Spontaneous Rupture of Leiomyoma Diagnosed Preoperatively with Noncontrast Computed Tomography.

BACKGROUND: Spontaneous rupture of benign uterine fibroids is extremely rare and has been associated with fibroid degeneration. It can cause acute intraperitoneal bleeding requiring immediate surgical intervention. CASE: A previously healthy 50-year-old, Caucasian, nullipara presented with syncope, hemodynamic instability, and an acute abdomen. Noncontrast computed tomography images showed a positive sentinel clot sign in the pelvis as well as a large uterine fibroid with internal hyperdense clot suggesting acute rupture. Urgent laparotomy and hysterectomy confirmed a ruptured, actively bleeding, uterine fibroid with final pathological diagnosis of a benign leiomyoma. CONCLUSION: Prompt diagnosis and emergency surgical intervention were necessary to control acute hemorrhage from a ruptured uterine fibroid. Noncontrast computed tomography is an important adjunct to contrast-enhanced computed tomography and was vital for diagnosis in this case.

MRI of the Prostate With and Without Endorectal Coil at 3 T: Correlation With Whole-Mount Histopathologic Gleason Score.

OBJECTIVE. The purpose of this article is to prospectively compare image quality and diagnostic accuracy of clinically significant prostate cancer with and without endorectal coil (ERC) at 3 T using a combination of T2-weighted and diffusion-weighted MRI. SUBJECTS AND METHODS. Twenty-three patients with biopsy-proven prostate cancer underwent MRI with and without ERC at the same visit. Patients subsequently underwent radical prostatectomy. Specimens were assessed by whole-mount histopathologic examination. Two radiologists reviewed MR images for image quality (5-point scale) and disease using Prostate Imaging Reporting and Data Systems version 2 (PI-RADSv2). Sensitivity, specificity, and area under the ROC curve (AUC) were calculated with and without ERC. Additionally, apparent diffusion coefficient (ADC) was correlated with Gleason score and ADC values of each lesion were compared with and without ERC. RESULTS. Image quality was comparable with and without ERC (3.8 vs 3.5). Twenty-nine cancer foci larger than 0.5 cm in diameter were found in 23 patients on histopathologic examination; 18 tumors had a Gleason score of 7 or greater. Two radiologists recorded AUC for tumors with a Gleason score of 7 or greater as 0.96 and 0.96 with ERC and 0.88 and 0.91 without ERC. All 13 tumors with a Gleason score of 3 + 4 were detected with ERC, but only 9 were detected without ERC. One of five tumors with Gleason scores less than 3 + 4 was missed with and without ERC. ADC significantly correlated with Gleason score. There was no significant difference in the ADC of a lesion on MRI with and without an ERC. CONCLUSION. MRI with and without ERC was equally accurate at showing prostate cancers with Gleason scores of 4 + 3 or greater. However, MRI with ERC was superior at showing cancer with a Gleason score of 3 + 4. There was no significant difference in ADC values between scores acquired with or without an ERC.

Metastatic Renal Cell Carcinoma to the Testis: A Clinicopathologic Analysis of Five Cases.

The testicular spread of renal cell carcinoma is extremely rare. Five cases of renal cell carcinoma metastatic to the testis are described. The patients ranged from 45 to 81 years of age. Four of the five patients had known renal cell carcinoma. The time intervals between the partial and radical nephrectomies for the primary kidney tumors and the occurrence of testicular metastases ranged from 29 to 34 months. In one patient, the testicular mass was the initial presentation leading to a diagnosis of renal cell carcinoma. There were three ipsilateral metastases, one contralateral metastasis, and one bilateral metastasis. The metastatic deposits ranged in size from 2.0 to 5.7 cm. One case had multiple metastatic tumor nodules. All of the metastatic tumors had clear cell histological features, microscopically concordant with the primary renal cell carcinoma subtype. Three patients died of the disease 17 to 42 months after orchiectomy. One patient is alive with additional metastatic lesions 13 months after orchiectomy. One patient had been free of disease at 87 months after orchiectomy but is now on targeted therapy for an additional metastasis at 93 months after orchiectomy. To date, this report is one of the largest single series of patients with renal cell carcinoma metastatic to the testis, and it has the longest follow-up and survival among all the reported cases.

Metastatic breast carcinoma to the urinary bladder-a report of 11 cases including a tumor to tumor metastasis.

