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Urethral adenocarcinoma associated with intestinal-type metaplasia, case report and literature review
Hale, Christopher S; Huang, Hongying; Melamed, Jonathan; Xu, Ruliang; Roberts, Larry; Wieczorek, Rosemary; Pei, Zhiheng; Lee, Peng
The presence of glandular epithelium in urinary tract biopsies poses a diagnostic challenge. Intestinal metaplasia of the urethra may be seen in many congenital, iatrogenic, and reactive conditions, as well as in association with malignant conditions such as urethral adenocarcinoma. We present a case of a 61 year-old woman presenting with microscopic hematuria. Successive biopsies showed glandular epithelium with focal atypia in close association with inflammation, but no overt malignancy. Only on surgical resection was the associated high grade adenocarcinoma revealed. When intestinal-type mucosa is present within a urinary tract biopsy, associated malignancy may be present only focally. Thorough sampling and consideration of the differential diagnosis is imperative.
PMCID:3726984
PMID: 23923086
ISSN: 1936-2625
CID: 484212
Interleukin-17 induces expression of chemokines and cytokines in prostatic epithelial cells but does not stimulate cell growth in vitro
Chapter by: You, Z; Ge, D; Liu, S; Zhang, Q; Borowsky, AD; Melamed, J
in: Prostate cancer cells : detection, growth and treatment by You, Zongbing [Eds]
New York : Nova Science, 2013
pp. 41-56
ISBN: 1622575253
CID: 1031892
National Mesothelioma Virtual Bank: A Platform for Collaborative Research and Mesothelioma Biobanking Resource to Support Translational Research
Amin, Waqas; Parwani, Anil V; Melamed, Jonathan; Flores, Raja; Pennathur, Arjun; Valdivieso, Federico; Whelan, Nancy B; Landreneau, Rodeny; Luketich, James; Feldman, Michael; Pass, Harvey I; Becich, Michael J
The National Mesothelioma Virtual Bank (NMVB), developed six years ago, gathers clinically annotated human mesothelioma specimens for basic and clinical science research. During this period, this resource has greatly increased its collection of specimens by expanding the number of contributing academic health centers including New York University, University of Pennsylvania, University of Pittsburgh Medical Center, and Mount Sinai School of Medicine. Marketing efforts at both national and international annual conferences increase awareness and availability of the mesothelioma specimens at no cost to approved investigators, who query the web-based NMVB database for cumulative and appropriate patient clinicopathological information on the specimens. The data disclosure and specimen distribution protocols are tightly regulated to maintain compliance with participating institutions' IRB and regulatory committee reviews. The NMVB currently has over 1120 annotated cases available for researchers, including paraffin embedded tissues, fresh frozen tissue, tissue microarrays (TMA), blood samples, and genomic DNA. In addition, the resource offers expertise and assistance for collaborative research. Furthermore, in the last six years, the resource has provided hundreds of specimens to the research community. The investigators can request specimens and/or data by submitting a Letter of Intent (LOI) that is evaluated by NMVB research evaluation panel (REP).
