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Sample records for melanomas uveales posteriores

  1. Regression of posterior uveal melanomas following cobalt-60 plaque radiotherapy

    SciTech Connect

    Cruess, A.F.; Augsburger, J.J.; Shields, J.A.; Brady, L.W.; Markoe, A.M.; Day, J.L.

    1984-12-01

    A method has been devised for evaluating the rate and extent of regression of the first 100 consecutive patients with a posterior uveal melanoma that had been managed by Cobalt-60 plaque radiotherapy at Wills Eye Hospital. It was found that the average posterior uveal melanoma in the series did not regress rapidly to a flat, depigmented scar but shrank slowly and persisted as a residual mass approximately 50% of the thickness of the original tumor at 54 months following Cobalt-60 plaque radiotherapy. The authors also found that the rate and extent of regression of the tumors in patients who subsequently developed metastatic melanoma were not appreciably different from the rate and extent of regression of the tumors in patients who remained well systemically. These observations indicate that the rate and extent of regression of posterior uveal melanomas following Cobalt-60 plaque radiotherapy are poor indicators of the prognosis of the affected patients for subsequent development of clinical metastatic disease.

  2. Iodine-125 radiation of posterior uveal melanoma

    SciTech Connect

    Packer, S.

    1987-12-01

    Twenty-eight cases of posterior choroidal melanoma were treated with iodine-125 in gold eye plaques. Eleven cases were located within 3.0 mm of the optic nerve (group A), nine were within 3.0 mm of the fovea (group B), and eight were within 3.0 mm of the optic nerve and fovea (group C). The mean follow-up of group A was 46.3 months; group B, 25.5 months; and group C, 42.7 months. Complications included macular edema, cataract and tumor growth. Visual acuity remained within two lines of that tested preoperatively for 4 of 11 patients in group A, 4 of 9 in group B, and 5 of 8 in group C. These results with iodine-125 suggest it as an appropriate treatment for patients with choroidal melanoma located near optic nerve and/or macula.

  3. Cobalt plaque therapy of posterior uveal melanomas

    SciTech Connect

    Shields, J.A.; Augsburger, J.J.; Brady, L.W.; Day, J.L.

    1982-10-01

    One hundred patients with choroidal melanomas who were treated by the authors with cobalt plaque radiotherapy were analyzed with regard to tumor regression, visual results, complications, and mortality rate. The follow-up period at the time of this writing ranged from one to five years. These preliminary observations indicate that cobalt plaque radiotherapy induces tumor regression in 96% of cases, preserves useful vision in many cases and has fewer complications during the one- to five-year follow-up period than previously believed.

  4. Association of specific chromosome alterations with tumour phenotype in posterior uveal melanoma

    PubMed Central

    Sisley, K; Parsons, M A; Garnham, J; Potter, A M; Curtis, D; Rees, R C; Rennie, I G

    2000-01-01

    Posterior uveal melanomas have recurrent alterations of chromosomes 1, 3, 6 and 8. In particular, changes of chromosomes 3 and 8 occur in association, appear to characterize those tumours with a ciliary body component, and have been shown to be of prognostic significance. The relevance of other chromosome alterations is less certain. We have performed cytogenetic analysis on 42 previously untreated primary posterior uveal melanomas. Of interest was the observation that as tumour size increased the involvement of specific chromosome changes, and the amount of chromosome abnormalities likewise increased. Loss, or partial deletions, of the short arm of chromosome 1 were found to associate with larger ciliary body melanomas; typically, loss of the short arm resulted from unbalanced translocations, the partners of which varied. Trisomy of chromosome 21 occurred more often in ciliary body melanomas, whilst rearrangements of chromosomes 6 and 11 were primarily related to choroidal melanomas. Our results imply that alterations of chromosome 1 are important in the progression of some uveal melanomas, and that other chromosome abnormalities, besides those of chromosomes 3 and 8, are associated with ocular tumours of particular locations. © 2000 Cancer Research Campaign PMID:10646885

  5. Cobalt-60 plaque radiotherapy vs enucleation for posterior uveal melanoma

    SciTech Connect

    Augsburger, J.J.; Gamel, J.W.; Lauritzen, K.; Brady, L.W. )

    1990-05-15

    We compared the survival of 302 patients with a primary choroidal or ciliary body melanoma treated by cobalt-60 plaque radiotherapy between 1976 and 1982 with the survival of 134 patients treated by enucleation during the same period. Tumor size, location of the anterior margin of the tumor, and patient age at the time of treatment were identified as simultaneous significant clinical variables for predicting melanoma-specific mortality by multivariate Cox proportional hazards modeling. We computed a prognostic index for each patient based on this model and found that patients in the enucleation group had slightly higher values of this index than did patients in the cobalt-60 plaque radiotherapy group. Risk ratios for the treatment effect computed from a Cox model incorporating prognostic index and the treatment variable were found to be approximately equal to 1, both for analysis of melanoma-specific mortality and total mortality. These results indicate that when one controls for differences in prognostic index between the groups, cobalt-60 plaque therapy and enucleation are essentially equivalent in their effect on survival.

  6. Uveal melanoma: estimating prognosis.

    PubMed

    Kaliki, Swathi; Shields, Carol L; Shields, Jerry A

    2015-02-01

    Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately. PMID:25827538

  7. Uveal melanoma: Estimating prognosis

    PubMed Central

    Kaliki, Swathi; Shields, Carol L; Shields, Jerry A

    2015-01-01

    Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms “uvea,” “iris,” “ciliary body,” “choroid,” “melanoma,” “uveal melanoma” and “prognosis,” “metastasis,” “genetic testing,” “gene expression profiling.” Relevant English language articles were extracted, reviewed, and referenced appropriately. PMID:25827538

  8. Culturing Uveal Melanoma Cells.

    PubMed

    Angi, Martina; Versluis, Mieke; Kalirai, Helen

    2015-04-01

    A major challenge in cancer research is the use of appropriate models with which to study a specific biological question. Cell lines have long been used to study cellular processes and the effects of individual molecules because they are easy to use, grow rapidly, produce reproducible results and have a strong track record in research. In uveal melanoma in particular, the absence of animal models that faithfully replicate the behavior of the human disease has propagated the generation and use of numerous cell lines by individual research groups. This in itself, however, can be viewed as a problem due to the lack of standardization when characterizing these entities to determine how closely they reflect the genetic and phenotypic characteristics of this disease. The alternative is to use in vitro primary cultures of cells obtained directly from uveal melanoma patient samples, but this too has its difficulties. Primary cell cultures are difficult to use, hard to obtain and can show considerable heterogeneity. In this article, we review the following: (1) the uveal melanoma cell lines that are currently available, discussing the importance of establishing a bank of those that represent the molecular heterogeneity of uveal melanoma; (2) the methods used to isolate and perform short-term cultures of primary uveal melanoma cells, and (3) the establishment of 3D tissue culture models that bridge the gap between 2D in vitro systems and in vivo models with which to dissect cancer biology and perform therapeutic screens. PMID:27171555

  9. Cell proliferation activity in posterior uveal melanoma after Ru-106 brachytherapy: an EORTC ocular oncology group study

    PubMed Central

    Pe'er, J.; Stefani, F.; Seregard, S.; Kivela, T.; Lommatzsch, P.; Prause, J.; Sobottka, B.; Damato, B.; Chowers, I.

    2001-01-01

    AIM—To evaluate the cell proliferation activity in posterior uveal melanomas after Ru-106 brachytherapy.
METHODS—Eyes containing choroidal or ciliary body melanoma from seven ocular oncology centres, which were enucleated after first being treated by Ru-106 brachytherapy and which had enough melanoma tissue to enable histological assessment, were included. The 57 eligible specimens were divided into a group of 44 eyes that were enucleated because of tumour regrowth, and a non-recurrent group of 13 eyes that were enucleated because of complications such as neovascular glaucoma. 46 non-irradiated eyes harbouring uveal melanoma served as a control group. All specimens underwent routine processing. They were cut into 5 µm sections, and were stained with two main cell proliferation markers: PC-10 for PCNA and MIB-1 for Ki-67. The stained sections were assessed, and the cells that were positive in the immunostaining were counted in each section. The results were evaluated by various statistical methods.
RESULTS—The PC-10 score showed a statistically significant difference across the three groups (p = 0.002). The control group showed the highest PC-10 score (median 31.0 PCC/HPF) followed by the tumour regrowth group (median 4.9 PCC/HPF). The lowest PC-10 scores were found in the non-recurrent tumours (median 0.05 PCC/HPF). The MIB-1 score in the control group (median 5.77 PCC/HPF) was similar to the regrowth group (median 5.4 PCC/HPF). In contrast, the MIB-1 score in the non-recurrent tumours was statistically significantly lower (median 0.42 PCC/HPF). The PC-10 and MIB-1 scores were similar in tumours composed of either spindle cells or epithelioid cells in all groups.
CONCLUSIONS—The non-recurrent melanomas demonstrate significantly lower cellular proliferation activity than melanomas that showed regrowth or that were not irradiated at all. In our hands, PCNA gave more meaningful information than Ki-67. Our findings strongly support the need

  10. Malignant melanoma of the eye: treatment of posterior uveal lesions by Co-60 plaque radiotherapy versus enucleation

    SciTech Connect

    Markoe, A.M.; Brady, L.W. Jr.; Shields, J.A.; Augsburger, J.J.; Micaily, B.; Damsker, J.I.; Day, J.L.; Gamel, J.W.

    1985-09-01

    Survival rates and visual acuity of 100 patients treated for posterior uveal malignant melanoma by cobalt-60 plaque radiotherapy were compared with 150 patients treated by enucleation for the same disease. Life-table comparisons of the entire group showed significant differences in survival rates, with plaque radiotherapy patients appearing to fare better. However, when patients with small or medium tumors were compared, only slight differences were seen, implying that criteria used to select patients for treatment may affect interpretation. The two groups were also compared using the Cox proportional hazards model, which predicts survival based on the impact of clinical variables. In this analysis, the survival rates of the plaque radiotherapy group were no worse than those of the enucleation group. The advantage of conservative therapy lies in the potential to preserve useful vision over a considerable time.

  11. Brachytherapy treatment simulation of strontium-90 and ruthenium-106 plaques on small size posterior uveal melanoma using MCNPX code

    NASA Astrophysics Data System (ADS)

    Barbosa, N. A.; da Rosa, L. A. R.; Facure, A.; Braz, D.

    2014-02-01

    Concave eye applicators with 90Sr/90Y and 106Ru/106Rh beta-ray sources are usually used in brachytherapy for the treatment of superficial intraocular tumors as uveal melanoma with thickness up to 5 mm. The aim of this work consisted in using the Monte Carlo code MCNPX to calculate the 3D dose distribution on a mathematical model of the human eye, considering 90Sr/90Y and 160Ru/160Rh beta-ray eye applicators, in order to treat a posterior uveal melanoma with a thickness 3.8 mm from the choroid surface. Mathematical models were developed for the two ophthalmic applicators, CGD produced by BEBIG Company and SIA.6 produced by the Amersham Company, with activities 1 mCi and 4.23 mCi respectively. They have a concave form. These applicators' mathematical models were attached to the eye model and the dose distributions were calculated using the MCNPX *F8 tally. The average doses rates were determined in all regions of the eye model. The *F8 tally results showed that the deposited energy due to the applicator with the radionuclide 106Ru/106Rh is higher in all eye regions, including tumor. However the average dose rate in the tumor region is higher for the applicator with 90Sr/90Y, due to its high activity. Due to the dosimetric characteristics of these applicators, the PDD value for 3 mm water is 73% for the 106Ru/106Rh applicator and 60% for 90Sr/90Y applicator. For a better choice of the applicator type and radionuclide it is important to know the thickness of the tumor and its location.

  12. General Information about Intraocular (Uveal) Melanoma

    MedlinePlus

    ... Intraocular (Uveal) Melanoma Treatment (PDQ®)–Patient Version General Information About Intraocular (Uveal) Melanoma Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  13. Recurrence of posterior uveal melanoma after /sup 60/Co episcleral plaque therapy

    SciTech Connect

    Karlsson, U.L.; Augsburger, J.J.; Shields, J.A.; Markoe, A.M.; Brady, L.W.; Woodleigh, R.

    1989-03-01

    The authors analyzed the clinical and follow-up data on 277 selected patients with primary choroidal or ciliochoroidal melanoma who were treated with /sup 60/Co plaque radiotherapy between 1976 and 1982. Local recurrence of the irradiated melanoma developed in 39 (14%) patients during the follow-up interval. The 5-year tumor recurrence rate (Kaplan-Meier) was estimated to be 12%. Multivariate prognostic factor analysis (Cox proportional hazards modeling) identified the largest linear tumor dimension and proximity of the posterior margin of the tumor to the optic nerve head as predictors of recurrence. The 5-year survival rate of patients whose tumors recurred (58%) was significantly (log-rank test P = 0.0023) worse than that of patients whose tumor remained clinically controlled (82%).

  14. Uveal Melanoma UK National Guidelines.

    PubMed

    Nathan, P; Cohen, V; Coupland, S; Curtis, K; Damato, B; Evans, J; Fenwick, S; Kirkpatrick, L; Li, O; Marshall, E; McGuirk, K; Ottensmeier, C; Pearce, N; Salvi, S; Stedman, B; Szlosarek, P; Turnbull, N

    2015-11-01

    The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website. PMID:26278648

  15. Animal Eye Models for Uveal Melanoma

    PubMed Central

    Cao, Jinfeng; Jager, Martine J.

    2015-01-01

    Animal models play an important role in understanding tumor growth and may be used to develop novel therapies against human malignancies. The significance of the results from animal experiments depends on the selection of the proper model. Many attempts have been made to create appropriate animal models for uveal melanoma and its characteristic metastatic behavior. One approach is to use transgenic animal models or to implant tumor cells. A variety of tumor types have been used for this purpose: tumor cells, such as Greene melanoma, murine B16 melanoma, and human uveal melanoma cells, may be implanted in the eyes of hamsters, rats, rabbits, and mice, among others. Various inoculation routes, including into the anterior chamber and posterior compartment, and retro-orbitally, have been applied to obtain tumor growth mimicking ocular uveal melanoma. However, when we choose animal models, we must be conscious of many disadvantages, such as variable tumor growth, or the need for immunosuppression in xenogeneic grafts. In this paper, we will discuss the various eye models. PMID:27172424

  16. Animal Eye Models for Uveal Melanoma.

    PubMed

    Cao, Jinfeng; Jager, Martine J

    2015-04-01

    Animal models play an important role in understanding tumor growth and may be used to develop novel therapies against human malignancies. The significance of the results from animal experiments depends on the selection of the proper model. Many attempts have been made to create appropriate animal models for uveal melanoma and its characteristic metastatic behavior. One approach is to use transgenic animal models or to implant tumor cells. A variety of tumor types have been used for this purpose: tumor cells, such as Greene melanoma, murine B16 melanoma, and human uveal melanoma cells, may be implanted in the eyes of hamsters, rats, rabbits, and mice, among others. Various inoculation routes, including into the anterior chamber and posterior compartment, and retro-orbitally, have been applied to obtain tumor growth mimicking ocular uveal melanoma. However, when we choose animal models, we must be conscious of many disadvantages, such as variable tumor growth, or the need for immunosuppression in xenogeneic grafts. In this paper, we will discuss the various eye models. PMID:27172424

  17. CDX-1401 and Poly-ICLC Vaccine Therapy With or Without CDX-301in Treating Patients With Stage IIB-IV Melanoma

    ClinicalTrials.gov

    2016-06-21

    Carcinoma of Unknown Primary Origin; Iris Melanoma; Medium/Large Size Posterior Uveal Melanoma; Mucosal Melanoma; Ocular Melanoma With Extraocular Extension; Small Size Posterior Uveal Melanoma; Stage IIB Skin Melanoma; Stage IIB Uveal Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIA Uveal Melanoma; Stage IIIB Skin Melanoma; Stage IIIB Uveal Melanoma; Stage IIIC Skin Melanoma; Stage IIIC Uveal Melanoma; Stage IV Skin Melanoma; Stage IV Uveal Melanoma

  18. Tumor Cell Plasticity in Uveal Melanoma

    PubMed Central

    Folberg, Robert; Arbieva, Zarema; Moses, Jonas; Hayee, Amin; Sandal, Tone; Kadkol, ShriHari; Lin, Amy Y.; Valyi-Nagy, Klara; Setty, Suman; Leach, Lu; Chévez-Barrios, Patricia; Larsen, Peter; Majumdar, Dibyen; Pe’er, Jacob; Maniotis, Andrew J.

    2006-01-01

    The histological detection of laminin-rich vasculogenic mimicry patterns in human primary uveal melanomas is associated with death from metastases. We therefore hypothesized that highly invasive uveal melanoma cells forming vasculogenic mimicry patterns after exposure to a laminin-rich three-dimensional microenvironment would differentially express genes associated with invasive and metastatic behavior. However, we discovered that genes associated with differentiation (GDF15 and ATF3) and suppression of proliferation (CDKNa1/p21) were up-regulated in highly invasive uveal melanoma cells forming vasculogenic mimicry patterns, and genes associated with promotion of invasive and metastatic behavior such as CD44, CCNE2 (cyclin E2), THBS1 (thrombospondin 1), and CSPG2 (chondroitin sulfate proteoglycan; versican) were down-regulated. After forming vasculogenic mimicry patterns, uveal melanoma cells invaded only short distances, failed to replicate, and changed morphologically from the invasive epithelioid to the indolent spindle A phenotype. In human tissue samples, uveal melanoma cells within vasculogenic mimicry patterns assumed the spindle A morphology, and the expression of Ki67 was significantly reduced in adjacent melanoma cells. Thus, the generation of vasculogenic mimicry patterns is accompanied by dampening of the invasive and metastatic uveal melanoma genotype and phenotype and underscores the plasticity of these cells in response to cues from the microenvironment. PMID:17003493

  19. Transhepatic Therapies for Metastatic Uveal Melanoma

    PubMed Central

    Eschelman, David J.; Gonsalves, Carin F.; Sato, Takami

    2013-01-01

    Despite successful treatment of the primary tumor, uveal melanoma has a propensity to metastasize to the liver. Prognosis is poor due to the very aggressive nature of these tumors. Because systemic therapies are relatively ineffective and patient survival correlates to disease control in the liver, locoregional therapies provide a means of prolonging survival. We review various techniques including chemoembolization, immunoembolization, radioembolization, arterial fotemustine infusion, and hepatic perfusion for the treatment of liver metastases from uveal melanoma. PMID:24436516

  20. Prognostic value of legumain in uveal melanoma

    PubMed Central

    WU, TONG; SUN, LEI; WU, YING; XIANG, RONG; LI, YUWEI; RONG, WEINING; SUN, FENGYUAN; WANG, NINGLI

    2016-01-01

    The present study aimed to assess the expression of legumain in uveal melanoma (UM) cell lines and primary UM specimens, and to determine the possible association between legumain expression and clinical as well as pathological characteristics to reveal its impact on the prognosis of patients with UM. Records of primary UM cases treated at Beijing Tongren Hospital and Tianjin Eye Hospital between 1996 and 2005 were retrieved for analysis and a total of 82 patients with uveal melanoma were included in the study. The expression of legumain in the formalin-fixed and paraffin-embedded surgical specimens of these 82 patients was determined using immunohistochemical analysis. In addition, the expression of legumain was examined in two uveal melanoma cell lines using polymerase chain reaction and western blot analyses. The association of legumain expression with clinical/pathological characteristics was analyzed using the χ2 and Fisher's exact test. In addition, the impact of legumain on the prognosis of patients with uveal melanoma was examined. Upregulation of legumain was more predominant in the highly invasive uveal melanoma cell line MUM-2B compared with that in the MUM-2C with low invasiveness. Of 82 primary uveal melanoma tissues, 35 exhibited high expression of legumain, while the other 47 specimens exhibited low or negative expression of legumain. High legumain expression was primarily associated with local invasion of UM. Overall survival analysis revealed that the patients with high legumain expression exhibited poorer survival than patients with low/negative legumain expression. These findings suggested that upregulation of legumain is associated with malignant behavior of UM and that legumain may be used as an negative prognostic factor as well as a therapeutic target. PMID:26846877

  1. Driver Mutations in Uveal Melanoma

    PubMed Central

    Decatur, Christina L.; Ong, Erin; Garg, Nisha; Anbunathan, Hima; Bowcock, Anne M.; Field, Matthew G.; Harbour, J. William

    2016-01-01

    IMPORTANCE Frequent mutations have been described in the following 5 genes in uveal melanoma (UM): BAP1, EIF1AX, GNA11, GNAQ, and SF3B1. Understanding the prognostic significance of these mutations could facilitate their use in precision medicine. OBJECTIVE To determine the associations between driver mutations, gene expression profile (GEP) classification, clinicopathologic features, and patient outcomes in UM. DESIGN, SETTING, AND PARTICIPANTS Retrospective study of patients with UM treated by enucleation by a single ocular oncologist between November 1, 1998, and July 31, 2014. MAIN OUTCOMES AND MEASURES Clinicopathologic features, patient outcomes, GEP classification (class 1 or class 2), and mutation status were recorded. RESULTS The study cohort comprised 81 participants. Their mean age was 61.5 years, and 37% (30 of 81) were female. The GEP classification was class 1 in 35 of 81 (43%), class 2 in 42 of 81 (52%), and unknown in 4 of 81 (5%). BAP1 mutations were identified in 29 of 64 (45%), GNAQ mutations in 36 of 81 (44%), GNA11 mutations in 36 of 81 (44%), SF3B1 mutations in 19 of 81 (24%), and EIF1AX mutations in 14 of 81 (17%). Sixteen of the mutations in BAP1 and 6 of the mutations in EIF1AX were previously unreported in UM. GNAQ and GNA11 mutations were mutually exclusive. BAP1, SF3B1, and EIF1AX mutations were almost mutually exclusive with each other. Using multiple regression analysis, BAP1 mutations were associated with class 2 GEP and older patient. EIF1AX mutations were associated with class 1 GEP and the absence of ciliary body involvement. SF3B1 mutations were associated with younger patient age. GNAQ mutations were associated with the absence of ciliary body involvement and greater largest basal diameter. GNA11 mutations were not associated with any of the analyzed features. Using Cox proportional hazards modeling, class 2 GEP was the prognostic factor most strongly associated with metastasis (relative risk, 9.4; 95% CI, 3.1–28.5) and

  2. Mutational status of IDH1 in uveal melanoma.

    PubMed

    Cimino, Patrick J; Kung, Yungtai; Warrick, Joshua I; Chang, Shu-Hong; Keene, C Dirk

    2016-06-01

    Uveal (intraocular) melanoma is an uncommon malignancy that comprises a small percentage of all melanoma cases. While many uveal melanomas harbor mutations in the BRCA-Associated Protein 1 (BAP1) gene, the genetics of non-BAP1 associated tumors are not completely understood. Recent studies have shown that a small subset of non-uveal melanomas hold mutations in isocitrate dehydrogenase (IDH), but the mutational status of IDH in uveal melanoma is unclear. Mutations in IDH are strongly prognostic and predictive of tumor behavior in other cancers, mainly diffuse gliomas, which commonly contain the IDH1-R132H mutation. For this study, we hypothesized that uveal melanoma may contain the IDH1-R132H mutation, similar to non-uveal melanoma and other cancers. A search of our institutional pathology files identified 50 consecutive cases of uveal melanoma with additional material utilized for retrospective IDH1-R132H immunohistochemical testing. The demographics of these patients included similar ages, gender distributions, and other clinical characteristics as described in previous studies. Similarly, histological subtype distributions and the presence of high risk pathologic features were consistent with other reports. All 50 of the uveal melanoma cases demonstrated negativity for IDH1-R132H by immunohistochemistry. This rate is unlike that of non-uveal melanoma and further supports their distinct molecular oncogenic profile. PMID:27155448

  3. In vivo and in vitro detection of dopamine d2 receptors in uveal melanomas.

    PubMed

    Bodei, Lisa; Hofland, Leo J; Ferone, Diego; Mooy, Cornelia M; Kros, Johan M; Paridaens, Dion A; Baarsma, Seerp G; Ferdeghini, Marco; Van Hagen, Martin P; Krenning, Eric P; Kwekkeboom, Dik J

    2003-12-01

    Scintigraphy with radiolabeled benzamides was used in melanoma patients. Studies with a newer benzamide called 123I-epidepride, a high-affinity D2 receptor (D2R) antagonist, showed high sensitivity in D2R-positive pituitary adenomas. We evaluated the presence of D2R in patients with uveal melanomas in vivo with 123I-epidepride, and in vitro in melanomas, using immunohistochemistry (IHC) and 125I-epidepride autoradiography. We studied the in vivo tumor-to-background (TB) ratios in six patients with posterior uveal melanoma (one previously enucleated). IHC was performed in 3 of 6 tumors after enucleation and in another 20 uveal melanomas, 7 metastatic lymph nodes from skin melanoma, and 2 normal specimens. 125I-epidepride autoradiography was performed in 10 uveal melanomas (3 of which were studied in vivo), 7 metastases, and 2 normal samples. Radioligand uptake was present in the affected eye of 5 patients with uveal melanoma (TB = 3.1-6.1) and absent in the operated one (TB = 1). Eight uveal tumors were positive at IHC (35%), 14 weakly positive (61%), and 1 negative (4%). Two metastases were positive (29%), 2 weakly positive (29%), and 3 negative (42%). Two uveal tumors were positive at autoradiography (20%), 7 had nonspecific binding (70%), and 1 was negative (10%). One metastasis was positive (14%), while 6 were negative (86%). 123I-epidepride scintigraphy in uveal melanomas seems promising for sensitivity and image quality. D2R was demonstrated in a significant proportion of the melanomas, although 123I-epidepride uptake might also be nonspecific and unrelated to D2R binding. Although further studies on larger series are needed, 123I-epidepride could represent a future tool to study the expression of D2R in other classes of neuroendocrine tumors. PMID:14969602

  4. Update on Metastatic Uveal Melanoma: Progress and Challenges.

    PubMed

    Spagnolo, Francesco; Picasso, Virginia; Spano, Laura; Tanda, Enrica; Venzano, Clary; Queirolo, Paola

    2016-06-01

    Uveal melanoma is a rare and biologically distinct type of melanoma arising from melanocytes of the uveal tract; it is associated with a poor prognosis due to the lack of effective systemic treatments. Recent advances in the pathogenesis of uveal melanoma offer an unprecedented opportunity for investigation of new compounds. The purpose of this paper was to analyse the existing evidence about the molecular pathology and immunobiology of advanced uveal melanoma and their implications for systemic targeted therapies and immunotherapy, as well as to discuss future treatment strategies based on data provided by clinical and translational research studies. PMID:27000042

  5. Uveal melanoma in children and teenagers

    PubMed Central

    Shields, Carol L.; Kaliki, Swathi; Arepalli, Sruthi; Atalay, Hatice Tuba; Manjandavida, Fairooz P.; Pieretti, Guilia; Shields, Jerry A.

    2013-01-01

    Purpose To review the features and prognosis of uveal melanoma in children. Methods Retrospective case series. Results Of 122 children with uveal melanoma, there were 53 (43%) male and 69 (57%) female patients. In this group, the mean age at presentation was 15 years (median 16 years, range 3–20 years). Age at presentation was 0 to 5 years in 4 (3%), 5.1 to 10 years in 14 (11%), 10.1 to 15 years in 43 (35%), and 15.1 to ⩽20 in 61 (50%). Associated ocular melanocytosis was present in 4 (3%). The melanoma was primarily located in the iris (n = 30, 25%), ciliary body (n = 10, 8%), or choroid (n = 82, 67%). The mean tumor basal dimension was 9.8 mm and mean thickness was 5.0 mm. The tumor color was pigmented (brown) (n = 102, 84%), nonpigmented (yellow) (n = 19, 16%), or mixed (n = 25, 21%). Subretinal fluid (n = 66, 54%) and hemorrhage (n = 9, 7%) were noted. Primary treatment involved laser photocoagulation (n = 3, 2%), transpupillary thermotherapy (n = 17, 14%), local tumor resection (n = 26, 21%), plaque radiotherapy (n = 42, 34%), or enucleation (n = 54, 44%). Kaplan Meier 5, 10, and 20-year estimates for uveal melanoma-related metastasis were 9%, 9%, and 20%, respectively, for children compared to 15%, 25%, and 36% for all ages. Conclusion Uveal melanoma in children tends to occur most often in the teenage years as a pigmented tumor involving the choroid or iris and with mean thickness of 5 mm. Prompt treatment is advised. PMID:24227986

  6. Malignant uveal melanoma and similar lesions studied by computed tomography

    SciTech Connect

    Mafee, M.F.; Peyman, G.A.; McKusick, M.A.

    1985-08-01

    Forty-four patients with intraocular disease were studied by computed tomography (CT); in 19 cases malignant uveal melanoma was considered the likely diagnosis. CT proved to be accurate in determining the location and size of uveal melanomas, demonstrating scleral invasion, and differentiating melanoma from choroidal detachment or angioma, toxocariasis, and senile macular degeneration. On CT, uveal melanomas appeared as hyperdense lesions with slight to moderate contrast enhancement. Tumors thinner than 2 mm could not be seen. Using dynamic CT, the authors noted moderate peak amplitude, normal or delayed tissue transit time, and persistently elevated washout phase (downslope), indicating increased permeability as the result of an impaired tumor blood barrier. Histological types of uveal melanoma could not be differentiated on the basis of circulatory patterns. Dynamic CT may be useful in distinguishing uveal melanoma from choroidal hemangioma or hematoma.

  7. Management of uveal tract melanoma: A comprehensive review.

    PubMed

    Kapoor, Akhil; Beniwal, Vimla; Beniwal, Surender; Mathur, Harsh; Kumar, Harvindra Singh

    2016-06-01

    Uveal tract melanoma is the most common primary intraocular malignancy in adults, accounting for about 5-10% of all the melanomas. Since there are no lymphatic vessels in the eye, uveal melanoma can only spread hematogenously leading to liver metastasis. A wide variety of treatment modalities are available for its management, leading to dilemma in selecting the appropriate therapy. This article reviews the diagnostic and therapeutic modalities available and thus, can help to individualize the treatment plan for each patient. PMID:26975730

  8. Uveal Melanoma in the Peripheral Choroid Masquerading as Chronic Uveitis

    PubMed Central

    Feng, Lei; Zhu, Jiang; Gao, Tao; Li, Baizhou; Yang, Yabo

    2014-01-01

    ABSTRACT Purpose To describe a case of uveal melanoma in the peripheral choroid masquerading as chronic uveitis and to raise awareness about malignant masquerade syndromes. Case Report A 36-year-old Chinese woman presented from an outside ophthalmologist with a 6-month history of unilateral chronic uveitis unresponsive to medical therapy in the left eye. She was found to have a uveal melanoma in the retinal periphery and underwent successful enucleation of her left eye. The histopathological diagnosis confirmed the clinical diagnosis. Conclusions When uveal melanoma presents in an atypical way, the diagnosis is more difficult. This case highlights the uncommon presentations of malignant melanoma of the choroid. It provides valuable information on how peripheral uveal melanoma can present with clinical signs consistent with an anterior uveitis. PMID:25036546

  9. Upcoming translational challenges for uveal melanoma

    PubMed Central

    Nabil, Amirouchene-Angelozzi; Marie, Schoumacher; Marc-Henri, Stern; Nathalie, Cassoux; Laurence, Desjardins; Sophie, Piperno-Neumann; Olivier, Lantz; Sergio, Roman-Roman

    2015-01-01

    The past few years have witnessed major advances in the understanding of the molecular landscape of uveal melanoma (UM). The discovery of a mutational background that is completely different from the one of skin melanoma has granted to UM a stand-alone status. The absence of effective therapy for metastatic disease offers now a chessboard for targeted therapy but at the same time urges preclinical science to develop accordingly, to guide the use of economical resources to the best profit of patients. This review describes the current knowledge on the biology of this disease and discusses the challenges that must be undertaken to translate this knowledge into real benefit for patients. PMID:26505679

  10. Animal Models of Uveal Melanoma: Methods, Applicability, and Limitations

    PubMed Central

    Stei, Marta M.; Loeffler, Karin U.; Holz, Frank G.; Herwig, Martina C.

    2016-01-01

    Animal models serve as powerful tools for investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic agents. They have facilitated rapid scientific progress in many tumor entities. However, for establishing a powerful animal model of uveal melanoma fundamental challenges remain. To date, no animal model offers specific genetic attributes as well as histologic, immunologic, and metastatic features of uveal melanoma. Syngeneic models with intraocular injection of cutaneous melanoma cells may suit best for investigating immunologic/tumor biology aspects. However, differences between cutaneous and uveal melanoma regarding genetics and metastasis remain problematic. Human xenograft models are widely used for evaluating novel therapeutics but require immunosuppression to allow tumor growth. New approaches aim to establish transgenic mouse models of spontaneous uveal melanoma which recently provided preliminary promising results. Each model provides certain benefits and may render them suitable for answering a respective scientific question. However, all existing models also exhibit relevant limitations which may have led to delayed research progress. Despite refined therapeutic options for the primary ocular tumor, patients' prognosis has not improved since the 1970s. Basic research needs to further focus on a refinement of a potent animal model which mimics uveal melanoma specific mechanisms of progression and metastasis. This review will summarise and interpret existing animal models of uveal melanoma including recent advances in the field. PMID:27366747

  11. Nanomedicine in the application of uveal melanoma

    PubMed Central

    You, Shuo; Luo, Jing; Grossniklaus, Hans E.; Gou, Ma-Ling; Meng, Ke; Zhang, Qing

    2016-01-01

    Rapid advances in nanomedicine have significantly changed many aspects of nanoparticle application to the eye including areas of diagnosis, imaging and more importantly drug delivery. The nanoparticle-based drug delivery systems has provided a solution to various drug solubility-related problems in ophthalmology treatment. Nanostructured compounds could be used to achieve local ocular delivery with minimal unwanted systematic side effects produced by taking advantage of the phagocyte system. In addition, the in vivo control release by nanomaterials encapsulated drugs provides prolong exposure of the compound in the body. Furthermore, certain nanoparticles can overcome important body barriers including the blood-retinal barrier as well as the corneal-retinal barrier of the eye for effective delivery of the drug. In summary, the nanotechnology based drug delivery system may serve as an important tool for uveal melanoma treatment. PMID:27588278

  12. Nanomedicine in the application of uveal melanoma.

    PubMed

    You, Shuo; Luo, Jing; Grossniklaus, Hans E; Gou, Ma-Ling; Meng, Ke; Zhang, Qing

    2016-01-01

    Rapid advances in nanomedicine have significantly changed many aspects of nanoparticle application to the eye including areas of diagnosis, imaging and more importantly drug delivery. The nanoparticle-based drug delivery systems has provided a solution to various drug solubility-related problems in ophthalmology treatment. Nanostructured compounds could be used to achieve local ocular delivery with minimal unwanted systematic side effects produced by taking advantage of the phagocyte system. In addition, the in vivo control release by nanomaterials encapsulated drugs provides prolong exposure of the compound in the body. Furthermore, certain nanoparticles can overcome important body barriers including the blood-retinal barrier as well as the corneal-retinal barrier of the eye for effective delivery of the drug. In summary, the nanotechnology based drug delivery system may serve as an important tool for uveal melanoma treatment. PMID:27588278

  13. Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma

    PubMed Central

    Harbour, J. William; Roberson, Elisha D. O.; Anbunathan, Hima; Onken, Michael D.; Worley, Lori A.; Bowcock, Anne M.