Metastatic breast carcinoma to the urinary bladder is rare. Eleven cases of metastatic breast carcinoma to the bladder are described in this report, including one case with a tumor to tumor metastasis. The patients ranged from 51 to 83 years of age. The time intervals between the diagnosis of primary breast cancer and the occurrence of bladder metastases ranged from 41 to 336 months. There were seven cases of invasive ductal carcinoma and four cases of invasive lobular carcinoma. In one case, a lobular carcinoma of the breast metastasized to a concurrent squamous cell carcinoma of the bladder. The immunophenotypic status of estrogen receptor and Her2 expression of the metastatic carcinomas were all concordant with the primary tumors. In nine patients with follow-up available, seven patients died of the disease ranging from 1 to 23 months after the diagnosis of the bladder metastasis and two patients were alive at 5 months of follow-up. To date, this report is the largest single series of patients with breast carcinoma metastatic to the bladder. It is the first reported instance of lobular carcinoma of the breast metastasizing to a squamous cell carcinoma of the bladder.

Comparing diagnostic accuracy of luminal water imaging with diffusion-weighted and dynamic contrast-enhanced MRI in prostate cancer: A quantitative MRI study.

Luminal water imaging (LWI) is a new MRI T2 mapping technique that has been developed with the aim of diagnosis of prostate carcinoma (PCa). This technique measures the fractional amount of luminal water in prostate tissue, and has shown promising preliminary results in detection of PCa. To include LWI in clinical settings, further investigation on the accuracy of this technique is required. In this study, we compare the diagnostic accuracy of LWI with those of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI in detection and grading of PCa. Fifteen patients with biopsy-proven PCa consented to participate in this ethics-board-approved prospective study. Patients were examined with LWI, DWI, and DCE sequences at 3 T prior to radical prostatectomy. Maps of MRI parameters were generated and registered to whole-mount histology. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic accuracy of individual and combined MR parameters. Correlation with Gleason score (GS) was evaluated using Spearman's rank correlation test. The results show that area under the ROC curve (AUC) obtained from LWI was equal to or higher than the AUC obtained from DWI, DCE, or their combination, in peripheral zone (0.98 versus 0.90, 0.89, and 0.91 respectively), transition zone (0.99 versus 0.98, n/a, and 0.98), and the entire prostate (0.85 versus 0.81, 0.75, and 0.84). The strongest correlation with GS was achieved from LWI (ρ = -0.81 ± 0.09, P < 0.001). Results of this pilot study show that LWI performs equally well as, or better than, DWI and DCE in detection of PCa. LWI provides significantly higher correlation with GS than DWI and DCE. This technique can potentially be included in clinical MRI protocols to improve characterization of tumors. However, considering the small size of the patient population in this study, a further study with a larger cohort of patients and broader range of GS is required to confirm the findings and draw a firm conclusion on the applicability of LWI in clinical settings.

Assessment of the need for DCE MRI in the detection of dominant lesions in the whole gland: Correlation between histology and MRI of prostate cancer.

The purpose of this study was to evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) in the detection of dominant prostate tumors with multi-parametric MRI of the whole gland. Combined diffusion tensor imaging (DTI) and DCE MRI from 16 patients with biopsy-proven prostate cancer and no previous treatment were acquired with a 3.0-T MRI scanner prior to radical prostatectomy, and used to identify dominant tumors. MRI results were validated by whole-mount histology. Paired t-test and Wilcoxon test, logistic generalized linear mixed effect models and receiver operating characteristic (ROC) analyses were used for the estimation of the statistical significance of the results. In the peripheral zone (PZ), the areas under the ROC curve (ROC-AUC) were 0.98 (sensitivity, 96%; specificity, 98%) for DTI, 0.96 (sensitivity, 92%; specificity, 97%) for DCE and 0.99 (sensitivity, 98%; specificity, 98%) for DTI + DCE. In the entire prostate, the ROC-AUC values were 0.96 (sensitivity, 84%; specificity, 95%) for DTI, 0.87 (sensitivity, 45%; specificity, 94%) for DCE and 0.96 (sensitivity, 88%; specificity, 98%) for DTI + DCE. The increase in ROC-AUC by the addition of DCE was not statistically significant in either PZ or the entire prostate. The results of this study have shown that DTI identified dominant tumors with high accuracy in both PZ and the entire prostate, whereas the inclusion of DCE MRI had no significant impact on the identification of either PZ or entire prostate dominant lesions. Our results suggest that the inclusion of DCE MRI may not increase the accuracy of dominant lesion detection, allowing for faster, better tolerated imaging studies.

