Validation of Prostate Tissue Composition by Using Hybrid Multidimensional MRI: Correlation with Histologic Findings.

Background Tissue estimates obtained by using microstructure imaging techniques, such as hybrid multidimensional (HM) MRI, may improve prostate cancer diagnosis but require histologic validation. Purpose To validate prostate tissue composition measured by using HM MRI, with quantitative histologic evaluation from whole-mount prostatectomy as the reference standard. Materials and Methods In this HIPAA-compliant study, from December 2016 to July 2018, prospective participants with biopsy-confirmed prostate cancer underwent 3-T MRI before radical prostatectomy. Axial HM MRI was performed with all combinations of echo times (57, 70, 150, and 200 msec) and b values (0, 150, 750, and 1500 sec/mm2). Data were fitted by using a three-compartment signal model to generate volumes for each tissue component (stroma, epithelium, lumen). Quantitative histologic evaluation was performed to calculate volume fractions for each tissue component for regions of interest corresponding to MRI. Tissue composition measured by using HM MRI and quantitative histologic evaluation were compared (paired t test) and correlated (Pearson correlation coefficient), and agreement (concordance correlation) was assessed. Receiver operating characteristic curve analysis for cancer diagnosis was performed. Results Twenty-five participants (mean age, 60 years ± 7 [standard deviation]; 30 cancers and 45 benign regions of interest) were included. Prostate tissue composition measured with HM MRI and quantitative histologic evaluation did not differ (stroma, 45% ± 11 vs 44% ± 11 [P = .23]; epithelium, 31% ± 15 vs 34% ± 15 [P = .08]; and lumen, 24% ± 13 vs 22% ± 11 [P = .80]). Between HM MRI and histologic evaluation, there was excellent correlation (Pearson r: overall, 0.91; stroma, 0.82; epithelium, 0.93; lumen, 0.90 [all P < .05]) and agreement (concordance correlation coefficient: overall, 0.91; stroma, 0.81; epithelium, 0.90; and lumen, 0.87). High areas under the receiver operating characteristic curve obtained with HM MRI (0.96 for epithelium and 0.94 for lumen, P < .001) and histologic evaluation (0.94 for epithelium and 0.88 for lumen, P < .001) were found for differentiation between benign tissue and prostate cancer. Conclusion Tissue composition measured by using hybrid multidimensional MRI had excellent correlation with quantitative histologic evaluation as the reference standard. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Muglia in this issue.

Directional and inter-acquisition variability in diffusion-weighted imaging and editing for restricted diffusion.

PURPOSE: To evaluate and quantify inter-directional and inter-acquisition variation in diffusion-weighted imaging (DWI) and emphasize signals that report restricted diffusion to enhance cancer conspicuity, while reducing the effects of local microscopic motion and magnetic field fluctuations. METHODS: Ten patients with biopsy-proven prostate cancer were studied under an Institutional Review Board-approved protocol. Individual acquisitions of DWI signal intensities were reconstructed to calculate inter-acquisition distributions and their statistics, which were compared for healthy versus cancer tissue. A method was proposed to detect and filter the acquisitions affected by motion-induced signal loss. First, signals that reflect restricted diffusion were separated from the acquisitions that suffer from signal loss, likely due to microscopic motion, by imposing a cutoff value. Furthermore, corrected apparent diffusion coefficient maps were calculated by employing a weighted sum of the multiple acquisitions, instead of conventional averaging. These weights were calculated by applying a soft-max function to the set of acquisitions per-voxel, making the analysis immune to acquisitions with significant signal loss, even if the number of such acquisitions is high. RESULTS: Inter-acquisition variation is much larger than the Rician noise variance, local spatial variations, and the estimates of diffusion anisotropy based on the current data, as well as the published values of anisotropy. The proposed method increases the contrast for cancers and yields a sensitivity of 98 . 8 % $$ 98.8\% $$ with a false positive rate of 3 . 9 % $$ 3.9\% $$ . CONCLUSION: Motion-induced signal loss makes conventional signal-averaging suboptimal and can obscure signals from areas with restricted diffusion. Filtering or weighting individual acquisitions prior to image analysis can overcome this problem.

Merlin immunohistochemistry is useful in diagnosis of tumours within the spectrum of biphasic hyalinizing psammomatous renal cell carcinoma.