    2013-01-01

    Uveal melanoma is the most common primary cancer of the eye and often results in fatal metastasis. Here, we describe mutations occurring exclusively at arginine-625 in splicing factor 3B subunit 1 (SF3B1) in low-grade uveal melanomas with good prognosis. Thus, uveal melanoma is among a small group of cancers associated with SF3B1 mutation, and these mutations denote a distinct molecular subset of uveal melanomas. PMID:23313955

  14. Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma.

    PubMed

    Harbour, J William; Roberson, Elisha D O; Anbunathan, Hima; Onken, Michael D; Worley, Lori A; Bowcock, Anne M

    2013-02-01

    Uveal melanoma is the most common primary cancer of the eye and often results in fatal metastasis. Here, we describe mutations occurring exclusively at codon 625 of the SF3B1 gene, encoding splicing factor 3B subunit 1, in low-grade uveal melanomas with good prognosis. Thus, uveal melanoma is among a small group of cancers associated with SF3B1 mutations, and these mutations denote a distinct molecular subset of uveal melanomas. PMID:23313955

  15. Oncogenic mutations in GNAQ occur early in uveal melanoma

    PubMed Central

    Onken, Michael D.; Worley, Lori A.; Long, Meghan D.; Duan, Shenghui; Council, M. Laurin; Bowcock, Anne M.; Harbour, J. William

    2008-01-01

    Purpose Early/initiating oncogenic mutations have been identified for many cancers, but such mutations remain unidentified in uveal melanoma (UM). An extensive search for such mutations was undertaken, focusing on the RAF/MEK/ERK pathway, which is often the target of initiating mutations in other types of cancer. Methods DNA samples from primary UMs were analyzed for mutations in 24 potential oncogenes that affect the RAF/MEK/ERK pathway. For GNAQ, a stimulatory αq G-protein subunit which was recently found to be mutated in uveal melanomas, re-sequencing was expanded to include 67 primary UMs and 22 peripheral blood samples. GNAQ status was analyzed for association with clinical, pathologic, chromosomal, immunohistochemical and transcriptional features. Results Activating mutations at codon 209 were identified in GNAQ in 33/67 (49%) primary UMs, including 2/9 (22%) iris melanomas and 31/58 (54%) posterior UMs. No mutations were found in the other 23 potential oncogenes. GNAQ mutations were not found in normal blood DNA samples. Consistent with GNAQ mutation being an early or initiating event, this mutation was not associated with any clinical, pathologic or molecular features associated with late tumor progression. Conclusions GNAQ mutations occur in about half of UMs, representing the most common known oncogenic mutation in this cancer. The presence of this mutation in tumors at all stages of malignant progression suggests that it is an early event in UM. Mutations in this G-protein provide new insights into UM pathogenesis and could lead to new therapeutic possibilities. PMID:18719078

  16. Modeling the Behavior of Uveal Melanoma in the Liver

    PubMed Central

    Folberg, Robert; Leach, Lu; Valyi-Nagy, Klara; Lin, Amy Y.; Apushkin, Marsha A.; Ai, Zhuming; Barak, Vivian; Majumdar, Dibyen; Pe'er, Jacob; Maniotis, Andrew J.

    2007-01-01

    Purpose To model the behavior of uveal melanoma in the liver. Methods A 15-μL suspension of metastatic MUM2B or either primary OCM1 or M619 uveal melanoma cells was injected into the liver parenchyma of 105 CB17 SCID mice through a 1-cm abdominal incision. Animals were killed at 2, 4, 6, or 8 weeks after injection. Before euthanatization, 3% FITC-BSA buffer was injected into the retro-orbital plexus of one eye of three mice. Liver tissues were examined by light and fluorescence microscopy, and were stained with human anti-laminin. Vasculogenic mimicry patterns were reconstructed from serial laser scanning confocal microscopic stacks. Results OCM1a cells formed microscopic nodules in the mouse liver within 2 weeks after injection and metastasized to the lung 6 weeks later. By contrast, M619 and MUM2B cells formed expansile nodules in the liver within 2 weeks and gave rise to pulmonary metastases within 4 weeks after injection. Vasculogenic mimicry patterns, composed of human laminin and identical with those in human primary and metastatic uveal melanomas, were detected in the animal model. The detection of human rather than mouse laminin in the vasculogenic mimicry patterns in this model demonstrates that these patterns were of tumor cell origin and were not co-opted from the mouse liver microenvironment. Conclusions There are currently no effective treatments for metastatic uveal melanoma. This direct-injection model focuses on critical interactions between the tumor cell and the liver. It provides for translationally relevant approaches to the development of new modalities to detect small tumor burdens in patients, to study the biology of clinical dormancy of metastatic disease in uveal melanoma, to design and test novel treatments to prevent the emergence of clinically manifest liver metastases after dormancy, and to treat established uveal melanoma metastases. PMID:17591861

  17. Metastatic disease in uveal melanoma: importance of a genetic profile?

    PubMed

    Van Beek, Jackelien G M; Koopmans, Anna E; Vaarwater, Jolanda; Verdijk, Rob M; de Klein, Annelies; Naus, Nicole C; Kiliç, Emine

    2015-10-01

    Mutation of SF3B1 has been identified in low-grade uveal melanoma with a good prognosis. In this study, we compare chromosomal aberrations and gene mutations between a primary uveal melanoma and its multiple hepatic and peripancreatic metastases. DNA was isolated from a large primary uveal melanoma after fractionated stereotactic radiotherapy and three distinct metastases (two liver samples and one peripancreatic lymph node) to perform single-nucleotide polymorphism array and fluorescent in-situ hybridization. We analyzed mutations in uveal melanoma target genes BAP1, GNAQ, GNA11, SF3B1, and EIF1AX. The primary tumor showed no abnormalities in chromosome 3, whereas metastases showed deletion of at least 3q12.1-q24 and the BAP1 gene was not mutated. All samples indicated the following consistent chromosomal aberrations: loss of 1p, gain of 6p, and gain of 8q. Subsequently, heterozygous SF3B1 and heterozygous GNA11 mutations were observed. The metastases showed more genetic aberrations than the primary tumor and may therefore represent the genetic status of the tumor before irradiation, whereas the current primary tumor shows presumably irradiation artifacts. An early occurring mutation in GNA11 was observed in all samples. The SF3B1 mutation seems to predispose for late metastatic disease in the absence of a BAP1 mutation. PMID:26086698

  18. Selumetinib for the treatment of metastatic uveal melanoma: past and future perspectives.

    PubMed

    Komatsubara, Kimberly M; Manson, Daniel K; Carvajal, Richard D

    2016-06-01

    Uveal melanoma is a rare but aggressive subtype of melanoma. Nearly 50% of patients will develop metastatic disease despite primary enucleation or radiation therapy. There is currently no standard of care therapy for metastatic uveal melanoma, and no therapy that has been shown to prolong overall survival. Uveal melanoma is characterized by activation of signaling pathways including the MAPK pathway and the PI3K/AKT pathway, among others, via mutations in the G-α-proteins GNAQ and GNA11. MEK inhibition with selumetinib has been evaluated as a therapeutic strategy in metastatic uveal melanoma. This review will discuss preclinical and clinical studies evaluating selumetinib in metastatic uveal melanoma, as well as potential future perspectives on MEK inhibition in the management of metastatic uveal melanoma. PMID:27044592

  19. Lipomatous Change in Uveal Melanoma: Histopathological, Immunohistochemical and Cytogenetic Analysis

    PubMed Central

    Yavuzyigitoglu, Serdar; Kilic, Emine; Vaarwater, Jolanda; de Klein, Annelies; Paridaens, Dion; Verdijk, Robert M.

    2016-01-01

    Purpose The aim of this study was to describe a case of lipomatous change in uveal melanoma. Procedures The patient presented with a 2-year history of blurry vision. A full examination of the right eye revealed a dome-shaped pigmented subretinal mass in the choroid with a thickness of 9 mm and a diameter of 15 mm. The eye was enucleated and prepared for histopathologic, genetic and molecular investigation. Results Histopathology revealed a small circumscribed area consisting of mature adipocytic appearing cells with abundant clear cytoplasm and small peripheral flattened nuclei within a spindle-cell melanoma of the uvea. The cytoplasm of the adipocytic cells stained negative for periodic acid-Schiff and Alcian blue and positive for Melan-A, HMB-45 and tyrosinase, confirming melanocytic lineage. Fluorescence in situ hybridization analysis confirmed trisomy of chromosome 6p22 and disomy of chromosome 3p13 in the nuclei of both the tumor spindle type B cells and in the nuclei of lipomatous tumor cells. Conclusions Lipomatous change can be added to the many histopathologic faces of uveal melanoma. To our knowledge, this is the first report of lipomatous change in uveal melanoma performed with cytogenetic investigations. PMID:27239451

  20. Radiation related complications after ruthenium plaque radiotherapy of uveal melanoma.

    PubMed Central

    Summanen, P; Immonen, I; Kivelä, T; Tommila, P; Heikkonen, J; Tarkkanen, A

    1996-01-01

    AIMS/BACKGROUND: To analyse radiation related complications and secondary enucleation after irradiation of malignant uveal melanoma with ruthenium-106 plaques. METHODS: A series of 100 consecutive eyes irradiated in 1981-91 was analysed using the life table method and the Cox proportional hazards model. The median apical and scleral tumour dose was 100 Gy (range 15-200 Gy) and 1000 Gy (range 200-1200 Gy), respectively. The median follow up time was 2.8 and 2.0 years (range 1 month to 10 years) for anterior and posterior segment complications, respectively. RESULTS: The 3 and 5 year probabilities of being without radiation cataract were 73% and 63%, without neovascular glaucoma 91% and 81%, without vitreous haemorrhage 83% and 74%, without radiation maculopathy 85% and 70%, and without radiation optic neuropathy 90% and 88%, respectively. The risk of radiation cataract was highest with large tumour size (T1 + T2 v T3, p = 0.0027; height < or = 5 v > 5 mm, p = 0.029; largest basal diameter (LBD) < or = 15 v > 15 mm, p < 0.0001) and location of anterior tumour margin anterior v posterior to the equator (p = 0.0003); the risk of neovascular glaucoma with large size (T1 + T2 v T3, p = 0.039; LBD < or = 15 mm v 15 mm, p = 0.021); and the risk of maculopathy and optic neuropathy with proximity of the posterior tumour margin to the fovea and the optic disc (< or = 1.5 v > 1.5 mm; p = 0.030 and p = 0.0004, respectively). In Cox's multivariate analysis the strongest risk indicator for radiation cataract (RR 1.5, 95% CI 1.4-1.6) and vitreous haemorrhage (RR 1.6, 95% CI 1.4-1.8) was the height of the tumour; for neovascular glaucoma the TNM class (RR 6.2, 95% CI 2.7-13.8); for radiation maculopathy location of posterior tumour margin within 2 mm from the fovea (RR 3.4, 95% CI 2.0-6.0); and for radiation optic neuropathy location of tumour margin within 1 DD of the optic disc (RR 6.1, 95% CI 3.0-12.4). The 3 and 5 year probabilities of avoiding enucleation were 92% and 85

  1. Uveal melanoma: From diagnosis to treatment and the science in between.

    PubMed

    Chattopadhyay, Chandrani; Kim, Dae Won; Gombos, Dan S; Oba, Junna; Qin, Yong; Williams, Michelle D; Esmaeli, Bita; Grimm, Elizabeth A; Wargo, Jennifer A; Woodman, Scott E; Patel, Sapna P

    2016-08-01

    Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the United States, and their age-adjusted risk is 5 per 1 million population. These less frequent melanomas are dissimilar to their more common cutaneous melanoma relative, with differing risk factors, primary treatment, anatomic spread, molecular changes, and responses to systemic therapy. Once uveal melanoma becomes metastatic, therapy options are limited and are often extrapolated from cutaneous melanoma therapies despite the routine exclusion of patients with uveal melanoma from clinical trials. Clinical trials directed at uveal melanoma have been completed or are in progress, and data from these well designed investigations will help guide future directions in this orphan disease. Cancer 2016;122:2299-2312. © 2016 American Cancer Society. PMID:26991400

  2. Frequent Mutation of BAP1 in Metastasizing Uveal Melanomas

    PubMed Central

    Harbour, J. William; Onken, Michael D.; Roberson, Elisha D.O.; Duan, Shenghui; Cao, Li; Worley, Lori A.; Council, M. Laurin; Matatall, Katie A.; Helms, Cynthia; Bowcock, Anne M.

    2011-01-01

    Metastasis is a defining feature of malignant tumors and is the most common cause of cancer-related death, yet the genetics of metastasis are poorly understood. We used massively parallel exome sequencing coupled with Sanger re-sequencing to search for metastasis-related mutations in highly metastatic uveal melanomas of the eye. Inactivating somatic mutations were identified in the gene encoding BRCA1-associated protein 1 (BAP1) on chromosome 3p21.1 in 26 of 31 (84%) metastasizing tumors, including 15 mutations causing premature protein termination, and six affecting its ubiquitin carboxy-terminal hydrolase (UCH) domains. One tumor harbored a frameshift mutation that was germline in origin, thus representing a susceptibility allele. These findings implicate loss of BAP1 in uveal melanoma metastasis and suggest the BAP1 pathway as a therapeutic target. PMID:21051595

  3. Biology of advanced uveal melanoma and next steps for clinical therapeutics.

    PubMed

    Luke, Jason J; Triozzi, Pierre L; McKenna, Kyle C; Van Meir, Erwin G; Gershenwald, Jeffrey E; Bastian, Boris C; Gutkind, J Silvio; Bowcock, Anne M; Streicher, Howard Z; Patel, Poulam M; Sato, Takami; Sossman, Jeffery A; Sznol, Mario; Welch, Jack; Thurin, Magdalena; Selig, Sara; Flaherty, Keith T; Carvajal, Richard D

    2015-03-01

    Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15-yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation's ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherapies are reviewed, and next steps in the development of clinical therapeutics are discussed. PMID:25113308

  4. Prognosis of uveal melanoma based on race in 8100 patients: The 2015 Doyne Lecture.

    PubMed

    Shields, C L; Kaliki, S; Cohen, M N; Shields, P W; Furuta, M; Shields, J A

    2015-08-01

    A retrospective, nonrandomized, interventional case series of 8100 patients with uveal melanoma were evaluated for melanoma-related metastasis based on patient race. The patient race was Caucasian (n=7918, 98%), Hispanic (n=105, 1%), Asian (n=44, <1%), or African American (n=33, <1%). On the basis of race (Caucasian, Hispanic, Asian, and African American), significant differences were noted in mean age at presentation (58, 48, 44, and 52 years; P<0.001), distance of posterior tumor margin to foveola (5, 5, 6, and 4 mm; P<0.001), distance of posterior tumor margin to optic disc (5, 5, 6, and 4 mm) (P<0.001), tumor base (11, 12, 12, and 13 mm; P<0.001), tumor thickness (5.4, 7.1, 6.5, and 7.5 mm; P<0.001), intraocular hemorrhage (10, 14, 11, and 24%; P=0.02), and rupture of Bruch's membrane (20, 27, 39, and 36%; P=0.001). On the basis of multivariate analysis, the rate of metastasis increased with increasing age (P<0.001), ciliary body location (P<0.001), increasing tumor base (P<0.001), increasing tumor thickness (P<0.001), pigmented tumor (P=0.001), subretinal fluid (P=0.001), intraocular hemorrhage (P=0.045), and extraocular extension (P=0.036). Kaplan-Meier estimates of metastasis at 3, 5, and 10 were 8, 15, and 25% in Caucasians; 13, 13, and 13% in Hispanics; 4, 4, and 36% in Asians; and 8, 8, and 8% in African Americans. Compared with Caucasians, despite relative risk for metastasis of 0.31 for African Americans, 0.73 for Hispanics, and 1.42 for Asians, there was no statistical difference in metastasis, or death from uveal melanoma based on race. In summary, uveal melanoma showed similar prognosis for all races. PMID:26248525

  5. Epacadostat and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma

    ClinicalTrials.gov

    2016-05-12

    Mucosal Melanoma; Recurrent Melanoma; Recurrent Uveal Melanoma; Stage IIIA Skin Melanoma; Stage IIIA Uveal Melanoma; Stage IIIB Skin Melanoma; Stage IIIB Uveal Melanoma; Stage IIIC Skin Melanoma; Stage IIIC Uveal Melanoma; Stage IV Skin Melanoma; Stage IV Uveal Melanoma

  6. Neovascular glaucoma after helium ion irradiation for uveal melanoma

    SciTech Connect

    Kim, M.K.; Char, D.H.; Castro, J.L.; Saunders, W.M.; Chen, G.T.; Stone, R.D.

    1986-02-01

    Neovascular glaucoma developed in 22 of 169 uveal melanoma patients treated with helium ion irradiation. Most patients had large melanomas; no eyes containing small melanomas developed anterior segment neovascularization. The mean onset of glaucoma was 14.1 months (range, 7-31 months). The incidence of anterior segment neovascularization increased with radiation dosage; there was an approximately three-fold increase at 80 GyE versus 60 GyE of helium ion radiation (23% vs. 8.5%) (P less than 0.05). Neovascular glaucoma occurred more commonly in larger tumors; the incidence was not affected by tumor location, presence of subretinal fluid, nor rate of tumor regression. Fifty-three percent of patients had some response with intraocular pressures of 21 mmHg or less to a combination of antiglaucoma treatments.

  7. Secondary glaucoma as initial manifestation of uveal melanoma

    PubMed Central

    Othman, Ihab Saad; Assem, Maher; Zaki, Iman M.A.

    2013-01-01

    Purpose Secondary glaucoma can be induced by a variety of local ocular problems. Intraocular tumors may initially present as secondary glaucoma. Methods 8 consecutive patients with secondary glaucoma were found to have uveal melanoma. Thorough examination included detailed history, fundus examination with scleral depression, B scan ultrasonography, and CT/MRI scanning techniques. Results A single case presented with spontaneous hyphema, two patients presented with secondary glaucoma, extraocular melanoma and metastases, a single case was found to have angle block by an iridociliary ring melanoma and 4 cases presented with neovascular glaucoma. Enucleation was necessary in all 8 cases. Conclusions General ophthalmologists should be aware of these rare initial manifestations of intraocular tumors as secondary glaucoma. Enucleation would be recommended in most cases of intraocular malignancy manifesting as secondary glaucoma. One should be extremely cautious in doing a penetrating surgery in such cases. PMID:24227987

  8. Biology of Advanced Uveal Melanoma and Next Steps for Clinical Therapeutics

    PubMed Central

    Luke, Jason J.; Triozzi, Pierre L.; McKenna, Kyle C.; Van Meir, Erwin G.; Gershenwald, Jeffrey E.; Bastian, Boris C.; Gutkind, J. Silvio; Bowcock, Anne M.; Streicher, Howard Z.; Patel, Poulam M.; Sato, Takami; Sossman, Jeffery A.; Sznol, Mario; Welch, Jack; Thurin, Magdalena; Selig, Sara; Flaherty, Keith T.; Carvajal, Richard D.

    2014-01-01

    Summary Uveal melanoma is the most common intraocular malignancy though it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15 year period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease and median survival remains poor. Here, as a joint effort between CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherpies are reviewed and next steps in the development of clinical therapeutics are discussed. PMID:25113308

  9. In-vivo xenograft murine human uveal melanoma model develops hepatic micrometastases

    PubMed Central

    Yang, Hua; Fang, Guofu; Huang, Xinping; Yu, Jie; Hsieh, Chia-Ling; Grossniklaus, Hans E.

    2009-01-01

    The purpose of the study is to develop a mouse ocular melanoma model with human uveal melanoma cells that forms hepatic micrometastases. Human uveal melanoma Mel290 cells were transfected with a lentiviral-enhanced green fluorescent protein (EGFP) expression vector. Proliferation assays were performed by comparing Mel290-EGFP and Mel290 cells. After stable expression of EGFP and proliferation was ascertained, 1 × 106 Mel290-EGFP cells were introduced into NU/NU mice by posterior compartment (PC) inoculation or tail vein injection. Control groups were inoculated or injected with Mel290 cells. Ocular and hepatic frozen sections were examined by fluorescence microscopy, and the number of hepatic micrometastases was determined. EGFP expression was observed at 24 h after transfection. At 72 h after transfection, more than 70% of Mel290 cells expressed EGFP. At 45 days (six passages), 90% of Mel290 cells stably expressed EGFP. Histologic examination showed that Mel290-EGFP cells formed hepatic micrometastases after either PC inoculation or tail vein injection. A significant difference in the number of hepatic micrometastases between PC inoculation and tail vein injection (P<0.01) was observed. Mel290-EGFP cells stably expressed green fluorescent protein in vitro at 45 days (six passages). These cells formed hepatic micrometastases in NU/NU mice after PC inoculation or tail vein injection, with significantly more micrometastases developing in the PC inoculation model than after tail vein injection. PMID:18337645

  10. Time trends and latitude dependence of uveal and cutaneous malignant melanoma induced by solar radiation

    PubMed Central

    Moan, Johan; Cicarma, Emanuela; Setlow, Richard; Porojnicu, Alina C; Grant, William B

    2010-01-01

    In order to evaluate the role of solar radiation in uveal melanoma etiology, the time and latitude dependency of the incidence rates of this melanoma type were studied in comparison with those of cutaneous malignant melanoma (CMM). Norway and several other countries with Caucasian populations were included. there is a marked north-south gradient of the incidence rates of CMM in Norway, with three times higher rates in the south than in the north. No such gradient is found for uveal melanoma. Similar findings have been published for CMM in other Caucasian populations, with the exception of Europe as a whole. In most populations the ratios of uveal melanoma incidence rates to those of CMM tend to decrease with increasing CMM rates. This is also true for Europe, in spite of the fact that in this region there is an inverse latitude gradient of CMM, with higher rates in the north than in the south. In Norway the incidence rates of CMM have increased until about 1990 but have been constant or even decreased (for young people) after that time, indicating constant or decreasing sun exposure. The uveal melanoma rates have been increasing after 1990. In most other populations the incidence rates of CMM have been increasing until recently while those of uveal melanoma have been decreasing. These data generally support the assumption that uveal melanomas are not generated by ultraviolet (UV) radiation and that solar UV, via its role in vitamin D photosynthesis, may have a protective effect. PMID:21547141

  11. Time trends and latitude dependence of uveal and cutaneous malignant melanoma induced by solar radiation

    SciTech Connect

    Moan, J.; Setlow, R.; Cicarma, E.; Porojnicu, A. C.; Grant, W. B.; Juzeniene, A.

    2010-01-01

    In order to evaluate the role of solar radiation in uveal melanoma etiology, the time and latitude dependency of the incidence rates of this melanoma type were studied in comparison with those of cutaneous malignant melanoma (CMM). Norway and several other countries with Caucasian populations were included. There is a marked north - south gradient of the incidence rates of CMM in Norway, with three times higher rates in the south than in the north. No such gradient is found for uveal melanoma. Similar findings have been published for CMM in other Caucasian populations, with the exception of Europe as a whole. In most populations the ratios of uveal melanoma incidence rates to those of CMM tend to decrease with increasing CMM rates. This is also true for Europe, in spite of the fact that in this region there is an inverse latitude gradient of CMM, with higher rates in the north than in the south. In Norway the incidence rates of CMM have increased until about 1990 but have been constant, or even decreased (for young people) after that time, indicating constant or decreasing sun exposure. The uveal melanoma rates have been increasing after 1990. In most other populations the incidence rates of CMM have been increasing until recently while those of uveal melanoma have been decreasing. These data generally support the assumption that uveal melanomas are not generated by ultraviolet (UV) radiation and that solar UV, via its role in vitamin D photosynthesis, may have a protective effect.

  12. Effectiveness of fractionated stereotactic radiotherapy for uveal melanoma

    SciTech Connect

    Muller, Karin; Nowak, Peter; Pan, Connie de; Marijnissen, Johannes P.; Paridaens, Dion A.; Levendag, Peter; Luyten, Gre P.M. . E-mail: g.p.m.luyten@erasmusmc.nl

    2005-09-01

    Purpose: To study the effectiveness and acute side effects of fractionated stereotactic radiation therapy (fSRT) for uveal melanoma. Methods and Materials: Between 1999 and 2003, 38 patients (21 male, 17 female) were included in a prospective, nonrandomized clinical trial (mean follow-up of 25 months). A total dose of 50 Gy was given in 5 consecutive days. A blinking light and a camera (to monitor the position of the diseased eye) were fixed to a noninvasive relocatable stereotactic frame. Primary end points were local control, best corrected visual acuity, and toxicity at 3, 6, 12, and 24 months, respectively. Results: After 3 months (38 patients), the local control was 100%; after 12 months (32 patients) and 24 months (15 patients), no recurrences were seen. The best corrected visual acuity declined from a mean of 0.21 at diagnosis to 0.06 2 years after therapy. The acute side effects after 3 months were as follows: conjunctival symptoms (10), loss of lashes or hair (6), visual symptoms (5), fatigue (5), dry eye (1), cataract (1), and pain (4). One eye was enucleated at 2 months after fSRT. Conclusions: Preliminary results demonstrate that fSRT is an effective and safe treatment modality for uveal melanoma with an excellent local control and mild acute side effects. The follow-up should be prolonged to study both long-term local control and late toxicity.

  13. Overexpression of Annexin II Receptor-Induced Autophagy Protects Against Apoptosis in Uveal Melanoma Cells.

    PubMed

    Zhang, Yuelu; Song, Hongyuan; Guo, Ting; Zhu, Yongzhe; Tang, Hailin; Qi, Zhongtian; Zhao, Ping; Zhao, Shihong

    2016-05-01

    Uveal melanoma is the most common primary malignant intraocular tumor in adults and still lacks effective systemic therapies. Annexin A2 receptor (AXIIR), a receptor for Annexin II, was demonstrated to play an important role in multiple cells, but its role in uveal melanoma cells remains exclusive. Herein, the authors reported that overexpression of AXIIR was able to reduce cell viability and activate apoptosis apparently in the Mum2C uveal melanoma cell line. Meanwhile, overexpression of AXIIR could induce autophagy and increase autophagy flux. After autophagy was inhibited by chloroquine, enhanced apoptosis and cytotoxicity could be detected. In summary, these data highlighted the crucial role of AXIIR in reducing Mum2C cell viability through inducing apoptosis, while autophagy played a protective role in this process. Interference of this gene may be a promising method for uveal melanoma therapy and combination with specific inhibitor of autophagy may serve as a supplementary. PMID:27183438

  14. Oncogenic GNAQ and GNA11 Mutations in Uveal Melanoma in Chinese

    PubMed Central

    Xu, Xiaolin; Wei, Wen Bin; Li, Bin; Gao, Fei; Zhang, Zhibao; Jonas, Jost B.

    2014-01-01

    Purpose To examine whether GNAQ and GNA11 somatic mutations previously identified in uveal melanomas of Caucasians are associated with uveal melanomas in Chinese patients. Methods Uveal melanomas treated by primary enucleation in Chinese patients underwent a mutation analysis of GNAQ and GNA11 with sequencing of exon 5 and exon 4. Results The study included 50 patients with uveal melanoma and with a mean age of 47.6±13.0 years. During the follow-up of at least 3 years, 20 (40%) patients developed extraocular metastases. The frequencies of GNAQ and GNA11 somatic mutations in uveal melanoma were 18% (9/50) and 20% (10/50), respectively. The mutations occurred exclusively in codon 209 of exon 5. No mutations were detected in exon 4. Mutations affecting codon 209 in GNAQ were c.626A>C(Q209P) (78%) and c.626A>T(Q209L) (22%). Mutations affecting codon 209 in GNA11 were exclusively c.626A>T(Q209L) (100%). In none of the tumors, mutations of BRAF and NRAS were detected. GNAQ/11 mutations were marginally (P = 0.045) associated with optic disc involvement. In Kaplan-Meier analysis, metastasis-free survival was not significantly (P = 0.94) associated with GNAQ/11 mutations. Conclusions Mutations of GNAQ and GNA11 can be found in Chinese patients as in Caucasian patients with uveal melanoma, with a higher frequency reported for Caucasian patients. PMID:25280020

  15. Clinical Characteristics of 582 Patients with Uveal Melanoma in China

    PubMed Central

    Liu, Yue Ming; Li, Yang; Wei, Wen Bin; Xu, Xiaolin; Jonas, Jost B.

    2015-01-01

    Objective To assess clinical characteristics, treatment and survival of patients with uveal melanoma in China. Methods The retrospective study included all patients with malignant uveal melanoma who were consecutively examined in the study period from January 2005 and June 2015 in the Beijing Tongren hospital. Results The mean age of the 582 patients (295(50.7%) women) was 44.6±12.6 years (range:5–77 years). The tumors were located most often in the superior temporal region (in 117(21.5%) patients) and least common in the inferior region (in 31(5.7%) patients). In 548(94.2%) patients, the tumors were located in the choroid, in 33(5.7%) patients in the ciliary body, and in one (0.2%) patient in the iris. Treatment included episcleral brachytherapy (415(71.3%) patients), local tumor resection (48(8.2%) patients) and primary enucleation (119(20.4%) patients). In 53 individuals out of the 415 patients with primary brachytherapy, episcleral brachytherapy was followed by enucleation, due to an increasing tumor size or due to uncontrolled neovascular glaucoma. Median follow-up time was of 30 months (range: 1–124 months; mean: 34.8 ± 24.4 months). Overall survival rate at 5 and 10 years was of 92.7% and 85.1%. Younger age (P = 0.017), tumor location in the nasal meridian(P = 0.004), smaller tumor size (P<0.001), hemispheric tumor shape (P = 0.025), histological tumor cell type (spindle-cell type versus epitheloid cell type;P = 0.014), and type of treatment (episcleral brachytherapy versus local tumor resection and versus primary enucleation; P<0.001) were significantly associated with the overall survival in univariate analysis, while in multivariate analysis only smaller tumor size was significantly (P<0.001; RR: 4.75; 95% confidence interval:2.11,10.7) associated with better overall survival. Conclusions In this study on clinical characteristics of uveal melanoma of a larger group of patients from China, the onset age was considerably younger and survival rate

  16. Histopathology of uveal melanomas treated with charged particle radiation

    SciTech Connect

    Crawford, J.B.; Char, D.H.

    1987-06-01

    The authors have treated 255 uveal melanomas with helium ion radiation. Twenty-three eyes have been enucleated because of complications and five eyes have been obtained at autopsy. We have evaluated 27 of these eyes. Neovascular glaucoma (10 eyes), painful keratitis (6 eyes), continued tumor growth (4 eyes), and vitreous hemorrhage (2 eyes) were the major complications of treatment that led to enucleation. The degree of tumor necrosis correlated with the size, pigmentation, and anterior extent of the tumor. It did not correlate with the interval from irradiation or with the amount of tumor shrinkage. Mitotic figures were extremely rare in treated tumors, suggesting that the tumor cells have lost their ability to cycle.

  17. Use of the Chick Embryo Model in Uveal Melanoma

    PubMed Central

    Kalirai, Helen; Shahidipour, Haleh; Coupland, Sarah E.; Luyten, Gregorius

    2015-01-01

    Animal models play a crucial role in basic and translational oncology research. Conventional rodent experiments, however, face ethical, practical and technical issues that limit their use. The chick embryo represents an accessible and economical in vivo model, which has long been used in developmental biology and for the study of angiogenesis. It is also a recognised xenograft model, and because of its lack of immune system in early development, the chick embryo has established itself as a key model system for cancer research, with which to study various steps in the metastatic process. In this chapter, we review the chick embryo model and the technical approaches adopted by cancer biologists, including advances in real-time imaging, and discuss how this has been or can be applied to improve our understanding of the biological events during uveal melanoma development and metastasis. PMID:27171889

  18. Effects of radiotherapy on uveal melanomas and adjacent tissues.

    PubMed

    Groenewald, C; Konstantinidis, L; Damato, B

    2013-02-01

    Most uveal melanomas are treated with radiotherapy. An adequate understanding of the effects of radiation on the tumour and the healthy ocular tissues is necessary. Ionizing radiation damages cell membranes, organelles, and DNA. Irradiated cells are lysed or undergo apoptosis, necrosis, and senescence. These effects occur in tumour cells and vascular endothelial cells, resulting in tumour shrinkage, ischaemia, infarction, exudation, and fibrosis, which can cause exudative maculopathy, serous retinal detachment, rubeosis, and neovascular glaucoma (ie, 'toxic tumour syndrome'). Such abnormalities must be distinguished from collateral damage to healthy ocular tissues that receive high doses of radiation, and these include radiation-induced retinopathy, optic neuropathy, choroidopathy, cataract, and scleral necrosis. Radiation retinopathy can be treated effectively with photodynamic therapy, anti-angiogenic agents, and intravitreal steroid injections. In some patients, optic neuropathy may improve with intravitreal steroids or anti-angiogenic agents. Neovascular glaucoma resolves with intra-cameral bevacizumab. Exudative retinal detachment can regress with intra-vitreal steroid injections. Cataract is treated in the usual manner. Scleral necrosis, if severe, may require grafting, possibly using a lamellar flap from the same eye. Depending on the bulk of the residual toxic tumour, treatment can consist of intra-vitreal steroids and/or anti-angiogenic agents, transpupillary thermotherapy or photodynamic therapy to the tumour, or surgical removal of the tumour by endo- or exo-resection. Measures aimed at preventing collateral damage include eccentric placement of ruthenium plaques or iodine seeds and delivery of a notched proton beam. The decision to treat a uveal melanoma with radiotherapy requires the ability to manage iatrogenic side effects and complications. PMID:23196647

  19. Relative survival rates after alternative therapies for uveal melanoma

    SciTech Connect

    Seddon, J.M.; Gragoudas, E.S.; Egan, K.M.; Glynn, R.J.; Howard, S.; Fante, R.G.; Albert, D.M. )

    1990-06-01

    Survival in a group of 556 patients with uveal melanoma treated by proton beam irradiation with a median follow-up of 5.3 years was compared with that of 238 patients enucleated during the same 10-year period as irradiated patients (July 1975 to December 1984) with a median follow-up of 8.8 years, and 257 patients enucleated during the preceding 10 years (January 1965 to June 1975) with a median follow-up of 17.0 years. Adjustments were made for known prognostic factors including age, tumor location, tumor height, and clinical estimate of tumor diameter (for enucleated patients this was estimated in a regression equation relating histologic to clinical measurement). The overall rate ratio for all cause mortality was 1.2 (95% confidence interval, 0.9-1.6) for the concurrent enucleation series versus proton beam, and 1.6 (95% confidence interval, 1.2-2.1) for the earlier enucleation series versus proton beam. Relative rates of metastatic death, cancer death, and all cause mortality comparing alternative treatments were found to vary with time after treatment. Interval-specific rate ratios were evaluated using proportional hazards models fitted to separate time intervals after treatment. For all three outcomes, rate ratios were over two and statistically significant for the first 2 years after treatment and closer to one and nonsignificant after year 6 comparing the two enucleation groups with proton beam. Results suggest that treatment choice has little overall influence on survival in patients with uveal melanoma.

