Faculty Bibliography

Osteoclastoma-like giant cell tumor of the renal pelvis, similar to the entity more commonly occurring in bone, is very rare, having been reported in twelve previous cases to our knowledge. This is the first report of this entity, to our knowledge, to include its cross-sectional imaging appearance. A hyperdense area within the lesion on non-contrast CT may correspond with extensive hemorrhagic content of the lesion identified histologically. As in most prior cases, an adjacent smaller urothelial carcinoma of the renal pelvis was also identified. In the limited reported cases, this entity has exhibited highly aggressive behavior with poor prognosis

PURPOSE: To assess the magnetic resonance imaging (MRI) features of a series of 9 cases of pathologically proven sarcomatoid renal cell carcinoma (SRCC). METHODS: Two radiologists in consensus retrospectively reviewed a spectrum of MRI features of nine cases of SRCC imaged at our institution between 2003 and 2009. RESULTS: SRCC had a mean diameter of 9.9 cm. All cases had an irregular or infiltrative morphology and demonstrated heterogeneous T2 signal intensity and enhancement. Internal necrosis was present in all cases, with four cases demonstrating >50% necrosis. Evidence of aggressive local behavior and/or distant spread was frequently observed. CONCLUSIONS: We have presented the largest case series to our knowledge of the MRI appearance of SRCC, with the lesions tending to appear as large heterogeneous masses with internal necrosis and evidence of aggressive local or distant behavior. However, these imaging features are non-specific, and histology remains necessary to establish the diagnosis

OBJECTIVES: To evaluate the accuracy and potential clinical value of intraoperative frozen section analysis (FSA) on urethral margin (UM) tissue during radical prostatectomy. Positive surgical margins increase the risk of post-operative cancer recurrence. Positive surgical margins are frequently found at the apex. The utility of intraoperative FSA of the margins is controversial. METHODS: We reviewed a consecutive series of radical prostatectomy cases (n = 1669) performed at our institution, in which UMs were routinely evaluated by intraoperative FSA. RESULTS: The submitted UM tissue contained cancer glands in 111 cases (6.7%). On FSA, the pathologists detected cancer in 55 cases (3.3%), missed cancer in 38 (2.3%), and reported atypical glands in 18 (1.1%). FSA of the UMs had a sensitivity of 59.1%, specificity of 99.8%, and positive and negative predictive value of 94.8% and 97.6%, respectively. The low sensitivity resulted from a substantial false-negative rate (n = 38), which was largely attributed to limited sampling on FSA (n = 31). Of the 55 patients (3.3%) whose positive UMs were detected by FSA, 20 (1.2%) had cancer-free margins after tissue re-excision. A positive final UM was associated with greater biochemical recurrence (P = .0073). However, the few patients limited the statistical analysis of the benefit of margin conversion through tissue re-excision (P = .35). CONCLUSIONS: Although experienced pathologists can evaluate the UMs on FSA with good accuracy, FSA has a relatively low sensitivity. Our data have indicated a low yield and a questionable value of routine FSA during radical prostatectomy

PURPOSE: To retrospectively assess the utility of fusion of T2-weighted images (T2WI) and high b-value diffusion-weighted images (DWI) for prostate cancer detection and localization. MATERIALS AND METHODS: In this IRB-approved HIPAA-compliant study, 42 patients with prostate cancer underwent MRI including multiplanar T2WI and axial DWI before prostatectomy. Two independent radiologists first assessed multiplanar T2WI and axial DWI(b-1000) images and recorded whether tumor was present in each sextant. Axial T2WI was then fused with axial DWI(b-1000) images, and the radiologists re-evaluated each sextant for tumor. Accuracy was compared using generalized estimating equations based on a binary logistic regression model. RESULTS: The accuracy, sensitivity, specificity, PPV, and NPV for tumor detection on a sextant-basis using separate and fused image sets was 65.1%, 50.8%, 78.0%, 67.8%, and 63.6% and 71.0%, 60.8%, 80.3%, 73.7%, and 69.3%, respectively, for reader 1, and 54.0%, 42.5%, 64.4%, 52.0%, and 55.2%, and 61.1%, 56.7%, 65.2%, 59.6%, and 62.3%, respectively, for reader 2. The improvements in accuracy, sensitivity, and NPV using fused images were statistically significant for both readers, as was the improvement in PPV for reader 2 (P ranging from <0.0001 to 0.041). With either separate or fused images, there was greater sensitivity for tumors of higher grade or larger size (P ranging from <0.001 to 0.099). CONCLUSION: Fusion of T2WI and high b-value DWI resulted in significant improvements in sensitivity and accuracy for tumor detection on a sextant-basis, with similar specificity. J. Magn. Reson. Imaging 2011;. (c) 2011 Wiley-Liss, Inc

Lymphoid enhancer-binding factor (LEF)1 is a major mediator and a target in canonical Wnt/beta-catenin pathway. Interactions between the androgen receptor (AR) and canonical Wnt pathways have been implicated in the development of the genitourinary organs. Here, we investigated the localization and role of LEF1-positive cells during development of the prostate gland in human and in the murine model. We show that during human prostate development, LEF1 is restricted to the basal epithelial layer of the urogenital sinus. During mouse development, Lef1 is also present in the urogenital mesenchyme in addition to the basal epithelial layer of the urogenital sinus. In the course of elongation and branching of the prostatic ducts, Lef1 is localized to the proliferating epithelium at the distal tips of the buds. Notably, during branching morphogenesis, domains of Lef1 and AR are mutually exclusive. We further employed the TOPGAL reporter strain to examine the dynamics of Wnt signaling in the context of prostate regression upon a 7-d treatment with a competitive AR inhibitor, bicalutamide. We found that Wnt/Lef1-positive basal cells are not dependent upon androgen for survival. Furthermore, upon bicalutamide treatment, Wnt/Lef1-positive basal progenitors repopulated the luminal compartment. We conclude that Wnt/Lef1 activity identifies an androgen-independent population of prostate progenitors, which is important for embryonic development and organ maintenance and regeneration in the adult

PURPOSE: High mobility group AT-hook 1 (HMGA1) is a non-histone nuclear binding protein that is developmentally regulated. HMGA1 is significantly overexpressed in and associated with high grade and advance stage of prostate cancer (PC). The oncogenic role of HMGA1 is at least mediated through chromosomal instability and structural aberrations. However, regulation of HMGA1 expression is not well understood. Identification of microRNA mediated HMGA1 regulation will provide a promising therapeutic target in treating PC. Experimental Designs: In this study, we examined the functional relation between miR-296 and HMGA1 expression in several prostate cancer cell lines and a large prostate cancer cohort. We further examined the oncogenic property of HMGA1 regulated by miR-296. RESULTS: Here we report that miR-296, a microRNA predicted to target HMGA1, specifically represses HMGA1 expression by promoting degradation and inhibiting HMGA1translation . Repression of HMGA1 by miR-296 is direct and sequence-specific. Importantly, ectopic miR-296 expression significantly reduced prostate cancer cell proliferation and invasion, in part through the down-regulation of HMGA1. Examining prostate cancer patient samples, we found an inverse correlation between HMGA1 and miR-296 expression: high levels of HMGA1 were associated with low miR-296 expression and strongly linked to more advanced tumor grade and stage. CONCLUSIONS: Our results indicate miR-296 regulates HMGA1 expression and is associated with PC growth and invasion