AIMS: Biphasic hyalinizing psammomatous (BHP) renal cell carcinoma (RCC) is a newly described emerging entity within the spectrum of papillary RCC in the WHO 2022 classification. Molecular analyses have discovered that BHP RCC consistently harbour somatic mutations in the neurofibromin 2 (NF2) gene. The NF2 gene product, merlin, is known to primarily function as a tumour suppressor. Merlin protein loss correlates closely with the presence of NF2 mutations in benign and malignant tumours arising in different sites. In the present study we explored the role of merlin immunohistochemistry (IHC) in tumours within the spectrum of BHP RCC to determine the diagnostic utility of this marker. MATERIALS AND METHODS: We performed merlin IHC in 13 BHP RCC, 18 papillary RCC, 10 TFE3-translocation RCC, 15 TFEB-altered RCC (including 13 TFEB-rearranged and 2 TFEB-amplified), and 10 mucinous tubular and spindle cell carcinomas of unknown mutational status. RESULTS: Unequivocal loss of merlin expression in >90% of the tumour cells was observed in 12/13 BHP-RCC (92%), with the remaining tumour demonstrating weak focal cytoplasmic expression in ~10% of the tumour. In contrast, merlin was diffusely or multifocally expressed in all papillary RCC, TFE3-translocation RCC, and TFEB-altered RCC, as well as in 70% of mucinous tubular and spindle carcinomas. CONCLUSIONS: In this study, merlin IHC was ~92% sensitive and ~94% specific for BHP RCC. These data suggest that merlin IHC is a reliable surrogate marker for the presence of underlying NF2 gene inactivation, being diagnostically useful to identify BHP RCC. CONCLUSIONS: In this study, merlin IHC was ~92% sensitive and ~94% specific for BHP RCC. These data suggest that merlin IHC is a reliable surrogate marker for the presence of underlying NF2 gene inactivation, being diagnostically useful to identify BHP RCC.

Multi-Site Concordance of Diffusion-Weighted Imaging Quantification for Assessing Prostate Cancer Aggressiveness.

BACKGROUND: Diffusion-weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease. PURPOSE: To compare 14 site-specific parametric fitting implementations applied to the same dataset of whole-mount pathologically validated DWI to test the hypothesis that cancer differentiation varies with different fitting algorithms. STUDY TYPE: Prospective. POPULATION: Thirty-three patients prospectively imaged prior to prostatectomy. FIELD STRENGTH/SEQUENCE: 3 T, field-of-view optimized and constrained undistorted single-shot DWI sequence. ASSESSMENT: Datasets, including a noise-free digital reference object (DRO), were distributed to the 14 teams, where locally implemented DWI parameter maps were calculated, including mono-exponential apparent diffusion coefficient (MEADC), kurtosis (K), diffusion kurtosis (DK), bi-exponential diffusion (BID), pseudo-diffusion (BID*), and perfusion fraction (F). The resulting parametric maps were centrally analyzed, where differentiation of benign from cancerous tissue was compared between DWI parameters and the fitting algorithms with a receiver operating characteristic area under the curve (ROC AUC). STATISTICAL TEST: Levene's test, P < 0.05 corrected for multiple comparisons was considered statistically significant. RESULTS: The DRO results indicated minimal discordance between sites. Comparison across sites indicated that K, DK, and MEADC had significantly higher prostate cancer detection capability (AUC range = 0.72-0.76, 0.76-0.81, and 0.76-0.80 respectively) as compared to bi-exponential parameters (BID, BID*, F) which had lower AUC and greater between site variation (AUC range = 0.53-0.80, 0.51-0.81, and 0.52-0.80 respectively). Post-processing parameters also affected the resulting AUC, moving from, for example, 0.75 to 0.87 for MEADC varying cluster size. DATA CONCLUSION: We found that conventional diffusion models had consistent performance at differentiating prostate cancer from benign tissue. Our results also indicated that post-processing decisions on DWI data can affect sensitivity and specificity when applied to radiological-pathological studies in prostate cancer. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

A prospective clinical and transcriptomic feasibility study of oral-only hormonal therapy with radiation for unfavorable prostate cancer in men 70 years of age and older or with comorbidity.

BACKGROUND: Androgen deprivation therapy (ADT) improves outcomes in unfavorable-risk prostate cancer (PCa) treated with radiation therapy (RT). It was hypothesized that replacing luteinizing hormone-releasing hormone (LHRH) agonists with a 5-α-reductase inhibitor (5-ARI) would improve hormonal health-related quality of life (HRQOL) without differentially suppressing androgen-responsive (AR) gene expression. METHODS: Patients with localized unfavorable-risk PCa, aged ≥70 years or Charlson Comorbidity Index score ≥2 were treated with oral ADT (oADT), consisting of 4 months of bicalutamide, a 5-ARI, and RT at 78 Gy. The primary end point was Expanded Prostate Cancer Index Composite HRQOL at 6 months ≤30%, and improvement compared with a synchronous standard of care (SOC) cohort receiving 4 months of bicalutamide and long-term LHRH agonist with RT. RNA sequencing was performed from matched pre-/post-ADT prostate tumor biopsies in a subset of men. Differential gene and pathway expressional changes were examined using gene set enrichment. RESULTS: Between 2011 and 2018, 40 and 30 men were enrolled in the oADT and SOC cohorts, respectively. Median follow-up was 40 months. Those with ≤30% decline in hormonal HRQOL at 6 months was 97% (oADT) and 93% (SOC). The average 6-month hormonal decline was 1% (oADT) versus 12% (SOC; P = .04). The 4-year freedom from biochemical failure was 88% (oADT) versus 81% (SOC; P = .48). RNA sequencing (n = 9) showed similar numbers of downregulated and upregulated genes between the treatment groups (fold-change = 2; false-discovery rate-adjusted P ≤ .05). Both treatments comparably decreased the expression of 20 genes in canonical androgen receptor signaling. CONCLUSIONS: For men with PCa undergoing RT, oral versus standard ADT may improve 6-month QOL and appears to have a similar impact on androgen-responsive gene expression.