PMCID:4437393
PMID: 26316942
ISSN: 2090-3197
CID: 1762532
Granulomatous pneumocystis pneumonia presenting as a lung mass and mimicking disease recurrence in diffuse large B cell lymphoma [Meeting Abstract]
Lee, Y; Mukherjee, V; Melamed, J; Leibert, E
Rationale Cases of granulomatous reaction to pneumocystis have been reported in immuno-compromised patients, most commonly in HIV infected patients but also rarely in patients with hematologic disease. Because of the low incidence of G-PCP, there are only case reports and case series describing different presentations. It has been suggested that because of low organism burden and distribution of disease, bronchoscopy with lavage and biopsy has a low yield in non-HIV patients in diagnosing granulomatous pneumocystis pneumonia (G-PCP). We reviewed our cumulative experience in G-PCP, to characterize the disease and diagnostic approach among patients with different underlying diseases. Method We reviewed the medical records of patients whose pathology results were G-PCP in our tertiary urban hospitals between 1993 and 2012 including demographics, underlying disease, radiographic findings and diagnostic approach. Result We identified 38 G-PCP patients; 27 medical records were available for review. Sixteen patients were HIV-infected. The 11 non-HIV patients had lymphoma or rheumatoid arthritis. Nine of the 11 non-HIV patients had non-diagnostic bronchoscopies and required either CT guided core or open lung biopsy. By contrast, 13 of the 16 HIV patients had diagnostic bronchoscopies(p value=0.002). Among the 11 non-HIV patients, 4 had diffuse large B cell lymphoma that had been treated with multiple cycles of chemotherapy and were subsequently found to have solitary or multiple lung masses. Disease recurrence was suspected based on CT-PET scan findings. However, all pathology specimens showed non-necrotizing granulomatous inflammation with pneumocystis. None showed malignancy or acid fast bacilli. Of note, none of these patients had respiratory symptoms and pneumocystis pneumonia was not considered in the differential diagnosis prior to biopsy. All responded well to anti-pneumocystis therapy. Conclusion The presentation of granulomatous pneumocystis pneumonia in patients without HIV is often atypical. Specifically, the diagnosis should be considered in patients with treated large B cell lymphoma who present with a lung mass on chest imaging. Non-bronchoscopic biopsy is usually required for diagnosis
EMBASE:71985115
ISSN: 1073-449x
CID: 1769002
Diffusion-Weighted Intravoxel Incoherent Motion Imaging of Renal Tumors With Histopathologic Correlation
Chandarana, Hersh; Kang, Stella K; Wong, Samson; Rusinek, Henry; Zhang, Jeff L; Arizono, Shigeki; Huang, William C; Melamed, Jonathan; Babb, James S; Suan, Edgar F; Lee, Vivian S; Sigmund, Eric E
PURPOSE: The aim of this study was to use intravoxel incoherent motion diffusion-weighted imaging to discriminate subtypes of renal neoplasms and to assess agreement between intravoxel incoherent motion (perfusion fraction, fp) and dynamic contrast-enhanced magnetic resonance imaging (MRI) metrics of tumor vascularity. SUBJECTS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved prospective study, 26 patients were imaged at 1.5-T MRI using dynamic contrast-enhanced MRI with high temporal resolution and diffusion-weighted imaging using 8 b values (range, 0-800 s/mm). Perfusion fraction (fp), tissue diffusivity (Dt), and pseudodiffusivity (Dp) were calculated using biexponential fitting of the diffusion data. Apparent diffusion coefficient (ADC) was calculated with monoexponential fit using 3 b values of 0, 400, and 800 s/mm. Dynamic contrast-enhanced data were processed with a semiquantitative method to generate model-free parameter cumulative initial area under the curve of gadolinium concentration at 60 seconds (CIAUC60). Perfusion fraction, Dt, Dp, ADC, and CIAUC60 were compared between different subtypes of renal lesions. Perfusion fraction was correlated with CIAUC60. RESULTS: We examined 14 clear cell, 4 papillary, 5 chromophobe, and 3 cystic renal cell carcinomas (RCCs). Although fp had higher accuracy (area under the curve, 0.74) for a diagnosis of clear cell RCC compared with Dt or ADC, the combination of fp and Dt had the highest accuracy (area under the curve, 0.78). The combination of fp and Dt diagnosed papillary RCC and cystic RCC with 100% accuracy, and clear cell RCC and chromophobe RCC, with 86.5% accuracy. There was significant strong correlation between fp and CIAUC60 (r = 0.82; P < 0.001). CONCLUSION: Intravoxel incoherent motion parameters fp and Dt can discriminate renal tumor subtypes. Perfusion fraction demonstrates good correlation with CIAUC60 and can assess degree of tumor vascularity without the use of exogenous contrast agent.
