D N Silvers

CUNY Graduate Center, New York City, New York, United States

Are you D N Silvers?

Claim your profile

Publications (88)365.6 Total impact

  • Leukemia & lymphoma. 10/2014;
  • M M Levender, D N Silvers, M E Grossman
    [Show abstract] [Hide abstract]
    ABSTRACT: IgA gammopathy and multiple myeloma have been associated with multiple neutrophilic dermatoses including subcorneal pustular dermatosis(1-4) erythema elevatum diutinum(5) , urticarial vasculitis,(6) Sweet's syndrome(7) and pyoderma gangrenosum.(8) We report an unusual urticaria-like neutrophilic dermatosis as the presenting sign of IgA myeloma. An 84 year old woman with cardiomyopathy, atrial fibrillation, rectal cancer in remission, and hypertension was admitted for syncope. She reported bone pain and an intermittent rash over the preceding months. Laboratory studies were notable for normocytic anemia, normal white blood cell count negative serologies for HTLV-1, RPR, hepatitis, and HIV, widespread osteolytic lesions on skeletal survey, elevated serum IgA (1080 mg/dL, normal: 70-350), decreased serum IgG (599 mg/dL, normal: 700-1700) and IgM (<6.5 mg/dL, normal: 50-300) and a monoclonal IgA Kappa on serum protein electrophoresis consistent with plasma cell dyscrasia and confirmed with bone marrow biopsy, demonstrating 15% atypical plasma cells. This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 12/2013; · 3.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The PI3K pathway is deregulated in a significant proportion of melanomas, and PI3K pathway activation in combination with constitutively active MAPK signaling shows synergistic effects in the process of melanoma tumorigenesis. Recently, a tumor suppressor function for the lipid phosphatase INPP4B has been described in breast and prostate cancer with impact on PI3K signaling output. Given the importance of PI3K pathway activity for melanoma formation and growth, we aimed to assess the role of INPP4B in melanocytic tumors. Our studies suggest that decreased INPP4B expression is an event correlating with aggressive melanocytic neoplasms in native tumors. We further demonstrate that INPP4B regulates PI3K/Akt signaling and exerts a tumor suppressor effect in melanocytic cells, impacting on the proliferative, invasive and tumorigenic capacity of the melanoma phenotype. INPP4B expression in melanocytic neoplasms may therefore have potential as a biomarker for disease progression and as a modulator for the prediction of treatment outcome.Journal of Investigative Dermatology accepted article preview online, 28 November 2013. doi:10.1038/jid.2013.511.
    Journal of Investigative Dermatology 11/2013; · 6.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The diagnosis of Spitz nevus in an elderly individual is often met with skepticism because the lesion can be difficult to distinguish from melanoma and because the probability of a malignant melanoma is higher in older patients. Recently, increased sensitivity for detection of malignant spitzoid neoplasms using 9p21 fluorescence in situ hybridization (FISH) has been described. In this study, we address the question of whether histopathologically typical Spitz nevi occurring in patients 50 years and older show any abnormalities regarding the 9p21 CDKN2A tumor suppressor gene locus. p16 immunohistochemistry (IHC), as well as dual-color FISH for assessment of diploid or hypodiploid status at 9p21, was performed in 25 classic Spitz nevi from patients 50 years and older and was compared with findings in a younger control population. All cases of typical Spitz nevi occurring in older patients retained p16 expression by immunohistochemistry and showed normal, diploid 9p21 FISH signals. Heterozygous loss of 9p21 by FISH was noted in a control case of a 9-year-old girl and is of unknown significance. These findings indicate that p16 expression by immunohistochemistry in classic Spitz nevi correlates well with absence of malignancy-associated cytogenetic abnormalities at 9p21 by FISH independent of the patient's age. Assessment of p16 expression by standard immunohistochemistry may therefore be reassuring in routine clinical practice when the patient is of advanced age, and can be helpful as a screening tool to select IHC-negative cases for extended FISH analysis targeting the 9p21 gene locus.