High spectral and spatial resolution MRI of prostate cancer: a pilot study.

PURPOSE: High spectral and spatial resolution (HiSS) MRI is a spectroscopic imaging method focusing on water and fat resonances that has good diagnostic utility in breast imaging. The purpose of this work was to assess the feasibility and potential utility of HiSS MRI for the diagnosis of prostate cancer. METHODS: HiSS MRI was acquired at 3 T from six patients who underwent prostatectomy, yielding a train of 127 phase-coherent gradient echo (GRE) images. In the temporal domain, changes in voxel intensity were analyzed and linear (R) and quadratic (R1, R2) quantifiers of signal logarithm decay were calculated. In the spectral domain, three signal scaling-independent parameters were calculated: water resonance peak width (PW), relative peak asymmetry (PRA), and relative peak distortion from ideal Lorentzian shape (PRD). Seven cancer and five normal tissue regions of interest were identified in correlation with pathology and compared. RESULTS: HiSS-derived quantifiers, except R2, showed high reproducibility (coefficients of variation, 5%-14%). Spectral domain quantifiers performed better than temporal domain quantifiers, with receiver operator characteristic areas under the curve ranging from of 0.83 to 0.91. For temporal domain parameters, the range was 0.74 to 0.91. Low absolute values of the coefficients of correlation between monoexponential decay markers (R, PW) and resonance shape markers (PRA, PRD) were observed (range, 0.23-0.38). CONCLUSION: The feasibility and potential diagnostic utility of HiSS MRI in the prostate at 3 T without an endorectal coil was confirmed. Weak correlation between well-performing markers indicates that complementary information could be leveraged to further improve diagnostic accuracy.

An abdominal wall mass of exogenous insulin amyloidosis in setting of metastatic sarcoma.

Exogenous insulin amyloidosis (AIns) is an iatrogenic form of amyloidosis which is found in diabetic patients, generally localized to the site of subcutaneous insulin administration. It may form a discrete mass that could come to clinical attention, and can contribute to abnormal pharmacokinetics of the exogenous insulin, resulting in worsened control of diabetes. In this case report, we describe such a lesion in a 72-year-old man with a history of type 2 diabetes and primary adrenal gland epithelioid sarcoma and discuss the diagnostic challenges it poses.

Incidental Gynecologic Tract Neoplasms in Women Undergoing Anterior Pelvic Exenteration for Urothelial Carcinoma.

Urothelial carcinoma (UC) invasive into the muscularis propria or tumors unresponsive to treatment are indications for cystectomy. In females, with the goal of achieving complete cancer eradication and for concerns of UC extension into the adjacent pelvic organs, this may also warrant resection of the gynecologic organs. This study is aimed to assess the prevalence of unanticipated gynecologic neoplasms in anterior pelvic exenteration specimens. A retrospective review of pathology reports to identify women undergoing anterior pelvic exenteration for UC was performed (N=221), and incidentally discovered gynecologic tract neoplasms were recorded. Concomitant malignant or premalignant lesions of the gynecologic tract were identified in 8 patients (3.6%). These included endometrial adenocarcinoma [endometrioid type, International Federation of Gynecology and Obstetrics grade 1 (n=2, 0.9%)], cervical high-grade squamous intraepithelial lesion (n=2, 0.9%), Sertoli-Leydig cell tumor of intermediate differentiation (n=1, 0.5%), endometrioid adenocarcinoma of the ovary (n=1, 0.5%), and high-grade serous carcinoma of the ovary (n=1, 0.5%) and fallopian tube (n=1, 0.5%). Benign uterine neoplasms included leiomyomas (n=81, 37%), adenomyoma (n=3, 1.4%), and adenomatoid tumors (n=2, 0.9%). Benign ovarian neoplasms included serous cystadenoma (n=7, 3%), serous cystadenofibroma (n=4, 2%), benign Brenner tumor (n=5, 2.3%), mature teratoma (n=4, 2%), stromal luteoma (n=2, 0.9%), mucinous cystadenoma (n=1, 0.5%), thecoma (n=1, 0.5%), and endometrioid cystadenoma (n=1, 0.5%). Involvement of the gynecologic tract by UC was identified in 11 patients (5%). Spread of UC to the reproductive organs is rare in anterior pelvic exenteration specimens. Coexisting neoplasms of the gynecologic tract are occasionally identified, therefore careful evaluation of these organs is necessary.

