CI 0.62-0.75) and 63.2%/65.6%. Size ≥ 19 mm optimized the accuracy for SVI with AUC/sensitivity/specificity of 0.75 (CI 0.66-0.83)/69.4%/70.6%. ADC metrics were not associated with pathological stage. Larger observation size (p = 0.032), lower ADC.min (p = 0.010), and lower ADC.ratio (p = 0.010) were associated with higher GS. Size correlated better to higher Gleason scores (p = 0.002) compared to ADC metrics (p = 0.09-0.11). CONCLUSION: Among PI-RADS v2.1 category 4 and 5 observations, size was associated with higher pathological stage whereas ADC metrics were not. Size, ADC.minimum, and ADC.ratio differed in tumors stratified by Gleason score. KEY POINTS: • Among PI-RADS category 4 and 5 observations, size but not ADC can differentiate between tumors by pathological stage. • An observation size threshold of 15 mm and 19 mm optimized the accuracy for diagnosis of extra-prostatic extension and seminal vesicle invasion. • Among PI-RADS category 4 and 5 observations, size, ADC.minimum, and ADC.ratio differed comparing tumors by Gleason score.

Characterization of clear cell renal cell carcinoma and other renal tumors: evaluation of dual-energy CT using material-specific iodine and fat imaging.

OBJECTIVE: This study aimed to assess material-specific iodine and fat images for diagnosis of clear cell renal cell carcinoma (cc-RCC) compared to papillary RCC (p-RCC) and other renal masses. MATERIALS AND METHODS: With IRB approval, we identified histologically confirmed solid renal masses that underwent rapid-kVp-switch DECT between 2016 and 2018: 25 cc-RCC (7 low grade versus 18 high grade), 11 p-RCC, and 6 other tumors (2 clear cell papillary RCC, 2 chromophobe RCC, 1 oncocytoma, 1 renal angiomyomatous tumor). A blinded radiologist measured iodine and fat concentration on material-specific iodine-water and fat-water basis pair images. Comparisons were performed between groups using univariate analysis and diagnostic accuracy calculated by ROC. RESULTS: Iodine concentration was higher in cc-RCC (6.14 ± 1.79 mg/mL) compared to p-RCC (1.40 ± 0.54 mg/mL, p < 0.001), but not compared to other tumors (5.0 ± 2.2 mg/mL, p = 0.370). Intratumoral fat was seen in 36.0% (9/25) cc-RCC (309.6 ± 234.3 mg/mL [71.1-762.3 ng/mL]), 9.1% (1/11) papillary RCC (97.11 mg/mL), and no other tumors (p = 0.036). Iodine concentration ≥ 3.99 mg/mL achieved AUC and sensitivity/specificity of 0.88 (CI 0.76-1.00) and 92.31%/82.40% to diagnose cc-RCC. To diagnose p-RCC, iodine concentration ≤ 2.5 mg/mL achieved AUC and sensitivity/specificity of 0.99 (0.98-1.00) and 100%/100%. The presence of intratumoral fat had AUC 0.64 (CI 0.53-0.75) and sensitivity/specificity of 34.6%/93.8% to diagnose cc-RCC. A logistic regression model combining iodine concentration and presence of fat increased AUC to 0.91 (CI 0.81-1.0) with sensitivity/specificity of 80.8%/93.8% to diagnose cc-RCC. CONCLUSION: Iodine concentration values are highly accurate to differentiate clear cell RCC from papillary RCC; however, they overlap with other tumors. Fat-specific images may improve differentiation of clear cell RCC from other avidly enhancing tumors. KEY POINTS: • Clear cell renal cell carcinoma (RCC) has significantly higher iodine concentration than papillary RCC, but there is an overlap in values comparing clear cell RCC to other renal tumors. • Iodine concentration ≤ 2.5 mg/mL is highly accurate to differentiate papillary RCC from clear cell RCC and other renal tumors. • The presence of microscopic fat on material-specific fat images was specific for clear cell RCC, helping to differentiate clear cell RCC from other avidly enhancing renal tumors.