Luminal Water Imaging: A New MR Imaging T2 Mapping Technique for Prostate Cancer Diagnosis.

Purpose To assess the feasibility of luminal water imaging, a quantitative T2-based magnetic resonance (MR) imaging technique, for the detection and grading of prostate cancer (PCa). Materials and Methods Eighteen patients with biopsy-proven PCa provided informed consent to be included in this institutional human ethics board-approved prospective study between January 2015 and January 2016. Patients underwent 3.0-T MR imaging shortly before radical prostatectomy. T2 distributions were generated with a regularized non-negative least squares algorithm from multiecho spin-echo MR imaging data. From T2 distributions, maps of seven MR parameters, Ncomp, T2short, T2long, geometric mean T2 (gmT2), luminal water fraction (LWF), Ashort, and Along, were generated and compared with digitized images of hematoxylin-eosin-stained whole-mount histologic slices. A paired t test was used to determine significant differences between MR parameters in malignant and nonmalignant tissue. Correlation with Gleason score (GS) was evaluated with the Spearman rank correlation test. Diagnostic accuracy was evaluated by using logistic generalized linear mixed-effect models and receiver operating characteristic (ROC) analysis. Results The average values of four MR parameters (gmT2, Ashort, Along, and LWF) were significantly different between malignant and nonmalignant tissue. All MR parameters except for T2long showed significant correlation (P < .05) with GS in the peripheral zone. The highest correlation with GS was obtained for LWF (-0.78 ± 0.11, P < .001). ROC analysis demonstrated high accuracy for tumor detection, with the highest area under the ROC curve obtained for LWF (0.97 in the peripheral zone and 0.98 in the transition zone). Conclusion Results of this pilot study demonstrated the feasibility of luminal water imaging in the detection and grading of PCa. A study with a larger cohort of patients and a broader range of GS is required to further evaluate this new technique in clinical settings. © RSNA, 2017.

MR measurement of luminal water in prostate gland: Quantitative correlation between MRI and histology.

PURPOSE: To determine the relationship between parameters measured from luminal water imaging (LWI), a new magnetic resonance imaging (MRI) T2 mapping technique, and the corresponding tissue composition in prostate. MATERIALS AND METHODS: In all, 17 patients with prostate cancer were examined with a 3D multiecho spin echo sequence at 3T prior to undergoing radical prostatectomy. Maps of seven MR parameters, called N, T2-short , T2-long , Ashort , Along , geometric mean T2 time (gmT2 ), and luminal water fraction (LWF), were generated using nonnegative least squares (NNLS) analysis of the T2 decay curves. MR parametric maps were correlated to digitized whole-mount histology sections. Percentage area of tissue components, including luminal space, nuclei, and cytoplasm plus stroma, was measured on the histology sections by using color-based image segmentation. Spearman's rank correlation test was used to evaluate the correlation between MR parameters and the corresponding tissue components, with particular attention paid to the correlation between LWF and percentage area of luminal space. RESULTS: N, T2-short , Along , gmT2 , and LWF showed significant correlation (P < 0.05) with percentage area of luminal space and stroma plus cytoplasm. T2-short and gmT2 also showed significant correlation (P < 0.05) with percentage area of nuclei. Overall, the strongest correlation was observed between LWF and luminal space (Spearman's coefficient of rank correlation = 0.75, P < 0.001). CONCLUSION: Results of this study show that LWF measured with MRI is strongly correlated with the fractional amount of luminal space in prostatic tissue. This result suggests that LWI can potentially be applied for evaluation of prostatic diseases in which the extent of luminal space differs between normal and abnormal tissues. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:861-869.

Post-radiation epithelioid angiosarcoma of the urinary bladder and prostate.

Angiosarcoma of the lower urinary tract is exceedingly rare. A minority of cases are associated with local radiotherapy. Epithelioid angiosarcoma is a variant of angiosarcoma composed of large rounded epithelioid endothelial cells that are positive for cytokeratin on immunostaining. There are only two cases of post-radiation epithelioid angiosarcoma reported in the urinary bladder, and none in the prostate gland. We report a case of epithelioid angiosarcoma involving the urinary bladder and prostate in a patient with a history of radiotherapy for prostatic adenocarcinoma. A brief review of literature regarding post-radiation epithelioid angiosarcomas in the lower urinary tract is discussed.