Comparison of T2-Weighted Imaging, DWI, and Dynamic Contrast-Enhanced MRI for Calculation of Prostate Cancer Index Lesion Volume: Correlation With Whole-Mount Pathology.

OBJECTIVE: The objective of our study was to investigate the comparative effectiveness of different MRI sequences for the estimation of index lesion volume in patients with prostate cancer (PCa) compared with ground truth volume measured on whole-mount pathology. MATERIALS AND METHODS: Patients with PCa underwent multiparametric MRI (mpMRI) on a 3-T MRI scanner before radical prostatectomy. Forty PCa index lesions were identified and outlined on histology by a pathologist. Two radiologists who were informed about the presence of PCa but were not aware of lesion outlines on histology worked in consensus to delineate PCa lesions on T2-weighted imaging, apparent diffusion coefficient (ADC) maps, and early-phase dynamic contrast-enhanced MRI (DCE-MRI). The lesion volumes from different mpMRI sequences and the percentage of volume underestimation compared with pathology were calculated and correlated with volume at pathology. The repeated-measures ANOVA with the posthoc Bonferroni test was performed to evaluate whether the difference between the estimated tumor volumes was statistically significant. RESULTS: The mean PCa lesion volume estimated from pathology, T2-weighted imaging, DWI (ADC maps), and DCE-MRI were 4.61 ± 4.99 (SD) cm3, 2.03 ± 2.96 cm3, 1.81 ± 2.76 cm3, and 3.48 ± 4.06 cm3, respectively. The lesion volumes on T2-weighted images (p = 0.000002), ADC maps (p = 0.000003), and DCE-MR images (p = 0.004412) were significantly lower than those from pathology. PCa lesion volume was significantly underestimated on T2-weighted images, ADC maps, and DCE-MR images compared with pathology by 54.98% ± 22.60% (mean ± SD), 58.59% ± 18.58%, and 18.33% ± 30.11%, respectively; underestimation using T2-weighted imaging (p = 1.01 × 10-11) and DWI (p = 2.94 × 10-11) was significantly higher than underestimation using DCE-MRI. Correlations between lesion volume estimated on T2-weighted images, ADC maps, and DCE-MR images with pathology were 0.91 (p = 9.03 × 10-16), 0.86 (p = 7.32 × 10-13), and 0.93 (p = 8.22 × 10-18), respectively. CONCLUSION: DCE-MRI performed better than T2-weighted imaging and DWI for estimation of index PCa volume and therefore can be preferred over these other two sequences for volume estimation.

Diagnosis of Prostate Cancer by Use of MRI-Derived Quantitative Risk Maps: A Feasibility Study.

OBJECTIVE. The purpose of this study was to develop a new quantitative image analysis tool for estimating the risk of cancer of the prostate by use of quantitative multiparametric MRI (mpMRI) metrics. MATERIALS AND METHODS. Thirty patients with biopsy-confirmed prostate cancer (PCa) who underwent preoperative 3-T mpMRI were included in the study. Quantitative mpMRI metrics-apparent diffusion coefficient (ADC), T2, and dynamic contrast-enhanced (DCE) signal enhancement rate (α)-were calculated on a voxel-by-voxel basis for the whole prostate and coregistered. A normalized risk value (0-100) for each mpMRI parameter was obtained, with high risk values associated with low T2 and ADC and high signal enhancement rate. The final risk score was calculated as a weighted sum of the risk scores (ADC, 40%; T2, 40%; DCE, 20%). Data from five patients were used as training set to find the threshold for predicting PCa. In the other 25 patients, any region with a minimum of 30 con-joint voxels (≈ 4.8 mm2) with final risk score above the threshold was considered positive for cancer. Lesion-based and sector-based analyses were performed by matching prostatectomyverified malignancy and PCa predicted with the risk analysis tool. RESULTS. The risk map tool had sensitivity of 76.6%, 89.2%, and 100% for detecting all lesions, clinically significant lesions (≥ Gleason 3 + 4), and index lesions, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for PCa detection for all lesions in the sector-based analysis were 78.9%, 88.5%, 84.4%, and 84.1%, respectively, with an ROC AUC of 0.84. CONCLUSION. The risk analysis tool is effective for detecting clinically significant PCa with reasonable sensitivity and specificity in both peripheral and transition zones.

Multiparametric MRI Features and Pathologic Outcome of Wedge-Shaped Lesions in the Peripheral Zone on T2-Weighted Images of the Prostate.