Evaluation of individual and cumulative sites of extrarenal tumor invasion in pT3a clear cell renal cell carcinoma.

INTRODUCTION: The Tumor-Node-Metastasis classification of renal cell carcinoma (RCC) for pT3a tumors includes sinus fat invasion (SFI), perinephric fat invasion (PFI), renal vein invasion (RVI), and/or pelvicaliceal system invasion (PSI). The purpose of this study was to determine the association between these patterns of invasion (assessed individually and cumulatively) with the development of metastases and cancer-specific mortality (CSM). MATERIALS AND METHODS: We identified 160 patients who underwent radical nephrectomy for pT3a clear cell RCC between 2011 and 2017. The association between individual patterns of invasion and metastases and cancer-specific survival were evaluated with multivariate logistic regression. Cox Hazard proportion ratios and Kaplan-Meier survival curves were generated for patterns of invasion (assessed individually and cumulatively). RESULTS: The number of individual invasive patterns was as follows: 97/160 (61%) presented with RVI, 91/160 with SFI (57%), 62/160 with PFI (39%), and 24/160 (15%) with PSI. At multivariate analysis, both PFI and RVI were associated with metastases (P < 0.001 and 0.028, respectively). PFI (hazard ratio [HR] 4.12, 95% confidence interval [CI] 2.14-7.92; P < 0.001), RVI (HR 2.44, 95% CI 1.18-5.01; P = 0.015), SFI (HR 2.13, 95% CI 1.05-4.34; P = 0.036) had higher CSM, while PSI (HR 1.43, 95% CI 0.65-3.16; p = 0.38) did not show increased CSM. Furthermore, cumulative analysis showed that multiple invasive patterns resulted in worse CSM (p < 0.001). CONCLUSIONS: In our study, PFI was associated with the most aggressive behavior while PSI was the most indolent. Furthermore, the presence of more than one pattern of invasion was associated with worse CSM. These results indicate that reporting of the individual location and cumulative amount of pT3a patterns of invasion in clear cell RCC is clinically relevant.

Macroscopic Fat in Adrenocortical Carcinoma: A Systematic Review.

OBJECTIVE. The objective of this systematic review was to determine the number and quality of reports of adrenocortical carcinoma (ACC) containing macroscopic fat; this information may inform guidelines for diagnosis and management of ACC. MATERIALS AND METHODS. A comprehensive search of databases of published studies was performed. Two reviewers independently selected original research, case series, or case reports of ACC with macroscopic fat on imaging and extracted data. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS. Three case reports and one retrospective study comprising a total of seven cases of ACC (lesion size: range, 6.5-22 cm) with macroscopic fat were included. ACC was symptomatic in all patients; neither locally invasive features nor metastases were reported. Four cases had less than 5% macroscopic fat on imaging, and the percentage fat on imaging was not reported for the remaining three cases. With regard to the risk of bias, one case had high risk for the index test domain because of potentially unreliable determination of macroscopic fat (i.e., no pathologic confirmation). All seven cases (from four studies) had unclear risk for the reference standard domain because there was insufficient information about the reference standard to determine whether ACC was correctly diagnosed. All studies were at low risk of bias in the flow and timing domain. CONCLUSION. There are few reports of macroscopic fat in ACC detected on imaging studies; among the reports of macroscopic fat in ACC, tumors were large (> 6 cm) and had a small proportion of gross fat (< 5%). The reliability of reported cases is questionable primarily because of insufficient details about pathologic diagnosis. Based on this information, a change in guideline recommendations may not be warranted. However, consideration of follow-up or biopsy of patients with large symptomatic tumors (> 6 cm) containing a small proportion of fat (< 5%) may be appropriate.

Cardiac Amyloid - A Hidden Contributor to Cardiac Dysfunction Following Cardiac Surgery: Case Report and Literature Review.