PMID: 22996315
ISSN: 0020-9996
CID: 179984
A histopathologic basis for surgical debridement to promote healing of venous ulcers
Blumberg, Sheila N; Maggi, Jason; Melamed, Jonathan; Golinko, Michael; Ross, Frank; Chen, Weiliam
BACKGROUND: Pathologic analysis of deep tissue obtained during debridement of venous ulcers is often unnoticed in its importance. We previously reported pathologic findings on 139 patients with venous ulcers. The objective of this study was to correlate the pathologic findings in venous ulcers with wound healing to establish a negative margin for debridement. STUDY DESIGN: Consecutive patients with a lower extremity venous ulcer present for at least 4 weeks, presenting to a single wound healing center, were included. Wounds underwent aggressive surgical debridement beyond the subcutaneous level until judged to have a viable base. Specimens were scored based on cellularity, vascularity, collagen composition, inflammation, and dense fibrosis, with a highest possible score of 13. Healing was the primary outcome for analysis. RESULTS: Of the 26 patients who met inclusion criteria, only 50% of them (13 patients) with a total of 18 venous ulcers underwent surgical debridement available for pathologic analysis. Mean ulcer area was 34.7 cm(2) at initial presentation, and 89% of patients had a continuous positive healing curve as measured by decreasing wound area (from 34.7 cm(2) to 14.3 cm(2)). However, specimens with dense fibrosis, decreased cellularity, mature collagen, and pathology score less than 10 were predominantly nonhealing ulcers. CONCLUSIONS: Presence of dense fibrosis and high levels of mature collagen in deep tissue specimens are significant correlative factors in nonhealing of venous ulcers. We recommend deep debridement on all venous ulcers that are refractory to healing until the level of absence of dense fibrosis and mature collagen is reached to promote venous ulcer healing.
PMID: 22981433
ISSN: 1072-7515
CID: 182442
Impact of delay after biopsy and post-biopsy haemorrhage on prostate cancer tumour detection using multi-parametric MRI: A multi-reader study
Rosenkrantz, A B; Mussi, T C; Hindman, N; Lim, R P; Kong, M X; Babb, J S; Melamed, J; Taneja, S S
AIM: To assess impact of haemorrhage and delay after biopsy on prostate tumour detection using multi-parametric (MP) magnetic resonance imaging (MRI) assessment. MATERIALS AND METHODS: Forty-four patients underwent prostate MRI at 1.5 T using a pelvic phased-array coil, including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) imaging, before prostatectomy. Three radiologists independently reviewed images during four sessions [T2WI, DWI, DCE, and all parameters combined (MP-MRI)] to assess for tumour in each sextant. In a separate session, readers reviewed T1WI to score the extent of haemorrhage per sextant. Accuracy was assessed using logistic regression for correlated data. RESULTS: There was no significant difference in accuracy between readers for any session (p >/= 0.166), and results were averaged across the three readers for remaining comparisons. Accuracy was significantly greater for MP-MRI than for any parameter alone (p = 0.020). For T2WI alone, there was a trend toward decreased sensitivity in sextants with extensive haemorrhage (p = 0.072). However, accuracy, sensitivity, and specificity were otherwise similar for sextants with and without extensive haemorrhage for all sessions (p = 0.192-0.934). No session showed a significant improvement in accuracy, sensitivity, or specificity in cases with delay after biopsy of over 4 weeks compared with shorter delay. CONCLUSION: Extensive haemorrhage and short delay after biopsy did not negatively impact accuracy for tumour detection using MP-MRI. Further studies using MP-MRI protocols and interpretation schemes from other institutions are required to confirm these observations.