  20. Effects of radiotherapy on uveal melanomas and adjacent tissues

    PubMed Central

    Groenewald, C; Konstantinidis, L; Damato, B

    2013-01-01

    Most uveal melanomas are treated with radiotherapy. An adequate understanding of the effects of radiation on the tumour and the healthy ocular tissues is necessary. Ionizing radiation damages cell membranes, organelles, and DNA. Irradiated cells are lysed or undergo apoptosis, necrosis, and senescence. These effects occur in tumour cells and vascular endothelial cells, resulting in tumour shrinkage, ischaemia, infarction, exudation, and fibrosis, which can cause exudative maculopathy, serous retinal detachment, rubeosis, and neovascular glaucoma (ie, ‘toxic tumour syndrome'). Such abnormalities must be distinguished from collateral damage to healthy ocular tissues that receive high doses of radiation, and these include radiation-induced retinopathy, optic neuropathy, choroidopathy, cataract, and scleral necrosis. Radiation retinopathy can be treated effectively with photodynamic therapy, anti-angiogenic agents, and intravitreal steroid injections. In some patients, optic neuropathy may improve with intravitreal steroids or anti-angiogenic agents. Neovascular glaucoma resolves with intra-cameral bevacizumab. Exudative retinal detachment can regress with intra-vitreal steroid injections. Cataract is treated in the usual manner. Scleral necrosis, if severe, may require grafting, possibly using a lamellar flap from the same eye. Depending on the bulk of the residual toxic tumour, treatment can consist of intra-vitreal steroids and/or anti-angiogenic agents, transpupillary thermotherapy or photodynamic therapy to the tumour, or surgical removal of the tumour by endo- or exo-resection. Measures aimed at preventing collateral damage include eccentric placement of ruthenium plaques or iodine seeds and delivery of a notched proton beam. The decision to treat a uveal melanoma with radiotherapy requires the ability to manage iatrogenic side effects and complications. PMID:23196647

  1. BAP1 deficiency causes loss of melanocytic cell identity in uveal melanoma

    PubMed Central

    2013-01-01

    Background Uveal melanoma is a highly aggressive cancer with a strong propensity for metastasis, yet little is known about the biological mechanisms underlying this metastatic potential. We recently showed that most metastasizing uveal melanomas, which exhibit a class 2 gene expression profile, contain inactivating mutations in the tumor suppressor BAP1. The aim of this study was to investigate the role of BAP1 in uveal melanoma progression. Methods Uveal melanoma cells were studied following RNAi-mediated depletion of BAP1 using proliferation, BrdU incorporation, flow cytometry, migration, invasion, differentiation and clonogenic assays, as well as in vivo tumorigenicity experiments in NOD-SCID-Gamma mice. Results Depletion of BAP1 in uveal melanoma cells resulted in a loss of differentiation and gain of stem-like properties, including expression of stem cell markers, increased capacity for self-replication, and enhanced ability to grow in stem cell conditions. BAP1 depletion did not result in increased proliferation, migration, invasion or tumorigenicity. Conclusions BAP1 appears to function in the uveal melanocyte lineage primarily as a regulator of differentiation, with cells deficient for BAP1 exhibiting stem-like qualities. It will be important to elucidate how this effect of BAP1 loss promotes metastasis and how to reverse this effect therapeutically. PMID:23915344

  2. Outcomes of Iodine-125 Plaque Brachytherapy for Uveal Melanoma With Intraoperative Ultrasonography and Supplemental Transpupillary Thermotherapy

    SciTech Connect

    Badiyan, Shahed N.; Rao, Rajesh C.; Apicelli, Anthony J.; Acharya, Sahaja; Verma, Vivek; Garsa, Adam A.; DeWees, Todd; Speirs, Christina K.; Garcia-Ramirez, Jose; Esthappan, Jacqueline; Grigsby, Perry W.; Harbour, J. William

    2014-03-15

    Purpose: To assess the impact on local tumor control of intraoperative ultrasonographic plaque visualization and selective application of transpupillary thermotherapy (TTT) in the treatment of posterior uveal melanoma with iodine-125 (I-125) episcleral plaque brachytherapy (EPB). Methods and Materials: Retrospective analysis of 526 patients treated with I-125 EPB for posterior uveal melanoma. Clinical features, dosimetric parameters, TTT treatments, and local tumor control outcomes were recorded. Statistical analysis was performed using Cox proportional hazards and Kaplan-Meier life table method. Results: The study included 270 men (51%) and 256 women (49%), with a median age of 63 years (mean, 62 years; range, 16-91 years). Median dose to the tumor apex was 94.4 Gy (mean, 97.8; range, 43.9-183.9) and to the tumor base was 257.9 Gy (mean, 275.6; range, 124.2-729.8). Plaque tilt >1 mm away from the sclera at plaque removal was detected in 142 cases (27%). Supplemental TTT was performed in 72 patients (13.7%). One or 2 TTT sessions were required in 71 TTT cases (98.6%). After a median follow-up of 45.9 months (mean, 53.4 months; range, 6-175 months), local tumor recurrence was detected in 19 patients (3.6%). Local tumor recurrence was associated with lower dose to the tumor base (P=.02). Conclusions: Ultrasound-guided plaque localization of I-125 EPB is associated with excellent local tumor control. Detection of plaque tilt by ultrasonography at plaque removal allows supplemental TTT to be used in patients at potentially higher risk for local recurrence while sparing the majority of patients who are at low risk. Most patients require only 1 or 2 TTT sessions.

  3. Combined PKC and MEK inhibition for treating metastatic uveal melanoma.

    PubMed

    Sagoo, M S; Harbour, J W; Stebbing, J; Bowcock, A M

    2014-09-25

    Uveal melanoma (UM) is the most common primary intraocular malignancy and the second most common form of melanoma. UM has a strong tendency for metastatic disease, and no effective treatments have yet been identified. Activating oncogenic mutations are commonly found in GNAQ and GNA11 in UM, and inhibiting key downstream effectors of the GNAQ/11 signaling pathway represents a rational therapeutic approach for treating metastatic UM. Chen et al., doi:10.1038/onc.2013.418, now confirm activation of the MAPK and PKC pathways as a result of GNAQ and GNA11 activating mutations in melanocytes, and they demonstrate that MAPK activation occurs downstream of PKC activation. PKC inhibitors disrupt MAPK signaling and block proliferation of GNAQ/11 mutant UM cell lines and slow the in vivo growth of xenografted UM tumors without inducing their shrinkage. However, a combination of PKC and MEK inhibition led to sustained MAPK pathway inhibition and tumor regression in vivo. Hence, the authors concluded that MEK and PKC inhibition is synergistic, with superior efficacy to treatment of GNAQ/GNA11 mutant UMs with either drug alone. PMID:24413085

  4. Combined PKC and MEK inhibition for treating metastatic uveal melanoma

    PubMed Central

    Sagoo, MS; Harbour, JW; Stebbing, J; Bowcock, AM

    2015-01-01

    Uveal melanoma (UM) is the most common primary intraocular malignancy and the second most common form of melanoma. UM has a strong tendency for metastatic disease, and no effective treatments have yet been identified. Activating oncogenic mutations are commonly found in GNAQ and GNA11 in UM, and inhibiting key downstream effectors of the GNAQ/11 signaling pathway represents a rational therapeutic approach for treating metastatic UM. Chen et al., doi:10.1038/onc.2013.418, now confirm activation of the MAPK and PKC pathways as a result of GNAQ and GNA11 activating mutations in melanocytes, and they demonstrate that MAPK activation occurs downstream of PKC activation. PKC inhibitors disrupt MAPK signaling and block proliferation of GNAQ/11 mutant UM cell lines and slow the in vivo growth of xenografted UM tumors without inducing their shrinkage. However, a combination of PKC and MEK inhibition led to sustained MAPK pathway inhibition and tumor regression in vivo. Hence, the authors concluded that MEK and PKC inhibition is synergistic, with superior efficacy to treatment of GNAQ/GNA11 mutant UMs with either drug alone. PMID:24413085

  5. Reduction of Nodular Growth Pattern of Metastatic Uveal Melanoma after Radioembolization of Hepatic Metastases

    PubMed Central

    Halenda, Kevin M.; Kudchadkar, Ragini R.; Lawson, David H.; Kies, Darren D.; Zhelnin, Kristen E.; Krasinskas, Alyssa M.; Grossniklaus, Hans E.

    2016-01-01

    Aim The aim of this study was to report a case of metastatic uveal melanoma in which radioembolized nodular liver metastases decreased in size while infiltrative sinusoidal metastases progressed, leading to jaundice without obstruction of the biliary ducts. Methods The relevant clinical features, imaging, and histopathologic findings of this case are reviewed. Results A 61-year-old Caucasian male with a history of uveal melanoma of the left eye status post plaque brachytherapy developed numerous liver metastases. After progression on systemic therapies, he underwent palliative radioembolization. Despite some radiographic improvement in the liver metastases, he developed hyperbilirubinemia without biliary tract obstruction or signs of liver failure. A biopsy of radiographically normal liver demonstrated extensive sinusoidal infiltration with melanoma. Conclusions Distinct angiographic and histopathologic growth patterns of metastatic uveal melanoma differ in their amenability to radioembolization. Sinusoidal infiltration may lead to hyperbilirubinemia in the absence of overt obstruction or liver failure. PMID:27239458

  6. Paraneoplastic cerebellar degeneration with anti-Yo antibodies associated with metastatic uveal melanoma.

    PubMed

    Valpione, Sara; Zoccarato, Marco; Parrozzani, Raffaele; Pigozzo, Jacopo; Giometto, Bruno; Laveder, Francesco; Aliberti, Camillo; Chiarion-Sileni, Vanna

    2013-12-15

    Paraneoplastic cerebellar degeneration (PCD) is characterized by subacute development of pancerebellar dysfunction as a remote effect of a systemic cancer and usually develops in patients affected by gynecological tumors. Uveal melanoma is a very rare disease with a severe prognosis. A 58-year-old man affected by uveal melanoma developed anti-Yo positive paraneoplastic cerebellar degeneration (PCD) 42 months after the initial diagnosis. The onset and worsening of the neurological symptoms were parallel to the course of liver metastasis. To our knowledge this is the first case of PCD in a patient with uveal melanoma. We speculate that the cerebellar degeneration-related protein 2 (CDR2), to which the anti-Yo antibodies are directed, may have been expressed in melanoma cells and conferred proliferative advantage to the disease. PMID:24035275

  7. Mda-9/Syntenin Is Expressed in Uveal Melanoma and Correlates with Metastatic Progression

    PubMed Central

    Gangemi, Rosaria; Mirisola, Valentina; Barisione, Gaia; Fabbi, Marina; Brizzolara, Antonella; Lanza, Francesco; Mosci, Carlo; Salvi, Sandra; Gualco, Marina; Truini, Mauro; Angelini, Giovanna; Boccardo, Simona; Cilli, Michele; Airoldi, Irma; Queirolo, Paola; Jager, Martine J.; Daga, Antonio; Pfeffer, Ulrich; Ferrini, Silvano

    2012-01-01

    Uveal melanoma is an aggressive cancer that metastasizes to the liver in about half of the patients, with a high lethality rate. Identification of patients at high risk of metastases may provide indication for a frequent follow-up for early detection of metastases and treatment. The analysis of the gene expression profiles of primary human uveal melanomas showed high expression of SDCBP gene (encoding for syndecan-binding protein-1 or mda-9/syntenin), which appeared higher in patients with recurrence, whereas expression of syndecans was lower and unrelated to progression. Moreover, we found that high expression of SDCBP gene was related to metastatic progression in two additional independent datasets of uveal melanoma patients. More importantly, immunohistochemistry showed that high expression of mda-9/syntenin protein in primary tumors was significantly related to metastatic recurrence in our cohort of patients. Mda-9/syntenin expression was confirmed by RT-PCR, immunofluorescence and immunohistochemistry in cultured uveal melanoma cells or primary tumors. Interestingly, mda-9/syntenin showed both cytoplasmic and nuclear localization in cell lines and in a fraction of patients, suggesting its possible involvement in nuclear functions. A pseudo-metastatic model of uveal melanoma to the liver was developed in NOD/SCID/IL2Rγ null mice and the study of mda-9/syntenin expression in primary and metastatic lesions revealed higher mda-9/syntenin in metastases. The inhibition of SDCBP expression by siRNA impaired the ability of uveal melanoma cells to migrate in a wound–healing assay. Moreover, silencing of SDCBP in mda-9/syntenin-high uveal melanoma cells inhibited the hepatocyte growth factor (HGF)-triggered invasion of matrigel membranes and inhibited the activation of FAK, AKT and Src. Conversely syntenin overexpression in mda-9/syntenin-low uveal melanoma cells mediated opposite effects. These results suggest that mda-9/syntenin is involved in uveal melanoma

  8. Case-control study on uveal melanoma (RIFA): rational and design

    PubMed Central

    Schmidt-Pokrzywniak, Andrea; Jöckel, Karl-Heinz; Bornfeld, Norbert; Stang, Andreas

    2004-01-01

    Background Although a rare disease, uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence rate of up to 1.0 per 100,000 persons per year in Europe. Only a few consistent risk factors have been identified for this disease. We present the study design of an ongoing incident case-control study on uveal melanoma (acronym: RIFA study) that focuses on radiofrequency radiation as transmitted by radio sets and wireless telephones, occupational risk factors, phenotypical characteristics, and UV radiation. Methods/Design We conduct a case-control study to identify the role of different exposures in the development of uveal melanoma. The cases of uveal melanoma were identified at the Division of Ophthalmology, University of Essen, a referral centre for tumours of the eye. We recruit three control groups: population controls, controls sampled from those ophthalmologists who referred cases to the Division of Ophthalmology, University of Duisburg-Essen, and sibling controls. For each case the controls are matched on sex and age (five year groups), except for sibling controls. The data are collected from the study participants by short self-administered questionnaire and by telephone interview. During and at the end of the field phase, the data are quality-checked. To estimate the effect of exposures on uveal melanoma risk, we will use conditional logistic regression that accounts for the matching factors and allows to control for potential confounding. PMID:15318944

  9. Precision, high dose radiotherapy: helium ion treatment of uveal melanoma

    SciTech Connect

    Saunders, W.M.; Char, D.H.; Quivey, J.M.; Castro, J.R.; Chen, G.T.Y.; Collier, J.M.; Cartigny, A.; Blakely, E.A.; Lyman, J.T.; Zink, S.R.

    1985-02-01

    The authors report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) the authors have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons.

  10. Uveal melanoma as a target for immune-therapy.

    PubMed

    Oliva, Marc; Rullan, Antonio J; Piulats, Josep M

    2016-05-01

    Uveal melanoma (UM) is a rare disease that can be deadly in spite of adequate local treatment. Systemic therapy with chemotherapy is usually ineffective and new-targeted therapies have not improved results considerably. The eye creates an immunosuppressive environment in order to protect eyesight. UM cells use similar processes to escape immune surveillance. Regarding innate immunity the production of macrophage inhibiting factor (MIF) and TGF-β, added to MHC class I upregulation, inhibits the action of natural killer (NK) cells. UM cells produce cytokines such as IL-6 and IL-10 that favor macrophage differentiation to the M2 subtype, which promote tumor growth instead of an effective immune response. UM cells also impair the adaptive immune response through production of indoleamine 2,3-dioxygenase (IDO), overexpression of programmed death ligand-1 (PD-L1), alteration of FasL expression, and resistance to perforin. This biological background suggests that immunotherapy could be effective in fighting UM. A Phase II clinical trial with Ipilimumab has shown promising results with mean Overall Survival rate of ten months, and close to 50% of the patients alive at one year. Clinical trials with anti-PD1 antibodies in monotherapy and in combination with anti-CTLA4 are currently recruiting patients worldwide. PMID:27275485

  11. Uveal melanoma as a target for immune-therapy

    PubMed Central

    Oliva, Marc; Rullan, Antonio J.

    2016-01-01

    Uveal melanoma (UM) is a rare disease that can be deadly in spite of adequate local treatment. Systemic therapy with chemotherapy is usually ineffective and new-targeted therapies have not improved results considerably. The eye creates an immunosuppressive environment in order to protect eyesight. UM cells use similar processes to escape immune surveillance. Regarding innate immunity the production of macrophage inhibiting factor (MIF) and TGF-β, added to MHC class I upregulation, inhibits the action of natural killer (NK) cells. UM cells produce cytokines such as IL-6 and IL-10 that favor macrophage differentiation to the M2 subtype, which promote tumor growth instead of an effective immune response. UM cells also impair the adaptive immune response through production of indoleamine 2,3-dioxygenase (IDO), overexpression of programmed death ligand-1 (PD-L1), alteration of FasL expression, and resistance to perforin. This biological background suggests that immunotherapy could be effective in fighting UM. A Phase II clinical trial with Ipilimumab has shown promising results with mean Overall Survival rate of ten months, and close to 50% of the patients alive at one year. Clinical trials with anti-PD1 antibodies in monotherapy and in combination with anti-CTLA4 are currently recruiting patients worldwide. PMID:27275485

  12. Expression of EpCAM in uveal melanoma

    PubMed Central

    Odashiro, Danilo N; Odashiro, Alexandre N; Pereira, Patrícia R; Godeiro, Katyanne; Antecka, Emilia; Di Cesare, Sebastian; Burnier, Miguel N

    2006-01-01

    Background Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults, and nearly 40% of UM will develop metastasis that will ultimately lead to death. The Epithelial Cell Adhesion Molecule (EpCAM) is a type I transmembrane glycoprotein expressed by carcinomas of head and neck, ovary, colon, breast, kidney and lung. Recently, antibodies against EpCAM such as Edrecolomab and Catumaxomab were developed, and clinical trials with these antibodies have been used in several types of neoplasia. We studied the expression of EpCAM in UM. Methods 25 enucleated formalin-fixed, paraffin-embedded UM specimens were immunostained for EpCAM. Histopathological analysis of the specimens with regards to prognostic factors such as cell type, largest (linear) tumor dimension, number of mitotic figures, scleral invasion and tumor infiltrating lymphocytes were done. Results None of them was positive for this EpCAM. Conclusion In our report, UM did not express EpCAM. Therefore, it is not a helpful immunohistochemical marker to predict the behavior of UM. Further studies are needed to verify if EpCAM could also be related with prognosis and treatment of UM. PMID:17125516

  13. iTRAQ Quantitative Proteomic Comparison of Metastatic and Non-Metastatic Uveal Melanoma Tumors

    PubMed Central

    Crabb, John W.; Hu, Bo; Crabb, John S.; Triozzi, Pierre; Saunthararajah, Yogen; Singh, Arun D.

    2015-01-01

    Background Uveal melanoma is the most common malignancy of the adult eye. The overall mortality rate is high because this aggressive cancer often metastasizes before ophthalmic diagnosis. Quantitative proteomic analysis of primary metastasizing and non-metastasizing tumors was pursued for insights into mechanisms and biomarkers of uveal melanoma metastasis. Methods Eight metastatic and 7 non-metastatic human primary uveal melanoma tumors were analyzed by LC MS/MS iTRAQ technology with Bruch’s membrane/choroid complex from normal postmortem eyes as control tissue. Tryptic peptides from tumor and control proteins were labeled with iTRAQ tags, fractionated by cation exchange chromatography, and analyzed by LC MS/MS. Protein identification utilized the Mascot search engine and the human Uni-Prot/Swiss-Protein database with false discovery ≤ 1%; protein quantitation utilized the Mascot weighted average method. Proteins designated differentially expressed exhibited quantitative differences (p ≤ 0.05, t-test) in a training set of five metastatic and five non-metastatic tumors. Logistic regression models developed from the training set were used to classify the metastatic status of five independent tumors. Results Of 1644 proteins identified and quantified in 5 metastatic and 5 non-metastatic tumors, 12 proteins were found uniquely in ≥ 3 metastatic tumors, 28 were found significantly elevated and 30 significantly decreased only in metastatic tumors, and 31 were designated differentially expressed between metastatic and non-metastatic tumors. Logistic regression modeling of differentially expressed collagen alpha-3(VI) and heat shock protein beta-1 allowed correct prediction of metastasis status for each of five independent tumor specimens. Conclusions The present data provide new clues to molecular differences in metastatic and non-metastatic uveal melanoma tumors. While sample size is limited and validation required, the results support collagen alpha-3(VI) and

  14. Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma

    PubMed Central

    Schally, Andrew V.; Block, Norman L; Dezso, Balazs; Olah, Gabor; Rozsa, Bernadett; Fodor, Klara; Buglyo, Armin; Gardi, Janos; Berta, Andras; Halmos, Gabor

    2013-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, these analogs could be considered for the LHRH receptor-based treatment of uveal melanoma. PMID:24077773

  15. Risk factors for residual and recurrent uveal melanoma after trans-scleral local resection.

    PubMed Central

    Damato, B E; Paul, J; Foulds, W S

    1996-01-01

    AIMS: The aims of this study were to report local tumour control after trans-scleral local resection of uveal melanoma and to identify risk factors for (i) clinical residual tumour recognised immediately after surgery, and (ii) delayed tumour recurrence from subclinical microscopic deposits. METHODS: The sample included 310 patients, treated by choroidectomy (188), cyclochoroidectomy (87), or iridocyclectomy (35), with follow up ranging from 42 days to 20.9 years (median 36 months), a mean basal largest tumour diameter of 13.2 mm, and a mean tumour thickness of 7.4 mm. RESULTS: There were 24 patients with residual tumour. Forward stepwise logistic regression indicated that posterior extension to within 1 disc diameter of the optic disc or fovea was the sole best indicator of the risk of residual disease (p < 0.001). After excluding these cases, 286 patients were studied for the development of delayed local recurrence, which occurred in 57 cases. Forward stepwise multivariate analysis showed the statistically significant predictors for recurrent tumour to be epithelioid cellularity (p = 0.002), posterior tumour extension to < 1 disc diameter of disc of fovea (p = 0.002), large tumour diameter > or = 16 mm (p = 0.019) and lack of adjunctive plaque radiotherapy (p = 0.018). CONCLUSIONS: The recurrence rate at 4 years varied from 6% if no risk factors were present to 57% if there were more than two risk factors. PMID:8814738

  16. Late prostatic metastasis of an uveal melanoma in a miniature Schnauzer dog.

    PubMed

    Delgado, Esmeralda; Silva, João X; Pissarra, Hugo; Peleteiro, Maria C; Dubielzig, Richard R

    2016-07-01

    This manuscript describes a previously unreported clinical case of canine uveal melanoma in a miniature Schnauzer dog with an unusual location of metastasis (prostate) and delayed occurrence (3 years after primary tumor diagnosis and enucleation). Immunohistochemical labeling of both tumors with Melan A, Ki-67, and c-kit added some valuable information. PMID:27386120

  17. Plaque Brachytherapy for Uveal Melanoma: A Vision Prognostication Model

    SciTech Connect

    Khan, Niloufer; Khan, Mohammad K.; Bena, James; Macklis, Roger; Singh, Arun D.

    2012-11-01

    Purpose: To generate a vision prognostication model after plaque brachytherapy for uveal melanoma. Methods and Materials: All patients with primary single ciliary body or choroidal melanoma treated with iodine-125 or ruthenium-106 plaque brachytherapy between January 1, 2005, and June 30, 2010, were included. The primary endpoint was loss of visual acuity. Only patients with initial visual acuity better than or equal to 20/50 were used to evaluate visual acuity worse than 20/50 at the end of the study, and only patients with initial visual acuity better than or equal to 20/200 were used to evaluate visual acuity worse than 20/200 at the end of the study. Factors analyzed were sex, age, cataracts, diabetes, tumor size (basal dimension and apical height), tumor location, and radiation dose to the tumor apex, fovea, and optic disc. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log rank analysis) were used to estimate freedom from vision loss. Results: Of 189 patients, 92% (174) were alive as of February 1, 2011. At presentation, visual acuity was better than or equal to 20/50 and better than or equal to 20/200 in 108 and 173 patients, respectively. Of these patients, 44.4% (48) had post-treatment visual acuity of worse than 20/50 and 25.4% (44) had post-treatment visual acuity worse than 20/200. By multivariable analysis, increased age (hazard ratio [HR] of 1.01 [1.00-1.03], P=.05), increase in tumor height (HR of 1.35 [1.22-1.48], P<.001), and a greater total dose to the fovea (HR of 1.01 [1.00-1.01], P<.001) were predictive of vision loss. This information was used to develop a nomogram predictive of vision loss. Conclusions: By providing a means to predict vision loss at 3 years after treatment, our vision prognostication model can be an important tool for patient selection and treatment counseling.

  18. Effects of Zeaxanthin on Growth and Invasion of Human Uveal Melanoma in Nude Mouse Model

    PubMed Central

    Xu, Xiaoliang L.; Iacob, Codrin; Jordan, Adrienne; Gandhi, Sandipkumar; Gierhart, Dennis L.; Rosen, Richard

    2015-01-01

    Uveal melanoma cells were inoculated into the choroid of nude mice and treated with or without intraocular injection of zeaxanthin. After 21 days, mice were sacrificed and the eyes enucleated. Histopathological analysis was performed in hematoxylin and eosin stained frozen sections. Melanoma developed rapidly in the control group (without treatment of zeaxanthin). Tumor-bearing eye mass and tumor mass in the control group were significantly greater than those in zeaxanthin treated group. Melanoma in the controlled eyes occupied a large part of the eye, was epithelioid in morphology, and was with numerous mitotic figures. Scleral perforation and extraocular extension were observed in half of the eyes. Melanomas in zeaxanthin treated eyes were significantly smaller with many necrosis and apoptosis areas and no extraocular extension could be found. Quantitative image analysis revealed that the tumor size was reduced by 56% in eyes treated with low dosages of zeaxanthin and 92% in eyes treatment with high dosages of zeaxanthin, as compared to the controls. This study demonstrated that zeaxanthin significantly inhibits the growth and invasion of human uveal melanoma in nude mice, suggesting that zeaxanthin may be a promising agent to be explored for the prevention and treatment of uveal melanoma. PMID:26682063

  19. [Study of a role of the expression of a transmembranous CD117/C-Kit receptor in the progression of uveal melanomas].

    PubMed

    Anurova, O A; Likhvantseva, V G; Vereshchagina, M V

    2007-01-01

    The authors studied the expression of the protooncogen receptor involved in the regulation of major cell cycle processes in uveal melanoma. The studies performed by a highly sensitive immunohistochemical technique. The findings have allowed the authors to state that the membranous CD117/C-Kit receptor plays an important role in the progression of uveal melanomas. It is suggested that the use of the new drug Glivec is promising in treating uveal melanoma. PMID:18078058

  20. High expression of immunotherapy candidate proteins gp100, MART-1, tyrosinase and TRP-1 in uveal melanoma.

    PubMed Central

    de Vries, T. J.; Trancikova, D.; Ruiter, D. J.; van Muijen, G. N.

    1998-01-01

    In the treatment of cutaneous melanoma, provisional therapeutic strategies have been designed to combat tumour load using T cells that are sensitized with peptides derived from melanoma autoantigens, such as glycoprotein 100 (gp100), melanoma antigen recognized by T cells 1 (MART-1 or MelanA), tyrosinase and tyrosinase-related protein 1 (TRP-1). We recently found that gp100, MART-1 and tyrosinase are heterogeneously expressed in human cutaneous melanoma (De Vries et al (1997) Cancer Res 57: 3223-3229). Here, we extended our investigations on expression of these immunotherapy candidate proteins to uveal melanoma lesions. Cryostat sections from 11 spindle-type, 21 mixed and epithelioid tumours and four metastasis lesions were stained with antibodies specifically recognizing gp100, MART-1, tyrosinase and TRP-1. In addition, we used the DOPA reaction to detect tyrosinase enzyme activity as a confirmation of the tyrosinase immunohistochemical results. High expression of gp100, MART-1 and tyrosinase was found in the uveal melanoma lesions: 80% of the lesions displayed 75-100% positive tumour cells. TRP-1 positivity was slightly less: approximately 65% of the lesions stained in the 75-100% positive tumour cell category. All uveal melanoma lesions were positive for the four markers studied, this being in contrast to cutaneous melanoma where 17% of the advanced primary lesions and metastases were negative. The presence of these antigens was a little lower in metastases. We conclude that uveal melanomas and their metastases express melanocyte-lineage immunotherapy candidate proteins very abundantly. Uveal melanomas differ in this respect from cutaneous melanoma, in which the expression of these immunotherapy antigens was much more heterogeneous. This makes uveal melanoma a suitable candidate tumour for immunotherapeutic approaches. Images Figure 1 Figure 3 PMID:9820172

  1. The use of pembrolizumab for the treatment of metastatic uveal melanoma.

    PubMed

    Kottschade, Lisa A; McWilliams, Robert R; Markovic, Svetomir N; Block, Matthew S; Villasboas Bisneto, Jose; Pham, Anthony Q; Esplin, Brandt L; Dronca, Roxana S

    2016-06-01

    Uveal melanoma is a rare type of melanoma, with only five to seven cases per one million persons diagnosed each year. Patients with metastatic melanoma of uveal origin tend to have lower response rates on traditional therapies. Herein we report our experience with 10 patients with metastatic uveal melanoma (MUM) who received pembrolizumab. Eligible patients were more than or equal to 18 years old, had unresectable MUM, progressed on prior ipilimumab therapy, had good performance status (Eastern Cooperative Oncology Group of 0 or 1), and adequate organ and marrow function. Patients could have central nervous system disease, but needed to be clinically stable. Patients were treated with 2 mg/kg pembrolizumab intravenously over 30 min every 3 weeks until disease progression, unacceptable toxicity, or for up to 2 years. Between April 2014 and October 2014, we treated a total of 10 patients with MUM with pembrolizumab. Median age was 65 years, with 70% being female. As of the data cutoff date of 14 May 2015, median progression-free survival was 18 weeks (range 3.14-49.3 weeks), with four patients still currently receiving therapy. Of eight evaluable patients, there was one complete response, two partial responses, and one patient with stable disease. Four patients had rapidly progressive disease. Toxicities were as expected and were usually grade 1/2 in nature. Although this cohort of patients was small, to our knowledge this is the first such report of outcomes in uveal melanoma patients being treated with anti-PD1 therapy. In the absence of a clinical trial, treatment with pembrolizumab appears to be a viable option for patients with MUM. PMID:26848796

  2. The impact of selected factors on early diagnosis of multiple primary cancers in patients with uveal melanoma

    PubMed Central

    Romanowska-Dixon, Bożena

    2013-01-01

    Aim of the study To find differences between a group of patients with intraocular melanoma and another primary cancer and a group of patients with no identifiable second primary cancer. Material and methods The analysis involved 240 participants, selected from patients who were treated for uveal melanoma at the Department of Ophthalmology and Ocular Oncology of the Jagiellonian University Medical College between the year 1998 and 2007. Among those patients 97 were diagnosed with one or more independent primary cancers. Those patients were subject to a comparative analysis with a second group of 143 patients who had uveal melanoma with no identifiable second primary cancer. Results Statistically significant differences between the group of patients with intraocular melanoma and another primary cancer, and the group of patients with uveal melanoma (but without another diagnosed primary neoplasm) were as follows: more common family history of cancer, better education, living in cities (especially with a population over 500 thousand), previous surgery except for uveal melanoma, and two or less than two pregnancies in the case of women. Conclusions This analysis revealed that more common family history of cancer, better education, living in cities (especially with a population over 500 thousand), previous surgery, except for uveal melanoma, and two or less than two pregnancies in the case of women, were associated with a higher rate of detection of multiple primary cancers. PMID:24592138

  3. ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma.

    PubMed

    Yoo, Jae Hyuk; Shi, Dallas S; Grossmann, Allie H; Sorensen, Lise K; Tong, ZongZhong; Mleynek, Tara M; Rogers, Aaron; Zhu, Weiquan; Richards, Jackson R; Winter, Jacob M; Zhu, Jie; Dunn, Christine; Bajji, Ashok; Shenderovich, Mark; Mueller, Alan L; Woodman, Scott E; Harbour, J William; Thomas, Kirk R; Odelberg, Shannon J; Ostanin, Kirill; Li, Dean Y

    2016-06-13

    Activating mutations in Gαq proteins, which form the α subunit of certain heterotrimeric G proteins, drive uveal melanoma oncogenesis by triggering multiple downstream signaling pathways, including PLC/PKC, Rho/Rac, and YAP. Here we show that the small GTPase ARF6 acts as a proximal node of oncogenic Gαq signaling to induce all of these downstream pathways as well as β-catenin signaling. ARF6 activates these diverse pathways through a common mechanism: the trafficking of GNAQ and β-catenin from the plasma membrane to cytoplasmic vesicles and the nucleus, respectively. Blocking ARF6 with a small-molecule inhibitor reduces uveal melanoma cell proliferation and tumorigenesis in a mouse model, confirming the functional relevance of this pathway and suggesting a therapeutic strategy for Gα-mediated diseases. PMID:27265506

  4. Management of Radiation-induced Severe Anophthalmic Socket Contracture in Patients with Uveal Melanoma

    PubMed Central

    Nasser, Qasiem J.; Gombos, Dan S.; Williams, Michelle D.; Guadagnolo, B. Ashleigh; Morrison, William H.; Garden, Adam S.; Beadle, Beth M.; Canseco, Elvia; Esmaeli, Bita

    2012-01-01

    Purpose High-dose radiotherapy can cause contracture of the anophthalmic socket, but the incidence of this complication in patients with enucleation for uveal melanoma has not previously been reported. We reviewed the surgical management and outcomes in terms of successful prosthesis wear in patients with severe contracture of the anophthalmic socket treated with high-dose radiotherapy for high-risk uveal melanoma and estimated the relative risk of this complication. Methods The medical records of all consecutive patients enrolled in a prospective uveal-melanoma tissue-banking protocol at our institution who underwent enucleation between January 2003 and December 2010 were reviewed. Patients who underwent adjuvant radiotherapy of the enucleated socket were further studied. Results Of the 68 patients enrolled in the prospective tissue banking protocol, 12 had high-risk histologic features (e.g., extrascleral spread or vortex vein invasion) and were treated with 60 Gy of external-beam radiotherapy after enucleation. Five of these patients (41.7%) experienced severe socket contracture precluding prosthesis wear. The median time to onset of contracture following completion of radiotherapy was 20 months. Three patients underwent surgery, which entailed scar tissue release, oral mucous membrane grafting, and socket reconstruction; 2 patients declined surgery. All 3 patients who had surgery experienced significant improvement of socket contracture that enabled patients to wear a prosthesis again. Conclusion High-dose radiotherapy after enucleation in patients with uveal melanoma caused severe socket contracture and inability to wear a prosthesis in approximately 40% of patients. Surgical repair of the contracted socket using oral mucous membrane grafting can allow resumption of prosthesis wear. PMID:22581085

  5. Charged Particle Radiation Therapy for Uveal Melanoma: A Systematic Review and Meta-Analysis

    SciTech Connect

    Wang, Zhen; Nabhan, Mohammed; Schild, Steven E.; Stafford, Scott L.; Petersen, Ivy A.; Foote, Robert L.; Murad, M. Hassan

    2013-05-01

    Charged particle therapy (CPT) delivered with either protons, helium ions, or carbon ions, has been used to treat uveal melanoma. The present analysis was performed to systematically evaluate the efficacy and adverse effects of CPT for uveal melanoma. We searched EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus and cross-referenced recent systematic reviews through January 2012. Two independent reviewers identified clinical trials and observational studies of CPT (protons, helium ions, and carbon ions). These reviewers extracted data and assessed study quality. Twenty-seven studies enrolling 8809 uveal melanoma patients met inclusion criteria. The rate of local recurrence was significantly less with CPT than with brachytherapy (odds ratio [OR] = 0.22, 95% confidence interval [CI], 0.21-0.23). There were no significant differences in mortality or enucleation rates. Results were robust in multiple sensitivity analyses. CPT was also associated with lower retinopathy and cataract formation rates. Data suggest better outcomes may be possible with charged particle therapy with respect to local recurrence, retinopathy, and cataract formation rates. The overall quality of the evidence is low, and higher quality comparative effectiveness studies are needed to provide better evidence.