    Human pathology 10/2013; · 3.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Spindle cell melanoma and desmoplastic melanoma differ clinically in prognosis and therapeutic implications; however, because of partially overlapping histopathological features, diagnostic distinction of spindle cell from desmoplastic melanoma is not always straightforward. A direct comparison of diagnostic and therapeutic biomarkers has not been performed. Meta-review of the literature discloses key clinicopathological differences between spindle cell and desmoplastic melanoma, including immunophenotypes. Using 50 biomarkers available in routine diagnostics, we examined 38 archival cases (n=16 spindle, 18 desmoplastic, 4 mixed spindle/desmoplastic melanoma). S100 remains as the most reliable routine marker to reach the diagnosis of melanoma in spindle cell and desmoplastic melanoma. We identified nine distinctly labeling markers with spindle cell melanoma showing positivity for laminin, p75, HMB45, c-kit, and MelanA, and desmoplastic melanoma preferentially labeling with collagen IV, trichrome, CD68, and MDM2. On the basis of comparisons of test performance measures, MelanA and trichrome were used to devise a 94% sensitive diagnostic algorithm for the distinction of desmoplastic from spindle cell melanoma. Gene amplification and expression status was assessed for a set of potentially drugable targets (HER2, EGFR, MET, MDM2, TP53, ALK, MYC, FLI-1, and KIT). Fluorescent in situ hybridizations did not reveal a significant number of gene aberrations/rearrangements; however, protein overexpression for at least one of these markers was identified in 35 of 38 cases (92%). In addition, we found BRAF mutations in 31% of spindle cell and 5% of desmoplastic melanoma, with an overall mutation frequency of 16% (n=6/38). We present the first comprehensive screening study of diagnostic and therapeutic biomarkers in spindle cell and desmoplastic melanoma. The devised algorithm allows diagnostic distinction of desmoplastic from spindle cell melanoma when routine histology is not decisive.Modern Pathology advance online publication, 20 September 2013; doi:10.1038/modpathol.2013.162.
    Modern Pathology 09/2013; · 5.25 Impact Factor
  • Sameera Husain, David N Silvers
    Journal of Cutaneous Pathology 07/2013; · 1.77 Impact Factor
  • International journal of dermatology 01/2013; · 1.18 Impact Factor
  • Basil A. Horst, G. William Niedt, David N. Silvers
    Journal of the American Academy of Dermatology 11/2012; 67(5):1068. · 4.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE To investigate whether Spitz nevi with typical histopathological features in older patients demonstrate chromosomal aberrations by 4-color fluorescence in situ hybridization (FISH). DESIGN Retrospective medical record review, with prospective masked histopathological and cytogenetic analyses. SETTING University-affiliated dermatology and dermatopathology setting. PATIENTS Twenty-five patients 50 years or older with melanocytic nevi showing histopathological features typical of Spitz nevi. MAIN OUTCOME MEASURES Three dermatopathologists masked to the patients' ages reviewed histopathological sections of melanocytic lesions for features typical of Spitz nevi. FISH was performed on samples with typical histopathological features by a 4-color FISH probe set used for the evaluation of malignant melanocytic neoplasms. RESULTS None of the study cases showing histopathological features typical of Spitz nevi had detectable chromosomal abnormalities by FISH. CONCLUSIONS Spitz nevi in older patients demonstrate molecular features similar to those of Spitz nevi in younger age groups. The findings of normal karyotypes in combination with typical histopathological features are reassuring of Spitz nevus diagnoses in older patients and suggest no correlation of increased malignant potential with advanced age per se.
