Clear cell, papillary, and chromophobe RCCs demonstrate different patterns of enhancement on two-time point clinical dynamic contrast-enhanced MR images, allowing their differentiation with high sensitivity and specificity.

PD-L1 expression in primary clear cell renal cell carcinoma (ccRCC) increases the likelihood of response to anti-PD-1 inhibition, but fails to identify all responders. We hypothesized that PD-L1 levels assessed in randomly selected areas of the primary tumors may not accurately reflect expression levels in metastatic lesions, which are the target of systemic therapy. Therefore, we compared PD-L1 expression in a series of primary ccRCC and their metastases. Tissue blocks from 53 primary ccRCCs and 76 corresponding metastases were retrieved. Areas with predominant and highest nuclear grade were selected. Slides were immunostained with a validated anti-PD-L1 antibody (405.9A11). Membranous expression in tumor cells was quantified using H-score. Expression in tumor-infiltrating mononuclear cells (TIMC) was quantified using a combined score. Discordant tumor cell PD-L1 staining between primary tumors and metastases was observed in 11/53 cases (20.8%). Overall, tumor cell PD-L1 levels were not different in primary tumors and metastases (p=0.51). Tumor cell PD-L1 positivity was associated with higher T stage (p=0.03) and higher Fuhrman Nuclear Grade (FNG) (p<0.01). Within individual lesions, PD-L1 positivity was heterogeneous and almost exclusively detected in high nuclear grade areas (p<0.001). No difference was found in PD-L1 levels in TIMCs between primary tumors and metastases (p=0.82). Heterogeneity of PD-L1 expression in ccRCC suggests that its assessment as predictive biomarker for PD-1 blockade may require analysis of metastatic lesions. Notably, since PD-L1 expression was mostly detected in high nuclear grade areas, to avoid false negative results, these areas should be specifically selected for assessment.

Magnetic resonance (MR) imaging is useful in the characterization of renal masses. The MR imaging manifestations and pathologic diagnoses of 82 renal masses were reviewed and correlated. The MR imaging appearance of clear cell type renal cell carcinoma varies depending on the presence of cystic components, hemorrhage, and necrosis. Papillary renal cell carcinomas appear as well-encapsulated masses with homogeneous low signal intensity on T2-weighted images and homogeneous low-level enhancement after the intravenous administration of contrast material, or as cystic hemorrhagic masses with peripheral enhancing papillary projections. Transitional cell carcinoma may be seen as an irregular, enhancing filling defect in the pelvicaliceal system or ureter. Lymphomatous masses are usually hypointense relative to the renal cortex on T2-weighted images and enhance minimally on delayed gadolinium-enhanced images. Bulk fat is a distinguishing feature of angiomyolipoma. Oncocytoma has a variable and nonspecific appearance at MR imaging. MR imaging findings may allow the characterization of various renal masses and can provide valuable information for their clinical management.

Purpose To identify and evaluate textural quantitative imaging signatures (QISes) for tumors occurring within the central gland (CG) and peripheral zone (PZ) of the prostate, respectively, as seen on in vivo 3 Tesla endorectal T2-weighted (T2w) Magnetic Resonance Imaging (MRI). Materials and Methods This study utilized 22 pre-operative prostate MRI datasets (16 PZ, 6 CG) acquired from men with confirmed prostate cancer (CaP) and scheduled for radical prostatectomy (RP). The prostate region-of-interest (ROI) was automatically delineated on T2w MRI, following which it was corrected for intensity-based acquisition artifacts. An expert pathologist manually delineated the dominant tumor regions on ex vivo sectioned and stained RP specimens as well as identified each of the studies as either a CG or PZ CaP. A non-linear registration scheme was employed to spatially align and then map CaP extent from the ex vivo RP sections onto the corresponding MRI slices. 110 texture features were then extracted on a per-voxel basis from all T2w MRI datasets. An information theoretic feature selection procedure was then applied to identify QISes comprising T2w MRI textural features specific to CG and PZ CaP, respectively. The QISes for CG and PZ CaP were evaluated via Quadratic Discriminant Analysis (QDA) on a per-voxel basis against the ground truth for CaP on T2w MRI, mapped from corresponding histology. Results The QDA classifier yielded an area under the Receiver Operating characteristic curve of 0.86 for the CG CaP studies, and 0.73 for the PZ CaP studies over 25 runs of randomized 3-fold cross-validation. By comparison, the accuracy of the QDA classifier was significantly lower when (a) using all 110 texture features (with no feature selection applied), as well as (b) a randomly selected combination of texture features. Conclusion CG and PZ prostate cancers have significantly differing textural quantitative imaging signatures on T2w endorectal in vivo MRI.