  6. The pharmacological NF-κB inhibitor BAY11-7082 induces cell apoptosis and inhibits the migration of human uveal melanoma cells.

    PubMed

    Hu, Shuiqing; Luo, Qingqiong; Cun, Biyun; Hu, Dan; Ge, Shengfang; Fan, Xianqun; Chen, Fuxiang

    2012-01-01

    Uveal melanomas are highly metastatic and have high rate of recurrence due to the lack of effective systemic therapy. The identification of important survival pathways in uveal melanomas provides novel therapeutic targets for effective treatment. In the present study, we found that the NF-κB signaling pathway was constitutively and highly activated in uveal melanoma cells. Treatment with the pharmacological NF-κB specific inhibitor BAY11-7082 markedly decreased the nuclear translocation of NF-κB. In a dose-dependent setting, BAY11-7082 inhibited the proliferation and growth of uveal melanoma cells by inducing apoptosis without effect on cell cycle. The migration capacity of uveal melanoma cells was also significantly suppressed by BAY11-7082 treatment. Mechanistically, BAY11-7082 increased the activity of caspase 3 and reduced the expression of anti-apoptotic protein Bcl-2, but did not influence the expression of pro-apoptotic protein Bax. Furthermore, BAY11-7082 induced uveal melanoma cell apoptosis and inhibited xenograft tumor growth in vivo. Collectively, the present study identified NF-κB as an important survival signal for uveal melanoma cells and suggested that administration of specific NF-κB inhibitor BAY11-7082 could serve as an effective treatment for patients with uveal melanoma. PMID:23443086

  7. The Pharmacological NF-κB Inhibitor BAY11-7082 Induces Cell Apoptosis and Inhibits the Migration of Human Uveal Melanoma Cells

    PubMed Central

    Hu, Shuiqing; Luo, Qingqiong; Cun, Biyun; Hu, Dan; Ge, Shengfang; Fan, Xianqun; Chen, Fuxiang

    2012-01-01

    Uveal melanomas are highly metastatic and have high rate of recurrence due to the lack of effective systemic therapy. The identification of important survival pathways in uveal melanomas provides novel therapeutic targets for effective treatment. In the present study, we found that the NF-κB signaling pathway was constitutively and highly activated in uveal melanoma cells. Treatment with the pharmacological NF-κB specific inhibitor BAY11-7082 markedly decreased the nuclear translocation of NF-κB. In a dose-dependent setting, BAY11-7082 inhibited the proliferation and growth of uveal melanoma cells by inducing apoptosis without effect on cell cycle. The migration capacity of uveal melanoma cells was also significantly suppressed by BAY11-7082 treatment. Mechanistically, BAY11-7082 increased the activity of caspase 3 and reduced the expression of anti-apoptotic protein Bcl-2, but did not influence the expression of pro-apoptotic protein Bax. Furthermore, BAY11-7082 induced uveal melanoma cell apoptosis and inhibited xenograft tumor growth in vivo. Collectively, the present study identified NF-κB as an important survival signal for uveal melanoma cells and suggested that administration of specific NF-κB inhibitor BAY11-7082 could serve as an effective treatment for patients with uveal melanoma. PMID:23443086

  8. Optimizing LINAC-based stereotactic radiotherapy of uveal melanomas: 7 years' clinical experience

    SciTech Connect

    Dieckmann, Karin . E-mail: Karin.Dieckmann@akhwien.at; Georg, Dietmar; Bogner, Joachim; Zehetmayer, Martin; Petersch, Bernhard; Chorvat, Martin; Weitmann, Hajo; Poetter, Richard

    2006-11-15

    Purpose: To report on the clinical outcome of LINAC-based stereotactic radiotherapy (SRT) of uveal melanomas. Additionally, a new prototype (hardware and software) for automated eye monitoring and gated SRT using a noninvasive eye fixation technique is described. Patients and Methods: Between June 1997 and March 2004, 158 patients suffering from uveal melanoma were treated at a LINAC with 6 MV (5 x 14 Gy; 5 x 12 Gy prescribed to 80% isodose) photon beams. To guarantee identical patient setup during treatment planning (CT and MRI) and treatment delivery, patients were immobilized with a BrainLAB thermoplastic mask. Eye immobilization was achieved by instructing the patient to fixate on a light source integrated into the mask system. A mini-video camera was used to provide on-line information about the eye and pupil position, respectively. A new CT and magnetic resonance (MR) compatible prototype, based on head-and-neck fixation and the infrared tracking system ExacTrac, has been developed and evaluated since 2002. This system records maximum temporal and angular deviations during treatment and, based on tolerance limits, a feedback signal to the LINAC enables gated SRT. Results: After a median follow-up of 33.4 months (range, 3-85 months), local control was achieved in 98%. Fifteen patients (9.0%) developed metastases. Secondary enucleation was performed in 23 patients (13.8%). Long-term side effects were retinopathy (n = 70; 44%), cataract (n = 30; 23%), optic neuropathy (n = 65; 41%), and secondary neovascular glaucoma (n = 23; 13.8%). Typical situations when preset deviation criteria were exceeded were slow drifts (fatigue), large sudden eye movements (irritation), or eye closing (fatigue). In these cases, radiation was reliably interrupted by the gating system. In our clinical setup, the novel system for computer-controlled gated SRT of uveal melanoma was well tolerated by about 30 of the patients treated with this system so far. Conclusion: LINAC-based SRT of

  9. Management of uveal melanoma: a consensus-based provincial clinical practice guideline

    PubMed Central

    Weis, E.; Salopek, T.G.; McKinnon, J.G.; Larocque, M.P.; Temple-Oberle, C.; Cheng, T.; McWhae, J.; Sloboda, R.; Shea-Budgell, M.

    2016-01-01

    Introduction Survival in uveal melanoma has remained unchanged since the early 1970s. Because outcomes are highly related to the size of the tumour, timely and accurate diagnosis can increase the chance for cure. Methods A consensus-based guideline was developed to inform practitioners. PubMed was searched for publications related to this topic. Reference lists of key publications were hand-searched. The National Guidelines Clearinghouse and individual guideline organizations were searched for relevant guidelines. Consensus discussions by a group of content experts from medical, radiation, and surgical oncology were used to formulate the recommendations. Results Eighty-four publications, including five existing guidelines, formed the evidence base. Summary Key recommendations highlight that, for uveal melanoma and its indeterminate melanocytic lesions in the uveal tract, management is complex and requires experienced specialists with training in ophthalmologic oncology. Staging examinations include serum and radiologic investigations. Large lesions are still most often treated with enucleation, and yet radiotherapy is the most common treatment for tumours that qualify. Adjuvant therapy has yet to demonstrate efficacy in reducing the risk of metastasis, and no systemic therapy clearly improves outcomes in metastatic disease. Where available, enrolment in clinical trials is encouraged for patients with metastatic disease. Highly selected patients might benefit from surgical resection of liver metastases. PMID:26966414

  10. Ki-67 immunostaining in uveal melanoma. The effect of pre-enucleation radiotherapy

    SciTech Connect

    Mooy, C.M.; de Jong, P.T.; Van der Kwast, T.H.; Mulder, P.G.; Jager, M.J.; Ruiter, D.J. )

    1990-10-01

    The reactivity of 33 choroidal and ciliary body melanomas with monoclonal antibody Ki-67, which recognizes a proliferation associated nuclear antigen, has been assessed and compared with clinicopathologic parameters. In 23 cases, 8 Gy irradiation was given 2 days before enucleation. Nonirradiated melanomas had a significantly higher proliferation rate as defined by staining with monoclonal antibody Ki-67 as compared with irradiated tumors (P = 0.007). Similarly, a strong relationship was found between pre-enucleation irradiation and low mitotic activity (P = 0.001). There was no significant correlation between the presence of Ki-67-positive nuclei and histologic classification, largest tumor diameter, localization of the tumor, age, sex, scleral invasion, pigmentation, and lymphocytic infiltration. The relevance of Ki-67 immunohistochemistry for the assessment of the life prognosis of patients with uveal melanoma has to be studied prospectively.

  11. Proton Beam Radiotherapy for Uveal Melanomas at Nice Teaching Hospital: 16 Years' Experience

    SciTech Connect

    Caujolle, Jean-Pierre; Mammar, Hamid; Chamorey, Emmanuel Phar; Pinon, Fabien; Herault, Joel; Gastaud, Pierre

    2010-09-01

    Purpose: To present the results of uveal melanomas treated at Nice Teaching Hospital. Methods and Materials: This retrospective study included 886 consecutive patients referred to our clinic for the treatment of uveal melanomas by proton beam radiotherapy from June 1991 to December 2007. Survival rates were determined by using Kaplan-Meier estimates, and prognostic factors were evaluated using the log-rank test or Cox model. Results: The number (percent total) of subjects staged according to the TNM classification system (6th edition) of malignant tumors included 39 stage T1 (4.4%), 420 stage T2 (47.40%), 409 stage T3 (46.16%), and 18 stage T4 (2.03%) patients. The median follow-up was 63.7 months. The Kaplan-Meier overall survival rate at 5 years according to the sixth edition TNM classification was 92% for T1, 89% for T2, 67% for T3, and 62% for T4; and at 10 years, 86% for T1, 78% for T2, 43% for T3, and 41% for T4. Five factors were found to be associated with an increased death rate: advanced age, tumor thickness, largest tumor basal diameter, tumor volume, and tumor volume-to-eyeball volume ratio. The metastasis-free survival rates were 88.3 % at 5 years and 76.4 % at 10 years. The local control rates were 93.9% at 5 years and 92.1% at 10 years. The ocular conservation rates were 91.1% at 5 years and 87.3% at 10 years. Conclusions: We report the results of a large series of patients treated for uveal melanomas with a very long follow-up. Despite the large tumor volume treated, our results were similar to previously published findings relating to proton beam therapy.

  12. Prognostic parameters in uveal melanoma and their association with BAP1 expression

    PubMed Central

    van Essen, T Huibertus; van Pelt, Sake I; Versluis, Mieke; Bronkhorst, Inge HG; van Duinen, Sjoerd G; Marinkovic, Marina; Kroes, Wilma GM; Ruivenkamp, Claudia AL; Shukla, Shruti; de Klein, Annelies; Kiliç, Emine; Harbour, J William; Luyten, Gregorius PM; van der Velden, Pieter A; Verdijk, Rob M; Jager, Martine J

    2016-01-01

    Aim To determine whether BAP1 gene and protein expression associates with different prognostic parameters in uveal melanoma and whether BAP1 expression correctly identifies patients as being at risk for metastases, following enucleation of the primary tumour. Methods Thirty cases of uveal melanoma obtained by enucleation between 1999 and 2004 were analysed for a variety of prognostic markers, including histological characteristics, chromosome aberrations obtained by fluorescence in situ hybridisation (FISH) and single nucleotide polymorphism (SNP) analysis and gene expression profiling. These parameters were compared with BAP1 gene expression and BAP1 immunostaining. Results The presence of monosomy of chromosome 3 as identified by the different chromosome 3 tests showed significantly increased HRs (FISH on isolated nuclei cut-off 30%: HR 11.6, p=0.002; SNP analysis: HR 20.3, p=0.004) for death due to metastasis. The gene expression profile class 2, based on the 15-gene expression profile, similarly provided a significantly increased HR for a poor outcome (HR 8.5, p=0.005). Lower BAP1 gene expression and negative BAP1 immunostaining (50% of 28 tumours were immunonegative) were both associated with these markers for prognostication: FISH cut-off 30% monosomy 3 (BAP1 gene expression: p=0.037; BAP1 immunostaining: p=0.001), SNP-monosomy 3 (BAP1 gene expression: p=0.008; BAP1 immunostaining: p=0.002) and class 2 profile (BAP1 gene expression: p<0.001; BAP1 immunostaining: p=0.001) and were themselves associated with an increased risk of death due to metastasis (BAP1 gene expression dichotomised: HR 8.7, p=0.006; BAP1 immunostaining: HR 4.0, p=0.010). Conclusions Loss of BAP1 expression associated well with all of the methods currently used for prognostication and was itself predictive of death due to metastasis in uveal melanoma after enucleation, thereby emphasising the importance of further research on the role of BAP1 in uveal melanoma. PMID:25147369

  13. Conservation treatment of the eye: Conformal proton reirradiation for recurrent uveal melanoma

    SciTech Connect

    Marucci, Laura; Lane, Anne M.; Li Wenjun; Egan, Kathleen M.; Gragoudas, Evangelos S.; Adams, Judy; Collier, John M.; Munzenrider, John E. . E-mail: jmunzenrider@partners.org

    2006-03-15

    Purpose: To evaluate the outcomes of a second course of proton beam radiation therapy (PBRT) in patients with recurrent uveal melanoma. Methods and Materials: Thirty-one patients received a second course of PBRT. The mean interval between the first and the second PBRT course was 50.2 months (range, 8-165 months). Most patients (87%) received 70 cobalt Gray equivalent (CGE) for both courses. Visual acuity was 20/200 or better in 30 patients initially and in 22 patients at the second treatment. The mean follow-up time after the second treatment was 50 months (range, 6-164 months). Results: At the time of the last follow-up, 20 patients were classified as having no evidence of disease, defined as tumor regression or an absence of tumor progression. Nine eyes (29%) were enucleated because of local recurrence (n = 5) or intractable pain (n = 4). The 5-year eye retention rate was 55% (95% confidence interval: 25.2-77.4). Six of the 22 patients who retained the eye (27%) had useful vision (20/200 or better). Conclusions A second course of PBRT for recurrent uveal melanoma to total doses between 118 and 140 CGE was associated with a relatively good probability of local control and a low enucleation rate. Although most patients lost vision, the majority were able to retain the reirradiated eye. Further evaluation is needed to assess metastasis-free survival of additional proton irradiation vs. enucleation after local recurrence.

  14. An Accurate, Clinically Feasible Multi-Gene Expression Assay for Predicting Metastasis in Uveal Melanoma

    PubMed Central

    Onken, Michael D.; Worley, Lori A.; Tuscan, Meghan D.; Harbour, J. William

    2010-01-01

    Uveal (ocular) melanoma is an aggressive cancer that often forms undetectable micrometastases before diagnosis of the primary tumor. These micrometastases later multiply to generate metastatic tumors that are resistant to therapy and are uniformly fatal. We have previously identified a gene expression profile derived from the primary tumor that is extremely accurate for identifying patients at high risk of metastatic disease. Development of a practical clinically feasible platform for analyzing this expression profile would benefit high-risk patients through intensified metastatic surveillance, earlier intervention for metastasis, and stratification for entry into clinical trials of adjuvant therapy. Here, we migrate the expression profile from a hybridization-based microarray platform to a robust, clinically practical, PCR-based 15-gene assay comprising 12 discriminating genes and three endogenous control genes. We analyze the technical performance of the assay in a prospective study of 609 tumor samples, including 421 samples sent from distant locations. We show that the assay can be performed accurately on fine needle aspirate biopsy samples, even when the quantity of RNA is below detectable limits. Preliminary outcome data from the prospective study affirm the prognostic accuracy of the assay. This prognostic assay provides an important addition to the armamentarium for managing patients with uveal melanoma, and it provides a proof of principle for the development of similar assays for other cancers. PMID:20413675

  15. MicroRNA-34b/c suppresses uveal melanoma cell proliferation and migration through multiple targets

    PubMed Central

    Dong, Feng

    2012-01-01

    Purpose MicroRNAs (miRNAs) are endogenously expressed, small noncoding RNAs that inhibit gene expression by binding to target mRNAs. Recent studies have revealed that miRNAs function as tumor suppressors or oncogenes. In the present study, we investigated the role of miRNA-34b/c in uveal melanoma. Methods Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect the expression level of miR-34b/c in uveal melanoma cells and primary samples. Subsequently, uveal melanoma cell proliferation was examined by the MTS (3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl] -2H-tetrazolium, inner salt) assay, clone formation assay, and flow cytometry. Cell apoptosis was measured by caspase3/7 assay. Cell migration was evaluated by transwell migration assay. The target of miR-34b/c was predicted by bioinformatics and validated by luciferase assay. In addition, the effect of miR-34b/c on c-Met, cell cycle-related proteins, v-akt murine thymoma viral oncogene homolog (Akt) and extracellular signal-regulated kinase (ERK) pathway was determined by western blotting. Results miR-34b/c expression, which was dramatically decreased in uveal melanoma cells and clinical samples, can be upregulated by doxorubicin and epigenetic drugs. The transfection of miR-34b/c into uveal melanoma cells leads to a significant reduction in cell growth and migration. miR-34b/c caused cell cycle G1 arrest rather than the induction of apoptosis. Met proto-oncogene (c-Met) was identified as a target of miR-34b/c in uveal melanoma cells. Furthermore, miR-34b/c was confirmed to downregulate the expression of c-Met, p-Akt, and cell cycle–related proteins by western blotting. Conclusions Our results demonstrate that both miR-34b and miR-34c act as tumor suppressors in uveal melanoma cell proliferation and migration through the downregulation of multiple targets. PMID:22419847

  16. Collaborative Ocular Oncology Group Report No. 1: Prospective Validation of a Multi-Gene Prognostic Assay in Uveal Melanoma

    PubMed Central

    Onken, Michael D.; Worley, Lori A.; Char, Devron H.; Augsburger, James J.; Correa, Zelia M; Nudleman, Eric; Aaberg, Thomas M.; Altaweel, Michael M.; Bardenstein, David S.; Finger, Paul T.; Gallie, Brenda L.; Harocopos, George J.; Hovland, Peter G.; McGowan, Hugh D.; Milman, Tatyana; Mruthyunjaya, Prithvi; Simpson, E. Rand; Smith, Morton E.; Wilson, David J.; Wirostko, William J.; Harbour, J. William

    2012-01-01

    Purpose This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk). Design Prospective, multicenter study. Participants 459 patients with posterior uveal melanoma were enrolled from 12 independent centers. Testing Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP to the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and to chromosome 3 status. Main Outcome Measures Patients were managed for their primary tumor and monitored for metastasis. Results The GEP assay successfully classified 446/459 (97.2%) cases. The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 (1.1%) class 1 cases and 44 (25.9%) class 2 cases (log rank test, P<10−14). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54/260 (20.8%) tumors were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log rank test, P=0.0001). Using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P=0.2). At three years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P=0.001) and 0.38 (P=0.004) over chromosome 3 status. Conclusions The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. GEP provided a highly significant

  17. A Rare Thyroid Metastasis from Uveal Melanoma and Response to Immunotherapy Agents

    PubMed Central

    Collins, Dearbhaile Catherine; Yela, Ruben; Horgan, Noel; Power, Derek Gerard

    2016-01-01

    Thyroid metastasis is a rare occurrence with cutaneous melanoma and even more uncommon with uveal melanoma. The management of such metastasis is uncertain due to its infrequency and, in the era of immunotherapy, the effect of these novel drugs on uncommon metastasis, such as to the thyroid, is unknown. We report the rare case of a thyroid metastasis in a patient diagnosed with ocular melanoma initially managed with enucleation. Metastatic disease developed in the lung and thyroid gland. The case patient received the immunotherapy ipilimumab with stable disease in the thyroid and progressive disease elsewhere. The patient was then further treated with a second immunotherapy agent, pembrolizumab, and remains with stable disease one year later. We discuss the current literature on thyroid metastases from all causes and the optimal known management strategies. Furthermore, we provide an original report on the response of this disease to the novel immunomodulators, ipilimumab, and pembrolizumab with stable disease four years after initial diagnosis of ocular melanoma. PMID:27110415

  18. Expression patterns of cyclin D1 and related proteins regulating G1-S phase transition in uveal melanoma and retinoblastoma

    PubMed Central

    Coupland, S; Bechrakis, N; Schuler, A; Anagnostopoulos, I; Hummel, M; Bornfeld, N; Stein, H

    1998-01-01

    BACKGROUND/AIMS—A checkpoint mechanism in late G1, whose regulation via loss of retinoblastoma protein (pRB) or p16, or overexpression of cyclin D1 or cyclin dependent kinase 4 (CDK4), has been proposed to constitute a common pathway to malignancy. The aims of this study were (a) to compare markers of cell cycle G1-S phase transition in an intraocular tumour with known pRB deficiency (retinoblastoma) and compare it with one with an apparently functional pRB (uveal melanoma); (b) to determine if one of these markers may have a role in the pathogenesis of uveal melanoma; and (c) to determine if there is a difference in cell cycle marker expression following treatment of uveal melanoma and retinoblastoma.
METHODS—90 eyes were enucleated from 89 patients for retinoblastoma (n=24) or for choroidal or ciliary body melanoma (n=66). Conventional paraffin sections were assessed for cell type and degree of differentiation. Additional slides were investigated applying standard immunohistochemical methods with antibodies specific for cyclin D1 protein, pRB, p53, p21, p16, BCL-2, and MIB-1.
RESULTS—Cyclin D1 protein and pRB were negative in retinoblastoma using the applied antibodies. In contrast, cyclin D1 protein expression was observed in 65% of uveal melanomas; a positive correlation between cyclin D1 cell positivity and tumour cell type, location, growth fraction, as well as with pRB positivity was observed. p53, p21, and p16 could be demonstrated in both tumours. An inverse relation between p53 and p21 expression was demonstrated in most choroidal melanomas and in some retinoblastomas. Apart from a decrease in the growth fractions of the tumours as determined by MIB-1, a significant difference in the expression of G1-S phase transition markers in vital areas of uveal melanoma and retinoblastoma following treatment with radiotherapy and/or chemotherapy was not observed.
CONCLUSION—Retinoblastomas and uveal melanomas, two tumours of differing pRB status

  19. The SDF-1/CXCR4 chemokine axis in uveal melanoma cell proliferation and migration.

    PubMed

    Bi, Jianjun; Li, Peng; Li, Chuanyin; He, Jie; Wang, Ying; Zhang, He; Fan, Xianqun; Jia, Renbing; Ge, Shengfang

    2016-03-01

    The stromal-cell-derived factor 1 (SDF-1)/chemokine receptor 4 (CXCR4) chemokine axis plays a key role in tumor migration. Here, we analyzed the axis in uveal melanoma (UM) proliferation and migration and investigated the effect of a chemical inhibitor of CXCR4, AMD3100, on UM. We found that CXCR4 was expressed in all five UM cell lines tested as well as the retinal pigment epithelium cell line ARPE-19 cells, while CXCR7 was only detected in OM290 and VUP cell lines. SDF-1 promotes the proliferation and migration of OCM-1 and OCM431 cell lines, while AMD3100 weakens this function. Taken together, our results show that the SDF-1/CXCR4 chemokine axis plays a key role in UM cell proliferation and migration and that AMD3100 can alleviate this function, which may offer a hint for UM treatment. PMID:26490988

  20. The role of Bax and Bcl-2 in gemcitabine-mediated cytotoxicity in uveal melanoma cells.

    PubMed

    Wang, Jing; Jia, Renbing; Zhang, Yidan; Xu, Xiaofang; Song, Xin; Zhou, Yixiong; Zhang, He; Ge, Shengfang; Fan, Xianqun

    2014-02-01

    Gemcitabine (GEM), a new cytotoxic agent, was shown to be effective against uveal melanoma (UM) which is noted for its resistance to chemotherapy. In this study, we found the different sensitivities to GEM in UM cell lines and identified apoptotic cell death as the cause of GEM cytotoxicity. Both UM cell lines showed an increase in Bax protein levels and activation of cleaved Caspase 3. Additionally, SP6.5 cells showed a gradual increase in Bcl-2 expression over time, whereas VUP cells showed almost none. After interfering in the expression of Bcl-2, the sensitivity to GEM was obviously enhanced in SP6.5 cells. These results suggest that an increase in Bax plays a crucial role in apoptotic cell death induced by GEM in the absence of p53. Moreover, inhibition of Bcl-2 expression can efficiently enhance the cytotoxic effect of, and sensitivity to, GEM in UM cells. PMID:24014050

  1. Local Recurrence After Uveal Melanoma Proton Beam Therapy: Recurrence Types and Prognostic Consequences

    SciTech Connect

    Caujolle, Jean-Pierre; Paoli, Vincent; Chamorey, Emmanuel; Maschi, Celia; Baillif, Stéphanie; Herault, Joël; Gastaud, Pierre; Hannoun-Levi, Jean Michel

    2013-04-01

    Purpose: To study the prognosis of the different types of uveal melanoma recurrences treated by proton beam therapy (PBT). Methods and Materials: This retrospective study analyzed 61 cases of uveal melanoma local recurrences on a total of 1102 patients treated by PBT between June 1991 and December 2010. Survival rates have been determined by using Kaplan-Meier curves. Prognostic factors have been evaluated by using log-rank test or Cox model. Results: Our local recurrence rate was 6.1% at 5 years. These recurrences were divided into 25 patients with marginal recurrences, 18 global recurrences, 12 distant recurrences, and 6 extrascleral extensions. Five factors have been identified as statistically significant risk factors of local recurrence in the univariate analysis: large tumoral diameter, small tumoral volume, low ratio of tumoral volume over eyeball volume, iris root involvement, and safety margin inferior to 1 mm. In the local recurrence-free population, the overall survival rate was 68.7% at 10 years and the specific survival rate was 83.6% at 10 years. In the local recurrence population, the overall survival rate was 43.1% at 10 years and the specific survival rate was 55% at 10 years. The multivariate analysis of death risk factors has shown a better prognosis for marginal recurrences. Conclusion: Survival rate of marginal recurrences is superior to that of the other recurrences. The type of recurrence is a clinical prognostic value to take into account. The influence of local recurrence retreatment by proton beam therapy should be evaluated by novel studies.

  2. Progress in the management of patients with uveal melanoma. The 2012 Ashton Lecture

    PubMed Central

    Damato, B

    2012-01-01

    Uveal melanomas are diverse in their clinical features and behaviour. More than 90% involve the choroid, the remainder being confined to the ciliary body and iris. Most patients experience visual loss and more than a third require enucleation, in some cases because of pain. Diagnosis is based on slit-lamp biomicroscopy and/or ophthalmoscopy, with ultrasonography, autofluorescence photography, and/or biopsy in selected cases. Conservation of the eye with useful vision has improved with advances in brachytherapy, proton beam radiotherapy, endoresection, exoresection, transpupillary thermotherapy, and photodynamic therapy. Despite ocular treatment, almost 50% of patients develop metastatic disease, which occurs almost exclusively in patients whose tumour shows chromosome 3 loss and/or class 2 gene expression profile. When the tumour shows such lethal genetic changes, the survival time depends on the anatomical stage and the histological grade of malignancy. Prognostication has improved as a result of progress in multivariate analysis including all the major risk factors. Screening for metastases is more sensitive as a consequence of advances in liver scanning with magnetic resonance imaging and other methods. More patients with metastases are living longer, benefiting from therapies such as: partial hepatectomy; radiofrequency ablation; ipilumumab immunotherapy; selective internal radiotherapy; intra-hepatic chemotherapy, possibly with isolated liver perfusion; and systemic chemotherapy. There is scope for improvement in the detection of uveal melanoma so as to maximise any opportunities for conserving the eye and vision, as well as preventing metastatic spread. Patient management has been enhanced by the formation of multidisciplinary teams in specialised ocular oncology centres. PMID:22744385

  3. Radioembolization as Locoregional Therapy of Hepatic Metastases in Uveal Melanoma Patients

    SciTech Connect

    Klingenstein, A.; Haug, A. R.; Zech, C. J.; Schaller, U. C.

    2013-02-15

    To retrospectively evaluate the overall survival, safety, and efficacy of metastatic uveal melanoma patients after radioembolization as salvage therapy. Thirteen patients were treated with radioembolization of branches of the hepatic artery with resin-based yttrium-90 ({sup 90}Y)-labelled microspheres. Twelve patients underwent a single application, and 1 patient underwent 4 interventions. Dosages from 644 to 2,450 MBq (mean activity 1,780) were applied. Treatment response was evaluated by way of liver magnetic resonance imaging and computed tomography (CT) as well as whole-body fluorodeoxyglucose positron emission tomography (PET)/CT with evaluation of percentage changes in SUV{sub max} before and at 2-3 months after therapy. Kaplan-Meier analysis was calculated to determine overall survival. Partial remission (PR) was observed in 8 (62 %), stable disease (SD) in 2 (15 %), and progressive disease (PD) in 3 (23 %) patients under terms of standard criteria and PR in 3 (23 %), SD in 3 (23 %), and PD in 7 (54 %) patients according to PET criteria. Neither RECIST nor PET criteria showed a significant difference in predicting overall survival (P = 0.12 and 0.11, respectively). Median survival time after radioembolization was 7 months. No acute toxicity with in-hospital morbidity was observed. One patient developed hepatomegaly, and 1 patient developed gastric ulceration. Throughout follow-up, progression of extrahepatic metastases was observed. Radioembolization may be a promising therapy in uveal melanoma patients with predominant hepatic metastases. At first follow-up, we observed PR or SD in 77 % patients under terms of standard criteria with an acceptable toxicity profile.

  4. Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations.

    PubMed

    Chen, X; Wu, Q; Tan, L; Porter, D; Jager, M J; Emery, C; Bastian, B C

    2014-09-25

    Uveal melanoma (UM) is a genetically and biologically distinct type of melanoma, and once metastatic there is no effective treatment currently available. Eighty percent of UMs harbor mutations in the Gαq family members GNAQ and GNA11. Understanding the effector pathways downstream of these oncoproteins is important to identify opportunities for targeted therapy. We report consistent activation of the protein kinase C (PKC) and MAPK pathways as a consequence of GNAQ or GNA11 mutation. PKC inhibition with AEB071 or AHT956 suppressed PKC and MAPK signalling and induced G1 arrest selectively in melanoma cell lines carrying GNAQ or GNA11 mutations. In contrast, treatment with two different MEK inhibitors, PD0325901 and MEK162, inhibited the proliferation of melanoma cell lines irrespective of their mutation status, indicating that in the context of GNAQ or GNA11 mutation MAPK activation can be attributed to activated PKC. AEB071 significantly slowed the growth of tumors in an allograft model of GNAQ(Q209L)-transduced melanocytes, but did not induce tumor shrinkage. In vivo and in vitro studies showed that PKC inhibitors alone were unable to induce sustained suppression of MAP-kinase signaling. However, combinations of PKC and MEK inhibition, using either PD0325901or MEK162, led to sustained MAP-kinase pathway inhibition and showed a strong synergistic effect in halting proliferation and in inducing apoptosis in vitro. Furthermore, combining PKC and MEK inhibition was efficacious in vivo, causing marked tumor regression in a UM xenograft model. Our data identify PKC as a rational therapeutic target for melanoma patients with GNAQ or GNA11 mutations and demonstrate that combined MEK and PKC inhibition is synergistic, with superior efficacy compared to treatment with either approach alone. PMID:24141786

  5. Genetic markers of pigmentation are novel risk loci for uveal melanoma.

    PubMed

    Ferguson, Robert; Vogelsang, Matjaz; Ucisik-Akkaya, Esma; Rai, Karan; Pilarski, Robert; Martinez, Carlos N; Rendleman, Justin; Kazlow, Esther; Nagdimov, Khagay; Osman, Iman; Klein, Robert J; Davidorf, Frederick H; Cebulla, Colleen M; Abdel-Rahman, Mohamed H; Kirchhoff, Tomas

    2016-01-01

    While the role of genetic risk factors in the etiology of uveal melanoma (UM) has been strongly suggested, the genetic susceptibility to UM is currently vastly unexplored. Due to shared epidemiological risk factors between cutaneous melanoma (CM) and UM, in this study we have selected 28 SNPs identified as risk variants in previous genome-wide association studies on CM or CM-related host phenotypes (such as pigmentation and eye color) and tested them for association with UM risk. By logistic regression analysis of 272 UM cases and 1782 controls using an additive model, we identified five variants significantly associated with UM risk, all passing adjustment for multiple testing. The three most significantly associated variants rs12913832 (OR = 0.529, 95% CI 0.415-0.673; p = 8.47E-08), rs1129038 (OR = 0.533, 95% CI 0.419-0.678; p = 1.19E-07) and rs916977 (OR = 0.465, 95% CI 0.339-0.637; p = 3.04E-07) are correlated (r(2) > 0.5) and map at 15q12 in the region of HERC2/OCA2, which determines eye-color in the human population. Our data provides first evidence that the genetic factors associated with pigmentation traits are risk loci of UM susceptibility. PMID:27499155

  6. Genetic markers of pigmentation are novel risk loci for uveal melanoma

    PubMed Central

    Ferguson, Robert; Vogelsang, Matjaz; Ucisik-Akkaya, Esma; Rai, Karan; Pilarski, Robert; Martinez, Carlos N.; Rendleman, Justin; Kazlow, Esther; Nagdimov, Khagay; Osman, Iman; Klein, Robert J.; Davidorf , Frederick H.; Cebulla, Colleen M.; Abdel-Rahman, Mohamed H.; Kirchhoff , Tomas

    2016-01-01

    While the role of genetic risk factors in the etiology of uveal melanoma (UM) has been strongly suggested, the genetic susceptibility to UM is currently vastly unexplored. Due to shared epidemiological risk factors between cutaneous melanoma (CM) and UM, in this study we have selected 28 SNPs identified as risk variants in previous genome-wide association studies on CM or CM-related host phenotypes (such as pigmentation and eye color) and tested them for association with UM risk. By logistic regression analysis of 272 UM cases and 1782 controls using an additive model, we identified five variants significantly associated with UM risk, all passing adjustment for multiple testing. The three most significantly associated variants rs12913832 (OR = 0.529, 95% CI 0.415–0.673; p = 8.47E-08), rs1129038 (OR = 0.533, 95% CI 0.419–0.678; p = 1.19E-07) and rs916977 (OR = 0.465, 95% CI 0.339–0.637; p = 3.04E-07) are correlated (r2 > 0.5) and map at 15q12 in the region of HERC2/OCA2, which determines eye-color in the human population. Our data provides first evidence that the genetic factors associated with pigmentation traits are risk loci of UM susceptibility. PMID:27499155

  7. Geant4 studies of the CNAO facility system for hadrontherapy treatment of uveal melanomas

    NASA Astrophysics Data System (ADS)

    Rimoldi, A.; Piersimoni, P.; Pirola, M.; Riccardi, C.