We present two patients who underwent cardiac surgery followed by post-operative low cardiac output, diastolic dysfunction and resistance to inotropic support. Despite aggressive medical management, both patients died. At autopsy, the hearts were enlarged and showed previously undiagnosed myocardial and vascular amyloidosis. Occult cardiac amyloidosis is an uncommon, often occult, contributor to post-operative complications post cardiac surgery. Pre-operative or intraoperative myocardial biopsy may be useful in patients with unexplained diastolic dysfunction. Brief Summary: We present two patients who underwent cardiac surgery followed by low cardiac output, diastolic dysfunction and resistance to inotropic support. Cardiac dysfunction was due to occult amyloidosis. Pre-operative or intra-operative myocardial biopsy may be useful in patients with unexplained diastolic dysfunction. With recent therapy advances, classification and possible treatment of amyloid are possible.

Dynamic Contrast-Enhanced MRI-Upgraded Prostate Imaging Reporting and Data System Version 2 Category 3 Peripheral Zone Observations Stratified by a Size Threshold of 15 mm.

OBJECTIVE. The purpose of this study is to evaluate dynamic contrast-enhanced (DCE) MRI (DCE-MRI)-upgraded Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) peripheral zone (PZ) observations stratified by a size threshold of 15 mm. MATERIALS AND METHODS. Two blinded radiologists independently assessed 301 patients with 326 clinically significant tumors (Gleason score [GS] ≥ 7) using multiparametric MRI performed before radical prostatectomy (RP) between 2012 and 2017 and then assigned PI-RADSv2 scores for the tumors. PI-RADSv2 category 3 PZ observations upgraded on the basis of abnormal DCE-MRI findings were tabulated, agreement was calculated, and discrepancies were resolved by consensus. The rate of detection of clinically significant cancer among upgraded observations was calculated. Size was measured at consensus review and was compared with pathologic outcomes on the basis of the PI-RADSv2 size threshold of 15 mm or more, with the use of chi-square tests. RESULTS. Reader 1 identified 5.2% (17/326) of DCE-MRI-upgraded PZ observations, and reader 2 identified 8.3% (27/326) of such observations. Interobserver agreement for PI-RADSv2 scoring was moderate (κ = 0.42) overall, but it was fair (κ = 0.23) when only DCE-MRI-upgraded observations were considered. Of the upgraded observations, which had a mean (± SD) size of 14 ± 6 mm (range, 6-29 mm), 10.4% (34/326) were agreed on after consensus review. Size smaller than 15 mm was noted for 61.8% (21/34) of observations. Among DCE-MRI-upgraded PZ observations, true- and false-positive detection rates for significant cancer were 91.2% (31/34) and 8.8% (3/34), respectively. Observations 15 mm or larger had no false-positive diagnoses and higher rates of extraprostatic extension (84.6% [11/13] vs 38.1% [8/21]; p = 0.016); however, there was no difference in GS (p = 0.354) compared with observations less than 15 mm in size. CONCLUSION. PZ observations upgraded on the basis of abnormal DCE-MRI findings have a high likelihood of being clinically significant cancer; however, agreement between readers was low. DCE-MRI-upgraded tumors of 15 mm or larger had no false-positive diagnoses and higher rates of extraprostatic extension, suggesting that they could be assigned to PI-RADSv2 assessment category 5.

Diagnostic Accuracy of Attenuation Difference and Iodine Concentration Thresholds at Rapid-Kilovoltage-Switching Dual-Energy CT for Detection of Enhancement in Renal Masses.