Purpose Fusion of the TMPRSS2 prostate-specific gene with the ERG transcription factor is a putatively oncogenic gene rearrangement that is commonly found in prostate cancer tissue from men undergoing prostatectomy. However, the prevalence of the fusion was less common in TURP samples from a Swedish cohort of incidental prostate cancer patients followed by watchful waiting, raising the question as to whether the high prevalence in prostatectomy specimens reflects selection bias. We sought to determine the prevalence of TMPRSS2-ERG gene fusion among PSA-screened men undergoing prostate biopsy in the United States. Experimental design We studied 140 prostate biopsies from the same number of patients for TMPRSS2-ERG fusion status with a FISH assay. 134 (100 cancer and 34 benign) were assessable. Results ERG gene rearrangement was detected in 46% prostate biopsies that were found to have prostate cancer and in 0% of benign prostate biopsies (p<0.0001). Evaluation of morphological features showed that cribriform growth, blue-tinged mucin, macronucleoli and collagenous micronodules were significantly more frequent in TMPRSS2-ERG fusion positive prostate cancer biopsies than gene fusion negative prostate cancer biopsies (p≤0.04). No significant association with Gleason score was detected. In addition, non-Caucasian patients were less likely to have positive fusion status (p=0.02). Conclusions This is the first prospective North American multi-center study to characterize the TMPRSS2-ERG prostate cancer prevalence in a cohort of patients undergoing needle biopsy irrespective of whether or not they subsequently undergo prostatectomy. Our results show that this gene rearrangement is common among North American men who have prostate cancer on biopsy, is absent in benign prostate biopsy, and is associated with specific morphological features. These findings indicate a need for prospective studies to evaluate the relationship of TMPRSS2-ERG rearrangement with clinical course of screening-detected prostate cancer in North American men, and development of non-invasive screening tests to detect TMPRSS2-ERG rearrangement.

Purpose: More than 1,300,000 prostate needle biopsies are done annually in the United States with up to 16% incidence of isolated high-grade prostatic intraepithelial neoplasia (HGPIN). HGPIN has low predictive value for identifying prostate cancer on subsequent needle biopsies in prostate-specific antigen^screened populations. In contemporary series, prostate cancer is detected in f20% of repeat biopsies following a diagnosis of HGPIN. Further, discrete histologic subtypes of HGPIN with clinical implication in management have not been characterized. The TMPRSS2-ERG gene fusion that has recently been described in prostate cancer has also been shown to occur in a subset of HGPIN. This may have significant clinical implications given that TMPRSS2-ERG fusion prostate cancer is associated with a more aggressive clinical course. Experimental Design: In this study, we assessed a series of HGPIN lesions and paired prostate cancer for the presence of TMPRSS2-ERG gene fusion. Results: Fusion-positive HGPIN was observed in 16% of the 143 number of lesions, and in all instances, the matching cancer shared the same fusion pattern. Sixty percent of TMPRSS2-ERG fusion prostate cancer had fusion-negative HGPIN. Conclusions: Given the more aggressive nature of TMPRSS2-ERG prostate cancer, the findings of this study raise the possibility that gene fusion-positive HGPIN lesions are harbingers of more aggressive disease. To date, pathologic, molecular, and clinical variables do not help stratify which men with HGPIN are at increased risk for a cancer diagnosis. Our results suggest that the detection of isolated TMPRSS2-ERG fusion HGPIN would improve the positive predictive value of findingTMPRSS2-ERG fusion prostate cancer in subsequent biopsies.

Bladder cancer can be categorized into organ confined and nonorgan confined tumors. This dichotomous grouping is better suited for evaluating adjuvant clinical trials. The pT stage of the bladder and prostate should be prospectively analyzed together to better define the clinical implications of prostatic involvement. In our opinion the histological subtypes do not affect outcome.

To perform a feature analysis of malignant renal tumors evaluated with magnetic resonance (MR) imaging and to investigate the correlation between MR imaging features and histopathological findings. MR examinations in 79 malignant renal masses were retrospectively evaluated, and a feature analysis was performed. Each renal mass was assigned to one of eight categories from a proposed MRI classification system. The sensitivity and specificity of the MRI classification system to predict the histologic subtype and nuclear grade was calculated. Subvoxel fat on chemical shift imaging correlated to clear cell type (p < 0.05); sensitivity = 42%, specificity = 100%. Large size, intratumoral necrosis, retroperitoneal vascular collaterals, and renal vein thrombosis predicted high-grade clear cell type (p < 0.05). Small size, peripheral location, low intratumoral SI on T2-weighted images, and low-level enhancement were associated with low-grade papillary carcinomas (p < 0.05). The sensitivity and specificity of the MRI classification system for diagnosing low grade clear cell, high-grade clear cell, all clear cell, all papillary, and transitional carcinomas were 50% and 94%, 93% and 75%, 92% and 83%, 80% and 94%, and 100% and 99%, respectively. The MRI feature analysis and proposed classification system help predict the histological type and nuclear grade of renal masses.