    2014-06-01

    The Italian National Centre of Hadrontherapy for Cancer Treatment (CNAO -Centro Nazionale di Adroterapia Oncologica) in Pavia, Italy, has started the treatment of selected cancers with the first patients in late 2011. In the coming months at CNAO plans are to activate a new dedicated treatment line for irradiation of uveal melanomas using the available active beam scan. The beam characteristics and the experimental setup should be tuned in order to reach the necessary precision required for such treatments. Collaboration between CNAO foundation, University of Pavia and INFN has started in 2011 to study the feasibility of these specialised treatments by implementing a MC simulation of the transport beam line and comparing the obtained simulation results with measurements at CNAO. The goal is to optimise an eye-dedicated transport beam line and to find the best conditions for ocular melanoma irradiations. This paper describes the Geant4 toolkit simulation of the CNAO setup as well as a modelised human eye with a tumour inside. The Geant4 application could be also used to test possible treatment planning systems. Simulation results illustrate the possibility to adapt the CNAO standard transport beam line by optimising the position of the isocentre and the addition of some passive elements to better shape the beam for this dedicated study.

  8. [Criteria for assessing the efficacy of brachytherapy of uveal melanomas, complications of therapy and there prevention].

    PubMed

    Brovkina, A F; Zarubeí, G D; Val'skií, V V

    1997-01-01

    The authors assess the efficacy of brachytherapy of uveal melanomas in 954 patients. Strontium ophthalmoapplicators were used in 652, rutenium ones in 302 patients. As a rule, Sr applicators were sutured in patients with tumors up to 3.5 mm thick and Ru ones in cases with tumors thicker than 3.5 mm. A special program was used for individual approach and improving the accuracy of planning. A total of 74.5% of patients have been followed up for at least 3 years, with check-ups every 3-6 months. The effect of brachytherapy was considered positive in cases with complete resorption or at least 50% decrease of the tumor and a stable clinical picture for 9-12 months. In 60% of patients the tumor regressed completely, in 16% partially, and in 24% there were signs of activation of melanoma growth one year after treatment. The frequency of radiation complications was as follows: retinopaty, 3.15%; neuroretinopathy, 1.1%; hemophthalmia, 0.9%; neovascular glaucoma, 1.1%; cataract, 0.63%. The incidence of radiation complications increases with increase of the applicator power and rigidity of exposure. Computer planning of brachytherapy with due consideration for the size of the tumor and the eye and localization of the neoplasm for each case will help decrease the incidence of complications. PMID:9265351

  9. Differential expression of TYRP1 in adult human retinal pigment epithelium and uveal melanoma cells

    PubMed Central

    QIU, CHUN; LI, PENG; BI, JIANJUN; WU, QING; LU, LINNA; QIAN, GUANXIANG; JIA, RENBING; JIA, RONG

    2016-01-01

    Uveal melanoma (UM) is the most frequently occurring primary intraocular malignancy in adults. Tyrosinase (TYR) is a copper-containing enzyme and a type I membrane protein that is involved in the generation of melanin, the main pigment in vertebrates. TYR-related protein 1 (TYRP1) is regarded to have a crucial role in the immunotherapy of melanoma. As biomarkers, the TYR-related proteins, TYRP1 and TYRP2, exhibit specific expression in melanocytes, while also contributing to melanin synthesis within melanosomes. In the present study, the differential expression of TYRP1 was investigated at the mRNA, protein and morphological levels in four human UM cell lines (SP6.5, OM431, OCM1 and OCM290) and the human retinal pigment epithelium (RPE) cell line, using polymerase chain reaction, western blotting, immunocytochemistry and immunofluorescence staining. It was found that SP6.5 cells expressed the highest level of TYRP1, in comparison to SP6.5 OCM1 and OM431 cells, which produced less TYRP1, and OCM290 cells, which produced almost no TYRP1. No TYRP1 protein expression was identified in the RPE cell line. These findings indicate the potential use of TYRP1 in the development of therapy for UM. PMID:27073483

  10. Nonlethal Levels of Zeaxanthin Inhibit Cell Migration, Invasion, and Secretion of MMP-2 via NF-κB Pathway in Cultured Human Uveal Melanoma Cells.

    PubMed

    Bi, Ming-Chao; Hose, Nicole; Xu, Cai-Lian; Zhang, Chen; Sassoon, Jodi; Song, E

    2016-01-01

    Zeaxanthin at nonlethal dosages (3-10 μM) significantly inhibited the cell migration of cultured uveal melanoma cells (C918 cell line) as determined by wound healing assay and Boyden chamber assay. Matrigel invasion assay showed that cell invasion of uveal melanoma cells could be significantly inhibited by zeaxanthin. Secretion of MMP-2 by melanoma cells was significantly inhibited by zeaxanthin in a dose-dependent manner as measured by ELISA kit. Zeaxanthin also significantly inhibited the NF-κB levels in nuclear extracts of the UM cells, which is the upstream of the MMP-2 secretion. These results suggest that zeaxanthin might be a potentially therapeutic approach in the prevention of metastasis in uveal melanoma. PMID:26942004

  11. Nonlethal Levels of Zeaxanthin Inhibit Cell Migration, Invasion, and Secretion of MMP-2 via NF-κB Pathway in Cultured Human Uveal Melanoma Cells

    PubMed Central

    Bi, Ming-Chao; Hose, Nicole; Xu, Cai-Lian; Zhang, Chen; Sassoon, Jodi; Song, E.

    2016-01-01

    Zeaxanthin at nonlethal dosages (3–10 μM) significantly inhibited the cell migration of cultured uveal melanoma cells (C918 cell line) as determined by wound healing assay and Boyden chamber assay. Matrigel invasion assay showed that cell invasion of uveal melanoma cells could be significantly inhibited by zeaxanthin. Secretion of MMP-2 by melanoma cells was significantly inhibited by zeaxanthin in a dose-dependent manner as measured by ELISA kit. Zeaxanthin also significantly inhibited the NF-κB levels in nuclear extracts of the UM cells, which is the upstream of the MMP-2 secretion. These results suggest that zeaxanthin might be a potentially therapeutic approach in the prevention of metastasis in uveal melanoma. PMID:26942004

  12. Radioembolization and Ipilimumab in Treating Patients With Uveal Melanoma With Liver Metastases

    ClinicalTrials.gov

    2016-03-09

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Iris Melanoma; Liver Metastases; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage IV Intraocular Melanoma

  13. Phase I trial combining gemcitabine and treosulfan in advanced cutaneous and uveal melanoma patients

    PubMed Central

    Corrie, P G; Shaw, J; Spanswick, V J; Sehmbi, R; Jonson, A; Mayer, A; Bulusu, R; Hartley, J A; Cree, I A

    2005-01-01

    Gemcitabine and treosulfan are DNA-damaging agents. Preclinical studies suggest that synergism exists when melanoma cells are exposed to both drugs concurrently. We conducted a phase I trial in advanced melanoma patients to determine the optimal dose of gemcitabine to be combined with treosulfan. Cohorts of three patients received increasing doses of gemcitabine, commencing at 0.5 g m−2, followed by a fixed dose of 5.0 g m−2 treosulfan on day one of a 21-day cycle. Patients alternately received a first cycle of single-agent gemcitabine or treosulfan before subsequent cycles of both drugs. Peripheral blood lymphocytes were collected in cycles 1 and 2 at various time points until 48 h post-treatment. The single-cell gel electrophoresis (Comet) assay was used to measure chemotherapy-induced DNA damage. A total of 27 patients were enrolled, no objective responses were observed, but two uveal melanoma patients had minor responses. Dose-limiting myelosuppression was reached at 3.0 g m−2 gemcitabine. DNA single-strand breaks were detected 4 h post-gemcitabine, repaired by 24 h. DNA interstrand crosslinks were detected 4 h post-treosulfan, fully removed by 48 h. Following combination chemotherapy, treosulfan-induced DNA crosslinks persisted, still being detectable 48 h post-treatment, supporting the hypothesis that gemcitabine potentiates treosulfan-induced cytotoxicity. The recommended regimen for further study is 2.5 g m−2 gemcitabine combined with 5.0 g m−2 treosulfan. PMID:15886706

  14. Automatic real-time surveillance of eye position and gating for stereotactic radiotherapy of uveal melanoma

    SciTech Connect

    Petersch, Bernhard; Bogner, Joachim; Dieckmann, Karin; Poetter, Richard; Georg, Dietmar

    2004-12-01

    A new prototype (hardware and software) for monitoring eye movements using a noninvasive technique for gated linac-based stereotactic radiotherapy (SRT) of uveal melanoma was developed. The prototype was tested within the scope of a study for 11 patients. Eye immobilization was achieved by having the patient fixate a light source integrated into the system. The system is used in conjunction with a Head and Neck mask system for immobilization, and uses infrared tracking technology for positioning (both BrainLAB AG Heimstetten/Germany). It was used during CT and MR image acquisition as well as during all of five treatment fractions (6 MeV, 5x12 Gy to 80% isodose) to guarantee identical patient setup and eye rotational state during treatment planning and treatment delivery. Maximum temporal and angular deviations tolerated during treatment delivery can be chosen by the physician, the radiation then being interrupted automatically and instantaneously if those criteria are being exceeded during irradiation. A graphical user interface displays life video images of the treated eye and information about the current and previous rotational deviation of the eye from its reference treatment position. The physician thus has online access to data directly linked to the success of the treatment and possible side effects. Mean angular deviations during CT/MR scans and treatment deliveries ranged from 1.61 deg. to 3.64 deg. (standard deviations 0.87 deg. to 2.09 deg.) which is in accordance with precision requirements for SRT. Typical situations when preset deviation criteria were exceeded are slow drifts (fatigue), sudden large eye movements (irritation), or if patients closed their eyes (fatigue). In these cases radiation was reliably interrupted by the gating system. In our clinical setup the novel system for computer-controlled eye movement gated treatments was well tolerated by all patients. The system yields quantitative real-time information about the eye's rotational state

  15. Anterior segment sparing to reduce charged particle radiotherapy complications in uveal melanoma

    NASA Technical Reports Server (NTRS)

    Daftari, I. K.; Char, D. H.; Verhey, L. J.; Castro, J. R.; Petti, P. L.; Meecham, W. J.; Kroll, S.; Blakely, E. A.; Chatterjee, A. (Principal Investigator)

    1997-01-01

    PURPOSE: The purpose of this investigation is to delineate the risk factors in the development of neovascular glaucoma (NVG) after helium-ion irradiation of uveal melanoma patients and to propose treatment technique that may reduce this risk. METHODS AND MATERIALS: 347 uveal melanoma patients were treated with helium-ions using a single-port treatment technique. Using univariate and multivariate statistics, the NVG complication rate was analyzed according to the percent of anterior chamber in the radiation field, tumor size, tumor location, sex, age, dose, and other risk factors. Several University of California San Francisco-Lawrence Berkeley National Laboratory (LBNL) patients in each size category (medium, large, and extralarge) were retrospectively replanned using two ports instead of a single port. By using appropriate polar and azimuthal gaze angles or by treating patients with two ports, the maximum dose to the anterior segment of the eye can often be reduced. Although a larger volume of anterior chamber may receive a lower dose by using two ports than a single port treatment. We hypothesize that this could reduce the level of complications that result from the irradiation of the anterior chamber of the eye. Dose-volume histograms were calculated for the lens, and compared for the single and two-port techniques. RESULTS: NVG developed in 121 (35%) patients. The risk of NVG peaked between 1 and 2.5 years posttreatment. By univariate and multivariate analysis, the percent of lens in the field was strongly correlated with the development of NVG. Other contributing factors were tumor height, history of diabetes, and vitreous hemorrhage. Dose-volume histogram analysis of single-port vs. two-port techniques demonstrate that for some patients in the medium and large category tumor groups, a significant decrease in dose to the structures in the anterior segment of the eye could have been achieved with the use of two ports. CONCLUSION: The development of NVG after

  16. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry.

    PubMed

    Feng, Xiaodong; Degese, Maria Sol; Iglesias-Bartolome, Ramiro; Vaque, Jose P; Molinolo, Alfredo A; Rodrigues, Murilo; Zaidi, M Raza; Ksander, Bruce R; Merlino, Glenn; Sodhi, Akrit; Chen, Qianming; Gutkind, J Silvio

    2014-06-16

    Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gαq family members, have been identified in ∼ 83% and ∼ 6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Gαq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cβ and the canonical Hippo pathway. Furthermore, we show that Gαq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11-initiated human malignancy. PMID:24882515

  17. Adjuvant Sunitinib or Valproic Acid in High-Risk Patients With Uveal Melanoma

    ClinicalTrials.gov

    2016-07-25

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Iris Melanoma; Stage I Intraocular Melanoma; Stage IIA Intraocular Melanoma; Stage IIB Intraocular Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIC Intraocular Melanoma

  18. The risk of enucleation after proton beam irradiation of uveal melanoma

    SciTech Connect

    Egan, K.M.; Gragoudas, E.S.; Seddon, J.M.; Glynn, R.J.; Munzenreider, J.E.; Goitein, M.; Verhey, L.; Urie, M.; Koehler, A. )

    1989-09-01

    Enucleation after proton beam irradiation of uveal melanomas occurred in 64 (6.4%) of 994 eyes with a median follow-up time of 2.7 years. The median time between irradiation and enucleation in the 64 enucleated eyes was 13 months. The probability of retaining the eye was 95 and 90%, 2 and 5 years postirradiation, respectively. Three percent of eyes were enucleated during posttreatment year 1, and the yearly rate was 1% by the fourth year. No patient had enucleation later than 5 1/2 years posttreatment. The complication most likely to result in enucleation was neovascular glaucoma although this was frequently managed without enucleation. Other common reasons for enucleation were documented or suspected tumor growth and complete retinal detachment with associated loss of vision. The leading risk factors for enucleation were anterior tumor margin involving the ciliary body, tumor height greater than 8 mm, and proximity of the tumor to the fovea. Based on the presence or absence of these factors, 5-year eye retention rates were 99, 92, and 76% for low-, moderate-, and high-risk groups, respectively. Thus, the probability of eye retention after proton beam irradiation is high even among those at greatest risk of enucleation.

  19. Embryonic Zebrafish: Different Phenotypes after Injection of Human Uveal Melanoma Cells.

    PubMed

    van der Ent, Wietske; Burrello, Claudia; de Lange, Mark J; van der Velden, Pieter A; Jochemsen, Aart G; Jager, Martine J; Snaar-Jagalska, B Ewa

    2015-04-01

    Although murine xenograft models for human uveal melanoma (UM) are available, they are of limited utility for screening large compound libraries for the discovery of new drugs. We need new preclinical models which can efficiently evaluate drugs that can treat UM metastases. The zebrafish embryonic model is ideal for drug screening purposes because it allows the investigation of potential antitumor properties of drugs within 1 week. The optical transparency of the zebrafish provides unique possibilities for live imaging of fluorescence-labelled cancer cells and their behavior. In addition, the adaptive immune response, which is responsible for the rejection of transplanted material, is not yet present in the early stages of fish development, and systemic immunosuppression is therefore not required to allow growth of tumor cells. We studied the behavior of UM cells following injection into zebrafish embryos and observed different phenotypes. We also analyzed cell migration, proliferation, formation of micrometastasis and interaction with the host microenvironment. Significant differences were noted between cell lines: cells derived from metastases showed more migration and proliferation than cells derived from the primary tumors. The addition of the c-Met inhibitor crizotinib to the water in which the larvae were kept reduced the migration and proliferation of UM cells expressing c-Met. This indicates the applicability of the zebrafish xenografts for testing novel inhibitory compounds and provides a fast and sensitive in vivo vertebrate model for preclinical drug screening to combat UM. PMID:27171126

  20. Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma

    PubMed Central

    Landreville, Solange; Agapova, Olga A.; Matatall, Katie A.; Kneass, Zachary T.; Onken, Michael D.; Lee, Ryan S.; Bowcock, Anne M.; Harbour, J. William

    2011-01-01

    Purpose Metastasis is responsible for the death of most cancer patients, yet few therapeutic agents are available which specifically target the molecular events that lead to metastasis. We recently showed that inactivating mutations in the tumor suppressor gene BAP1 are closely associated with loss of melanocytic differentiation in uveal melanoma and metastasis (UM). The purpose of this study was to identify therapeutic agents that reverse the phenotypic effects of BAP1 loss in UM. Experimental Design In silico screens were performed to identify therapeutic compounds predicted to differentiate UM cells using Gene Set Enrichment Analysis and Connectivity Map databases. Valproic acid, trichostatin A, LBH-589 and suberoylanilide hydroxamic acid were evaluated for their effects on UM cells using morphologic evaluation, MTS viability assays, BrdU incorporation, flow cytometry, clonogenic assays, gene expression profiling, histone acetylation and ubiquitination assays, and a murine xenograft tumorigenicity model. Results HDAC inhibitors induced morphologic differentiation, cell cycle exit, and a shift to a differentiated, melanocytic gene expression profile in cultured UM cells. Valproic acid inhibited the growth of UM tumors in vivo. Conclusions These findings suggest that HDAC inhibitors may have therapeutic potential for inducing differentiation and prolonged dormancy of micrometastatic disease in UM. PMID:22038994

  1. BRD4-targeted therapy induces Myc-independent cytotoxicity in Gnaq/11-mutatant uveal melanoma cells

    PubMed Central

    Ambrosini, Grazia; Sawle, Ashley D.; Musi, Elgilda; Schwartz, Gary K.

    2015-01-01

    Uveal melanoma (UM) is an aggressive intraocular malignancy with limited therapeutic options. Both primary and metastatic UM are characterized by oncogenic mutations in the G-protein alpha subunit q and 11. Furthermore, nearly 40% of UM has amplification of the chromosomal arm 8q and monosomy of chromosome 3, with consequent anomalies of MYC copy number. Chromatin regulators have become attractive targets for cancer therapy. In particular, the bromodomain and extra-terminal (BET) inhibitor JQ1 has shown selective inhibition of c-Myc expression with antiproliferative activity in hematopoietic and solid tumors. Here we provide evidence that JQ1 had cytotoxic activity in UM cell lines carrying Gnaq/11 mutations, while in cells without the mutations had little effects. Using microarray analysis, we identified a large subset of genes modulated by JQ1 involved in the regulation of cell cycle, apoptosis and DNA repair. Further analysis of selected genes determined that the concomitant silencing of Bcl-xL and Rad51 represented the minimal requirement to mimic the apoptotic effects of JQ1 in the mutant cells, independently of c-Myc. In addition, administration of JQ1 to mouse xenograft models of Gnaq-mutant UM resulted in significant inhibition of tumor growth. Collectively, our results define BRD4 targeting as a novel therapeutic intervention against UM with Gnaq/Gna11 mutations. PMID:26397223

  2. BRD4-targeted therapy induces Myc-independent cytotoxicity in Gnaq/11-mutatant uveal melanoma cells.

    PubMed

    Ambrosini, Grazia; Sawle, Ashley D; Musi, Elgilda; Schwartz, Gary K

    2015-10-20

    Uveal melanoma (UM) is an aggressive intraocular malignancy with limited therapeutic options. Both primary and metastatic UM are characterized by oncogenic mutations in the G-protein alpha subunit q and 11. Furthermore, nearly 40% of UM has amplification of the chromosomal arm 8q and monosomy of chromosome 3, with consequent anomalies of MYC copy number. Chromatin regulators have become attractive targets for cancer therapy. In particular, the bromodomain and extra-terminal (BET) inhibitor JQ1 has shown selective inhibition of c-Myc expression with antiproliferative activity in hematopoietic and solid tumors. Here we provide evidence that JQ1 had cytotoxic activity in UM cell lines carrying Gnaq/11 mutations, while in cells without the mutations had little effects. Using microarray analysis, we identified a large subset of genes modulated by JQ1 involved in the regulation of cell cycle, apoptosis and DNA repair. Further analysis of selected genes determined that the concomitant silencing of Bcl-xL and Rad51 represented the minimal requirement to mimic the apoptotic effects of JQ1 in the mutant cells, independently of c-Myc. In addition, administration of JQ1 to mouse xenograft models of Gnaq-mutant UM resulted in significant inhibition of tumor growth.Collectively, our results define BRD4 targeting as a novel therapeutic intervention against UM with Gnaq/Gna11 mutations. PMID:26397223

  3. Uveal melanomas near the optic disc or fovea. Visual results after proton beam irradiation

    SciTech Connect

    Seddon, J.M.; Gragoudas, E.S.; Egan, K.M.; Glynn, R.J.; Munzenrider, J.E.; Austin-Seymour, M.; Goitein, M.; Verhey, L.; Urie, M.; Koehler, A.

    1987-04-01

    Proximity to the disc and fovea is a risk factor for visual loss after proton beam irradiation of uveal melanomas. Of 562 eyes treated over a 10-year period with pretreatment visual acuity of 20/200 or better, 363 (64.6%) contained tumors within 2 disc diameters (DD) of the disc or fovea. Rates of visual loss after treatment to worse than 20/200 and causes of visual decline were evaluated using Kaplan-Meier analysis. Cumulative rates of visual loss among subjects with tumors near the disc or fovea were 33 and 47% 1 and 2 years after treatment compared to 17 and 28%, respectively, for subjects with tumors located farther from both structures. The leading cause of visual loss in the first year among eyes with tumors near the disc or fovea was retinal detachment. Controlling for other predictors of visual loss to worse than 20/200, location near the disc or fovea was independently related to visual loss primarily due to retinal detachment, cataract, and radiation retinopathy. Despite the unfavorable location of these tumors, over half of patients with 20/200 or better pretreatment visual acuity had useful vision 2 years after treatment.

  4. Ion therapy for uveal melanoma in new human eye phantom based on GEANT4 toolkit.

    PubMed

    Mahdipour, Seyed Ali; Mowlavi, Ali Asghar

    2016-01-01

    Radiotherapy with ion beams like proton and carbon has been used for treatment of eye uveal melanoma for many years. In this research, we have developed a new phantom of human eye for Monte Carlo simulation of tumors treatment to use in GEANT4 toolkit. Total depth-dose profiles for the proton, alpha, and carbon incident beams with the same ranges have been calculated in the phantom. Moreover, the deposited energy of the secondary particles for each of the primary beams is calculated. The dose curves are compared for 47.8MeV proton, 190.1MeV alpha, and 1060MeV carbon ions that have the same range in the target region reaching to the center of tumor. The passively scattered spread-out Bragg peak (SOBP) for each incident beam as well as the flux curves of the secondary particles including neutron, gamma, and positron has been calculated and compared for the primary beams. The high sharpness of carbon beam׳s Bragg peak with low lateral broadening is the benefit of this beam in hadrontherapy but it has disadvantages of dose leakage in the tail after its Bragg peak and high intensity of neutron production. However, proton beam, which has a good conformation with tumor shape owing to the beam broadening caused by scattering, can be a good choice for the large-size tumors. PMID:26831752

  5. Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers

    PubMed Central

    Abdel-Rahman, Mohamed H; Pilarski, Robert; Cebulla, Colleen M; Massengill, James B; Christopher, Benjamin N; Boru, Getachew; Hovland, Peter; Davidorf, Frederick H

    2013-01-01

    Objective To investigate the potential contribution of germline sequence alterations in the BAP1 gene in uveal melanoma (UM) patients with possible predisposition to hereditary cancer. Design A total of 53 unrelated UM patients with high risk for hereditary cancer and five additional family members of one proband were studied. Mutational screening was carried out by direct sequencing. Results Of the 53 UM patients studied, a single patient was identified with a germline BAP1 truncating mutation, c. 799 C→T (p.Q267X), which segregated in several family members and was associated with UM and other cancers. Biallelic inactivation of BAP1 and decreased BAP1 expression were identified in the UM, lung adenocarcinoma and meningioma tumours from three family members with this germline BAP1 mutation. Germline BAP1 variants of uncertain significance, likely non-pathogenic, were also identified in two additional UM patients. Conclusion This study reports a novel hereditary cancer syndrome caused by a germline BAP1 mutation that predisposes patients to UM, lung carcinoma, meningioma, and possibly other cancers. The results indicate that BAP1 is the candidate gene in only a small subset of hereditary UM, suggesting the contribution of other candidate genes. PMID:21941004

  6. Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma

    PubMed Central

    Karydis, Ioannis; Chan, Pui Ying; Wheater, Matthew; Arriola, Edurne; Szlosarek, Peter W.; Ottensmeier, Christian H.

    2016-01-01

    ABSTRACT Background: Untreated metastatic uveal melanoma (UM) carries a grave prognosis. Unlike cutaneous melanoma (CM), there are no established treatments known to significantly improve outcomes for a meaningful proportion of patients. Inhibition of the PD1–PDL1 axis has shown promise in the management of CM and we here report a two center experience of UM patients receiving pembrolizumab. Methods: To assess the efficacy and safety of pembrolizumab, we retrospectively analyzed outcome data of 25 consecutive UM patients participating in the MK3475 expanded access program (EAP) who received pembrolizumab at 2 mg/kg 3 weekly. Tumor assessment was evaluated using RECIST 1.1 and immune-related Response Criteria (irRC) by CT scanning. Toxicity was recorded utilizing Common Terminology Criteria for Adverse Events (“CTCAE”) v4.03. Results: Twenty-five patients were identified receiving a median of six cycles of treatment. Two patients achieved a partial response and six patients stable disease. After a median follow-up of 225 d median progression free survival (PFS) was 91 d and overall survival (OS) was not reached. There was a significant trend for improved outcomes in patients with extrahepatic disease progression as opposed to liver only progression at the outset. Five patients experienced grade 3 or 4 adverse events (AEs); there were no treatment related deaths. Conclusions: Pembrolizumab 2mg/kg q3w is a safe option in UM patients. Disease control rates, particularly in the subgroup of patients without progressive liver disease at the outset are promising; these results merit further investigation in clinical trials possibly incorporating liver targeted treatment modalities.

  7. A phase 2 trial of everolimus and pasireotide long-acting release in patients with metastatic uveal melanoma.

    PubMed

    Shoushtari, Alexander N; Ong, Leonard T; Schoder, Heiko; Singh-Kandah, Shahnaz; Abbate, Kelly T; Postow, Michael A; Callahan, Margaret K; Wolchok, Jedd; Chapman, Paul B; Panageas, Katherine S; Schwartz, Gary K; Carvajal, Richard D

    2016-06-01

    The aim of this study was to test the hypothesis that inhibiting mammalian target of rapamycin and insulin-like growth factor-1 receptor would be efficacious in metastatic uveal melanoma. This was a phase 2 trial of everolimus 10 mg daily plus pasireotide long-acting release 60 mg every 28 days enrolling patients with progressive, metastatic uveal melanoma to treatment until progression by Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) or unacceptable toxicity. The primary endpoint was clinical benefit rate, defined as any objective response or RECIST 1.1 stable disease at 16 weeks. A subset of patients underwent baseline indium-111-octreotide scans. A total of 14 patients were enrolled, of which 13 were evaluable for the primary endpoint, before the study was terminated due to poor accrual. Three of 13 (26%) patients obtained clinical benefit. Seven of 13 (54%) had stable disease lasting for a median of 8 weeks (range: 8-16 weeks). Grade 3 adverse events deemed at least possibly related to study drugs were hyperglycemia (n=7), oral mucositis (n=2), diarrhea (n=1), hypophosphatemia (n=1), and anemia (n=1). Seven of 14 (50%) patients required at least one dose reduction due to toxicity. Seven of eight (88%) patients with baseline indium-111-octreotide scans had at least one avid lesion, with significant intrapatient heterogeneity. There was a trend toward an association between octreotide avidity and cytostatic response to therapy (P=0.078). The combination of everolimus and pasireotide has limited clinical benefit in this small metastatic uveal melanoma cohort. Dose reductions for side effects were common. Further investigation into the relationship between somatostatin receptor expression and cytostatic activity of somatostatin analogues is warranted. PMID:26795274

  8. Uveal Melanoma Recurrence After Fractionated Proton Beam Therapy: Comparison of Survival in Patients Treated With Reirradiation or With Enucleation

    SciTech Connect

    Marucci, Laura; Ancukiewicz, Marek; Lane, Anne Marie; Collier, John M.; Gragoudas, Evangelos S.; Munzenrider, John E.

    2011-03-01

    Purpose: To retrospectively compare survival in recurrent uveal melanoma, between patients treated by enucleation or by a second course of fractionated proton beam therapy (PBT). Methods and Materials: Tumor recurrence was documented in 73 patients treated with PBT for uveal melanoma. Of the patients, 31 received a second course of PBT and 42 underwent enucleation. The mean patient age was 56 and 61 years for those undergoing enucleation and those undergoing reirradiation, respectively. Both primary and recurrent tumors were larger in patients undergoing enucleation. Tumor location and the presence or absence of ciliary body involvement did not differ significantly between the groups. The median follow-up after enucleation and after re-treatment was 79 and 59 months, respectively. Cumulative rates of outcomes and differences in rates between the reirradiated and enucleation groups were calculated by the Cox proportional hazards model and the log-rank test, respectively. Results: The median survival duration in the enucleated and reirradiated groups was 42 and 90 months, respectively. The median time free of metastases was 38 months in enucleated patients and 97 months in reirradiated patients. At 5 years after enucleation and after reirradiation, the probability of overall survival was 36% and 63%, respectively (p = 0.040, log-rank test); the probability of freedom from metastases was 31% and 66%, respectively (p = 0.028, log-rank test). These differences persisted after adjustment for recurrent tumor largest diameter and volume at the time of reirradiation or enucleation. Conclusions: This retrospective analysis suggests that survival in reirradiated patients is not compromised by administration of a second course of PBT for recurrent uveal melanoma.

  9. Quality of life in the follow-up of uveal melanoma patients after CyberKnife treatment.

    PubMed

    Klingenstein, Annemarie; Fürweger, Christoph; Nentwich, Martin M; Schaller, Ulrich C; Foerster, Paul I; Wowra, Berndt; Muacevic, Alexander; Eibl, Kirsten H

    2013-12-01

    To assess quality of life in uveal melanoma patients within the first and second year after CyberKnife radiosurgery. Overall, 91 uveal melanoma patients were evaluated for quality of life through the Short-form (SF-12) Health Survey at baseline and at every follow-up visit over 2 years after CyberKnife radiosurgery. Statistical analysis was carried out using SF Health Outcomes Scoring Software and included subgroup analysis of patients developing secondary glaucoma and of patients maintaining a best corrected visual acuity (BCVA) of the treated eye of 0.5 log(MAR) or better. Analysis of variance, Greenhouse-Geisser correction, Student's t-test, and Fisher's exact test were used to determine statistical significance. Physical Functioning (PF) and Role Physical (RP) showed a significant decrease after CyberKnife radiosurgery, whereas Mental Health (MH) improved (P=0.007, P<0.0001 and P=0.023). MH and Social Functioning (SF) increased significantly (P=0.0003 and 0.026) in the no glaucoma group, MH being higher compared with glaucoma patients (P=0.02). PF and RP were significantly higher in patients with higher BCVA at the second follow-up (P=0.02). RP decreased in patients with BCVA<0.5 log(MAR) (P=0.013). Vitality (VT) increased significantly in patients whose BCVA could be preserved (P=0.031). Neither tumor localization nor size influenced the development of secondary glaucoma or change in BCVA. Although PF and RP decreased over time, MH improved continuously. Prevention of secondary glaucoma has a significant influence on both SF and MH, whereas preservation of BCVA affects VT. Emotional stability throughout follow-up contributes positively toward overall quality of life. CyberKnife radiosurgery may contribute to attenuation of emotional distress in uveal melanoma patients. PMID:24048223

  10. Antitumor effects of the investigational selective MEK inhibitor TAK733 against cutaneous and uveal melanoma cell lines

    PubMed Central

    2012-01-01

    Background TAK733 is a novel allosteric, non-ATP-binding, inhibitor of the BRAF substrates MEK-1/2. Methods The growth inhibitory effects of TAK733 were assessed in a panel of 27 cutaneous and five uveal melanoma cell lines genotyped for driver oncogenic mutations. Flow cytometry, Western blots and metabolic tracer uptake assays were used to characterize the changes induced by exposure to TAK733. Results Fourteen cutaneous melanoma cell lines with different driver mutations were sensitive to the antiproliferative effects of TAK733, with a higher proportion of BRAFV600E mutant cell lines being highly sensitive with IC50s below 1 nM. The five uveal melanoma cell lines had GNAQ or GNA11 mutations and were either moderately or highly sensitive to TAK733. The tested cell lines wild type for NRAS, BRAF, GNAQ and GNA11 driver mutations were moderately to highly resistant to TAK733. TAK733 led to a decrease in pERK and G1 arrest in most of these melanoma cell lines regardless of their origin, driver oncogenic mutations and in vitro sensitivity to TAK733. MEK inhibition resulted in increase in pMEK more prominently in NRASQ61L mutant and GNAQ mutant cell lines than in BRAFV600E mutant cell lines. Uptake of the metabolic tracers FDG and FLT was inhibited by TAK733 in a manner that closely paralleled the in vitro sensitivity assays. Conclusions The MEK inhibitor TAK733 has antitumor properties in melanoma cell lines with different oncogenic mutations and these effects could be detectable by differential metabolic tracer uptake. PMID:22515704

  11. Oncogenic role of microRNA-20a in human uveal melanoma

    PubMed Central

    Zhou, Jinzi; Jiang, Jian; Wang, Shuhong; Xia, Xiaobo

    2016-01-01

    As a member of the microRNA (miR)-17-92 cluster, miR-20a has been indicated to be involved in the regulation of the proliferation and invasion of various cancer cells. Previous studies have observed elevated plasma levels of miR-20a in patients with uveal melanoma (UM), compared with normal controls. In the present study, the potential function of miR-20a in UM was investigated. Reverse transcription-quantitative polymerase chain reaction analysis was performed to detect the expression levels of miR-20a in UM cells and tissues. The functions of miR-20a on cell proliferation, migration and invasion were determined in vitro using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays, respectively. The expression levels of miR-20a were significantly increased in the UM cells and tissues (P<0.05). Subsequently, miR-20a mimics were transfected into UM cells, which led to increases in cell growth, migration and invasion activities. By contrast, miR-20a inhibition markedly suppressed the viability and motility of UM cells in vitro. These data provided convincing evidence that miR-20a may function as an oncogenic miRNA, and may be involved in promoting cell growth and motility in the molecular etiology of UM, suggesting its potential as a candidate therapeutic target for the treatment of patients with UM. PMID:27356499

  12. Development and External Validation of a Prognostic Nomogram for Metastatic Uveal Melanoma

    PubMed Central

    Valpione, Sara; Moser, Justin C.; Parrozzani, Raffaele; Bazzi, Marco; Mansfield, Aaron S.; Mocellin, Simone; Pigozzo, Jacopo; Midena, Edoardo; Markovic, Svetomir N.; Aliberti, Camillo; Campana, Luca G.; Chiarion-Sileni, Vanna

    2015-01-01

    Background Approximately 50% of patients with uveal melanoma (UM) will develop metastatic disease, usually involving the liver. The outcome of metastatic UM (mUM) is generally poor and no standard therapy has been established. Additionally, clinicians lack a validated prognostic tool to evaluate these patients. The aim of this work was to develop a reliable prognostic nomogram for clinicians. Patients and Methods Two cohorts of mUM patients, from Veneto Oncology Institute (IOV) (N=152) and Mayo Clinic (MC) (N=102), were analyzed to develop and externally validate, a prognostic nomogram. Results The median survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort. Percentage of liver involvement (HR 1.6), elevated levels of serum LDH (HR 1.6), and a WHO performance status=1 (HR 1.5) or 2–3 (HR 4.6) were associated with worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM conferred a survival advantage (HR 0.9). The nomogram had a concordance probability of 0.75 (SE .006) in the development dataset (IOV), and 0.80 (SE .009) in the external validation (MC). Nomogram predictions were well calibrated. Conclusions The nomogram, which includes percentage of liver involvement, LDH levels, WHO performance status and disease free-interval accurately predicts the prognosis of mUM and could be useful for decision-making and risk stratification for clinical trials. PMID:25780931

  13. Calcium regulation by temperature-sensitive transient receptor potential channels in human uveal melanoma cells.

    PubMed

    Mergler, Stefan; Derckx, Raissa; Reinach, Peter S; Garreis, Fabian; Böhm, Arina; Schmelzer, Lisa; Skosyrski, Sergej; Ramesh, Niraja; Abdelmessih, Suzette; Polat, Onur Kerem; Khajavi, Noushafarin; Riechardt, Aline Isabel

    2014-01-01

    Uveal melanoma (UM) is both the most common and fatal intraocular cancer among adults worldwide. As with all types of neoplasia, changes in Ca(2+) channel regulation can contribute to the onset and progression of this pathological condition. Transient receptor potential channels (TRPs) and cannabinoid receptor type 1 (CB1) are two different types of Ca(2+) permeation pathways that can be dysregulated during neoplasia. We determined in malignant human UM and healthy uvea and four different UM cell lines whether there is gene and functional expression of TRP subtypes and CB1 since they could serve as drug targets to either prevent or inhibit initiation and progression of UM. RT-PCR, Ca(2+) transients, immunohistochemistry and planar patch-clamp analysis probed for their gene expression and functional activity, respectively. In UM cells, TRPV1 and TRPM8 gene expression was identified. Capsaicin (CAP), menthol or icilin induced Ca(2+) transients as well as changes in ion current behavior characteristic of TRPV1 and TRPM8 expression. Such effects were blocked with either La(3+), capsazepine (CPZ) or BCTC. TRPA1 and CB1 are highly expressed in human uvea, but TRPA1 is not expressed in all UM cell lines. In UM cells, the CB1 agonist, WIN 55,212-2, induced Ca(2+) transients, which were suppressed by La(3+) and CPZ whereas CAP-induced Ca(2+) transients could also be suppressed by CB1 activation. Identification of functional TRPV1, TRPM8, TRPA1 and CB1 expression in these tissues may provide novel drug targets for treatment of this aggressive neoplastic disease. PMID:24084605

  14. Detection of GNAQ mutations and reduction of cell viability in uveal melanoma cells with functionalized gold nanoparticles

    PubMed Central

    Latorre, Alfonso; Crosby, Michelle B.; Celli, Anna; Latorre, Ana; Vujic, Igor; Sanlorenzo, Martina; Green, Gary A.; Weier, Jingly; Zekhtser, Mitchell; Ma, Jeffrey; Monico, Gabriela; Char, Devron H.; Jusufbegovic, Denis; Rappersberger, Klemens; Somoza, Álvaro; Ortiz-Urda, Susana

    2015-01-01

    Background Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Early treatment may improve any chances of preventing metastatic disease, but diagnosis of small UM is challenging. Up to 95 % of all UMs carry somatic mutations in the G-coupled proteins GNAQ and GNA11 promoting anchorage-independent growth and proliferation. About 50%of UMs are fatal. Once metastatic, patients have limited options for successful therapy. Methods We have developed functionalized gold nanoparticles (AuNPs) to visualize transcripts of mutant GNAQ mRNA in living cells. In addition to their suitability as a specific tool for GNAQ mutation detection, we have developed a novel linker that enables conjugation of siRNAs to AuNPs allowing for greater and more rapid intracellular release of siRNAs compared to previously described approaches. Results Binding of modified AuNPs to matching target mRNA leads to conformational changes, resulting in a detectable fluorescent signal that can be used for mutation detection in living cells. Knockdown of GNAQ with siRNA-AuNPs effectively reduced downstream signals and decreased cell viability in GNAQ mutant uveal melanoma cells. Conclusion AuNPs may in future be developed to serve as sensors for mutations of vital importance. The new release system for siRNA-AuNP improves previous systems, which conceivably will be useful for future therapeutic gene regulatory approaches. PMID:25653058

  15. Risk Factors for Neovascular Glaucoma After Proton Beam Therapy of Uveal Melanoma: A Detailed Analysis of Tumor and Dose–Volume Parameters

    SciTech Connect

    Mishra, Kavita K.; Daftari, Inder K.; Weinberg, Vivian; Cole, Tia; Quivey, Jeanne M.; Castro, Joseph R.; Phillips, Theodore L.; Char, Devron H.