PMID: 22981729
ISSN: 0009-9260
CID: 182452
Histogram analysis of whole-lesion enhancement in differentiating clear cell from papillary subtype of renal cell cancer
Chandarana, Hersh; Rosenkrantz, Andrew B; Mussi, Thais C; Kim, Sooah; Ahmad, Afshan A; Raj, Sean D; McMenamy, John; Melamed, Jonathan; Babb, James S; Kiefer, Berthold; Kiraly, Atilla P
Purpose: To compare histogram analysis of voxel-based whole-lesion (WL) enhancement to qualitative assessment and region-of-interest (ROI)-based enhancement analysis in discriminating the renal cell cancer (RCC) subtype clear cell RCC (ccRCC) from papillary RCC (pRCC). Materials and Methods: In this institutional review board-approved, HIPAA-compliant retrospective study, 73 patients underwent magnetic resonance (MR) imaging prior to surgery for RCC between January 2007 and January 2010. Three-dimensional fat-suppressed T1-weighted gradient-echo corticomedullary phase acquisitions, obtained before and after contrast agent administration, were transferred to a workstation at which automated registration followed by semiautomated segmentation of the RCC was performed. Percent enhancement was computed on a per-voxel basis: (SI(post) - SI(pre))/SI(pre) .100, where SI(pre) and SI(post) indicate signal intensity before and after contrast enhancement, respectively. The WL quantitative parameters of mean, median, and third quartile enhancement and histogram distribution parameters kurtosis and skewness were computed for each lesion. WL enhancement parameters were compared with ROI-based analysis and qualitative assessment with regards to diagnostic accuracy and interreader agreement in differentiating ccRCC from pRCC. Results: There were 19 pRCCs and 55 ccRCCs at pathologic examination. ccRCC had significantly higher WL mean, median, and third quartile enhancement compared with pRCC and hade significantly lower kurtosis and skewness (all P < .001). Third quartile enhancement had the highest accuracy (94.6%; area under the curve, 0.980) in discriminating ccRCC from pRCC, which was significantly higher than the accuracy of qualitative assessment (86.0%; P = .04) but not significantly higher than that of ROI enhancement (89.2%; P = .52). WL enhancement parameters had higher interreader agreement (kappa = 0.91-1.0) compared with ROI enhancement or qualitative assessment (kappa = 0.83 and 0.7, respectively) in discriminating ccRCC from pRCC. Conclusion: WL enhancement histogram analysis is feasible and can potentially be used to differentiate ccRCC from pRCC with high accuracy. (c) RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12111281/-/DC1.
PMID: 23175544
ISSN: 0033-8419
CID: 185062
Angiomyolipoma with Minimal Fat: Can It Be Differentiated from Clear Cell Renal Cell Carcinoma by Using Standard MR Techniques?
Hindman, Nicole; Ngo, Long; Genega, Elizabeth M; Melamed, Jonathan; Wei, Jesse; Braza, Julia M; Rofsky, Neil M; Pedrosa, Ivan
Purpose: To retrospectively assess whether magnetic resonance (MR) imaging with opposed-phase and in-phase gradient-echo (GRE) sequences and MR feature analysis can differentiate angiomyolipomas (AMLs) that contain minimal fat from clear cell renal cell carcinomas (RCCs), with particular emphasis on small (<3-cm) masses. Materials and Methods: Institutional review board approval and a waiver of informed consent were obtained for this HIPAA-compliant study. MR images from 108 pathologically proved renal masses (88 clear cell RCCs and 20 minimal fat AMLs from 64 men and 44 women) at two academic institutions were evaluated. The signal intensity (SI) of each renal mass and spleen on opposed-phase and in-phase GRE images was used to calculate an SI index and tumor-to-spleen SI ratio. Two radiologists who were blinded to the pathologic results independently assessed the subjective presence of intravoxel fat (ie, decreased SI on opposed-phase images compared with that on in-phase images), SI on T1-weighted and T2-weighted images, cystic degeneration, necrosis, hemorrhage, retroperitoneal collaterals, and renal vein thrombosis. Results were analyzed by using the Wilcoxon rank sum test, two-tailed Fisher exact test, and multivariate logistic regression analysis for all renal masses and for small masses. A P value of less than .05 was considered to indicate a statistically significant difference. Results: There were no differences between minimal fat AMLs and clear cell RCCs for the SI index (8.05% +/- 14.46 vs 14.99% +/- 19.9; P = .146) or tumor-to-spleen ratio (-8.96% +/- 16.6 and -15.8% +/- 22.4; P = .227) when all masses or small masses were analyzed. Diagnostic accuracy (area under receiver operating characteristic curve) for the SI index and tumor-to-spleen ratio was 0.59. Intratumoral necrosis and larger size were predictive of clear cell RCC (P < .001) for all lesions, whereas low SI (relative to renal parenchyma SI) on T2-weighted images, smaller size, and female sex correlated with minimal fat AML (P < .001) for all lesions. Conclusion: The diagnostic accuracy of opposed-phase and in-phase GRE MR imaging for the differentiation of minimal fat AML and clear cell RCC is poor. In this cohort, low SI on T2-weighted images relative to renal parenchyma and small size suggested minimal fat AML, whereas intratumoral necrosis and large size argued against this diagnosis. (c) RSNA, 2012.