OBJECTIVE: This study investigates the multiparametric MRI (mpMRI) characteristics and pathologic outcome of wedge-shaped lesions observed on T2-weighted images. MATERIALS AND METHODS: Seventy-six patients with histologically confirmed prostate cancer underwent preoperative 3-T MRI before undergoing radical prostatectomy. Two radiologists worked in consensus to mark wedge-shaped regions of hypointensity on T2-weighted images and assess their appearance on apparent diffusion coefficient (ADC) maps (to determine the degree of hypointensity) and dynamic contrast-enhanced (DCE) MRI (DCE-MRI) (to assess whether they showed early enhancement). The pathologic outcome of wedge-shaped lesions was assessed by matching MR images with whole-mount histologic specimens retrospectively. The difference in quantitative ADC values between malignant and benign wedge-shaped lesions was assessed using a t test. RESULTS: Thirty-five wedge-shaped regions were identified, 12 (34%) of which were found be malignant. Most malignant wedge-shaped regions were highly hypointense (10/12; 83%) on ADC maps and showed early enhancement on DCE-MRI (7/12; 58%). However, benign wedge-shaped lesions were predominantly mildly hypointense (13/23; 57%) on ADC maps and showed no early enhancement (15/23; 65%). Histologic correlates of the benign wedge-shaped regions showed prostatitis (acute inflammation [7/23; 30%] or chronic inflammation [9/23; 39%]), hemosiderin-laden macrophages (6/23; 26%), prominent blood vessels (7/23; 30%), intraluminal blood (6/23; 26%), and nonspecific atrophy (6/23; 26%). The mean (± SD) quantitative ADC value of malignant wedge-shaped regions (1.13 ± 0.11 µm2/ms) was significantly lower (p = 0.0001) than that of benign wedge-shaped regions (1.52 ± 0.27 µm2/ms). CONCLUSION: This study shows that a greater percentage of wedge-shaped features are malignant than was previously thought. Of importance, mpMRI (specifically, ADC maps) can distinguish between malignant and benign wedge-shaped features.

Diagnosis of Prostate Cancer with Noninvasive Estimation of Prostate Tissue Composition by Using Hybrid Multidimensional MR Imaging: A Feasibility Study.

Purpose To evaluate whether compartmental analysis by using hybrid multidimensional magnetic resonance (MR) imaging can be used to diagnose prostate cancer and determine its aggressiveness. Materials and Methods Twenty-two patients with prostate cancer underwent preoperative 3.0-T MR imaging. Axial images were obtained with hybrid multidimensional MR imaging by using all combinations of echo times (47, 75, 100 msec) and b values of 0, 750, 1500 sec/mm2, resulting in a 3 × 3 array of data associated with each voxel. Volumes of the tissue components stroma, epithelium, and lumen were calculated by fitting the hybrid data to a three-compartment signal model, with distinct, paired apparent diffusion coefficient (ADC) and T2 values associated with each compartment. Volume fractions and conventional ADC and T2 were measured for regions of interest in sites of prostatectomy-verified malignancy (n = 28) and normal tissue (n = 71). Receiver operating characteristic (ROC) analysis was used to evaluate the performance of various parameters in differentiating prostate cancer from benign tissue. Results Compared with normal tissue, prostate cancer showed significantly increased fractional volumes of epithelium (23.2% ± 7.1 vs 48.8% ± 9.2, respectively) and reduced fractional volumes of lumen (26.4% ± 14.1 vs 14.0% ± 5.2) and stroma (50.5% ± 15.7 vs 37.2% ± 9.1) by using hybrid multidimensional MR imaging. The fractional volumes of tissue components show a significantly higher Spearman correlation coefficient with Gleason score (epithelium: ρ = 0.652, P = .0001; stroma: ρ = -0.439, P = .020; lumen: ρ = -0.390, P = .040) compared with traditional T2 values (ρ = -0.292, P = .132) and ADCs (ρ = -0.315, P = .102). The area under the ROC curve for differentiation of cancer from normal prostate was highest for fractional volume of epithelium (0.991), followed by fractional volumes of lumen (0.800) and stroma (0.789). Conclusion Fractional volumes of prostatic lumen, stroma, and epithelium change significantly when cancer is present. These parameters can be measured noninvasively by using hybrid multidimensional MR imaging and have the potential to improve the diagnosis of prostate cancer and determine its aggressiveness. © RSNA, 2018 Online supplemental material is available for this article.

Concordance study of PD-L1 expression in primary and metastatic bladder carcinomas: comparison of four commonly used antibodies and RNA expression.