    Archives of dermatology 10/2012; 148(10):1152-6. · 4.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: GAB2 is a scaffold protein with diverse upstream and downstream effectors. MAPK and PI3K signaling pathways are known effectors of GAB2. It is amplified and overexpressed in a variety of human tumors including melanoma. Here we show a previously undescribed role for GAB2 in NRAS-driven melanoma. Specifically, we found that GAB2 is co-expressed with mutant NRAS in melanoma cell lines and tumor samples and its expression correlated with metastatic potential. Co-expression of GAB2(WT) and NRAS(G12D) in melanocytes and in melanoma cells increased anchorage-independent growth by providing GAB2-expressing cells a survival advantage through upregulation of BCL-2 family of anti-apoptotic factors. Of note, collaboration of GAB2 with mutant NRAS enhanced tumorigenesis in vivo and led to an increased vessel density with strong CD34 and VEGFR2 activity. We found that GAB2 facilitiated an angiogenic switch by upregulating HIF-1α and VEGF levels. This angiogenic response was significantly suppressed with the MEK inhibitor PD325901. These data suggest that GAB2-mediated signaling cascades collaborate with NRAS-driven downstream activation for conferring an aggressive phenotype in melanoma. Second, we show that GAB2/NRAS signaling axis is non-linear and non-redundant in melanocytes and melanoma, and thus are acting independent of each other. Finally, we establish a link between GAB2 and angiogenesis in melanoma for the first time. In conclusion, our findings provide evidence that GAB2 is a novel regulator of tumor angiogenesis in NRAS-driven melanoma through regulation of HIF-1α and VEGF expressions mediated by RAS-RAF-MEK-ERK signaling.Oncogene advance online publication, 27 August 2012; doi:10.1038/onc.2012.367.
    Oncogene 08/2012; · 8.56 Impact Factor
  • Cutis; cutaneous medicine for the practitioner 04/2012; 89(4):173-4. · 0.82 Impact Factor
  • David N Silvers
    Journal of Cutaneous Pathology 03/2011; 38(3):320. · 1.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Improvements in imaging technologies have dramatically increased the ability to accurately diagnose and treat many urological disease processes. As urological patients often have chronic kidney disease, the well characterized nephrotoxicity of contrast induced nephropathy when using iodine based contrast materials has long been a concern. With the development of gadolinium based contrast agents it seemed that the concern regarding nephrotoxicity had been resolved. In 1997 a new disorder, nephrogenic systemic fibrosis, appeared in patients with severe renal failure. Nephrogenic systemic fibrosis is a serious and potentially devastating disorder characterized by progressive thickening and hardening of the skin and other body tissues, and complicated by flexion contractures of the joints. We performed a survey of the available literature on nephrogenic systemic fibrosis and magnetic resonance contrast media. We focused on mechanisms in the development of nephrogenic systemic fibrosis as well as its association with magnetic resonance contrast media, disease treatment and prevention, and its relevance to clinical urology. An association between nephrogenic systemic fibrosis and gadolinium based contrast agents has been reported. Gadolinium is a toxic metal and it must be chelated to be a safe injectable contrast agent. It is now hypothesized that the majority of nephrogenic systemic fibrosis cases present with gadolinium based contrast agent exposure as the triggering factor, although this mechanism has not been elucidated. As gadolinium enhanced magnetic resonance imaging is an important tool in the diagnosis and surveillance of urological diseases, the severe consequences of nephrogenic systemic fibrosis demand that practicing urologists understand and know its history and treatment strategies. This review provides clarification of the gadolinium based contrast agent characteristics, tissue interactions that lead to the development of nephrogenic systemic fibrosis, prevention possibilities and available treatment options.
    The Journal of urology 11/2009; 183(1):27-33. · 3.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Premature ageing of the skin (photoageing) results from the action of ultraviolet radiation (UVR) on skin. One of the histopathological findings of photoageing is the presence of solar elastosis in the dermis. Skin pigmentation is protective against UVR. To evaluate the presence of solar elastosis in dark-skinned people. Normal facial skin biopsies of 147 dark-skinned and 140 light-skinned people were examined histopathologically for solar elastosis. The degree of solar elastosis was graded on a five-point scale by a panel of dermatopathologists blinded to patient demographics. There were 112 of 140 (80%) light-skinned and 50 of 147 (34%) dark-skinned patients with high-grade solar elastosis. In the dark-skinned patient group, high-grade solar elastosis was seen in 29 of 61 (47.5%) Hispanic and 5 of 49 (10.2%) African American subjects. Dark-skinned people are not completely protected from the effects of UVR.
