Faculty Bibliography

Prostatectomy or irradiation is the most common traditional treatments for localized prostate cancer. In the event of recurrence and/or metastasis, androgen ablation therapy has been the mainstay treatment for many years. Although initially effective, the cancer inevitably recurs as androgen-independent PCa, a disease with limited effective treatments. Enhanced predictive biomarkers are needed at the time of diagnosis to better tailor therapies for patients. MicroRNAs are short nucleotide sequences which can complementary bind to and control gene expression at the post-transcriptional level. Recent studies have demonstrated that many miRNAs are variably expressed in cancers vs. normal tissues, including PCa. In this review, we summarize PCa-specific miRNAs that show potential for their utilization as identifiers of aggressive disease and predictors for risk of recurrence. Additionally, we discuss their potential clinical applications as biomarkers and therapeutic targets.

BACKGROUND: Tumors of the kidney are uncommon in children and young adults. Accurate classification is crucial for both prognostication and therapeutic intervention. However, majority of the tumors in this age group have unusual morphology that renders classification challenging. Tubulopapillary architecture is one of the most common morphological patterns observed in renal tumors of children and young adults. METHODS: A patient with epithelial predominant Wilms tumor was reported. Differential diagnosis of renal tumors with tubulopapillary morphology was discussed with an emphasis on the histological and immunohistochemical features, and the literature was reviewed. RESULTS: A 25 year-old female patient presented with bilateral multilocular cystic masses. She underwent right radical nephrectomy and left partial nephrectomy. The pathological examination revealed a tumor with tubulopapillary architecture which was lined with low columnar epithelial cells. During the work-up of this case, several entities were considered and ruled out by careful gross, microscopic examination and prudent use of immunohistochemistry. The tumor cells were positive for WT-1, and variably positive for cytokeratin AE1/3, CD56, CD57, and negative for cytokeratin 7 and EMA. Fluorescent in-situ hybridization revealed no gain of chromosome 7 and 17. A diagnosis of epithelial predominant adult Wilms tumors was rendered for both kidneys. The patient received systemic chemotherapy and radiation to the remnant left kidney and was free of disease three years after the initial surgery. CONCLUSION: The differential diagnosis of renal tumors with tubulopapillary features in children and young adults include papillary renal cell carcinoma, metanephric adenoma, epithelial predominant Wilms tumor, translocation renal cell carcinoma and metastatic adenocarcinoma to the kidney. An accurate classification relies on careful examination of clinical and pathological features and immunohistochemical characteristics.

Large cell neuroendocrine carcinoma of the prostate (LCNEC), de novo in particular, is an extremely rare entity that has only been described in the literature in case reports. Historically, the majority of the cases of LCNEC reported in the literature represent typical prostatic adenocarcinomas that transformed after long standing androgen deprivation therapy (ADT). These cases were admixed with histological areas of usual adenocarcinoma and showed hybrid features of both neuroendocrine and usual adenocarcinoma. Here we present a case of an LCNEC without admixed areas of usual prostatic adenocarcinoma arising de novo in a patient without prior history of hormonal therapy. The tumor also shows morphologic evidence of neuroendocrine differentiation; composed of large sheets and nests of cells with moderate amphophilic cytoplasm with peripheral palisading, and vesicular clumpy chromatin with prominent nucleoli. The carcinoma's prostatic origin is indicated by positive immunohistochemical staining for PSA, PAP, PSMA, racemase, and Nkx3.1. Diffusely positive staining for chromogranin and synaptophysin, as well as the presence of secretory granules in the cytoplasm of the tumor cells demonstrated by electron microscopy supports the NE differentiation. NE prostate cancer usually does not express AR and is refractory to ADT therapy while AR and ERG are positive in this case. In summary, we report a de novo LCNEC of the prostate with review of literature, in particular, clinical implications.

AIM: To assess a novel method of three-dimensional (3D) co-registration of prostate cancer digital histology and in-vivo multiparametric magnetic resonance imaging (mpMRI) image sets for clinical usefulness. MATERIAL AND METHODS: A software platform was developed to achieve 3D co-registration. This software was prospectively applied to three patients who underwent radical prostatectomy. Data comprised in-vivo mpMRI [T2-weighted, dynamic contrast-enhanced weighted images (DCE); apparent diffusion coefficient (ADC)], ex-vivo T2-weighted imaging, 3D-rebuilt pathological specimen, and digital histology. Internal landmarks from zonal anatomy served as reference points for assessing co-registration accuracy and precision. RESULTS: Applying a method of deformable transformation based on 22 internal landmarks, a 1.6 mm accuracy was reached to align T2-weighted images and the 3D-rebuilt pathological specimen, an improvement over rigid transformation of 32% (p = 0.003). The 22 zonal anatomy landmarks were more accurately mapped using deformable transformation than rigid transformation (p = 0.0008). An automatic method based on mutual information, enabled automation of the process and to include perfusion and diffusion MRI images. Evaluation of co-registration accuracy using the volume overlap index (Dice index) met clinically relevant requirements, ranging from 0.81-0.96 for sequences tested. Ex-vivo images of the specimen did not significantly improve co-registration accuracy. CONCLUSION: This preliminary analysis suggests that deformable transformation based on zonal anatomy landmarks is accurate in the co-registration of mpMRI and histology. Including diffusion and perfusion sequences in the same 3D space as histology is essential further clinical information. The ability to localize cancer in 3D space may improve targeting for image-guided biopsy, focal therapy, and disease quantification in surveillance protocols.