A standardized protocol for identifying and counting lymph nodes harvested by pelvic lymph node dissection at the time of radical cystectomy.

INTRODUCTION: Lymph node counts have become a surrogate measure for the extent and quality of pelvic lymph node dissection (PLND) at radical cystectomy, but little consideration has been given to the methodology of lymph node processing. We report results from a prospective series comparing a conventional protocol for processing PLND specimens to a fat-emulsifying protocol. We hypothesized that the rate of node positivity would increase with the fat-emulsifying protocol. METHODS: Patients undergoing radical cystectomy for cTis-T4aN0-1M0 urothelial carcinoma of the bladder were eligible for this trial. Palpable lymph nodes were isolated from the PLND specimens in the conventional protocol. The remaining tissue was then processed with fat-emulsifying solution to identify further nodes visually. Nodal counts were compared between techniques. RESULTS: The median number of nodes counted in the PLND specimens of 26 patients was 24.5 (range: 20-40) with conventional processing and 37 (range: 24-52) with the fat-emulsifying solution (p < 0.001). Three patients had lymph node positive disease detected by conventional means, and a single patient was found to have a single positive node by the fat-emulsifying solution alone. The study was closed early after conducting a futility analysis. CONCLUSIONS: A fat-emulsifying protocol identified more lymph nodes than a conventional protocol and may be an appropriate method to standardize lymph node processing following PLND. However, we were unable to show that such a standardized approach significantly increased the rate of node positivity in patients undergoing radical cystectomy.

In vivo 3T and ex vivo 7T diffusion tensor imaging of prostate cancer: Correlation with histology.

The purpose of this work was to test whether fractional anisotropy (FA) can contribute to the diagnosis and grading of prostate cancer. Turbo spin echo T2-weighted (T2W) and single shot echo planar imaging diffusion tensor imaging (EPI DTI) data were collected from 13 subjects with biopsy proven prostate cancer prior to surgical removal of the gland. Rapid acquisition with relaxation enhancement (RARE) T2W and spin-echo DTI data were acquired ex-vivo from the fixed prostatectomy specimens. Digitized whole mount histology sections, examined and annotated by a pathologist, were registered to the in-vivo and ex-vivo DTI data, and the average values of apparent diffusion coefficient (ADC) and FA were calculated from ROIs encompassing normal and cancerous peripheral zone (PZ). In addition, Monte Carlo simulations were carried out to assess the dependence of the apparent FA on the ADC values for different signal to noise ratios (SNRs). ADC values were significantly lower in tumors than in normal PZ both in-vivo and ex-vivo, while the difference in FA values between tumors and normal PZ was significant only in-vivo. Paired t-test showed significant difference between in-vivo and ex-vivo FA values in tumors, but not in the normal PZ. The simulations showed that lower SNR results in an increasing overestimation of the FA values with decreasing ADC. These results suggest that the in-vivo increase in FA values in tumors is due to low SNR, rather than the presence of cancer. The results of this study suggest that FA does not contribute significantly to the diagnostic capabilities of DTI in prostate cancer.

A data-driven approach to prostate cancer detection from dynamic contrast enhanced MRI.

Magnetic resonance imaging (MRI), particularly dynamic contrast enhanced (DCE) imaging, has shown great potential in prostate cancer diagnosis and staging. In the current practice of DCE-MRI, diagnosis is based on quantitative parameters extracted from the series of T1-weighted images acquired after the injection of a contrast agent. To calculate these parameters, a pharmacokinetic model is fitted to the T1-weighted intensities. Most models make simplistic assumptions about the perfusion process. Moreover, these models require accurate estimation of the arterial input function, which is challenging. In this work we propose a data-driven approach to characterization of the prostate tissue that uses the time series of DCE T1-weighted images without pharmacokinetic modeling. This approach uses a number of model-free empirical parameters and also the principal component analysis (PCA) of the normalized T1-weighted intensities, as features for cancer detection from DCE MRI. The optimal set of principal components is extracted with sparse regularized regression through least absolute shrinkage and selection operator (LASSO). A support vector machine classifier was used with leave-one-patient-out cross validation to determine the ability of this set of features in cancer detection. Our data is obtained from patients prior to radical prostatectomy and the results are validated based on histological evaluation of the extracted specimens. Our results, obtained on 449 tissue regions from 16 patients, show that the proposed data-driven features outperform the traditional pharmacokinetic parameters with an area under ROC of 0.86 for LASSO-isolated PCA parameters, compared to 0.78 for pharmacokinetic parameters. This shows that our novel approach to the analysis of DCE data has the potential to improve the multiparametric MRI protocol for prostate cancer detection.