    Clinical and Experimental Dermatology 10/2009; 35(4):392-6. · 1.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this article is to review the current knowledge about nephrogenic systemic fibrosis (NSF) and how to prevent it. More than 300 cases of NSF in patients with severe chronic renal insufficiency or acute renal failure or in patients undergoing dialysis have been reported in the peer-reviewed literature, with an overwhelming majority occurring within weeks to months after injection of a gadolinium-based contrast agent (GBCA). Because administration of a high dose of a GBCA is a primary risk factor and because most high-dose magnetic resonance (MR) imaging applications involve abdominal imaging (eg, liver and abdominal MR angiography), NSF cases have been associated with abdominal MR imaging. Additional major risk factors for developing NSF include proinflammatory conditions, failure to perform dialysis promptly after GBCA administration, use of nonionic linear contrast agents, hyperphosphatemia, and younger age. Recent recommendations to use GBCAs with caution in patients with acute renal failure, patients receiving dialysis, or patients with an estimated glomerular filtration rate of less than 30 mL/min have resulted in virtually no new NSF cases being reported with onset in 2008 or 2009 in spite of a high level of awareness about this entity. In conclusion, NSF has been virtually eliminated by using caution in administering GBCAs to patients known to have severe or acute renal failure. In these patients, avoid high doses; and for patients undergoing dialysis, schedule MR imaging to occur just before a dialysis session to ensure rapid elimination of gadolinium.
    Radiographics 10/2009; 29(6):1565-74. · 2.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: The objective of this article is to illustrate the spectrum of imaging findings with photographic and histopathologic correlation in patients with biopsy-proven nephrogenic systemic fibrosis (NSF). CONCLUSION: Features of NSF may be evident on the patient's skin as well as on routine imaging studies, although these imaging findings are nonspecific and are more likely to occur with other diseases.
    American Journal of Roentgenology 08/2009; 193(1):61-9. · 2.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Gain-of-function mutations in BRAF, NRAS, or KIT are associated with distinct melanoma subtypes with KIT mutations and/or copy number changes frequently observed among melanomas arising from sun-protected sites, such as acral skin (palms, soles, and nail bed) and mucous membranes. GAB2 has recently been implicated in melanoma pathogenesis, and increased copy numbers are found in a subset of melanomas. We sought to determine the association of increased copy numbers of GAB2 among melanoma subtypes in the context of genetic alterations in BRAF, NRAS, and KIT. A total of 85 melanomas arising from sun-protected (n = 23) and sun-exposed sites (n = 62) were analyzed for copy number changes using array-based comparative genomic hybridization and for gain-of-function mutations in BRAF, NRAS, and KIT. GAB2 amplifications were found in 9% of the cases and were associated with melanomas arising from acral and mucosal sites (P = 0.005). Increased copy numbers of the KIT locus were observed in 6% of the cases. The overall mutation frequencies for BRAF and NRAS were 43.5% and 14%, respectively, and were mutually exclusive. Among the acral and mucosal melanomas studied, the genetic alteration frequency was 26% for GAB2, 13% for KIT, 30% for BRAF, and 4% for NRAS. Importantly, the majority of GAB2 amplifications occurred independent from genetic events in BRAF, NRAS, and KIT. GAB2 amplification is critical for melanomas arising from sun-protected sites. Genetic alterations in GAB2 will help refine the molecular classification of melanomas.
