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De novo large cell neuroendocrine carcinoma of the prostate, case report and literature review
Acosta-Gonzalez, Gabriel; Qin, Jia; Wieczorek, Rosemary; Melamed, Jonathan; Deng, Fang-Ming; Zhou, Ming; Makarov, Danil; Ye, Fei; Pei, Zhiheng; Pincus, Matthew R; Lee, Peng
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.
PMCID:4297330
PMID: 25606580
ISSN: 2330-1910
CID: 1440202
PROSTATE TUMOR VOLUMES: AGREEMENT BETWEEN MRI AND HISTOLOGY USING NOVEL CO-REGISTRATION SOFTWARE [Meeting Abstract]
Le Nobin, Julien; Orczyk, Clement; Deng, Fang-Ming; Melamed, Jonathan; Rusinek, Henry; Taneja, Samir; Rosenkrantz, Andrew
ISI:000350277902471
ISSN: 1527-3792
CID: 1871812
ACSL4 IN PROSTATE CANCER GROWTH, INVASION AND HORMONAL RESISTANCE [Meeting Abstract]
Wu, Xinyu; Li, Yirong; Du, Xinxin; Ren, Qinghu; Kong, Max X; Wang, Jinhua; Wang, LingHang; Yang, Yang; Zhang, Valerio; Zhang, David; Ye, Fei; Daniels, Garrett; Deng, Fangming; Wei, Jianjun; Melamed, Jonathan; Monaco, Marie E; Lee, Peng
ISI:000350277901227
ISSN: 1527-3792
CID: 2245772
Preliminary experience with a novel method of three-dimensional co-registration of prostate cancer digital histology and in vivo multiparametric MRI
Orczyk, C; Rusinek, H; Rosenkrantz, A B; Mikheev, A; Deng, F-M; Melamed, J; Taneja, S S
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.
PMCID:3884198
PMID: 23993149
ISSN: 0009-9260
CID: 614232
Clinical utility of immunohistochemistry for the detection of the BRAF v600e mutation in papillary thyroid carcinoma
Zagzag, Jonathan; Pollack, Aron; Dultz, Linda; Dhar, Shumon; Ogilvie, Jennifer B; Heller, Keith S; Deng, Fang-Ming; Patel, Kepal N
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.
PMCID:4100700
PMID: 23931769
ISSN: 0039-6060
CID: 629892
Computed diffusion-weighted imaging of the prostate at 3 T: impact on image quality and tumour detection
Rosenkrantz, Andrew B; Chandarana, Hersh; Hindman, Nicole; Deng, Fang-Ming; Babb, James S; Taneja, Samir S; Geppert, Christian
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 = 0.024). However, computed b-1,500 DWI showed less distortion and ghosting than direct b-1,000 and direct b-1,500 DWI for both readers (P = 0.067). Direct and computed b-1,500 images showed better sensitivity and positive predictive value (PPV) for tumour detection than direct b-1,000 images for both readers (P = 0.062), with no difference in sensitivity or PPV between direct and computed b-1,500 images (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.
PMID: 23756956
ISSN: 0938-7994
CID: 573582
Prostate Cancer Localization Using Multiparametric MR Imaging: Comparison of Prostate Imaging Reporting and Data System (PI-RADS) and Likert Scales
Rosenkrantz, Andrew B; Kim, Sooah; Lim, Ruth P; Hindman, Nicole; Deng, Fang-Ming; Babb, James S; Taneja, Samir S
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.
PMID: 23788719
ISSN: 0033-8419
CID: 586172
Utility of diffusional kurtosis imaging as a marker of adverse pathologic outcomes among prostate cancer active surveillance candidates undergoing radical prostatectomy
Rosenkrantz, Andrew B; Prabhu, Vinay; Sigmund, Eric E; Babb, James S; Deng, Fang-Ming; Taneja, Samir S
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; = 25% of biopsy cores positive for tumor; = 50% tumor involvement of any individual core; = 20% tumor involvement across all cores) who underwent prostatectomy and preoperative 3-T MRI including diffusional kurtosis imaging (b values, 0, 500, 1000, 1500, and 2000 s/mm(2)) were included. Adverse pathologic features at prostatectomy were defined using two schemes of varying stringency. One scheme (less stringent) was presence of a Gleason score greater than 6 or extracapsular extension (n = 19). The other scheme (more stringent) was presence of a Gleason score greater than 6, extracapsular extension, or an index tumor 10 mm or larger (n = 35). Parametric maps displaying standard apparent diffusion coefficient (ADC), kurtosis (K) representing nongaussian diffusion behavior, and diffusion (D) representing a diffusion coefficient adjusted for nongaussian (kurtosis) behavior were reviewed, and the most abnormal region was recorded for each metric. Associations between these metrics and the presence of adverse final pathologic findings were assessed with unpaired Student t tests and receiver operating characteristic analyses. RESULTS. For both schemes, only D was significantly lower in patients with adverse final pathologic findings (p = 0.006, p = 0.025). K tended to be greater in patients with adverse final pathologic findings for the more stringent scheme (p = 0.072). ADC was not significantly different in the presence of adverse final pathologic findings for either scheme (p = 0.357, p = 0.383). With either scheme, D had a larger area under the receiver operating characteristics curve (AUC) for predicting adverse final pathologic results (AUC, 0.691 and 0.743) than did ADC (AUC, 0.569 and 0.655) or K (AUC, 0.617 and 0.714), but the difference was not significant (p = 0.183, p = 0.734). CONCLUSION. Preliminary results suggest that diffusional kurtosis imaging findings may have more value than findings at conventional diffusion-weighted MRI as a marker of adverse final pathologic outcome among active surveillance candidates.