MR elastography and diffusion-weighted imaging of ex vivo prostate cancer: quantitative comparison to histopathology.

The purpose of this work was (1) to develop a magnetic resonance elastography (MRE) system for imaging of the ex vivo human prostate and (2) to assess the diagnostic power of mono-frequency and multi-frequency MRE and diffusion weighted imaging (DWI) alone and combined as correlated with histopathology in a patient study. An electromagnetic driver was designed specifically for MRE studies in small-bore MR scanners. Ex vivo prostate specimens (post-fixation) of 14 patients who underwent radical prostatectomy were imaged with MRE at 7 T (nine cases had DWI). In six patients, the MRE examination was performed at three frequencies (600, 800, 1000 Hz) to extract the power-law exponent Gamma. The images were registered to wholemount pathology slides marked with the Gleason score. The areas under the receiver-operator-characteristic curves (AUC) were calculated. The methods were validated in a phantom study and it was demonstrated that (i) the driver does not interfere with the acquisition process and (ii) the driver can generate amplitudes greater than 100 µm for frequencies less than 1 kHz. In the quantitative study, cancerous tissue with Gleason score at least 3 + 3 was distinguished from normal tissue in the peripheral zone (PZ) with an average AUC of 0.75 (Gd ), 0.75 (Gl ), 0.70 (Gamma-Gd ), 0.68 (apparent diffusion coefficient, ADC), and 0.82 (Gd + Gl + ADC). The differentiation between PZ and central gland was modest for Gd (p < 0.07), Gl (p < 0.06) but not significant for Gamma (p < 0.2). A correlation of 0.4 kPa/h was found between the fixation time of the prostate specimen and the stiffness of the tissue, which could affect the diagnostic power results. DWI and MRE may provide complementary information; in fact MRE performed better than ADC in distinguishing normal from cancerous tissue in some cases. Multi-frequency (Gamma) analysis did not appear to improve the results. However, in light of the effect of tissue fixation, the clinical implication of our results may be inconclusive and more experiments are needed.

MR elastography of prostate cancer: quantitative comparison with histopathology and repeatability of methods.

The purpose of this work was to assess trans-perineal prostate magnetic resonance elastography (MRE) for (1) repeatability in phantoms/volunteers and (2) diagnostic power as correlated with histopathology in prostate cancer patients. The three-dimensional (3D) displacement field was obtained using a fractionally encoded gradient echo sequence using a custom-made transducer. The repeatability of the method was assessed based on three repeat studies and by changing the driving frequency by 3% in studies on a phantom and six healthy volunteers. Subsequently, 11 patients were examined with MRE prior to radical prostatectomy. The areas under the receiver operating characteristic curves were calculated using a windowed voxel-to-voxel approach by comparing the 2D registered slides, masked with the Gleason score. For the repeatability study, the average intraclass correlation coefficient for elasticity images was 99% for repeat phantom studies, 98% for ±6 Hz phantom studies, 95% for volunteer repeat studies with 2 min acquisition time, 82% for ±2 Hz volunteer studies with 2 min acquisition time and 73% for repeat volunteer studies with 8 min acquisition time. For the patient study, the average elasticity was 8.2 ± 1.7 kPa in the prostate capsule, 7.5 ± 1.9 kPa in the peripheral zone (PZ), 9.7 ± 3.0 kPa in the central gland (CG) and 9.0 ± 3.4 kPa in the transition zone. In the patient study, cancerous tissue with Gleason score at least 3 + 3 was significantly (p < 0.05) different from normal tissue in 10 out of 11 cases with tumors in the PZ, and 6 out of 9 cases with tumors in the CG. However, the overall case-averaged area under the curve was 0.72 in the PZ and 0.67 in the CG. Cancerous tissue was not always stiffer than normal tissue. The inversion algorithm was sensitive to (i) vibration amplitude and displacement nodes and (ii) misalignment of the 3D wave field due to subject movement.