    2013-10-01

    Purpose: To determine neovascular glaucoma (NVG) incidence and identify contributing tumor and dosing factors in uveal melanoma patients treated with proton beam radiation therapy (PBRT). Methods and Materials: A total of 704 PBRT patients treated by a single surgeon (DHC) for uveal melanoma (1996-2010) were reviewed for NVG in our prospectively maintained database. All patients received 56 GyE in 4 fractions. Median follow-up was 58.3 months. Analyses included the Kaplan-Meier method to estimate NVG distributions, univariate log–rank tests, and Cox's proportional hazards multivariate analysis using likelihood ratio tests to identify independent risk factors of NVG among patient, tumor, and dose–volume histogram parameters. Results: The 5-year PBRT NVG rate was 12.7% (95% confidence interval [CI] 10.2%-15.9%). The 5-year rate of enucleation due to NVG was 4.9% (95% CI 3.4%-7.2%). Univariately, the NVG rate increased significantly with larger tumor diameter (P<.0001), greater height (P<.0001), higher T stage (P<.0001), and closer proximity to the disc (P=.002). Dose–volume histogram analysis revealed that if >30% of the lens or ciliary body received ≥50% dose (≥28 GyE), there was a higher probability of NVG (P<.0001 for both). Furthermore, if 100% of the disc or macula received ≥28 GyE, the NVG rate was higher (P<.0001 and P=.03, respectively). If both anterior and posterior doses were above specified cut points, NVG risk was highest (P<.0001). Multivariate analysis confirmed significant independent risk factors to include tumor height (P<.0001), age (P<.0001), %disc treated to ≥50% Dose (<100% vs 100%) (P=.0007), larger tumor diameter (P=.01), %lens treated to ≥90% Dose (0 vs >0%-30% vs >30%) (P=.01), and optic nerve length treated to ≥90% Dose (≤1 mm vs >1 mm) (P=.02). Conclusions: Our current PBRT patients experience a low rate of NVG and resultant enucleation compared with historical data. The present analysis shows that tumor height

  16. Prognostic Implications of Tumor Diameter in Association With Gene Expression Profile for Uveal Melanoma

    PubMed Central

    Walter, Scott D.; Chao, Daniel L.; Feuer, William; Schiffman, Joyce; Char, Devron H.; Harbour, J. William

    2016-01-01

    IMPORTANCE Uveal melanoma (UM) can be divided into prognostically significant subgroups based on a prospectively validated and widely used 15-gene expression profile (GEP) test. Class 1 UMs have a low risk and class 2 UMs have a high risk for metastasis. OBJECTIVE To determine whether any clinicopathologic factors provide independent prognostic information that may enhance the accuracy of the GEP classification. DESIGN, SETTING, AND PARTICIPANTS This retrospective observational study performed at 2 ocular oncology referral centers included 339 patients in a primary cohort and 241 patients in a validation cohort. Both cohorts had a diagnosis of UM arising from the ciliary body and/or choroid. All patients underwent tumor biopsy for GEP prognostic testing. Clinicopathologic variables included patient age and sex, tumor thickness, largest basal tumor diameter (LBD), ciliary body involvement, and pathologic cell type. Patients from the primary cohort were enrolled from November 1, 1998, to March 16, 2012; from the validation cohort, from November 4, 1996, to November 7, 2013. Follow-up for the primary cohort was completed on August 18, 2013; for the validation cohort, December 10, 2013. Data were analyzed from November 12, 2013, to November 25, 2015. MAIN OUTCOME AND MEASURES Progression-free survival (PFS). The secondary outcome was overall survival. RESULTS The primary cohort included 339 patients (175 women [51.6%]; mean [SD] age, 61.8 [13.6] years). The most significant prognostic factor was GEP classification (exp[b], 10.33; 95% CI, 4.30–24.84; P < .001). The only other variable that provided independent prognostic information was LBD (exp[b], 1.13; 95% CI, 1.02–1.26; P = .02). Among class 2 UMs, LBD showed a modest but significant association with PFS (exp[b], 1.13; 95% CI, 1.04–1.24; P = .005). The 5-year actuarial metastasis-free survival estimates (SE) were 97% (3%) for class 1 UMs with LBD of less than 12 mm, 90% (4%) for class 1 UMs with LBD of at

  17. Ruthenium-106 brachytherapy for thick uveal melanoma: reappraisal of apex and base dose radiation and dose rate

    PubMed Central

    Jaberi, Ramin; Sedaghat, Ahad; Azma, Zohreh; Nojomi, Marzieh; Falavarjani, Khalil Ghasemi; Nazari, Hossein

    2016-01-01

    Purpose To evaluate the outcomes of ruthenium-106 (106Ru) brachytherapy in terms of radiation parameters in patients with thick uveal melanomas. Material and methods Medical records of 51 patients with thick (thickness ≥ 7 mm and < 11 mm) uveal melanoma treated with 106Ru brachytherapy during a ten-year period were reviewed. Radiation parameters, tumor regression, best corrected visual acuity (BCVA), and treatment-related complications were assessed. Results Fifty one eyes of 51 consecutive patients including 25 men and 26 women with a mean age of 50.5 ± 15.2 years were enrolled. Patients were followed for 36.1 ± 26.5 months (mean ± SD). Mean radiation dose to tumor apex and to sclera were 71 (± 19.2) Gy and 1269 (± 168.2) Gy. Radiation dose rates to tumor apex and to sclera were 0.37 (± 0.14) Gy/h and 6.44 (± 1.50) Gy/h. Globe preservation was achieved in 82.4%. Preoperative mean tumor thickness of 8.1 (± 0.9) mm decreased to 4.5 (± 1.6) mm, 3.4 (± 1.4) mm, and 3.0 (± 1.46) mm at 12, 24, and 48 months after brachytherapy (p = 0.03). Four eyes that did not show regression after 6 months of brachytherapy were enucleated. Secondary enucleation was performed in 5 eyes because of tumor recurrence or neovascular glaucoma. Tumor recurrence was evident in 6 (11.8%) patients. Mean Log MAR (magnification requirement) visual acuity declined from 0.75 (± 0.63) to 0.94 (± 0.5) (p = 0.04). Best corrected visual acuity of 20/200 or worse was recorded in 37% of the patients at the time of diagnosis and 61.7% of the patients at last exam (p = 0.04). Non-proliferative and proliferative radiation-induced retinopathy was observed in 20 and 7 eyes. Conclusions Thick uveal melanomas are amenable to 106Ru brachytherapy with less than recommended apex radiation dose and dose rates. PMID:26985199

  18. Complications after proton beam therapy for uveal malignant melanoma. A clinical and histopathologic study of five cases

    SciTech Connect

    Kincaid, M.C.; Folberg, R.; Torczynski, E.; Zakov, Z.N.; Shore, J.W.; Liu, S.J.; Planchard, T.A.; Weingeist, T.A.

    1988-07-01

    Proton beam therapy for uveal malignant melanoma has been advocated as effective therapy because of documented reduction in tumor size and few clinical complications. However, some eyes have been removed because of adverse effects. The authors report the clinical courses and pathologic findings of five eyes enucleated after proton beam irradiation. Neovascular glaucoma had developed in three eyes, two eyes had vitreous hemorrhage, and two had extraocular extension. The tumors in the radiation treatment field showed continued postirradiation growth clinically in four of the five eyes, and mitotic activity histologically in all five cases. Two and one half years after irradiation, and nearly 2 years after subsequent enucleation, one of those two patients had biopsy-proven liver metastases, and later died. Despite the considerable success rate of proton beam irradiation, the potential for clinical complications and subsequent tumor growth remains.

  19. Uveal Melanoma Treated With Iodine-125 Episcleral Plaque: An Analysis of Dose on Disease Control and Visual Outcomes

    SciTech Connect

    Perez, Bradford A.; Mettu, Pradeep; Vajzovic, Lejla; Rivera, Douglas; Alkaissi, Ali; Steffey, Beverly A.; Cai, Jing; Stinnett, Sandra; Dutton, Jonathan J.; Buckley, Edward G.; Halperin, Edward; Marks, Lawrence B.; Mruthyunjaya, Prithvi; Kirsch, David G.

    2014-05-01

    Purpose: To investigate, in the treatment of uveal melanomas, how tumor control, radiation toxicity, and visual outcomes are affected by the radiation dose at the tumor apex. Methods and Materials: A retrospective review was performed to evaluate patients treated for uveal melanoma with {sup 125}I plaques between 1988 and 2010. Radiation dose is reported as dose to tumor apex and dose to 5 mm. Primary endpoints included time to local failure, distant failure, and death. Secondary endpoints included eye preservation, visual acuity, and radiation-related complications. Univariate and multivariate analyses were performed to determine associations between radiation dose and the endpoint variables. Results: One hundred ninety patients with sufficient data to evaluate the endpoints were included. The 5-year local control rate was 91%. The 5-year distant metastases rate was 10%. The 5-year overall survival rate was 84%. There were no differences in outcome (local control, distant metastases, overall survival) when dose was stratified by apex dose quartile (<69 Gy, 69-81 Gy, 81-89 Gy, >89 Gy). However, increasing apex dose and dose to 5-mm depth were correlated with greater visual acuity loss (P=.02, P=.0006), worse final visual acuity (P=.02, P<.0001), and radiation complications (P<.0001, P=.0009). In addition, enucleation rates were worse with increasing quartiles of dose to 5 mm (P=.0001). Conclusions: Doses at least as low as 69 Gy prescribed to the tumor apex achieve rates of local control, distant metastasis–free survival, and overall survival that are similar to radiation doses of 85 Gy to the tumor apex, but with improved visual outcomes.

  20. Uveal Melanoma Cell Growth Is Inhibited by Aminoimidazole Carboxamide Ribonucleotide (AICAR) Partially Through Activation of AMP-Dependent Kinase

    PubMed Central

    Al-Moujahed, Ahmad; Nicolaou, Fotini; Brodowska, Katarzyna; Papakostas, Thanos D.; Marmalidou, Anna; Ksander, Bruce R.; Miller, Joan W.; Gragoudas, Evangelos; Vavvas, Demetrios G.

    2014-01-01

    Purpose. To evaluate the effects and mechanism of aminoimidazole carboxamide ribonucleotide (AICAR), an AMP-dependent kinase (AMPK) activator, on the growth of uveal melanoma cell lines. Methods. Four different cell lines were treated with AICAR (1–4 mM). Cell growth was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. Cell cycle analysis was conducted by flow cytometry; additionally, expression of cell-cycle control proteins, cell growth transcription factors, and downstream effectors of AMPK were determined by RT-PCR and Western blot. Results. Aminoimidazole carboxamide ribonucleotide inhibited cell growth, induced S-phase arrest, and led to AMPK activation. Aminoimidazole carboxamide ribonucleotide treatment was associated with inhibition of eukaryotic translation initiation factor 4E-BP1 phosphorylation, a marker of mammalian target of rapamycin (mTOR) pathway activity. Aminoimidazole carboxamide ribonucleotide treatment was also associated with downregulation of cyclins A and D, but had minimal effects on the phosphorylation of ribosomal protein S6 or levels of the macroautophagy marker LC3B. The effects of AICAR were abolished by treatment with dipyridamole, an adenosine transporter inhibitor that blocks the entry of AICAR into cells. Treatment with adenosine kinase inhibitor 5-iodotubericidin, which inhibits the conversion of AICAR to its 5′-phosphorylated ribotide 5-aminoimidazole-4-carboxamide-1-D-ribofuranosyl-5′-monophosphate (ZMP; the direct activator of AMPK), reversed most of the growth-inhibitory effects, indicating that some of AICAR's antiproliferative effects are mediated at least partially through AMPK activation. Conclusions. Aminoimidazole carboxamide ribonucleotide inhibited uveal melanoma cell proliferation partially through activation of the AMPK pathway and downregulation of cyclins A1 and D1. PMID:24781943

  1. M2/M1 ratio of tumor associated macrophages and PPAR-gamma expression in uveal melanomas with class 1 and class 2 molecular profiles.

    PubMed

    Herwig, Martina C; Bergstrom, Chris; Wells, Jill R; Höller, Tobias; Grossniklaus, Hans E

    2013-02-01

    Macrophages have been found to be negative predictors of outcome in patients with uveal melanoma. In particular, recent studies point toward a disease-progressing role of proangiogenic M2 macrophages in melanomas with monosomy 3. Although most studies implicate a protective effect of PPAR-gamma activation in tumors, PPAR-gamma has also been shown to promote the polarization of M1 macrophages toward the M2 phenotype. The purpose of this investigation was first, to characterize the phenotype of tumor infiltrating macrophages and second, to study PPAR-gamma expression in uveal melanomas with molecular gene expression profile as prognostic predictors for patients' outcome. Twenty specimens from patients with uveal melanoma were analyzed for clinical and histologic tumor characteristics. The molecular RNA profile (class 1 or class 2) was commercially determined. Using immunohistochemical techniques, the specimens were dual labeled for CD68 and CD163. CD68 + CD163- M1 macrophages and CD68 + CD163+ M2 macrophages were analyzed in ten high power fields sparing macrophage-poor areas and a mean value was calculated for each tumor. The tumors were immunostained for von Willebrand factor and the micro vascular density (MVD) was analyzed according to Foss. To assess the proliferative rate of each tumor, Ki67 expression was evaluated in ten high power fields followed by calculation of a mean value. Expression of PPAR-gamma was evaluated using a score from 0 (no staining) to 3 (tumor entirely stained). Statistical analysis and a respective correlation were made between histologic characteristics, molecular profile, type of tumor infiltrating macrophages (M1 vs. M2), MVD, proliferative rate, and PPAR-gamma expression. Our results showed a correlation between the ratio of M2/M1 macrophages and the molecular profile with a ratio of approximately 1 corresponding to molecular class 1 and a ratio of approximately 2 corresponding to molecular class 2 (p = 0.01). The ratio of M2/M1

  2. Lymphadenectomy promotes tumor growth and cancer cell dissemination in the spontaneous RET mouse model of human uveal melanoma.

    PubMed

    Pin, Yeo Kim; Khoo, Karen; Tham, Muly; Karwai, Tan; Hwee, Thiam Chung; Puaux, Anne-Laure; Phua, Meow Ling Cindy; Kato, Masashi; Angeli, Veronique; Abastado, Jean-Pierre

    2015-12-29

    Resection of infiltrated tumor-draining lymph nodes (TDLNs) is a standard practice for the treatment of several cancers including breast cancer and melanoma. However, many randomized prospective trials have failed to show convincing clinical benefits associated with LN removal and the role of TDLNs in cancer dissemination is poorly understood. Here, we found in a well-characterized spontaneous mouse model of uveal melanoma that the growth of the primary tumor was accompanied by increased lymphangiogenesis and cancer cell colonization in the LNs draining the eyes. But, unexpectedly, early resection of the TDLNs increased the growth of the primary tumor and associated blood vessels as well as promoted cancer cell survival and dissemination. These effects were accompanied by increased tumor cell proliferation and expression of phosphorylated AKT. Topical application of a broad anti-inflammatory agent, Tobradex, or an oral treatment with cyclooxygenase-2 specific inhibitor, Celecoxib, reversed tumor progression observed after complete lymphadenectomy. Our study confirms the importance of tumor homeostasis in cancer progression by showing the enhancing effects of TDLN removal on tumor growth and cancer cell dissemination, and suggests that TDLN resection may only be beneficial if used in combination with anti-inflammatory drugs such as Tobradex and Celecoxib. PMID:26575174

  3. Lymphadenectomy promotes tumor growth and cancer cell dissemination in the spontaneous RET mouse model of human uveal melanoma

    PubMed Central

    Pin, Yeo Kim; Khoo, Karen; Tham, Muly; Karwai, Tan; Hwee, Thiam Chung; Puaux, Anne-Laure; Cindy Phua, Meow Ling; Kato, Masashi

    2015-01-01

    Resection of infiltrated tumor-draining lymph nodes (TDLNs) is a standard practice for the treatment of several cancers including breast cancer and melanoma. However, many randomized prospective trials have failed to show convincing clinical benefits associated with LN removal and the role of TDLNs in cancer dissemination is poorly understood. Here, we found in a well-characterized spontaneous mouse model of uveal melanoma that the growth of the primary tumor was accompanied by increased lymphangiogenesis and cancer cell colonization in the LNs draining the eyes. But, unexpectedly, early resection of the TDLNs increased the growth of the primary tumor and associated blood vessels as well as promoted cancer cell survival and dissemination. These effects were accompanied by increased tumor cell proliferation and expression of phosphorylated AKT. Topical application of a broad anti-inflammatory agent, Tobradex, or an oral treatment with cyclooxygenase-2 specific inhibitor, Celecoxib, reversed tumor progression observed after complete lymphadenectomy. Our study confirms the importance of tumor homeostasis in cancer progression by showing the enhancing effects of TDLN removal on tumor growth and cancer cell dissemination, and suggests that TDLN resection may only be beneficial if used in combination with anti-inflammatory drugs such as Tobradex and Celecoxib. PMID:26575174

  4. Serum vascular endothelial growth factor (VEGF) levels correlate with number and location of micrometastases in a murine model of uveal melanoma

    PubMed Central

    Crosby, Michelle B; Yang, Hua; Gao, Weiqing; Zhang, Lane

    2010-01-01

    Background A preliminary animal study was performed to determine if hepatic micrometastases from uveal melanoma secrete vascular endothelial growth factor (VEGF) that is measurable in serum. Methods We analysed the serum of a C57Bl/6 mouse model of uveal melanoma (n=10) at days 4, 7, 14 and 21 post-inoculation for VEGF levels. We compared the serum VEGF levels with the number and location of hepatic micrometastases and their respective expression of VEGF mRNA. Results Serum VEGF levels rose after inoculation of C57Bl/6 mice eyes with B16LS9 cutaneous melanoma cells. Beginning on day 14 there was a statistically significant (p<0.05) increase in VEGF levels, rising to an average peak level of 37.985 pg/ml at day 21. Peak serum VEGF levels correlated with the total number of hepatic micrometastases (R=0.444) and there was moderate correlation of peak VEGF serum levels with micrometastases in more hypoxic locations (R=0.572). VEGF mRNA expression by micrometastases was highest in the most hypoxic regions of the hepatic lobule. Conclusions Hepatic micrometastastic melanoma arising in a mouse model of ocular melanoma secretes VEGF. The number and location of the micrometastases correlate with serum VEGF levels. PMID:20819828

  5. Reduced FANCD2 influences spontaneous SCE and RAD51 foci formation in uveal melanoma and Fanconi anaemia

    PubMed Central

    Gravells, P; Hoh, L; Solovieva, S; Patil, A; Dudziec, E; Rennie, I G; Sisley, K; Bryant, H E

    2013-01-01

    Uveal melanoma (UM) is unique among cancers in displaying reduced endogenous levels of sister chromatid exchange (SCE). Here we demonstrate that FANCD2 expression is reduced in UM and that ectopic expression of FANCD2 increased SCE. Similarly, FANCD2-deficient fibroblasts (PD20) derived from Fanconi anaemia patients displayed reduced spontaneous SCE formation relative to their FANCD2-complemented counterparts, suggesting that this observation is not specific to UM. In addition, spontaneous RAD51 foci were reduced in UM and PD20 cells compared with FANCD2-proficient cells. This is consistent with a model where spontaneous SCEs are the end product of endogenous recombination events and implicates FANCD2 in the promotion of recombination-mediated repair of endogenous DNA damage and in SCE formation during normal DNA replication. In both UM and PD20 cells, low SCE was reversed by inhibiting DNA-PKcs (DNA-dependent protein kinase, catalytic subunit). Finally, we demonstrate that both PD20 and UM are sensitive to acetaldehyde, supporting a role for FANCD2 in repair of lesions induced by such endogenous metabolites. Together, these data suggest FANCD2 may promote spontaneous SCE by influencing which double-strand break repair pathway predominates during normal S-phase progression. PMID:23318456

  6. Class III-specific HDAC inhibitor Tenovin-6 induces apoptosis, suppresses migration and eliminates cancer stem cells in uveal melanoma

    PubMed Central

    Dai, Wei; Zhou, Jingfeng; Jin, Bei; Pan, Jingxuan

    2016-01-01

    Uveal melanoma (UM) is the most common intraocular malignancy in adults. Despite improvements in surgical, radiation and chemotherapy treatments, the overall survival of UM and prognosis remain poor. In the present study, we hypothesized that Sirtuin 1 and 2 (SIRT1/2), class III histone deacetylases (HDACs), were critical in controlling the destiny of bulk tumor cells and cancer stem cells (CSCs) of UM. We testified this hypothesis in four lines of UM cells (92.1, Mel 270, Omm 1 and Omm 2.3). Our results showed that inhibition of SIRT1/2 by Tenovin-6 induced apoptosis in UM cells by activating the expression of tumor suppressor genes such as p53 and elevating reactive oxygen species (ROS). Tenovin-6 inhibited the growth of UM cells. Tenovin-6 and vinblastine was synergistic in inducing apoptosis of UM cell line 92.1 and Mel 270. Furthermore, Tenovin-6 eliminated cancer stem cells in 92.1 and Mel 270 cells. In conclusion, our findings suggest that Tenovin-6 may be a promising agent to kill UM bulk tumor cells and CSCs. PMID:26940009

  7. Monte Carlo calculations and measurements of absorbed dose per monitor unit for the treatment of uveal melanoma with proton therapy

    PubMed Central

    Koch, Nicholas; Newhauser, Wayne D; Titt, Uwe; Gombos, Dan; Coombes, Kevin; Starkschall, George

    2014-01-01

    The treatment of uveal melanoma with proton radiotherapy has provided excellent clinical outcomes. However, contemporary treatment planning systems use simplistic dose algorithms that limit the accuracy of relative dose distributions. Further, absolute predictions of absorbed dose per monitor unit are not yet available in these systems. The purpose of this study was to determine if Monte Carlo methods could predict dose per monitor unit (D/MU) value at the center of a proton spread-out Bragg peak (SOBP) to within 1% on measured values for a variety of treatment fields relevant to ocular proton therapy. The MCNPX Monte Carlo transport code, in combination with realistic models for the ocular beam delivery apparatus and a water phantom, was used to calculate dose distributions and D/MU values, which were verified by the measurements. Measured proton beam data included central-axis depth dose profiles, relative cross-field profiles and absolute D/MU measurements under several combinations of beam penetration ranges and range-modulation widths. The Monte Carlo method predicted D/MU values that agreed with measurement to within 1% and dose profiles that agreed with measurement to within 3% of peak dose or within 0.5 mm distance-to-agreement. Lastly, a demonstration of the clinical utility of this technique included calculations of dose distributions and D/MU values in a realistic model of the human eye. It is possible to predict D/MU values accurately for clinical relevant range-modulated proton beams for ocular therapy using the Monte Carlo method. It is thus feasible to use the Monte Carlo method as a routine absolute dose algorithm for ocular proton therapy. PMID:18367789

  8. Comparing the Prognostic Value of BAP1 Mutation Pattern, Chromosome 3 Status, and BAP1 Immunohistochemistry in Uveal Melanoma.

    PubMed

    van de Nes, Johannes A P; Nelles, Jasmin; Kreis, Stefan; Metz, Claudia H D; Hager, Thomas; Lohmann, Dietmar R; Zeschnigk, Michael

    2016-06-01

    Uveal melanoma (UM), a tumor of the eye, can be divided into 2 major classes correlating with patients' prognosis. Gene expression profiles and chromosome 3 status are correlated with tumor classification and prognosis. Somatic BAP1 mutations are another feature largely restricted to metastatic UM. Here we performed thorough BAP1 mutation analysis including sequencing and gene dosage analysis of all BAP1 coding exons as well as methylation analysis of the promoter CpG island in a set of 66 UMs. The results were compared with the BAP1 protein expression as determined by immunohistochemistry and the tumor-related survival of the patients. BAP1 sequencing and gene dosage analysis of BAP1 exons by multiplex ligation-dependent probe amplification revealed a mutation in 33 (89%) of 37 tumors with monosomy 3 (M3) or isodisomy 3. BAP1 mutations were not detected in any of the 28 tumors with disomy 3 or partial monosomy 3 (partM3). Most of the sequence mutations (21 of 28) were frame-shift, splice-site, or nonsense mutations leading to a premature termination codon. BAP1 protein as determined by immunohistochemistry was absent in all samples with a BAP1 mutation irrespective of the functional type of mutation. Kaplan-Meier analysis revealed a highly significant association between BAP1 protein staining and patients' survival (P=0.0004). The association between BAP1 mutation status and tumor-related survival was less pronounced but still significant (P=0.0023). We conclude that BAP1 protein staining is favorable over BAP1 mutation screening by Sanger sequencing for prognostic testing of UM patients. PMID:27015033

  9. Establishment of novel cell lines recapitulating the genetic landscape of uveal melanoma and preclinical validation of mTOR as a therapeutic target.

    PubMed

    Amirouchene-Angelozzi, Nabil; Nemati, Fariba; Gentien, David; Nicolas, André; Dumont, Amaury; Carita, Guillaume; Camonis, Jacques; Desjardins, Laurence; Cassoux, Nathalie; Piperno-Neumann, Sophie; Mariani, Pascale; Sastre, Xavier; Decaudin, Didier; Roman-Roman, Sergio

    2014-12-01

    Uveal melanoma (UM) is the most common primary tumor of the eye in adults. There is no standard adjuvant treatment to prevent metastasis and no effective therapy in the metastatic setting. We have established a unique panel of 7 UM cell lines from either patient's tumors or patient-derived tumor xenografts (PDXs). This panel recapitulates the molecular landscape of the disease in terms of genetic alterations and mutations. All the cell lines display GNAQ or GNA11 activating mutations, and importantly four of them display BAP1 (BRCA1 associated protein-1) deficiency, a hallmark of aggressive disease. The mTOR pathway was shown to be activated in most of the cell lines independent of AKT signaling. mTOR inhibitor Everolimus reduced the viability of UM cell lines and significantly delayed tumor growth in 4 PDXs. Our data suggest that mTOR inhibition with Everolimus, possibly in combination with other agents, may be considered as a therapeutic option for the management of uveal melanoma. PMID:24994677

  10. Clinico-Pathological Association of Delineated miRNAs in Uveal Melanoma with Monosomy 3/Disomy 3 Chromosomal Aberrations

    PubMed Central

    Venkatesan, Nalini; Kanwar, Jagat; Deepa, Perinkulam Ravi; Khetan, Vikas; Crowley, Tamsyn M.; Raguraman, Rajeswari; Sugneswari, Ganesan; Rishi, Pukhraj; Natarajan, Viswanathan; Biswas, Jyotirmay; Krishnakumar, Subramanian

    2016-01-01

    Purpose To correlate the differentially expressed miRNAs with clinico-pathological features in uveal melanoma (UM) tumors harbouring chromosomal 3 aberrations among South Asian Indian cohort. Methods Based on chromosomal 3 aberration, UM (n = 86) were grouped into monosomy 3 (M3; n = 51) and disomy 3 (D3; n = 35) by chromogenic in-situ hybridisation (CISH). The clinico-pathological features were recorded. miRNA profiling was performed in formalin fixed paraffin embedded (FFPE) UM samples (n = 6) using Agilent, Human miRNA microarray, 8x15KV3 arrays. The association between miRNAs and clinico-pathological features were studied using univariate and multivariate analysis. miRNA-gene targets were predicted using Target-scan and MiRanda database. Significantly dys-regulated miRNAs were validated in FFPE UM (n = 86) and mRNAs were validated in frozen UM (n = 10) by qRT-PCR. Metastasis free-survival and miRNA expressions were analysed by Kaplen-Meier analysis in UM tissues (n = 52). Results Unsupervised analysis revealed 585 differentially expressed miRNAs while supervised analysis demonstrated 82 miRNAs (FDR; Q = 0.0). Differential expression of 8 miRNAs: miR-214, miR-149*, miR-143, miR-146b, miR-199a, let7b, miR-1238 and miR-134 were studied. Gene target prediction revealed SMAD4, WISP1, HIPK1, HDAC8 and C-KIT as the post-transcriptional regulators of miR-146b, miR-199a, miR-1238 and miR-134. Five miRNAs (miR-214, miR146b, miR-143, miR-199a and miR-134) were found to be differentially expressed in M3/ D3 UM tumors. In UM patients with liver metastasis, miR-149* and miR-134 expressions were strongly correlated. Conclusion UM can be stratified using miRNAs from FFPE sections. miRNAs predicting liver metastasis and survival have been identified. Mechanistic linkage of de-regulated miRNA/mRNA expressions provide new insights on their role in UM progression and aggressiveness. PMID:26812476

  11. A Unifying Concept of Uveal Pigment Cell Distribution and Dissemination Based on an Animal Model: Insights into Ocular Melanogenesis.

    PubMed

    Schwab, Christoph; Wackernagel, Werner; Grinninger, Petra; Mayer, Christoph; Schwab, Katharina; Langmann, Gerald; Richtig, Erika; Wedrich, Andreas; Hofmann-Wellenhof, Rainer; Zalaudek, Iris

    2016-01-01

    Pigmented cells are derived from neural crest cells, which migrate along the peripheral nerve sheets into their specific final region. During their migration, cells progressively acquire pigment-producing capabilities, maturation, and the shape of melanocytes. These insights, along with specific clinical characteristics of melanocytic nevi, have led to new concepts of cutaneous, periocular, and iris nevogenesis. To further elucidate the specific ocular embryogenic melanoblast distribution and dissemination - that could explain the distinct distribution of uveal melanocytic neoplasms - we investigated the ocular pigmentation of dogs affected by a specific mutation called Merle, which results in either pigment- (wild type) or non-pigment- (mutated type) producing cells. Based on our observations, we propose a unifying concept of uveal pigment cell distribution and dissemination, which postulates melanoblast migration and maturation following the trigeminal V1 branch and, later, their entrance into the eye along the ciliary nerves and their finest iris branches. Our concept provides an explanation not only for the specific distribution of ocular melanocytic lesions, including uveal and iris nevi, but also for the different locations depending on the metastatic potential of the ocular melanoma. Though speculative, the higher metastatic potential of posterior uveal melanomas compared to iris melanomas may be related to a less differentiated stage in the maturation of migrating melanocytes in the posterior segment compared to the anterior segment of the eye. However, there is a need of further studies focusing on cell differentiation markers of melanocytes at different locations in the eye. PMID:27002320

  12. Iodine 125 Brachytherapy With Vitrectomy and Silicone Oil in the Treatment of Uveal Melanoma: 1-to-1 Matched Case-Control Series

    SciTech Connect

    McCannel, Tara A. McCannel, Colin A.