OBJECTIVE. The objective of our study was to evaluate iodine concentration and attenuation change in Hounsfield unit (ΔHU) thresholds to diagnose enhancement in renal masses at rapid-kilovoltage-switching dual-energy CT (DECT). MATERIALS AND METHODS. We evaluated 30 consecutive histologically confirmed solid renal masses (including nine papillary renal cell carcinomas [RCCs]) and 27 benign cysts (17 simple and 10 hemorrhagic or proteinaceous cysts) with DECT December 2016 and May 2018. A blinded radiologist measured iodine concentration (in milligrams per milliliter) and ΔHU (attenuation on enhanced CT - attenuation on unenhanced CT) using 70-keV corticomedullary (CM) phase virtual monochromatic and 120-kVp nephrographic (NG) phase images. The accuracies of previously described enhancement thresholds were compared by ROC curve analysis. RESULTS. An iodine concentration of ≥ 2.0 mg/mL and an iodine concentration of ≥ 1.2 mg/mL achieved sensitivity, specificity, and the area under the ROC curve (AUC) of 73.3%, 100.0%, and 0.87 and 86.7%, 100.0%, and 0.93, respectively. On 70-keV CM phase images, ΔHU ≥ 20 HU and ΔHU ≥ 15 HU yielded sensitivity, specificity, and AUC of 80.0%, 100.0%, and 0.90 and 90.0%, 100.0%, and 0.95, respectively. The numbers of incorrectly classified papillary RCCs were as follows: iodine concentration of ≥ 2.0 mg/mL, 77.8% (7/9; range, 0.7-1.6 mg/mL); iodine concentration of ≥ 1.2 mg/mL, 44.4% (4/9; range, 0.7-0.9 mg/mL); ΔHU ≥ 20 HU on 70-keV CM phase images, 66.7% (6/9; range, 4-17 HU); and ΔHU ≥ 15 HU on 70-keV DECT images, 33.3% (3/9; 4-12 HU). No cyst pseudoenhancement occurred on DECT. For 120-kVp NG phase DECT, ΔHU ≥ 20 HU and ΔHU ≥ 15 HU yielded sensitivity, specificity, and AUC of 93.3%, 96.3%, and 0.95 and 100.0%, 88.9%, and 0.94, respectively. With ΔHU ≥ 20 HU, 22.2% (2/9) (range, 15-18 HU) of papillary RCCs were misclassified and there was one pseudoenhancing cyst. With ΔHU ≥ 15 HU, no papillary RCCs were misclassified but 11.1% (3/27) of cysts showed pseudoenhancement. Only an iodine concentration of ≥ 2.0 mg/mL showed significantly lower accuracy than other measures (p = 0.031-0.045). CONCLUSION. DECT applied in the CM phase performed best using an iodine concentration of ≥ 1.2 mg/mL or a 70-keV ΔHU ≥ 15 HU; these parameters improved sensitivity for the detection of enhancement in renal masses without instances of cyst pseudoenhancement.

Can MRI be used to diagnose histologic grade in T1a (< 4 cm) clear cell renal cell carcinomas?

OBJECTIVE: To assess whether MRI can differentiate low-grade from high-grade T1a cc-RCC. MATERIALS AND METHODS: With IRB approval, 49 consecutive solid < 4 cm cc-RCC (low grade [Grade 1 or 2] N = 38, high grade [Grade 3] N = 11) with pre-operative MRI before nephrectomy were identified between 2013 and 2018. Tumor size, apparent diffusion coefficient (ADC) histogram analysis, enhancement wash-in and wash-out rates, and chemical shift signal intensity index (SI index) were assessed by a blinded radiologist. Subjectively, two blinded Radiologists also assessed for (1) microscopic fat, (2) homogeneity (5-point Likert scale), and (3) ADC signal (relative to renal cortex); discrepancies were resolved by consensus. Outcomes were studied using Chi square, multivariate analysis, logistic regression modeling, and ROC. Inter-observer agreement was assessed using Cohen's kappa. RESULTS: Tumor size was 24 ± 7 (13-39) mm with no association to grade (p = 0.45). Among quantitative features studied, corticomedullary phase wash-in index (p = 0.015), SI index (p = 0.137), and tenth-centile ADC (p = 0.049) were higher in low-grade tumors. 36.8% (14/38) low-grade tumors versus zero high-grade tumors demonstrated microscopic fat (p = 0.015; Kappa = 0.67). Microscopic fat was specific for low-grade disease (100.0% [71.5-100.0]) with low sensitivity (36.8% [21.8-54.6]). Other subjective features did not differ between groups (p > 0.05). A logistic regression model combining microscopic fat + wash-in index + tenth-centile-ADC yielded area under ROC curve 0.98 (Confidence Intervals 0.94-1.0) with sensitivity/specificity 87.5%/100%. CONCLUSION: The combination of microscopic fat, higher corticomedullary phase wash-in and higher tenth-centile ADC is highly accurate for diagnosis of low-grade disease among T1a clear cell RCC.