Multiparametric 3D in vivo ultrasound vibroelastography imaging of prostate cancer: Preliminary results.

PURPOSE: Ultrasound-based solutions for diagnosis and prognosis of prostate cancer are highly desirable. The authors have devised a method for detecting prostate cancer using a vibroelastography (VE) system developed in our group and a tissue classification approach based on texture analysis of VE images. METHODS: The VE method applies wide-band mechanical vibrations to the tissue. Here, the authors report on the use of this system for cancer detection and show that the texture of VE images characterized by the first and the second order statistics of the pixel intensities form a promising set of features for tissue typing to detect prostate cancer. The system was used to image patients prior to radical surgery. The removed specimens were sectioned and studied by an experienced histopathologist. The authors registered the whole-mount histology sections to the ultrasound images using an automatic registration algorithm. This enabled the quantitative evaluation of the performance of the authors' imaging method in cancer detection in an unbiased manner. The authors used support vector machine (SVM) classification to measure the cancer detection performance of the VE method. Regions of tissue of size 5 × 5 mm, labeled as cancer and noncancer based on automatic registration to histology slides, were classified using SVM. RESULTS: The authors report an area under ROC of 0.81 ± 0.10 in cancer detection on 1066 tissue regions from 203 images. All cancer tumors in all zones were included in this analysis and were classified versus the noncancer tissue in the peripheral zone. This outcome was obtained in leave-one-patient-out validation. CONCLUSIONS: The developed 3D prostate vibroelastography system and the proposed multiparametric approach based on statistical texture parameters from the VE images result in a promising cancer detection method.

Registration of whole-mount histology and volumetric imaging of the prostate using particle filtering.

Registration of histological slices to volumetric imaging of the prostate is an important task that can be used to optimize imaging for cancer detection. Such registration is challenging due to physical changes of the specimen during excision and fixation, and misalignment of the histological slices during preparation and digital scanning. In this work, we consider a multi-slice to volume registration method in which a stack of sparse, unaligned 2-D whole-mount histological slices is registered to a 3-D volumetric imaging of the prostate. We propose a particle filtering framework to contend with the high dimensionality of the search space and multimodal nature of the optimization. Such framework allows modeling of the uncertainty in the pose of the slices and in the imaged information, in order to derive optimal registration parameters in a Bayesian approach. Intensity-, region-, and point-based similarity metrics were incorporated into the registration algorithm to account for different imaging modalities. We demonstrate and evaluate our method on a diverse set of data that includes a synthetic volume, ex vivo and in vivo magnetic resonance imaging, and in vivo ultrasound.

Genitourinary tuberculosis masquerading as a ureteral calculus.

The genitourinary tract is a common extrapulmonary site of tuberculosis infection, yet remains a rare clinical entity in North America. We report the case of a 37-year-old man who presented for extracorporeal shock wave lithotripsy for a suspected ureteral stone on imaging. Further workup confirmed a diagnosis of genitourinary tuberculosis. Medical management was undertaken and, ultimately, nephrectomy performed. This case highlights the importance of maintaining a high index of clinical suspicion for genitourinary tuberculosis.

From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer.

The current paradigm of cancer care relies on predictive nomograms which integrate detailed histopathology with clinical data. However, when predictions fail, the consequences for patients are often catastrophic, especially in prostate cancer where nomograms influence the decision to therapeutically intervene. We hypothesized that the high dimensional data afforded by massively parallel sequencing (MPS) is not only capable of providing biological insights, but may aid molecular pathology of prostate tumours. We assembled a cohort of six patients with high-risk disease, and performed deep RNA and shallow DNA sequencing in primary tumours and matched metastases where available. Our analysis identified copy number abnormalities, accurately profiled gene expression levels, and detected both differential splicing and expressed fusion genes. We revealed occult and potentially dormant metastases, unambiguously supporting the patients' clinical history, and implicated the REST transcriptional complex in the development of neuroendocrine prostate cancer, validating this finding in a large independent cohort. We massively expand on the number of novel fusion genes described in prostate cancer; provide fresh evidence for the growing link between fusion gene aetiology and gene expression profiles; and show the utility of fusion genes for molecular pathology. Finally, we identified chromothripsis in a patient with chronic prostatitis. Our results provide a strong foundation for further development of MPS-based molecular pathology.