Therapy with anti-PD-L1 immune check-point inhibitors is approved for several cancers, including advanced urothelial carcinomas. PD-L1 prevalence estimates vary widely in bladder cancer, and lack of correlation between expression and clinical outcomes and immunotherapy response may be attributed to methodological differences of the immunohistochemical reagents and procedures. We characterized PD-L1 expression in 235 urothelial carcinomas including 79 matched pairs of primary and metastatic cancers using a panel of four PD-L1 immunoassays in comparison with RNAscope assay using PD-L1-specific probe (CD274). The antibody panel included three FDA-approved clones (22C3 for pembrolizumab, 28.8 for nivolumab, SP142 for atezolizumab), and a commonly used clone E1L3N. Manual scoring of tissue microarrays was performed in each of 235 tumors (624 tissue cores) and compared to an automated image analysis. Expression of PD-L1 in tumor cells by ≥1 marker was detected in 41/142 (28.9%) primary tumors, 13/77 (16.9%) lymph nodes, and 2/16 (12.5%) distant metastases. In positive cases, high PD-L1 expression (>50% cells) was detected in 34.1% primary and 46.7% metastases. Concordant PD-L1 expression status was present in 71/79 (89.9%) cases of matched primary and metastatic urothelial carcinomas. PD-L1 sensitivity ranked from highest to lowest as follows: RNAscope, clone 28.8, 22C3, E1L3N, and SP142. Pairwise concordance correlation coefficients between the four antibodies in 624 tissue cores ranged from 0.76 to 0.9 for tumor cells and from 0.30 to 0.85 for immune cells. RNA and protein expression levels showed moderate to high agreement (0.72-0.87). Intra-tumor expression heterogeneity was low for both protein and RNA assays (interclass correlation coefficients: 0.86-0.94). Manual scores were highly concordant with automated Aperio scores (0.94-0.97). A significant subset of 56/235 (23.8%) urothelial carcinomas stained positive for PD-L1 with high concordance between all four antibodies and RNA ISH assay. Despite some heterogeneity in staining, the overall results are highly concordant suggesting diagnostic equivalence of tested assays.

Solid pseudopapillary neoplasm (SPN) of the testis: Comprehensive mutational analysis of 6 testicular and 8 pancreatic SPNs.

BACKGROUND: Recently, we came with the theory of a possible relationship between a group of testicular and pancreatic tumors. We used one case of a pancreatic analogue solid pseudopapillary neoplasm of the testis composed partially of areas reminiscent of solid pseudopapillary neoplasm (SPN) of the pancreas and partially of structures identical to primary signet ring stromal tumor of the testis (PSRSTT) as a connecting link between these two entities. After demonstrating that PSRSTT and pancreatic analogue SPN of the testis share the same immunoprofile and genetic features characteristic for pancreatic SPN, we came to the conclusion that pancreatic analogue SPN of the testis and PSRSTT represent a morphological spectrum of a single entity and that both are related to the pancreatic SPN. DESIGN: The aim of this study is to present a series of 6 cases of testicular tumors, which lacked the signet ring cell component and were thus morphologically very similar to the SPN of the pancreas. The goal of this study is to compare the genetic background of these testicular tumors that are obviously related to the PSRSTT/pancreatic analogue SPN of the testis with the series of 8 pancreatic SPN. RESULTS: The mutational analysis revealed an oncogenic somatic mutation in the exon 3 of the CTNNB1 (ß-catenin) gene in all analyzable (5/6) testicular and all pancreatic (8/8) tumors. The immunoprofile (positivity with ß-catenin, CD10, vimentin, NSE, CD56, and negativity with inhibin, calretinin, chromogranin) was identical in all testicular and pancreatic tumors. CONCLUSION: This study expanded the morphological spectrum of the PSRSTT/pancreatic analogue SPN of the testis by adding 6 cases without the signet ring cell component. Considering the obvious analogy of PSRSTT/pancreatic analogue SPN of the testis/SPN of the testis and their relationship to the pancreatic SPN we propose the collective term "solid pseudopapillary neoplasm of the testis" for these tumors. The mutational profile of the SPN of the testis and pancreas was the same in both groups of tumors which we consider as a final proof that SPN of the testis is identical to the SPN of the pancreas.

MRI evaluation of benign prostatic hyperplasia: Correlation with international prostate symptom score.

PURPOSE: To investigate the correlation between magnetic resonance imaging (MRI)-derived prostate parameters and benign prostatic hyperplasia (BPH) type with the International Prostate Symptom Score (IPSS). MATERIALS AND METHODS: In all, 61 patients (median age, 60; range, 41-81 years) who underwent preoperative MRI and prostatectomy were included in this retrospective study. The MRI-based parameters including total prostate volume (TPV), transition zone (TZ) volume (TZV), TZ index, intravesical prostatic protrusion (IPP), the anterior fibromuscular stroma (AFMS) distance, prostatic urethral angle, bladder wall thickness, urethral wall thickness, urethral compression, urethral wall changes, and BPH type were correlated with total IPSS, IPSS-storage symptom (IPSS-ss), IPSS-voiding symptom (IPSS-vs), and responses to the individual IPSS questions using Spearman (ρ) or Pearson (r) correlation coefficients, one-way analysis of variance (ANOVA), and multiple linear regression. RESULTS: TPV (r = 0.414, P = 0.001), TZV (r = 0.405, P = 0.001), IPP (r = 0.270, P = 0.04), and AFMS distance (r = 0.363, P = 0.004) correlated with total IPSS. In multiple linear regression analysis, TZV was the only predictor for total IPSS (P = 0.001), IPSS-ss (P < 0.001), IPSS-vs (P = 0.03), and the scores for the IPSS questions 1 (P = 0.03) and 4 (P = 0.001). TPV was a predictor of the scores for questions 2 (P = 0.003), 3 (P = 0.009), and 7 (P < 0.001). CONCLUSION: Several MRI-derived prostate measurements (TPV, TZV, IPP, AFMS distance) correlated with total IPSS. TZV was the only predictor for total IPSS based on multiple regression analysis. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:917-925.