    Clinical Cancer Research 07/2009; 15(13):4288-91. · 7.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Intravascular breast cancer metastases to the skin can have several clinically distinct manifestations. Carcinoma telangiectoides, which presents as an erythematous patch with prominent telangiectasias or lymphangioma circumscriptum-like lesions, is a rare manifestation of cutaneous metastatic breast cancer and has been proposed to spread via dermal blood vessels. Carcinoma erysipelatoides, which presents as an erysipelas-like patch or plaque, has been proposed to spread via lymphatics. Clinical variants with nodular lesions that show tumor cells within vessels and in the extravascular space are seen more commonly. It has not been demonstrated conclusively whether dermal blood vessels or whether dermal lymph vessels are principally involved in these clinically distinct forms of cutaneous breast cancer metastases. We sought to determine if carcinoma telangiectoides affects predominantly dermal blood vessels and if carcinoma erysipelatoides affects predominantly dermal lymph vessels. Serial sections of biopsy specimens from patients with a characteristic clinical presentation of carcinoma telangiectoides and carcinoma erysipelatoides were labeled for cytokeratin to identify malignant cells. Subsequently, these sections were labeled for CD31 (a marker for blood and lymph vessels) and podoplanin (a marker for lymph vessels, but not for blood vessels), to differentiate blood vessels from lymph vessels in these sections. Sections from carcinoma telangiectoides showed malignant tumor cells strictly within dermal blood vessels, but not in lymph vessels. In contrast, sections from carcinoma erysipelatoides showed malignant tumor cells strictly in dermal lymphatics. We used typical clinical cases to demonstrate the distinct involvement of blood and lymph vessels in these variants of cutaneous metastatic breast cancer. A larger case series is needed to confirm these findings. Immunolabeling for CD31 and podoplanin of cutaneous lesions of metastatic breast cancer confirms the spread of tumor cells predominantly via lymphatics in carcinoma erysipelatoides and predominantly via blood vessels in carcinoma telangiectoides.
    Journal of the American Academy of Dermatology 05/2009; 60(4):633-8. · 4.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pralatrexate is a novel antifolate, which shows increased antitumor activity in human tumor xenograft studies in mice compared with methotrexate. We investigated the effects of pralatrexate in a patient with adult T-cell lymphoma/leukemia with significant skin involvement. Atypical lymphocytes in epidermal Pautrier microabscesses were positive for HTLV-1. After the patient presented with leukemic conversion and with worsening of an erythematous generalized papular rash, he received one dose of pralatrexate. Within one week, his skin developed innumerable small erosions limited to the areas of the papular rash, sparing unaffected skin. Here we present in vivo evidence that pralatrexate-induced erosions in skin affected by adult T-cell lymphoma/leukemia are a manifestation of apoptosis of tumor cells infiltrating the epidermis and are not the result of cytotoxicity by pralatrexate on keratinocytes. This distinction is critical and may profoundly influence the clinical decision to continue pralatrexate treatment. Pralatrexate-induced skin erosions may indicate response to treatment.
    Blood 05/2009; 113(25):6338-41. · 9.78 Impact Factor
  • Journal of Cardiovascular Magnetic Resonance 01/2009; · 4.44 Impact Factor

Publication Stats

915 Citations
365.60 Total Impact Points

Institutions

  • 1991–2013
    • CUNY Graduate Center
      New York City, New York, United States
  • 1989–2013
    • New York Presbyterian Hospital
      • • Department of Dermatology
      • • Department of Cardiology
      • • Department of Pathology
      New York City, New York, United States
  • 1981–2013
    • Columbia University
      • • Department of Dermatology
      • • College of Physicians and Surgeons
      New York City, NY, United States
  • 2009
    • Cornell University
      • Department of Radiology
      Ithaca, NY, United States
  • 1992
    • University of Texas Medical School
      • Department of Dermatology
      Houston, Texas, United States