    2014-06-01

    Purpose: We initially reported the radiation-attenuating effect of silicone oil 1000 centistokes for iodine 125. The purpose of this report was to compare the clinical outcomes in case patients who had iodine 125 brachytherapy with vitrectomy and silicone oil 1000 centistokes with the outcomes in matched control patients who underwent brachytherapy alone. Methods and Materials: Consecutive patients with uveal melanoma who were treated with iodine 125 plaque brachytherapy and vitrectomy with silicone oil with minimum 1-year follow-up were included. Control patients who underwent brachytherapy alone were matched for tumor size, location, and sex. Baseline patient and tumor characteristics and tumor response to radiation, final visual acuity, macular status, central macular thickness by ocular coherence tomography (OCT), cataract progression, and metastasis at last follow-up visit were compared. Surgical complications were also determined. Results: Twenty case patients met the inclusion criteria. The average follow-up time was 22.1 months in case patients and 19.4 months in control patients. The final logMAR vision was 0.81 in case patients and 1.1 in control patients (P=.071); 8 case patients and 16 control patients had abnormal macular findings (P=.011); and the average central macular thickness by OCT was 293.2 μm in case patients and 408.5 μm in control patients (P=.016). Eleven case patients (55%) and 1 control patient (5%) had required cataract surgery at last follow-up (P=.002). Four patients in the case group and 1 patient in the control group experienced metastasis (P=.18). Among the cases, intraoperative retinal tear occurred in 3 patients; total serous retinal detachment and macular hole developed in 1 case patient each. There was no case of rhegmatogenous retinal detachment, treatment failure, or local tumor dissemination in case patients or control patients. Conclusions: With up to 3 years of clinical follow-up, silicone oil during brachytherapy

  13. Color flow mapping: a non-invasive tool for characterizing and differentiating between uveal melanomas and choroidal metastases.

    PubMed

    Neudorfer, Meira; Waisbourd, Michael; Anteby, Irene; Liran, Alon; Goldenberg, Dafna; Barak, Adiel; Kessler, Ada

    2011-01-01

    The objective of this study was to characterize and differentiate vascular patterns of choroidal melanomas and choroidal metastases by color flow mapping (CFM). We conducted a retrospective chart study on CFM findings in 18 patients with choroidal melanomas and 10 patients with choroidal metastases. We evaluated the possibilities of applying CFM to identify hypo- versus hyper-vascularity within the tumor, a central 'dominant vessel', and Doppler signals in the tumor's center and/or periphery. CFM demonstrated hypervascular patterns in 33% melanomas and 100% metastases (p<0.0001). CFM identified a central dominant vessel in 94% melanomas and 0/10 metastases (p<0.0001). Vascularity occupied the center of 11/18 melanomas and 0/10 metastases (p<0.0001), the periphery of 2/18 melanomas and 9/10 metastases (p<0.0001), and equally occupied the tumor's center and periphery of 5/18 melanomas and 1/10 metastases (p<0.0001). Based on our findings, we conclude that CFM was capable of non-invasively demonstrating different and distinct vascular patterns in malignant choroidal melanomas and choroidal metastases. PMID:21109962

  14. Hypoxia-inducible factor 1 upregulation of both VEGF and ANGPTL4 is required to promote the angiogenic phenotype in uveal melanoma

    PubMed Central

    Rodrigues, Murilo; Deshpande, Monika; Puchner, Brooks; Kashiwabuchi, Fabiana; Hassan, Syed Junaid; Asnaghi, Laura; Handa, James T.; Merbs, Shannath; Eberhart, Charles G.; Semenza, Gregg L.; Montaner, Silvia; Sodhi, Akrit

    2016-01-01

    Purpose Expression of the hypoxia-inducible factor (HIF)-1-regulated gene product, vascular endothelial growth factor (VEGF), correlates with tumor vascularity in patients with uveal melanoma (UM). While the relationship between HIF-1 and VEGF in cancer is well-studied, their relative contribution to the angiogenic phenotype in UM has not previously been interrogated. Here we evaluate the contribution of HIF-1, VEGF, and a second HIF-1-regulated gene product, angiopoietin-like 4 (ANGPTL4), to angiogenesis in UM. Experimental Design UM cells were examined for expression of HIF-1α, VEGF, and ANGPTL4. Their contribution to the angiogenic potential of UM cells was assessed using the endothelial cell tubule formation and directed in vivo angiogenesis assays. These results were corroborated in tissue from UM animal models and in tissue from patients with UM. Results Inhibition of VEGF partially reduced tubule formation promoted by conditioned medium from UM cells. Inhibition of ANGPTL4, which was highly expressed in hypoxic UM cells, a UM orthotopic transplant model, a UM tumor array, and vitreous samples from UM patients, inhibited the angiogenic potential of UM cells in vitro and in vivo; this effect was additive to VEGF inhibition. Conclusions Targeting both ANGPTL4 and VEGF may be required for the effective inhibition of angiogenesis in UM. PMID:26761211

  15. Resistance of uveal melanoma to the interstrand cross-linking agent mitomycin C is associated with reduced expression of CYP450R

    PubMed Central

    Gravells, P; Hoh, L; Canovas, D; Rennie, I G; Sisley, K; Bryant, H E

    2011-01-01

    Background: Uveal melanoma (UM) is the most common primary intraocular tumour of adults, frequently metastasising to the liver. Hepatic metastases are difficult to treat and are mainly unresponsive to chemotherapy. To investigate why UM are so chemo-resistant we explored the effect of interstrand cross-linking agents mitomycin C (MMC) and cisplatin in comparison with hydroxyurea (HU). Methods: Sensitivity to MMC, cisplatin and HU was tested in established UM cell lines using clonogenic assays. The response of UM to MMC was confirmed in MTT assays using short-term cultures of primary UM. The expression of cytochrome P450 reductase (CYP450R) was analysed by western blotting, and DNA cross-linking was assessed using COMET analysis supported by γ-H2AX foci formation. Results: Both established cell lines and primary cultures of UM were resistant to the cross-linking agent MMC (in each case P<0.001 in Student's t-test compared with controls). In two established UM cell lines, DNA cross-link damage was not induced by MMC (in both cases P<0.05 in Students's t-test compared with damage induced in controls). In all, 6 out of 6 UMs tested displayed reduced expression of the metabolising enzyme CYP450R and transient expression of CYP450R increased MMC sensitivity of UM. Conclusion: We suggest that reduced expression of CYP450R is responsible for MMC resistance of UM, through a lack of bioactivation, which can be reversed by complementing UM cell lines with CYP450R. PMID:21386838

  16. Double-Blinded, Randomized Phase II Study Using Embolization with or without Granulocyte–Macrophage Colony-Stimulating Factor in Uveal Melanoma with Hepatic Metastases

    PubMed Central

    Valsecchi, Matias E.; Terai, Mizue; Eschelman, David J.; Gonsalves, Carin F.; Chervoneva, Inna; Shields, Jerry A.; Shields, Carol L.; Yamamoto, Akira; Sullivan, Kevin L.; Laudadio, MaryAnn; Berd, David; Mastrangelo, Michael J.

    2015-01-01

    Purpose To investigate the effects of immunoembolization with granulocyte–macrophage colony-stimulating factor (GM-CSF) in patients with uveal melanoma (UM) with liver-only metastasis. Materials and Methods In this double-blind phase II clinical trial, patients were randomized to undergo immunoembolization or bland embolization (BE). Lobar treatment was performed with GM-CSF or normal saline solution mixed with ethiodized oil followed by embolization with gelatin sponge emulsified with iodinated contrast medium. Fifty-two patients (immunoembolization, n = 25; BE, n = 27) were enrolled. Response was assessed after every two treatments. The primary endpoint was overall response rate (ORR) of liver metastases. Progression-free survival (PFS), overall survival (OS), and immunologic responses were secondary endpoints. Results There were five partial responses in the immunoembolization group (ORR, 21.2%; 90% confidence interval [CI], 10.3%–30.5%) and three in the BE group (ORR, 16.7%; 90% CI, 6.3%–26.9%). Stable disease was seen in 12 patients in the immunoembolization group and 19 in the BE group. OS times were 21.5 months (95% CI, 18.5–24.8 mo) with immunoembolization and 17.2 months (95% CI, 11.9–22.4 mo) with BE. The degree of proinflammatory cytokine production was more robust after immunoembolization and correlated with time to “systemic” extrahepatic progression. In the immunoembolization group, interleukin (IL)-6 levels at 1 hour (P = .001) and IL-8 levels at 18 hours after the procedure (P < .001) were significant predictors of longer systemic PFS. Moreover, a dose–response pattern was evident between posttreatment serum cytokine concentrations and systemic PFS. Conclusions Immunoembolization induced more robust inflammatory responses, which correlated with the delayed progression of extrahepatic systemic metastases. PMID:25678394

  17. Transscleral visible/near-infrared spectroscopy for quantitative assessment of melanin in a uveal melanoma phantom of ex vivo porcine eyes.

    PubMed

    Krohn, Jørgen; Xu, Can T; Svenmarker, Pontus; Khoptyar, Dmitry; Andersson-Engels, Stefan

    2010-02-01

    Optical spectroscopy has been used as a supplement to conventional techniques for analyzing and diagnosing cancer in many human organs. Because ocular tumors may be characterized by their different melanin content, we investigated the feasibility of using transscleral visible/near-infrared spectroscopy (Vis/NIRS) to estimate the quantity of melanin in a novel uveal melanoma phantom of ex vivo porcine eyes. The phantoms were made by injecting a freshly prepared suspension of 15% (wt/vol) gelatin, 10 mg/ml titanium dioxide (TiO(2)), and natural melanin, isolated from the ink sac of cuttlefish (Sepia officinalis), into the suprachoroidal space of 30 enucleated porcine eyes. The melanin concentrations used were 1 mg/ml, 2 mg/ml, and 3 mg/ml, with 10 eyes in each group. After gelation, the size and location of the phantoms were documented by B-scan ultrasonography and transillumination. Vis/NIRS recordings, covering the wavelength region from 550 to 1000 nm, were performed with two optical fibers separated by 6 mm to deliver and collect the light through the sclera. During all measurements, the exact pressure exerted by the fiber probe on the scleral surface was monitored by placing the eye on an electronic scale. Transscleral Vis/NIRS was performed across the phantom inclusion, as well as on the opposite (normal) side of each eye. A total of three consecutive measurements were carried out alternately on each side of the globe. The spectral data were analyzed using partial least squares regression. In the melanin concentration groups of 1 mg/ml (n = 10), 2 mg/ml (n = 10), and 3 mg/ml (n = 10), the largest basal phantom diameters (mean +/- SD) were 14.9 +/- 1.6 mm, 14.6 +/- 1.5 mm, and 14.3 +/- 1.0 mm, respectively (p > 0.05). The largest phantom thicknesses (mean +/- SD) were 4.0 +/- 0.5 mm, 4.4 +/- 0.7 mm, and 4.5 +/- 0.5 mm, respectively (p > 0.05). Statistical regression modeling of the Vis/NIRS data revealed that it was possible to correctly classify the phantoms

  18. Bilateral choroidal melanoma--case analysis and literature review.

    PubMed

    Kowal, Joanna; Strzałka, Anna; Markiewicz, Anna; Romanowska-Dixon, Bożena; Bogdali, Anna

    2015-01-01

    Uveal melanoma is the most common primary intraocular neoplasm in adults. Its bilateral localization is extremely rare. The aim of the paper is analysis of the cases of bilateral uveal melanoma. Five bilateral uveal melanoma patients were diagnosed in the Department of Ophtalmology and Ocular Oncology beetwen 1980 and 2014. Both eyes of four patients were threated with brachytherapy. Final enulcleation of the one eye was performed in three patients. It was the primary treatment in one patient. The presence of uveal melanoma was confirmed by pathological examination in all cases after surgical removal of eyeball and in one after local resection of iris tumor. Metastatic lesions were diagnosed in lungs and liver in two patients. Three patients are still followed-up at our institution. The possibility of bilateral uveal melanoma should considered although it is extremely rare. bilateral uveal melanoma, brachytherapy, enucleation. PMID:26638545

  19. Melanoma

    MedlinePlus

    Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma ...

  20. Stages of Intraocular (Uveal) Melanoma

    MedlinePlus

    ... eye : A procedure in which high-energy sound waves (ultrasound) are bounced off the internal tissues of ... a small probe that sends and receives sound waves is placed gently on the surface of the ...

  1. Melanoma

    MedlinePlus

    ... to other parts of the body very quickly. Melanoma treatment can cause side effects, including pain, nausea, and ... Livingstone; 2013:chap 69. National Cancer Institute: PDQ Melanoma Treatment. Bethesda, MD: National Cancer Institute. Last modified March ...

  2. Melanoma

    MedlinePlus

    ... have melanoma that has spread. Help the patient’s immune system fight the cancer Ipilimumab (Yervoy®), which was FDA ... How ipilimumab works : This drug helps the patient’s immune system to recognize, target, and attack cancer cells. Healthy ...

  3. [Melanoma].

    PubMed

    Uhara, Hisashi

    2016-04-01

    Since 2011, several effective drugs for patients with metastatic melanoma, including BRAF inhibitors, MEK inhibitors, and immune checkpoint inhibitors, have been approved. The combination of BRAF and MEK inhibitors achieve response rates of 70% and a median progression-free survival of >11 months in patients. The combination of ipilimumab and nivolumab has shown response rates of up to 60-70% and a median progression-free survival of 11-14 months, despite increased toxicities. Moreover, many clinical trials for new combination therapies are still ongoing. PMID:27220785

  4. Lacrimal Gland Radiosensitivity in Uveal Melanoma Patients

    SciTech Connect

    Muller, Karin Nowak, Peter J.C.M.; Naus, Nicole; Pan, Connie de; Santen, Cornelis A. van; Levendag, Peter; Luyten, Gre P.M.

    2009-06-01

    Purpose: To find a dose-volume effect for inhomogeneous irradiated lacrimal glands. Methods and Materials: Between 1999 and 2006, 72 patients (42 men and 30 women) were treated with fractionated stereotactic radiotherapy in a prospective, nonrandomized clinical trial (median follow-up, 32 months). A total dose of 50 Gy was given on 5 consecutive days. The mean of all Schirmer test results obtained {>=}6 months after treatment was correlated with the radiation dose delivered to the lacrimal gland. Also, the appearance of dry eye syndrome (DES) was related to the lacrimal gland dose distribution. Results: Of the 72 patients, 17 developed a late Schirmer value <10 mm; 9 patients developed DES. A statistically significant relationship was found between the received median dose in the lacrimal gland vs. reduced tear production (p = 0.000) and vs. the appearance of DES (p = 0.003), respectively. A median dose of 7 Gy/fraction to the lacrimal gland caused a 50% risk of low Schirmer results. A median dose of 10 Gy resulted in a 50% probability of DES. Conclusion: We found a clear dose-volume relationship for irradiated lacrimal glands with regard to reduced tear production and the appearance of DES.

  5. Treatment Options for Intraocular (Uveal) Melanoma

    MedlinePlus

    ... eye : A procedure in which high-energy sound waves (ultrasound) are bounced off the internal tissues of ... a small probe that sends and receives sound waves is placed gently on the surface of the ...

  6. Treatment Option Overview (Intraocular [Uveal] Melanoma)

    MedlinePlus

    ... eye : A procedure in which high-energy sound waves (ultrasound) are bounced off the internal tissues of ... a small probe that sends and receives sound waves is placed gently on the surface of the ...

  7. Cytogenetics of melanoma: a review.

    PubMed

    James, Aaron W; Chang, Le; Shrestha, Swati; Cochran, Alistair; Binder, Scott; Tirado, Carlos A

    2014-01-01

    Malignant melanoma is an aggressive cutaneous neoplasm whose incidence has continued to increase worldwide. Currently, histopathologic examination of specimens is the gold standard for the diagnosis and categorization of melanoma. Cytogenetic analysis represents a powerful, and currently underused, adjunct to traditional histologic examination in distinguishing nevi and melanomas. Chromosomal studies have shown that malignant melanomas often contain multiple chromosomal alterations, most commonly of chromosomes 1, 6, 7, 9, 10 and 11. These chromosomes often include genes within the MAPK molecular pathway, which is involved in the development and progression of melanoma. Fluorescence in situ hybridization (FISH) can detect a number of recurrent anomalies, and commercially available kits for melanoma detection have been devised. The utility of cytogenetics in melanocytic lesions at certain anatomic sites has been evaluated, including acral lesions, uveal lesions, and lymph node metastases. Recurring cytogenetic anomalies have been defined in various challenging histologic subtypes, such as desmoplastic melanomas and Spitzoid lesions. Cytogenetic analysis may also be used to provide supplementary information in prognostication, particularly in uveal melanomas. We provide a brief review of the molecular pathways found in melanoma and a summary of what is known and remains unknown regarding cytogenetic aberrations associated with malignant melanoma. PMID:26030295

  8. Progressive Scleral Necrosis following I-125 Plaque Radiotherapy for Ciliochoroidal Melanoma with Protruding Extraocular Mass

    PubMed Central

    Hill, Jordan R.; Corrêa, Zélia M.

    2016-01-01

    Purpose The aim of this study was to describe the side effects of I-125 brachytherapy in the treatment of uveal melanoma. Methods This study was conducted as a case report. Results We report a case of scleral necrosis and protruding episcleral mass following the treatment of uveal melanoma with I-125 brachytherapy. Conclusions Scleral necrosis after plaque radiotherapy can clinically simulate tumor recurrence with extraocular extension. The management of uveal melanoma requires a careful clinical follow-up, weighing the implications of treatment morbidity and mortality. PMID:27239452

  9. Enucleation vs cobalt plaque radiotherapy for malignant melanomas of the choroid and ciliary body

    SciTech Connect

    Augsburger, J.J.; Gamel, J.W.; Sardi, V.F.; Greenberg, R.A.; Shields, J.A.; Brady, L.W.

    1986-05-01

    Clinical risk factors were assessed prospectively in a nonrandomized concurrent observational study of 237 patients with posterior uveal malignant melanoma. One hundred forty of these patients were treated with enucleation, and 97 underwent cobalt plaque radiotherapy. Tumor size and location of the anterior tumor margin proved to be the most significant clinical risk factors for death from metastatic melanoma. When Cox proportional hazards modeling was used to adjust for recognized intergroup differences in risk factors, the effect of therapy (enucleation vs cobalt plaque radiotherapy) on survival time was not statistically significant. We discuss the implications of this study for a randomized clinical trial of enucleation vs cobalt plaque therapy or comparable forms of irradiation.

  10. Choroid Melanoma Metastasis to Spine: A Rare Case Report

    PubMed Central

    Mandaliya, Hiren; Singh, Nandini; George, Sanila; George, Mathew

    2016-01-01

    Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated. PMID:26989537

  11. Choroid Melanoma Metastasis to Spine: A Rare Case Report.

    PubMed

    Mandaliya, Hiren; Singh, Nandini; George, Sanila; George, Mathew

    2016-01-01

    Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated. PMID:26989537

  12. Ocular surface foreign bodies: novel findings mimicking ocular malignant melanoma

    PubMed Central

    Maudgil, A; Wagner, B E; Rundle, P; Rennie, I G; Mudhar, H S

    2014-01-01

    Purpose Malignant melanoma of the eye is an uncommon condition that is important to recognise. We describe three cases in which ocular foreign bodies have masqueraded as ocular malignant melanoma. Methods Interventional case reports. Results Case 1 describes diathermy-induced carbon particle implantation, during plaque therapy for the treatment of uveal melanoma, mimicking recurrence with extra-scleral invasion. Case 2 shows a foreign body called ‘mullite' mimicking conjunctival melanoma. Case 3 demonstrates a conjunctival foreign body called ‘illite' that mimicked a limbal melanocytic lesion, clinically thought to be either melanocytoma or melanoma. Conclusion This report highlights the importance of careful history taking, examination, and appropriate biopsy in cases of suspected malignant melanoma, to prevent unnecessary and potentially radical treatment. PMID:25104745

  13. Retinoinvasive malignant melanoma of the uvea

    PubMed Central

    Kivela, T.; Summanen, P.

    1997-01-01

    AIMS—To define a retinoinvasive phenotype of uveal melanoma based on an informative case and survey of literature.
METHODS—A 65-year-old woman developed a circumscribed mixed cell type melanoma of the ciliary body that was locally excised. After 6 years, secondary glaucoma evolved. Three years later a ring melanoma was diagnosed and the eye was enucleated. The histopathological material was analysed by immunohistochemistry.
RESULTS—A spindle cell type ring melanoma infiltrated the iris and ciliary body diffusely, and extended through the aqueous outflow channels and iridocyclectomy flap extrasclerally. The choroid was uninvolved. Instead, tumour cells spread to the vitreous and along the ciliary epithelium, adhered to the hyaloid face and retinal surface, and extensively invaded the neuroretina, the retrobulbar optic nerve, and perineural space. They were labelled for S-100 protein, vimentin, and in the neuroretina for cytokeratins 8 and 18. No evidence of systemic disease is evident 5 years after enucleation. Three identical tumours of the iris and ciliary body that extensively infiltrated the neuroretina and retrobulbar optic nerve were identified from previous literature.
CONCLUSION—Retinoinvasive melanoma is a rare but distinct phenotype of uveal melanoma, different from circumscribed and most diffuse melanomas that may erode the overlying retina and infiltrate the optic nerve but that do not invade non-adjacent retina. Retinoinvasive tumours tend to evolve from a ring melanoma and they grow slowly, which may favour emergence of tumour clones able to migrate, adhere to, and invade into the neuroretina, analogous to the metastatic cascade. Frequent secondary angle closure glaucoma may promote invasion into the optic nerve.

 PMID:9349160

  14. Sympathetic ophthalmia complicating helium ion irradiation of a choroidal melanoma

    SciTech Connect

    Fries, P.D.; Char, D.H.; Crawford, J.B.; Waterhouse, W.

    1987-11-01

    Sympathetic ophthalmia was diagnosed 49 months after helium ion irradiation of a left choroidal melanoma. The patient maintained good vision until 18 months after therapy, when she developed neovascular glaucoma. This complication required multiple therapeutic procedures, including topical anti-inflammatory and antiglaucomatous drops, 360 degrees peripheral panretinal cryoblation, and a single 180 degrees application of inferior cyclocryotherapy over a 2 1/2-year period. Four weeks after the cyclocryotherapy, inflammation was noted in both eyes, and, one month later, enucleation of the left sympathogenic eye was performed. Serial histopathologic sections showed a full-thickness, fibrovascular, scleral scar and tantalum marker ring suture without uveal incarceration. Penetrating surgical trauma, a uveal melanoma, and multiple nonpenetrating treatments resulted in the development of sympathetic ophthalmia.

  15. Amelanotic Irido-Ciliary Ring Melanoma: A Clinicopathological Correlation

    PubMed Central

    Aziz, Hassan A.; Modi, Yasha S.; Plesec, Thomas P.; Singh, Arun D.

    2016-01-01

    Purpose To report a case of an amelanotic irido-ciliary ring melanoma. Design Interventional case report. Results A 44-year-old male was followed for asymptomatic amelanotic iris nevus of the right eye that was noted to have a localized ciliary body mass with ring extension along the trabecular meshwork. Fine needle aspiration biopsy was consistent with malignant melanoma. The patient underwent enucleation and remains disease free at 9 years of follow-up. Histopathology revealed malignant melanoma involving the iris and ciliary body with a 360-degree extension along the trabecular meshwork. The tumor was composed of a mixture of spindled and epithelioid cells with scant pigmentation. Conclusions Amelanotic irido-ciliary ring melanoma with growth along the trabecular meshwork is a rare form of uveal melanoma that could present as an inconspicuous amelanotic iris mass. PMID:27239456

  16. Radio-guided occult lesion localisation using iodine 125 Seeds “ROLLIS” to guide surgical removal of an impalpable posterior chest wall melanoma metastasis

    SciTech Connect

    Dissanayake, Shashini; Dissanayake, Deepthi; Taylor, Donna B

    2015-09-15

    Cancer screening and surveillance programmes and the use of sophisticated imaging tools such as positron emission tomography-computed tomography (PET-CT) have increased the detection of impalpable lesions requiring imaging guidance for excision. A new technique involves intra-lesional insertion of a low-activity iodine-125 ({sup 125}I) seed and detection of the radioactive signal in theatre using a hand-held gamma probe to guide surgery. Whilst several studies describe using this method to guide the removal of impalpable breast lesions, only a handful of publications report its use to guide excision of lesions outside the breast. We describe a case in which radio-guided occult lesion localisation using an iodine 125 seed was used to guide excision of an impalpable posterior chest wall metastasis detected on PET-CT.

  17. Outcomes of Proton Therapy for the Treatment of Uveal Metastases

    SciTech Connect

    Kamran, Sophia C.; Collier, John M.; Lane, Anne Marie; Kim, Ivana; Niemierko, Andrzej; Chen, Yen-Lin E.; MacDonald, Shannon M.; Munzenrider, John E.; Gragoudas, Evangelos; Shih, Helen A.

    2014-12-01

    Purpose/Objective(s): Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. Proton therapy can be used to treat uveal tumors efficiently and with expectant minimization of normal tissue injury. Here, we report the use of proton beam therapy for the management of uveal metastases. Methods and Materials: A retrospective chart review was made of all patients with uveal metastases treated at our institution with proton therapy between June 2002 and June 2012. Patient and tumor characteristics, fractionation and dose schemes, local control, and toxicities are reported. Results: Ninety patients were identified. Of those, 13 were excluded because of missing information. We report on 77 patients with 99 affected eyes with available data. Patients were 68% female, and the most common primary tumor was breast carcinoma (49%). The median age at diagnosis of uveal metastasis was 57.9 years. Serous retinal detachment was seen in 38% of treated eyes. The median follow-up time was 7.7 months. The median dose delivered to either eye was 20 Gy(relative biological effectiveness [RBE]) in 2 fractions. Local control was 94%. The median survival after diagnosis of uveal metastases was 12.3 months (95% confidence interval, 7.7-16.8). Death in all cases was secondary to systemic disease. Radiation vasculopathy, measured decreased visual acuity, or both was observed in 50% of evaluable treated eyes. The actuarial rate of radiation vasculopathy, measured decreased visual acuity, or both was 46% at 6 months and 73% at 1 year. The 6 eyes with documented local failure were successfully salvaged with retreatment. Conclusions: Proton therapy is an effective and efficient means of treating uveal metastases. Acutely, the majority of patients experience minor adverse effects. For longer-term survivors, the risk of retinal injury with vision loss increases significantly over the first year.

  18. The association of viruses with urveal melanoma.

    PubMed Central

    Albert, D M

    1979-01-01

    Electron microscopic examination of 57 ocular melanomas (54 human, two feline and one canine) revealed the presence of viral particles in six specimens. Herpesviruses particles were observed in one human specimen and were passed in human fibroblasts (WI-38), where they gave rise to intranuclear inclusions. A-type oncornavirus particles (oncogenic RNA virus) were observed in a second case, both in cells of tumor directly removed from an enucleated eye as well as in cells grown in tissue culture. In three human specimens and one feline specimen, togavirus particles were observed. Rubella is a member of this group, and the possibility that the presence of togavirus in these tumors is the result of latent ocular infection by rubella virus is raised. Herpes virus and RNA tumor viruses are widely considered as having a possible etiologic role for certain human cancers. The observation of togavirus is unexpected, as this virus has not been previously implicated in human or animal tumors. Injection of an RNA tumor virus (Gardner strain feline sarcoma virus) into the anterior chamber of newborn kittens resulted in the development of iris and ciliary body melanomas, many of which showed invasion and, in one instance, metastasis. This is the first animal model of a viral-induced uveal melanoma, and the histology and ultrastructure are described. These results emphasize the need for the continued investigation of the role of these viruses in uveal melanoma. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 18 FIGURE 19 FIGURE 20 FIGURE 21 FIGURE 22 FIGURE 23 PMID:545833

  19. Melanoma susceptibility genes and risk assessment.

    PubMed

    Marzuka-Alcalá, Alexander; Gabree, Michele Jacobs; Tsao, Hensin

    2014-01-01

    Familial melanoma accounts for approximately a tenth of all melanoma cases. The most commonly known melanoma susceptibility gene is the highly penetrant CDKN2A (p16INK4a) locus, which is transmitted in an autosomal dominant fashion and accounts for approximately 20-50 % of familial melanoma cases. Mutated p16INK4a shows impaired capacity to inhibit the cyclin D1-CDK4 complex, allowing for unchecked cell cycle progression. Mutations in the second protein coded by CDKN2A, p14ARF, are much less common and result in proteasomal degradation of p53 with subsequent accumulation of DNA damage as the cell progresses through the cell cycle without a functional p53-mediated DNA damage response. Mutations in CDK4 that impair the inhibitory interaction with p16INK4a also increase melanoma risk but these mutations are extremely rare. Genes of the melanin biosynthetic pathway, including MC1R and MITF, have also been implicated in melanomagenesis. MC1R variants were traditionally thought to increase risk for melanoma secondary to intensified UV-mediated DNA damage in the setting of absent photoprotective eumelanin. Accumulation of pheomelanin, which appears to have a carcinogenic effect regardless of UV exposure, may be a more likely mechanism. Impaired SUMOylation of the E318K variant of MITF results in increased transcription of genes that confer melanocytes with a pro-malignant phenotype. Mutations in the tumor suppressor BAP1 enhance the metastatic potential of uveal melanoma and predispose to cutaneous/ocular melanoma, atypical melanocytic tumors, and other internal malignancies (COMMON syndrome). Genome-wide association studies have identified numerous low-risk alleles. Although several melanoma susceptibility genes have been identified, risk assessment tools have been developed only for the most common gene implicated with hereditary melanoma, CDKN2A. MelaPRO, a validated model that relies on Mendelian inheritance and Bayesian probability theories, estimates carrier

  20. Risk Factors and Relationship of Cutaneous and Uveal Melanocytic Lesions in Monozygotic and Dizygotic Twin Pairs

    PubMed Central

    Varga, Anita; Szabó, Hajnalka; Orvos, Hajnalka; Kemény, Lajos; Oláh, Judit

    2016-01-01

    Background The similar genetic background of a pair of twins, and the similar environmental impacts to which they are exposed allow an exact and objective investigation of various constitutional and environmental factors in naevus development. As far as we are aware, this is the first published survey that simultaneously examines cutaneous and ocular pigmented lesions in an appreciable sample of identical and non-identical twins. Methods 172 pairs of twins of Caucasian origin were included in this study. A whole-body skin examination and a detailed ophthalmological examination were performed to determine the density of melanocytic lesions. A standardized questionnaire was used to assess the data relating to constitutional, sun exposure and other variables. Results A notably high proportion of the subjects (36.78%) manifested one or more clinically atypical melanocytic naevi (CAMNs), and approximately one-third (31.4%) of them at least one benign uveal pigmented lesion (BUPL). The incidence of iris freckles (IFs), iris naevi (INs) and choroidal naevi (CHNs) proved to be 25.35%, 5.98% and 3.52%, respectively. The interclass correlation coefficients for common melanocytic naevi (CMNs), CAMNs, and INs were 0.77, 0.76 and 0.86 in monozygotic twins, as compared with 0.5, 0.27 and 0.25 in dizygotic twin pairs, respectively. A statistically significant correlation was found between the prevalence of CAMNs and that of INs. Conclusions This significant correlation suggests the existence of a subgroup of Caucasian people with an increased susceptibility to both cutaneous and ocular naevus formation. There is accumulating evidence that, besides the presence of cutaneous atypical naevi, INs can serve as a marker of a predisposed phenotype at risk of uveal melanoma. The correlation between cutaneous and ocular pigmented lesions underlines the need for the adequate ophthalmological screening of subjects with CAMNs and INs. PMID:27486750

  1. Population-based incidence of vulvar and vaginal melanoma in various races and ethnic groups with comparisons to other site-specific melanomas.

    PubMed

    Hu, Dan-Ning; Yu, Guo-Pei; McCormick, Steven A

    2010-04-01

    Little is known on the difference in the incidence of vulvar and vaginal melanomas in various racial/ethnic groups. Population-based incidence of these melanomas in Asian and Hispanic individuals is almost unknown. Using 1992-2005 data provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program, we calculated age-adjusted incidence rates of vulvar and vaginal melanomas in various racial/ethnic groups. From 1992 to 2005, there were 324 vulvar melanomas and 125 vaginal melanomas diagnosed in this group. The annual age-adjusted incidence rates (per million female population) of vulvar and vaginal melanomas in the different racial/ethnic groups was 0.87 (Blacks), 0.75 (American-Indian), 1.03 (Asians and Pacific Islanders), 1.22 (Hispanics), and 1.90 (non-Hispanic Whites). The overall white/black incidence ratio in vulvar and vaginal melanomas was 3.14 : 1 and 1.02 : 1, respectively; which is much less than that of cutaneous melanoma (13 : 1-17 : 1) and uveal melanoma (18 : 1) and is similar to that of conjunctival melanoma (2.6 : 1) and other mucosal melanomas (2.1 : 1-2.3 : 1). The low racial difference in vulvar and vaginal melanomas (as well as conjunctival and other mucosal melanomas) may be determined by their microenvironment factors (all originate from mucosa or semi-mucosa tissues). The incidence of vulvar and vaginal melanomas has does not increased in recent decades or toward the south (more sun exposure), indicating that ultraviolet radiation is not a causative factor in these melanomas. The slight decrease of incidence of vulvar melanoma in dark pigmented individuals may be related to the biochemical protective effects of melanin (as an antioxidant) rather than their photo-screen effects. PMID:20147857

  2. Melanoma (image)

    MedlinePlus

    ... tumor that involves the skin cells that produce pigment (melanin). The risk of melanoma increases with age, but frequently effects young, otherwise healthy people. Melanoma is an aggressive type of cancer that can spread very rapidly.