Pilot Study of the Use of Hybrid Multidimensional T2-Weighted Imaging-DWI for the Diagnosis of Prostate Cancer and Evaluation of Gleason Score.

OBJECTIVE: The objective of our study was to evaluate the role of a hybrid T2-weighted imaging-DWI sequence for prostate cancer diagnosis and differentiation of aggressive prostate cancer from nonaggressive prostate cancer. MATERIALS AND METHODS: Twenty-one patients with prostate cancer who underwent preoperative 3-T MRI and prostatectomy were included in this study. Patients underwent a hybrid T2-weighted imaging-DWI examination consisting of DW images acquired with TEs of 47, 75, and 100 ms and b values of 0 and 750 s/mm(2). The apparent diffusion coefficient (ADC) and T2 were calculated for cancer and normal prostate ROIs at each TE and b value. Changes in ADC and T2 as a function of increasing the TE and b value, respectively, were analyzed. A new metric termed "PQ4" was defined as the percentage of voxels within an ROI that has increasing T2 with increasing b value and has decreasing ADC with increasing TE. RESULTS: ADC values were significantly higher in normal ROIs than in cancer ROIs at all TEs (p < 0.0001). With increasing TE, the mean ADC increased 3% in cancer ROIs and increased 12% in normal ROIs. T2 was significantly higher in normal ROIs than in cancer ROIs at both b values (p ≤ 0.0002). The mean T2 decreased with increasing b value in cancer ROIs (ΔT2 = -17 ms) and normal ROIs (ΔT2 = -52 ms). PQ4 clearly differentiated normal ROIs from prostate cancer ROIs (p = 0.0004) and showed significant correlation with Gleason score (ρ = 0.508, p < 0.0001). CONCLUSION: Hybrid MRI measures the response of ADC and T2 to changing TEs and b values, respectively. This approach shows promise for detecting prostate cancer and determining its aggressiveness noninvasively.

Quantitative Multiparametric MRI Features and PTEN Expression of Peripheral Zone Prostate Cancer: A Pilot Study.

OBJECTIVE: The objective of our study was to investigate associations between quantitative image features of multiparametric MRI of the prostate and PTEN expression of peripheral zone prostate cancer. MATERIALS AND METHODS: A total of 45 peripheral zone cancer foci from 30 patients who had undergone multiparametric prostate MRI before prostatectomy were identified by a genitourinary pathologist and a radiologist who reviewed histologic findings and MR images. Histologic sections of cancer foci underwent immunohistochemical analysis and were scored according to the percentage of tumor-positive cells expressing PTEN as negative (0-20%), mixed (20-80%), or positive (80-100%). Average and 10th percentile apparent diffusion coefficient (ADC) values, skewness of T2-weighted signal intensity histogram, and quantitative perfusion parameters (i.e., forward volume transfer constant [K(trans)], extravascular extracellular volume fraction [ve], and reverse reflux rate constant between the extracellular space and plasma [k(ep)]) from the Tofts model were calculated for each cancer focus. Associations between the quantitative image features and PTEN expression were analyzed with the Spearman rank correlation coefficient (r). RESULTS: Analysis of the 45 cancer foci revealed that 21 (47%) were PTEN-positive, 12 (27%) were PTEN-negative, and 12 (27%) were mixed. There was a weak but significant negative correlation between Gleason score and PTEN expression (r = -0.30, p = 0.04) and between k(ep) and PTEN expression (r = -0.35, p = 0.02). There was no significant correlation between other multiparametric MRI features and PTEN expression. CONCLUSION: This preliminary study of radiogenomics of peripheral zone prostate cancer revealed weak-but significant-associations between the quantitative dynamic contrast-enhanced MRI feature k(ep) and Gleason score with PTEN expression. These findings warrant further investigation and validation with the aim of using multiparametric MRI to improve risk assessment of patients with prostate cancer.

Dynamic Contrast-enhanced MR Imaging Curve-type Analysis: Is It Helpful in the Differentiation of Prostate Cancer from Healthy Peripheral Zone?