PMID: 24059373
ISSN: 0361-803x
CID: 542842
Cystic lesions of the adrenal gland: our experience over the last 20 years
Sebastiano, Christopher; Zhao, Xiangrong; Deng, Fang-Ming; Das, Kasturi
Cystic lesions of the adrenal gland are uncommon, often presenting with nonspecific clinical and radiologic findings, and are thus underrecognized. They are occasionally associated with malignant neoplasms, which can greatly mimic benign lesions and carry detrimental clinical consequences if misdiagnosed. Here we present our 20-year experience (1992-2012) with these lesions at an academic medical center. Among more than 4500 adrenal gland specimens, 31 cases of adrenal lesions with a predominant cystic component were identified in 30 patients with an age range of 34 to 86 years (median, 55.5 years) and a male/female ratio of 13:17. Macroscopic descriptions, available histologic and immunostain slides, and available radiologic records were reviewed for all included cases. Radiologic studies and gross examination correlated well, and hemorrhage (26 cases; 84%) and encapsulation (25 cases; 81%) appeared to be nonspecific radiologic/gross features shared across histologic subtypes. Microscopic review identified 12 cases (39%) of pseudocysts, 2 cases (6%) of endothelium-derived cysts, and 17 cases (55%) of epithelium-derived cysts. Among these 31 cystic adrenal lesions, 2 cases (6%) were malignant neoplasms (1 epithelioid angiosarcoma, 1 adrenocortical carcinoma). Radiologic impression and histopathologic diagnosis were concordant in 11 (73%) of the 15 cases for which radiologic records were available. This study represents the second largest case series to date on cystic adrenal lesions and presents a comprehensive review on their demographic, clinical, radiologic, and gross and microscopic pathologic features, as well as their differential diagnoses.
PMID: 23618356
ISSN: 0046-8177
CID: 512822
Prostate cancer: comparison of dynamic contrast-enhanced MRI techniques for localization of peripheral zone tumor
Rosenkrantz, Andrew B; Sabach, Amy; Babb, James S; Matza, Brent W; Taneja, Samir S; Deng, Fang-Ming
OBJECTIVE. The objective of this study was to compare the performance of different methodologies for interpretation of dynamic contrast-enhanced MRI (DCE-MRI) in localization of peripheral zone prostate cancer. MATERIALS AND METHODS. Forty-three men (mean age, 59 +/- 8 years) with biopsy-proven prostate cancer who underwent prostate MRI including DCE-MRI before prostatectomy were included. Two observers independently reviewed DCE-MRI data using three methodologies: qualitative, in which kinetic curves of signal intensity versus time were generated for foci showing rapid enhancement on subtracted contrast-enhanced images; semiquantitative, in which a biexponential heuristic model was used to generate color-coded maps depicting maximum slope and washout of contrast enhancement; and quantitative, in which a Tofts model was used to generate color-coded influx rate transfer constant (K(trans)) and efflux rate transfer constant (Kep) maps. Findings were stratified by whether suspicious foci showed evidence of washout with each method and compared with histopathologic results in each sextant. RESULTS. There was similar accuracy for the semiquantitative and quantitative models for both observers irrespective of requiring evidence of washout. For the more experienced observer, requiring washout resulted in lower sensitivity and higher specificity for the qualitative and semiquantitative models. Also for the more experienced observer, use of either a semiquantitative or quantitative model provided greater sensitivity compared with a qualitative model when requiring washout. There was no association between tumor detection and Gleason score for any DCE-MRI methodology for either reader. CONCLUSION. For the experienced reader, sensitivity for peripheral zone tumor was increased by use of either a semiquantitative or quantitative model compared with a qualitative model and decreased by requiring washout. We failed to identify a difference in performance between semiquantitative and quantitative models.
PMID: 23971479
ISSN: 0361-803x
CID: 512942