BACKGROUND: BRAF V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC). We used a mutation-specific antibody for immunohistochemical (IHC) detection of the BRAF V600E mutation and correlated expression with clinicopathologic features. The study was designed to validate the accuracy and determine the clinical importance of IHC detection of the BRAF V600E mutation in PTC. METHODS: Direct sequencing and IHC for BRAF V600E mutation was performed in 37 consecutive patients with PTCs. IHC was scored on an intensity proportion scale. IHC positive tumors were stratified into intensity categories. The categories were assessed for clinicopathologic variables, including age, extrathyroidal extension, lymphovascular invasion, and lymph node metastases. RESULTS: A total of 25 PTCs were BRAF V600E-positive and 12 were BRAF mutation-negative on IHC. The BRAF V600E mutation-specific antibody had a sensitivity of 89% and specificity of 100% for detecting the mutation. Tumors with high-intensity staining were more likely to have extrathyroidal extension. CONCLUSION: IHC is an accurate method for the detection of the BRAF V600E mutation in PTC, and its ability to quantify the mutation expression may serve as a better predictor of tumor behavior than molecular sequencing. It provides a potentially rapid, easily applicable, and economic alternative to current techniques.

OBJECTIVES: To investigate the impact of prostate computed diffusion-weighted imaging (DWI) on image quality and tumour detection. METHODS: Forty-nine patients underwent 3-T magnetic resonance imaging using a pelvic phased-array coil before prostatectomy, including DWI with b values of 50 and 1,000 s/mm(2). Computed DW images with b value 1,500 s/mm(2) were generated from the lower b-value images. Directly acquired b-1,500 DW images were obtained in 39 patients. Two radiologists independently assessed DWI for image quality measures and location of the dominant lesion. A third radiologist measured tumour-to-peripheral-zone (PZ) contrast. Pathological findings from prostatectomy served as the reference standard. RESULTS: Direct and computed b-1,500 DWI showed better suppression of benign prostate tissue than direct b-1,000 DWI for both readers (P /= 0.180). Tumour-to-PZ contrast was greater on computed b-1,500 than on either direct DWI set (P < 0.001). CONCLUSION: Computed DWI of the prostate using b value >/=1,000 s/mm(2) improves image quality and tumour detection compared with acquired standard b-value images. KEY POINTS: * Diffusion weighted MRI is increasingly used for diagnosing and assessing prostate carcinoma. * Prostate computed DWI can extrapolate high b-value images from lower b values. * Computed DWI provides greater suppression of benign tissue than lower b-value images. * Computed DWI provides less distortion and artefacts than images using same b value. * Computed DWI provides better diagnostic performance than lower b-value images.

Purpose: To compare the recently proposed Prostate Imaging Reporting and Data System (PI-RADS) scale that incorporates fixed criteria and a standard Likert scale based on overall impression in prostate cancer localization using multiparametric magnetic resonance (MR) imaging. Materials and Methods: This retrospective study was HIPAA compliant and institutional review board approved. Seventy patients who underwent 3-T pelvic MR imaging, including T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast material-enhanced imaging, with a pelvic phased-array coil before radical prostatectomy were included. Three radiologists, each with 6 years of experience, independently scored 18 regions (12 peripheral zone [PZ], six transition zone [TZ]) using PI-RADS (range, scores 3-15) and Likert (range, scores 1-5) scales. Logistic regression for correlated data was used to compare scales for detection of tumors larger than 3 mm in maximal diameter at prostatectomy. Results: Maximal accuracy was achieved with score thresholds of 8 and higher and of 3 and higher for PI-RADS and Likert scales, respectively. At these thresholds, in the PZ, similar accuracy was achieved with the PI-RADS scale and the Likert scale for radiologist 1 (89.0% vs 88.2%, P = .223) and radiologist 3 (88.5% vs 88.2%, P = .739) and greater accuracy was achieved with the PI-RADS scale than the Likert scale for radiologist 2 (89.6% vs 87.1%, P = .008). In the TZ, accuracy was lower with the PI-RADS scale than with the Likert scale for radiologist 1 (70.0% vs 87.1%, P < .001), radiologist 2 (87.6% vs 92.6%, P = .002), and radiologist 3 (82.9% vs 91.2%, P < .001). For tumors with Gleason score of at least 7, sensitivity was higher with the PI-RADS scale than with the Likert scale for radiologist 1 (88.6% vs 82.6%, P = .032), and sensitivity was similar for radiologist 2 (78.0% vs 76.5, P = .467) and radiologist 3 (77.3% vs 81.1%, P = .125). Conclusion: Radiologists performed well with both PI-RADS and Likert scales for tumor localization, although, in the TZ, performance was better with the Likert scale than the PI-RADS scale. (c) RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122233/-/DC1.

OBJECTIVE. The purpose of this study was to compare findings at nongaussian diffusional kurtosis imaging and conventional diffusion-weighted MRI as markers of adverse pathologic outcomes among prostate cancer patients who are active surveillance candidates and choose to undergo prostatectomy. MATERIALS AND METHODS. Fifty-eight active surveillance candidates (prostate-specific antigen concentration, < 10 ng/mL; clinical tumor category less than T2a; Gleason score, 3 + 3;