PURPOSE: To evaluate the performance and interobserver agreement of qualitative dynamic contrast material enhanced magnetic resonance (MR) imaging curve analysis as described in the Prostate Imaging Reporting and Data System (PI-RADS) for the differentiation of prostate cancer (PCa) from healthy prostatic tissue in the peripheral zone (PZ). MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act-compliant institutional review board-approved retrospective analysis included 120 consecutive pretreatment dynamic contrast-enhanced (DCE) MR imaging PCa examinations. Regions of interest (ROIs) were placed in 251 spots, including 95 (37.8%) in healthy PZ tissue and 156 (62.2%) in PCa, by using detailed histologic-multiparametric MR correlation review. Three radiologists reviewed the DCE time curves and assessed qualitative curve types as described in PI-RADS: type 1 (progressive), type 2 (plateau), or type 3 (washout). Receiver operating characteristic curve analysis was used to assess accuracy in differentiating PCa from healthy tissue on the basis of curve type, and κ was calculated to assess interobserver agreement. RESULTS: Receiver operating characteristic curves were similar for all observers, but mean areas under the receiver operating characteristic curve were poor (0.58 ± 0.04 [standard deviation] to 0.63 ± 0.04). No differences in accuracy were seen for varying DCE time resolution and imaging length. Observer agreement in assessment of type 3 versus types 1 or 2 curves was substantial (0.66 < κ < 0.79), better for PCa ROIs than for healthy-tissue ROIs. The agreement between type 1 and type 2 curves was moderate to substantial (0.49 < κ < 0.78). CONCLUSION: Qualitative DCE MR imaging time-curve-type analysis performs poorly for differentiation of PCa from healthy prostatic tissue. Interobserver agreement is excellent in assessment of type 3 curves but only moderate for type 1 and 2 curves.

MRI-based prostate volume-adjusted prostate-specific antigen in the diagnosis of prostate cancer.

PURPOSE: To determine whether prostate-specific antigen (PSA) levels adjusted by prostate and zonal volumes estimated from magnetic resonance imaging (MRI) improve the diagnosis of prostate cancer (PCa) and differentiation between patients who harbor high-Gleason-sum PCa and those without PCa. MATERIALS AND METHODS: This retrospective study was Health Insurance Portability and Accountability Act (HIPAA)-compliant and approved by the Institutional Review Board of participating medical institutions. T2 -weighted MR images were acquired for 61 PCa patients and 100 patients with elevated PSA but without PCa. Computer methods were used to segment prostate and zonal structures and to estimate the total prostate and central-gland (CG) volumes, which were then used to calculate CG volume fraction, PSA density, and PSA density adjusted by CG volume. These quantities were used to differentiate patients with and without PCa. Area under the receiver operating characteristic curve (AUC) was used as the figure of merit. RESULTS: The total prostate and CG volumes, CG volume fraction, and PSA density adjusted by the total prostate and CG volumes were statistically significantly different between patients with PCa and patients without PCa (P ≤ 0.007). AUC values for the total prostate and CG volumes, and PSA density adjusted by CG volume, were 0.68 ± 0.04, 0.68 ± 0.04, and 0.66 ± 0.04, respectively, and were significantly better than that of PSA (P < 0.02), for differentiation of PCa patients from patients without PCa. CONCLUSION: The total prostate and CG volumes estimated from T2 -weighted MR images and PSA density adjusted by these volumes can improve the effectiveness of PSA for the diagnosis of PCa and differentiation of high-Gleason-sum PCa patients from patients without PCa.

IV Administered Gadodiamide Enters the Lumen of the Prostatic Glands: X-Ray Fluorescence Microscopy Examination of a Mouse Model.

OBJECTIVE: Dynamic contrast-enhanced MRI (DCE-MRI) has become a standard component of multiparametric protocols for MRI examination of the prostate, and its use is incorporated into current guidelines for prostate MRI examination. Analysis of DCE-MRI data for the prostate is usually based on the distribution of gadolinium-based agents, such as gadodiamide, into two well-mixed compartments, and it assumes that gadodiamide does not enter into the glandular lumen. However, this assumption has not been directly tested. The purpose of this study was to use x-ray fluorescence microscopy (XFM) imaging in situ to measure the concentration of gadodiamide in the epithelia and lumens of the prostate of healthy mice after IV injection of the contrast agent. MATERIALS AND METHODS: Six C57Bl6 male mice (age, 28 weeks) were sacrificed 10 minutes after IV injection of gadodiamide (0.13 mmol/kg), and three mice were sacrificed after saline injection. Prostate tissue samples obtained from each mouse were harvested and frozen; 7-µm-thick slices were sectioned for XFM imaging, and adjacent 5-µm-thick slices were sectioned for H and E staining. Elemental concentrations were determined from XFM images. RESULTS: A mean (± SD) baseline concentration of gadolinium of 0.01 ± 0.01 mM was determined from XFM measurements of prostatic tissue samples when no gadodiamide was administered, and it was used to determine the measurement error. When gadodiamide was added, the mean concentrations of gadolinium in the epithelia and lumens in 32 prostatic glands from six mice were 1.00 ± 0.13 and 0.36 ± 0.09 mM, respectively. CONCLUSION: Our data suggest that IV administration of gadodiamide results in uptake of contrast agent by the glandular lumens of the mouse prostate. We were able to quantitatively determine gadodiamide distributions in mouse prostatic epithelia and lumens.