PMCID:3480813
PMID: 23012463
ISSN: 0033-8419
CID: 180602
Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma
Pass, Harvey I; Levin, Stephen M; Harbut, Michael R; Melamed, Jonathan; Chiriboga, Luis; Donington, Jessica; Huflejt, Margaret; Carbone, Michele; Chia, David; Goodglick, Lee; Goodman, Gary E; Thornquist, Mark D; Liu, Geoffrey; de Perrot, Marc; Tsao, Ming-Sound; Goparaju, Chandra
BACKGROUND: New biomarkers are needed to detect pleural mesothelioma at an earlier stage and to individualize treatment strategies. We investigated whether fibulin-3 in plasma and pleural effusions could meet sensitivity and specificity criteria for a robust biomarker. METHODS: We measured fibulin-3 levels in plasma (from 92 patients with mesothelioma, 136 asbestos-exposed persons without cancer, 93 patients with effusions not due to mesothelioma, and 43 healthy controls), effusions (from 74 patients with mesothelioma, 39 with benign effusions, and 54 with malignant effusions not due to mesothelioma), or both. A blinded validation was subsequently performed. Tumor tissue was examined for fibulin-3 by immunohistochemical analysis, and levels of fibulin-3 in plasma and effusions were measured with an enzyme-linked immunosorbent assay. RESULTS: Plasma fibulin-3 levels did not vary according to age, sex, duration of asbestos exposure, or degree of radiographic changes and were significantly higher in patients with pleural mesothelioma (105+/-7 ng per milliliter in the Detroit cohort and 113+/-8 ng per milliliter in the New York cohort) than in asbestos-exposed persons without mesothelioma (14+/-1 ng per milliliter and 24+/-1 ng per milliliter, respectively; P<0.001). Effusion fibulin-3 levels were significantly higher in patients with pleural mesothelioma (694+/-37 ng per milliliter in the Detroit cohort and 636+/-92 ng per milliliter in the New York cohort) than in patients with effusions not due to mesothelioma (212+/-25 and 151+/-23 ng per milliliter, respectively; P<0.001). Fibulin-3 preferentially stained tumor cells in 26 of 26 samples. In an overall comparison of patients with and those without mesothelioma, the receiver-operating-characteristic curve for plasma fibulin-3 levels had a sensitivity of 96.7% and a specificity of 95.5% at a cutoff value of 52.8 ng of fibulin-3 per milliliter. In a comparison of patients with early-stage mesothelioma with asbestos-exposed persons, the sensitivity was 100% and the specificity was 94.1% at a cutoff value of 46.0 ng of fibulin-3 per milliliter. Blinded validation revealed an area under the curve of 0.87 for plasma specimens from 96 asbestos-exposed persons as compared with 48 patients with mesothelioma. CONCLUSIONS: Plasma fibulin-3 levels can distinguish healthy persons with exposure to asbestos from patients with mesothelioma. In conjunction with effusion fibulin-3 levels, plasma fibulin-3 levels can further differentiate mesothelioma effusions from other malignant and benign effusions. (Funded by the Early Detection Research Network, National Institutes of Health, and others.).
PMCID:3761217
PMID: 23050525
ISSN: 0028-4793
CID: 179282