  3. BRAF and NRAS mutations are uncommon in melanomas arising in diverse internal organs

    PubMed Central

    Wong, C W; Fan, Y S; Chan, T L; Chan, A S W; Ho, L C; Ma, T K F; Yuen, S T; Leung, S Y

    2005-01-01

    Background: Malignant melanoma arising from different body compartments may be associated with differing aetiological factors and clinical behaviour, and may manifest diverse molecular genetic profiles. Although many studies have focused on cutaneous melanoma, little is known of mucosal and other types of melanoma. In particular, malignant melanoma of soft parts is different from other melanomas in many respects, yet manifests a common melanocytic differentiation. Mutation of BRAF is now known to be common in cutaneous melanomas, and raises possible new therapeutic options of anti-RAF treatment for these patients. Few data are available for non-cutaneous melanomas. Aims: To study the incidence of BRAF and NRAS mutations in melanomas arising in diverse internal organs. Methods: Fifty one melanomas from various internal organs were investigated for BRAF and NRAS mutation by direct DNA sequencing. Results: BRAF and NRAS mutations were found in two and five mucosal melanomas arising from the aerodigestive and female genital tracts (n = 36). Their occurrence is mutually exclusive, giving a combined mutation incidence rate of 19.4% in mucosal melanomas. Both BRAF and NRAS mutations were absent in malignant melanoma of soft parts (n = 7). BRAF mutation was also absent in uveal melanoma (n = 6), but was seen in two of five cutaneous melanomas. The incidence of BRAF or combined BRAF/NRAS mutations in all non-cutaneous groups was significantly lower than published rates for cutaneous melanomas. Conclusion: Each melanoma subtype may have a unique oncogenetic pathway of tumour development, and only a small fraction of non-cutaneous melanomas may benefit from anti-RAF treatment. PMID:15917418

  4. Zebrafish Melanoma.

    PubMed

    Kaufman, Charles K

    2016-01-01

    Melanoma skin cancer is a potentially deadly disease in humans and has remained extremely difficult to treat once it has metastasized. In just the last 10 years, a number of models of melanoma have been developed in the zebrafish that are biologically faithful to the human disease and have already yielded important insights into the fundamental biology of melanoma and offered new potential avenues for treatment. With the diversity and breadth of the molecular genetic tools available in the zebrafish, these melanoma models will continue to be refined and expanded upon to keep pace with the rapidly evolving field of melanoma biology. PMID:27165365

  5. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

    SciTech Connect

    Krauthammer, Michael; Kong, Yong; Ha, Byung Hak; Evans, Perry; Bacchiocchi, Antonella; McCusker, James P.; Cheng, Elaine; Davis, Matthew J.; Goh, Gerald; Choi, Murim; Ariyan, Stephan; Narayan, Deepak; Dutton-Regester, Ken; Capatana, Ana; Holman, Edna C.; Bosenberg, Marcus; Sznol, Mario; Kluger, Harriet M.; Brash, Douglas E.; Stern, David F.; Materin, Miguel A.; Lo, Roger S.; Mane, Shrikant; Ma, Shuangge; Kidd, Kenneth K.; Hayward, Nicholas K.; Lifton, Richard P.; Schlessinger, Joseph; Boggon, Titus J.; Halaban, Ruth

    2012-10-11

    We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1{sup P29S}) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1{sup P29S} showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.

  6. Ocular immune privilege and ocular melanoma: parallel universes or immunological plagiarism?

    PubMed

    Niederkorn, Jerry Y

    2012-01-01

    Evidence of immune privilege in the eye was recorded almost 140 years ago, yet interest in immune privilege languished for almost a century. However, the past 35 years have witnessed a plethora of research and a rekindled interest in the mechanisms responsible for immune privilege in the anterior chamber of the eye. This research has demonstrated that multiple anatomical, structural, physiological, and immunoregulatory processes contribute to immune privilege and remind us of the enormous complexity of this phenomenon. It is widely accepted that immune privilege is an adaptation for reducing the risk of immune-mediated inflammation in organs such as the eye and brain whose tissues have a limited capacity to regenerate. Recent findings suggest that immune privilege also occurs in sites where stem cells reside and raise the possibility that immune privilege is also designed to prevent the unwitting elimination of stem cells by immune-mediated inflammation at these sites. Uveal melanoma arises within the eye and as such, benefits from ocular immune privilege. A significant body of research reveals an intriguing parallel between the mechanisms that contribute to immune privilege in the eye and those strategies used by uveal melanoma cells to evade immune elimination once they have disseminated from the eye and establish metastatic foci in the liver. Uveal melanoma metastases seem to have "plagiarized" the blueprints used for ocular immune privilege to create "ad hoc immune privileged sites" in the liver. PMID:22707951

  7. Histopathologic and mutational analysis of a case of blue nevus-like melanoma.

    PubMed

    Dai, Julia; Tetzlaff, Michael T; Schuchter, Lynn M; Elder, David E; Elenitsas, Rosalie

    2016-09-01

    Blue nevi are a heterogeneous group of dermal melanocytic proliferations that share a common clinical appearance but remain controversial in their histopathologic and biologic distinction. While common blue nevi and cellular blue nevi are well-defined entities that are classified without significant controversy, the distinction between atypical cellular blue nevi and blue nevus-like melanoma remains diagnostically challenging. We report a case of a 46-year-old female with recurrent blue nevus-like melanoma of the scalp with liver metastases; mutational analysis showed GNA11 Q209L and BAP1 Q393 mutations. To our knowledge, this is the first case of blue nevus-like melanoma with GNA11 and BAP1 mutations. These particular mutations and the predilection for liver metastases in our patient's case underscore a fundamental biological relationship between blue nevi and uveal melanoma and suggest the two entities may prove amenable to similar diagnostic and prognostic testing and targeted therapies. PMID:27152652

  8. The role of germline alterations in the DNA damage response genes BRIP1 and BRCA2 in melanoma susceptibility.

    PubMed

    Tuominen, Rainer; Engström, Pär G; Helgadottir, Hildur; Eriksson, Hanna; Unneberg, Per; Kjellqvist, Sanela; Yang, Muyi; Lindén, Diana; Edsgärd, Daniel; Hansson, Johan; Höiom, Veronica

    2016-07-01

    We applied a targeted sequencing approach to identify germline mutations conferring a moderately to highly increased risk of cutaneous and uveal melanoma. Ninety-two high-risk melanoma patients were screened for inherited variation in 120 melanoma candidate genes. Observed gene variants were filtered based on frequency in reference populations, cosegregation with melanoma in families and predicted functional effect. Several novel or rare genetic variants in genes involved in DNA damage response, cell-cycle regulation and transcriptional control were identified in melanoma patients. Among identified genetic alterations was an extremely rare variant (minor allele frequency of 0.00008) in the BRIP1 gene that was found to cosegregate with the melanoma phenotype. We also found a rare nonsense variant in the BRCA2 gene (rs11571833), previously associated with cancer susceptibility but not with melanoma, which showed weak association with melanoma susceptibility in the Swedish population. Our results add to the growing knowledge about genetic factors associated with melanoma susceptibility and also emphasize the role of DNA damage response as an important factor in melanoma etiology. © 2016 Wiley Periodicals, Inc. PMID:27074266

  9. Management of advanced melanoma

    SciTech Connect

    Nathanson, L. )

    1986-01-01

    This book presents papers on the subject of management of advanced melanoma. The topics covered are: non-investigational cytotoxic agents; high-dosage chemotherapy in antologous bone marrow transplantation; Radiotherapy of melanomas; hyperthermia; ureal melanoma; surgical treatment of recurrent a metastatic melanoma; role of interferons in management of melanoma and molecular genetics of melanoma.

  10. The utility of ultrasound in patients with melanoma.

    PubMed

    Uren, Roger F; Sanki, Amira; Thompson, John F

    2007-11-01

    The highest quality gray-scale ultrasound images are obtained with high-frequency transducers; however, such high frequencies do not penetrate more than a few centimeters into body tissue. Fortunately, in patients with melanoma, the structures of interest are close to the skin surface, making them ideal targets for examination with high-resolution ultrasound. These include primary cutaneous melanomas, uveal melanomas and the regional lymph nodes draining the skin that lie in the axilla, groin, neck and other locations. Although ultrasound study of primary melanomas arising in the skin and eye has provided some insights, a major role for ultrasound has evolved recently, to provide early detection of metastatic melanoma in regional lymph nodes. Ultrasound is clearly superior to clinical palpation of the nodes during follow-up and, when combined with guided fine-needle biopsy, allows the earliest possible surgical intervention for regional nodal metastases. In the future the use of ultrasound contrast agents may improve the sensitivity of ultrasound in the detection of very small metastatic deposits. PMID:18020929

  11. Analysis of SDHD promoter mutations in various types of melanoma

    PubMed Central

    Scholz, Simone L.; Horn, Susanne; Murali, Rajmohan; Möller, Inga; Sucker, Antje; Sondermann, Wiebke; Stiller, Mathias; Schilling, Bastian; Livingstone, Elisabeth; Zimmer, Lisa; Reis, Henning; Metz, Claudia H.; Zeschnigk, Michael; Paschen, Annette; Steuhl, Klaus-Peter; Schadendorf, Dirk; Westekemper, Henrike; Griewank, Klaus G.

    2015-01-01

    Objectives Recently, recurrent mutations in regulatory DNA regions, such as promoter mutations in the TERT gene were identified in melanoma. Subsequently, Weinhold et al. reported SDHD promoter mutations occurring in 10% of melanomas and being associated with a lower overall survival rate. Our study analyzes the mutation rate and clinico-pathologic associations of SDHD promoter mutations in a large cohort of different melanoma subtypes. Methods 451 melanoma samples (incl. 223 non-acral cutaneous, 38 acral, 33 mucosal, 43 occult, 43 conjunctival and 51 uveal melanoma) were analyzed for the presence of SDHD promoter mutations by Sanger-sequencing. Statistical analysis was performed to screen for potential correlations of SDHD promoter mutation status with various clinico-pathologic criteria. Results The SDHD promoter was successfully sequenced in 451 tumor samples. ETS binding site changing SDHD promoter mutations were identified in 16 (4%) samples, of which 5 mutations had not been described previously. Additionally, 5 point mutations not located in ETS binding elements were identified. Mutations in UV-exposed tumors were frequently C>T. One germline C>A SDHD promoter mutation was identified. No statistically significant associations between SDHD promoter mutation status and various clinico-pathologic variables or overall patient survival were observed. Conclusions Melanomas harbor recurrent SDHD promoter mutations, which occur primarily as C>T alterations in UV-exposed melanomas. In contrast to the initial report and promoter mutations in the TERT gene, our analysis suggests that SDHD promoter mutations are a relatively rare event in melanoma (4% of tumors) of unclear clinical and prognostic relevance. PMID:26327518

  12. Bilateral Diffuse Uveal Melanocytic Proliferation Presenting as a Giant Unilateral Choroidal Nevus: A Case Report

    PubMed Central

    Menezes, Carlos; Carvalho, Rui; Neves-Martins, Joana; Teixeira, Carla

    2015-01-01

    Background/Aims The aim of our study was to report a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) with a markedly asymmetric presentation and fundoscopic response to palliative chemotherapy. Case Report We report a 67-year-old Caucasian man who presented with vision loss in his right eye. The best-corrected visual acuities were 2/10 in the right eye and 10/10 in the left eye, and biomicroscopy revealed bilateral mild cataracts. Fundoscopy of the right eye showed a macular flat and pigmented lesion extending beyond the posterior pole with areas of giraffe-type pigmentation and an overlying exudative retinal detachment. Nothing remarkable was detected in the left eye apart from a small round hypopigmented area of retinal pigment epithelium atrophy in the papillomacular bundle. BDUMP was diagnosed, and the workup for systemic malignancy revealed a pulmonary adenocarcinoma. After chemotherapy, not only did the right eye's visual acuity improve and the serous detachment resolve, but also the pigmentation decreased. Conclusion BDUMP presentation can be markedly asymmetric and resemble a giant unilateral choroidal nevus. Response to chemotherapy was unique not only for the usual retinal detachment resolution, but also because of an evident regression of pigmentation. PMID:27171585

  13. Mutational dichotomy in desmoplastic malignant melanoma corroborated by multigene panel analysis.

    PubMed

    Jahn, Stephan W; Kashofer, Karl; Halbwedl, Iris; Winter, Gerlinde; El-Shabrawi-Caelen, Laila; Mentzel, Thomas; Hoefler, Gerald; Liegl-Atzwanger, Bernadette

    2015-07-01

    Desmoplastic malignant melanoma is a distinct melanoma entity histologically subtyped into mixed and pure forms due to significantly reduced lymph node metastases in the pure form. Recent reports investigating common actionable driver mutations have demonstrated a lack of BRAF, NRAS, and KIT mutation in pure desmoplastic melanoma. In search for alternative driver mutations next generation amplicon sequencing for hotspot mutations in 50 genes cardinal to tumorigenesis was performed and in addition the RET G691S polymorphism was investigated. Data from 21 desmoplastic melanomas (12 pure and 9 mixed) were retrieved. Pure desmoplastic melanomas were either devoid of mutations (50%) or displayed mutations in tumor suppressor genes (TP53, CDKN2A, and SMAD4) singularly or in combination with the exception of a PIK3CA double-mutation lacking established biological relevance. Mixed desmoplastic melanomas on the contrary were frequently mutated (89%), and 67% exhibited activating mutations similar to common-type cutaneous malignant melanomas (BRAF, NRAS, FGFR2, and ERBB2). Separate analysis of morphologically heterogeneous tumor areas in four mixed desmoplastic malignant melanomas displayed no difference in mutation status and RET G691 status. GNAQ and GNA11, two oncogenes in BRAF and NRAS wild-type uveal melanomas, were not mutated in our cohort. The RET G691S polymorphism was found in 25% of pure and 38% of mixed desmoplastic melanomas. Apart from RET G691S our findings demonstrate absence of activating driver mutations in pure desmoplastic melanoma beyond previously investigated oncogenes (BRAF, NRAS, and KIT). The findings underline the therapeutic dichotomy of mixed versus pure desmoplastic melanoma with regard to activating mutations primarily of the mitogen-activated protein kinase pathway. PMID:25769001

  14. Choroidal melanoma

    PubMed Central

    Singh, Parul; Singh, Abhishek

    2012-01-01

    Choroidal melanoma is the most common primary intra-ocular malignant tumor and second most common site of ten malignant melanoma sites in the body. Current diagnosis of choroidal melanoma is based on both the clinical experience of the specialist and modern diagnostic techniques such as indirect ophthalmoscopy, A- and B-ultrasonography scans, fundus fluorescein angiography, and transillumination. Invasive studies such as fine needle aspiration cytology can have significant morbidity and should only be considered if therapeutic intervention is indicated and diagnosis cannot be established by any other means. Several modes of treatment are available for choroidal melanoma. Multiple factors are taken into account when deciding one approach over other approaches, such as visual acuity of the affected eye, visual acuity of the contralateral eye, tumor size, location, ocular structures involved and presence of metastases. A comprehensive review of literature available in books and indexed journals was done. This article discusses in detail epidemiology, diagnosis, current available treatment options, and prognosis and survival of choroidal melanoma. PMID:22557869

  15. Melanoma Diagnosis

    NASA Astrophysics Data System (ADS)

    Horsch, Alexander

    The chapter deals with the diagnosis of the malignant melanoma of the skin. This aggressive type of cancer with steadily growing incidence in white populations can hundred percent be cured if it is detected in an early stage. Imaging techniques, in particular dermoscopy, have contributed significantly to improvement of diagnostic accuracy in clinical settings, achieving sensitivities for melanoma experts of beyond 95% at specificities of 90% and more. Automatic computer analysis of dermoscopy images has, in preliminary studies, achieved classification rates comparable to those of experts. However, the diagnosis of melanoma requires a lot of training and experience, and at the time being, average numbers of lesions excised per histology-proven melanoma are around 30, a number which clearly is too high. Further improvements in computer dermoscopy systems and their competent use in clinical settings certainly have the potential to support efforts of improving this situation. In the chapter, medical basics, current state of melanoma diagnosis, image analysis methods, commercial dermoscopy systems, evaluation of systems, and methods and future directions are presented.

  16. Malignant Melanoma

    PubMed Central

    Perera, Eshini; Gnaneswaran, Neiraja; Jennens, Ross; Sinclair, Rodney

    2013-01-01

    Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns and improved rates of early diagnosis. Survival of melanoma has increased to over 90%. Management of melanoma involves a number of components: excision, tumor staging, re-excision with negative margins, adjuvant therapies (chemo, radiation or surgery), treatment of stage IV disease, follow-up examination for metastasis, lifestyle modification and counseling. Sentinel lymph node status is an important prognostic factor for survival in patients with a melanoma >1 mm. However, sentinel lymph node biopsies have received partial support due to the limited data regarding the survival advantage of complete lymph node dissection when a micrometastasis is detected in the lymph nodes. Functional mutations in the mitogen-activated pathways are commonly detected in melanomas and these influence the growth control. Therapies that target these pathways are rapidly emerging, and are being shown to increase survival rates in patients. Access to these newer agents can be gained by participation in clinical trials after referral to a multidisciplinary team for staging and re-excision of the scar. PMID:27429256

  17. A novel multi-CDK inhibitor P1446A-05 restricts melanoma growth and produces synergistic effects in combination with MAPK pathway inhibitors.

    PubMed

    Eliades, Philip; Miller, David M; Miao, Benchun; Kumar, Raj; Taylor, Michael; Buch, Shama; Srinivasa, Sreesha P; Flaherty, Keith T; Tsao, Hensin

    2016-07-01

    Nearly 100% of melanomas have a defect in the p16(INK4A):cyclin D-CDK4/6:RB pathway, leading to abnormal cell cycle control and unregulated cellular proliferation. Here, we report that P1446A-05, a novel multi-CDK inhibitor has significant inhibitory activity against cutaneous and uveal melanoma. Mechanistic studies revealed that P1446A-05 inhibits phosphorylation targets of CDK members, and induces cell cycle arrest and apoptosis irrespective of melanoma genotype or phenotype. Additionally, we show preclinical evidence that P1446A-05 can synergize with other small molecule inhibitors previously studied in melanoma. Collectively, these data demonstrate that targeting cell cycle and transcriptional CDKs with a small molecule multi-CDK inhibitor is a viable approach for developing novel anti-melanoma therapeutics. PMID:26810603

  18. Bilateral diffuse uveal melanocytic proliferation: a management dilemma

    PubMed Central

    Alrashidi, Salah; Aziz, Ayman A; Krema, Hatem

    2014-01-01

    A female patient suffered from gradual decline of vision for few months. She presented with bilateral multiple pigmented choroidal tumours, associated with overlying retinal changes. The clinical presentation suggested bilateral diffuse uveal melanocytic proliferation (BDUMP) syndrome, which is a paraneoplastic disease, although there was no evidence of any concurrent malignancy. The periodic systemic surveillance that was undertaken for the following 4 years failed to reveal any occult cancer. Nevertheless, there has been relentless progressive deterioration in vision as a consequence of BDUMP syndrome. The management of the declining vision in BDUMP syndrome is challenging and controversial. PMID:24855079

  19. CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma.

    PubMed

    Betti, M; Aspesi, A; Biasi, A; Casalone, E; Ferrante, D; Ogliara, P; Gironi, L C; Giorgione, R; Farinelli, P; Grosso, F; Libener, R; Rosato, S; Turchetti, D; Maffè, A; Casadio, C; Ascoli, V; Dianzani, C; Colombo, E; Piccolini, E; Pavesi, M; Miccoli, S; Mirabelli, D; Bracco, C; Righi, L; Boldorini, R; Papotti, M; Matullo, G; Magnani, C; Pasini, B; Dianzani, I

    2016-08-10

    BAP1 germline mutations predispose to a cancer predisposition syndrome that includes mesothelioma, cutaneous melanoma, uveal melanoma and other cancers. This co-occurrence suggests that these tumors share a common carcinogenic pathway. To evaluate this hypothesis, we studied 40 Italian families with mesothelioma and/or melanoma. The probands were sequenced for BAP1 and for the most common melanoma predisposition genes (i.e. CDKN2A, CDK4, TERT, MITF and POT1) to investigate if these genes may also confer susceptibility to mesothelioma. In two out of six families with both mesothelioma and melanoma we identified either a germline nonsense mutation (c.1153C > T, p.Arg385*) in BAP1 or a recurrent pathogenic germline mutation (c.301G > T, p.Gly101Trp) in CDKN2A. Our study suggests that CDKN2A, in addition to BAP1, could be involved in the melanoma and mesothelioma susceptibility, leading to the rare familial cancer syndromes. It also suggests that these tumors share key steps that drive carcinogenesis and that other genes may be involved in inherited predisposition to malignant mesothelioma and melanoma. PMID:27181379

  20. Microgenomics profile the endogenous angiogenic phenotype in subpopulations of aggressive melanoma.

    PubMed

    Demou, Zoe N; Hendrix, Mary J C

    2008-10-01

    Beyond the elemental role of blood vessels in tumor growth, fluid conducting networks lacking endothelium (termed vasculogenic mimicry) were identified previously in metastatic melanoma and other cancer types. The etiology remains unclear, though it appears to involve dysregulation of the tumor-specific phenotype and transdifferentiation. Instigating the molecular deciphering of this phenomenon, we established a novel technique for microdissecting the spontaneously formed vascular-like networks and the randomly arranged cells (nests) from living 3D cultures of melanoma and performed microgenomics analysis. For the first time we show that despite the shared genotype, transcription was differentially regulated among the phenotypically distinct melanoma structures in vasculogenic mimicry. Several angiogenesis-specific genes were differentially expressed in higher levels in network cells of both uveal and cutaneous melanoma with intriguing representation of the ephrin family of angiogenesis factors, which was confirmed with immunocytochemistry. Interestingly, the adjacent nest-cells over-expressed ECM-related genes. Moreover, expression of angiogenesis-specific genes in melanoma resembled that of normal microvascular cells and was enhanced in melanoma disseminating hematogenously. The findings suggest that melanoma plasticity could enable autopoiesis of vascular-mimicking elements within the tumor infrastructure with significant clinical implications, such as response to anti-angiogenic treatments. Identifying factors regulating tumor plasticity and heterogeneity at the molecular level is essential in designing effective anti-cancer therapies. PMID:18655191

  1. [Vulvar melanoma].

    PubMed

    Chokoeva, A; Tchernev, G; Wollina, U

    2015-01-01

    Malignant melanoma of the vulva is a rare disease with aggressive behavior and poor prognosis. It consist < 5% of all cases of melanoma in females, as the ratio of its manifestation, compared with the cutaneous melanoma is 1:71. Higher risk of developing melanoma of the vulva is established in white women, as the peak of the incidence is between 60 and 70 years of age. Clinically, MM of the vulva manifests as asymptomatic pigmented, rarely a pigmented lesion, as the usual clinical form is superficial spreading MM and much less common nodular MM, which is associated with a poorer prognosis in. general. The diagnosis is confirmed by histological examination. Conduction of PCR and DNA analysis for detection of BRAF mutations, NRAS mutations and KIT amplification is also appropriate. Advanced age, black race, tumor size, tumor thickness, ulceration, presence of satellite lesions, involvement of adjacent organs (vagina, urethra), and the presence of regional or distant metastases are identified as the most important prognostic markers. Radical wide excision followed by bilateral lymphadenectomy id considered as the optimal therapeutic approach. PMID:25909143

  2. Malignant Melanoma of the Foot

    MedlinePlus

    ... Javascript in your browser. Malignant Melanoma of the Foot What is Malignant Melanoma? Melanoma is a cancer ... age groups, even the young. Melanoma in the Foot Melanoma that occurs in the foot or ankle ...

  3. Prospective study of surveillance testing for metastasis in 100 high-risk uveal melanoma patients.

    PubMed

    Piperno-Neumann, S; Servois, V; Mariani, P; Plancher, C; Lévy-Gabriel, C; Lumbroso-Le Rouic, L; Couturier, J; Asselain, B; Desjardins, L; Cassoux, N

    2015-06-01

    Despite advances in the local treatment of UM, half of patients develop metastases typically to the liver with poor survival. Microscopic complete surgical resection (R0) of liver metastases improves survival in high selected patients. Early identification of high-risk patients might allow detection of asymptomatic metastases, and increase R0 liver surgery rate. From October 2006 to December 2009, we conducted a prospective study to detect early minimal lesions with 6-monthly liver function tests (LFTs) and liver MRI in 100 high-risk patients. High risk was defined by primary tumor clinical or genomic criteria: thickness>8mm or diameter>15 mm, or extra-scleral extension, or monosomy 3 by FISH or aCGH. With a median follow-up of 49 months, the 5-year metastasis-free survival and overall survival were 47 and 33%, respectively. Of the 60 patients who became metastatic, 50 (83%) had exclusive liver metastasis. LFTs screening had no sufficient accurary, but biannual MRI showed high predictive value to detect metastasis and select patients eligible for curative surgery: 25/50 underwent laparotomy and among them, 8/25 (32%) had a R0 surgery. Median survival after metastasis was 14 months, mean survival reached 40 months in the R0 resected population. Six-monthly liver MRI screening is recommended in patients with large tumors or genomic high risk in order to detect early patient candidates to complete resection of liver metastases. PMID:25978872

  4. Malicious masquerade: myxoid melanoma.

    PubMed

    Hitchcock, M G; White, W L

    1998-08-01

    The morphological spectrum of malignant melanoma is broad. Unusual stromal changes can distract pathologists from the correct diagnosis. Fibroblastic, chondroid, osteoid, and myxoid stroma have been documented in melanomas. Myxoid melanoma is problematic--introducing carcinomas and soft tissue sarcomas into the differential diagnosis. This review examines the clinicopathologic aspects of myxoid malignant melanoma, with emphasis on its differential diagnosis. PMID:9711669

  5. Solitary (primary) uveal T-cell lymphoma in a horse.

    PubMed

    Trope, Gareth D; McCowan, Christina I; Tyrrell, Dayle; Lording, Peter M; Maggs, David J

    2014-03-01

    A 22-year-old Australian stockhorse gelding was presented with anterior uveitis in the right eye which was nonresponsive to anti-inflammatory therapy. Clinical examination revealed corneal edema and vascularization, marked hypopyon, and thickening of the dorsal iris, which was confirmed by ultrasonography. Hematologic and biochemical analyses, abdominal and thoracic ultrasonography, and abdominocentesis with cytologic and biochemical analysis revealed no significant abnormalities. Cytological examination of an aqueous humor sample revealed a population of predominantly large lymphoblasts with high nuclear-to-cytoplasmic ratio, round or irregular nuclei, clumped nuclear chromatin, multiple large prominent nucleoli, and a small volume of basophilic cytoplasm. The cytologic diagnosis was intraocular lymphoma. Biopsy of the right submandibular lymph node revealed no evidence of neoplastic invasion. Euthanasia and a complete necropsy were performed and revealed no evidence of neoplasia in any tissue other than the right eye, which had an extensive, well-defined infiltrate of neoplastic lymphocytes expanding the ciliary body and iris, infiltrating the ciliary epithelium, and extending into the pars plana and peripheral choroid. Immunohistochemistry confirmed that neoplastic cells expressed the T-cell marker CD3. To the authors' knowledge, this is the first description of primary, solitary uveal T-cell lymphoma in a horse. Although apparently rare, lymphoma should be considered in horses with uveitis, even when inflammation is unilateral and in the absence of extraocular signs of neoplasia. Aqueocentesis and cytological examination provided an antemortem diagnosis in this case and should be considered as a diagnostic tool for investigation of uveal thickening and hypopyon. PMID:23802547

  6. Nutrition and melanoma prevention.

    PubMed

    Jensen, J Daniel; Wing, Gregory J; Dellavalle, Robert P

    2010-01-01

    Melanoma has continued to rise in incidence despite public efforts to promote sun protection behaviors. Because sunscreen use does not completely prevent skin cancer induced by ultraviolet radiation, additional chemopreventive methods for protecting against and reversing the effects of ultraviolet photodamage need evaluation. Recent years have brought increased interest in dietary factors, such as natural botanicals and vitamins, for the prevention of melanoma. This contribution provides a narrative review of the relevant, nutrition-related literature found by searching the keywords "melanoma chemoprevention," "nutrition and melanoma," "dietary botanicals and melanoma prevention," "green tea and melanoma," "vitamin D and melanoma," and "vitamin E and melanoma" in the PubMed database. Although randomized controlled trials of humans are lacking, basic science and epidemiologic studies show promising benefits of many natural products in chemoprevention for melanoma. Future studies, hopefully, will yield concrete answers and clarify the role of commonly available dietary nutrients in melanoma chemoprevention. PMID:21034988

  7. Recombinant Interferon Alfa-2b in Treating Patients With Melanoma

    ClinicalTrials.gov

    2016-05-17

    Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  8. Axitinib in Treating Patients With Melanoma That is Metastatic or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-05-31

    Extraocular Extension Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIA Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIB Melanoma; Stage IIIC Intraocular Melanoma; Stage IIIC Melanoma; Stage IV Intraocular Melanoma; Stage IV Melanoma

  9. Fine needle aspiration biopsy of suspected metastatic cancers to the posterior uvea.

    PubMed Central

    Augsburger, J J

    1988-01-01

    This thesis presents the author's experience with diagnostic intraocular fine needle aspiration biopsy in 18 patients with a suspected metastatic choroidal or ciliary body tumor. The author has reviewed the literature on biopsy of intraocular tumors and has specified what he believes to be valid indications for diagnostic biopsy of posterior uveal tumors. He has evaluated the accuracy, limitations, and complications of diagnostic fine needle aspiration biopsy in this series and others, and he has suggested methods for improving the recovery of sufficient cells for cytologic diagnosis and lessening the risks of tumor cell seeding during the biopsy. The author has concluded that fine needle aspiration biopsy appears to be a relatively safe, generally reliable means of establishing the pathologic diagnosis of a choroidal or ciliary body tumor in highly selected patients suspected of having metastatic cancer. In spite of its apparent safety and reliability, however, the author has cautioned against the routine use of fine needle aspiration biopsy in patients with posterior uveal tumors since its long-term safety has not been established. The author has suggested that diagnostic fine needle aspiration biopsy of posterior uveal tumors be performed only in medical centers where there can be input from and cooperation among ophthalmologists, ophthalmic pathologists, and cytopathologists who are experienced in the diagnosis of intraocular malignancies. Images FIGURE 3 A FIGURE 3 B FIGURE 4 A FIGURE 4 B FIGURE 4 C FIGURE 4 D FIGURE 5 A FIGURE 5 B FIGURE 5 C FIGURE 5 D FIGURE 6 A FIGURE 6 B FIGURE 7 A FIGURE 7 B FIGURE 7 C FIGURE 7 D FIGURE 8 A FIGURE 8 B FIGURE 8 C FIGURE 8 D FIGURE 9 A FIGURE 9 B FIGURE 9 C FIGURE 9 D FIGURE 10 A FIGURE 10 B FIGURE 10 C FIGURE 11 PMID:2979028

  10. Vasculogenic mimicry has no prognostic significance in pT3 and pT4 cutaneous melanoma.

    PubMed

    Massi, Daniela; Franchi, Alessandro; Paglierani, Milena; Ketabchi, Sheyda; Borgognoni, Lorenzo; Reali, Umberto Maria; Santucci, Marco

    2004-04-01

    The concept of vasculogenic mimicry has been introduced to define periodic acid-Schiff (PAS)-positive channels and loops lined by tumor cells, instead of endothelium, able to contribute to microcirculation in uveal melanomas. Previous studies have shown that the PAS-positive patterns are associated with a poor prognosis in uveal melanoma. The aim of the current study was to investigate whether vasculogenic mimicry has a prognostic impact in pT3 and pT4 cutaneous melanoma. Fifteen patients with pT3 and pT4 cutaneous melanoma who did not experience progression after 10 years of follow-up and 30 matched controls who underwent progression were selected. Tumor sections were stained with PAS reaction, omitting the nuclear counterstaining. For immunohistochemistry, sections were stained with CD31, CD105 (endoglin), and laminin. Differences in the distribution of the PAS-positive patterns and a series of clinicopathological variables were evaluated by the Pearson chi(2) and Mann-Whitney U tests. We observed PAS-positive linear sheets, arcs, elliptical loops, and networks encircling roundish to oval aggregates of melanoma cells. The overall distribution of the PAS-positive patterns did not match with the blood microvessels' architecture as detected by immunohistochemical analysis. No statistically significant differences in the distribution of PAS-positive patterns were found between cases and controls. The presence of a parallel pattern correlated significantly with thickness (P = 0.04), whereas an inverse correlation was found with vessel area (P = 0.05). In conclusion, our results suggest that there is a mismatch between vasculogenic mimicry and tumor angiogenesis and do not support any prognostic role of vasculogenic mimicry in thick cutaneous melanoma. PMID:15116332

  11. Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye

    ClinicalTrials.gov

    2015-06-25

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage IV Intraocular Melanoma

  12. North-South gradients of melanomas and non-melanomas: A role of vitamin D?

    PubMed

    Moan, Johan; Grigalavicius, Mantas; Baturaite, Zivile; Juzeniene, Asta; Dahlback, Arne

    2013-01-01

    Incidence rates of skin cancer increase with decreasing latitude in Norway, as in many other countries with white populations. The latitudinal trends of the incidence rates of skin cancer were studied and compared with data for vitamin D-induced by UV and for vitamin D intake. The north-south gradient for CMM incidence rates on sun exposed skin is much smaller than those for BCC and SCC, and that for BCC is smaller than that for SCC. This indicates that SCC and BCC are mainly due to solar UVB, while UVA may play a significant role for CMM and a smaller role for BCC, since the north-south gradient of annual UVB fluences is larger than that of UVA fluences. However, there is an inverse latitudinal gradient of skin cancer in central Europe. This is probably due to a gradient of skin color, since white skin is an important determinant of increased risk of skin cancer. The role of vitamin D for skin cancer risk is difficult to evaluate, since serum levels of 25-hydroxyvitamin D, as well as vitamin D intakes, are widely different from country to country. Still, epidemiological evidence indicates a role: for melanomas arising on non-sun exposed body localizations (uveal melanomas, melanomas arising in the vulva and perianal/anorectal regions) there appears to be no latitudinal gradient, or, a negative gradient, i.e., increasing rates with decreasing latitude as would be expected if UV-generated vitamin D plays a protective role. Both skin cancer risk and vitamin D photosynthesis decrease with increasing skin darkness. PMID:24494053

  13. Malignant melanoma (image)

    MedlinePlus

    ... tumor that involves the skin cells that produce pigment (melanin). The risk of melanoma increases with age, but frequently affects young, otherwise healthy people. Melanoma is the number one cause of cancer death in women aged 25 to 30.

  14. General Information about Melanoma

    MedlinePlus

    ... Screening Research Melanoma Treatment (PDQ®)–Patient Version General Information About Melanoma Go to Health Professional Version Key ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  15. Melanoma - neck (image)

    MedlinePlus

    This melanoma on the neck is variously colored with a very darkly pigmented area found centrally. It has irregular ... be larger than 0.5 cm. Prognosis in melanoma is best defined by its depth on resection.

  16. Melanoma International Foundation

    MedlinePlus

    ... Gershenwald, MD May 09, 2015 Our Awards Melanoma International Foundation Our Mission: To develop personalized strategies with ... the state of Pennsylvania, certificate #29498 © 2013 Melanoma International Foundation. All Rights Reserved. Privacy Policy | Terms of ...

  17. Fundus image fusion in EYEPLAN software: An evaluation of a novel technique for ocular melanoma radiation treatment planning

    SciTech Connect

    Daftari, Inder K.; Mishra, Kavita K.; O'Brien, Joan M.; and others

    2010-10-15

    patients developed distant metastasis and all three patients have since died. The replanning of six patients with their original fundus photograph superimposed showed that in four cases, the treatment field adequately covered the tumor volume. In the other two patients, the overlaid fundus photographs indicated the area of marginal miss. The replanning with the fundus photograph showed improved tumor coverage in these two macular lesions. For the remaining patients without local failure, replanning with fundus photograph superimposition confirmed the tumor volume as drawn in the original treatment plan. Conclusions: Local control was excellent in patients receiving 56 GyE of PBRT for uveal melanomas in the macular region, which traditionally can be more difficult to control. Posterior lesions are better defined with the additional use of fundus image since they can be difficult to mark surgically. In one-third of treatment failing patients, the superposition of the fundus photograph would have clearly allowed improved localization of tumor. The current practice standard is to use the superimposition of the fundus photograph in addition to the surgeon's clinical and clip mapping of the tumor and ultrasound measurement to draw the tumor volume.

  18. Vaccine Therapy in Treating Patients With Stage IIC-IV Melanoma

    ClinicalTrials.gov

    2014-05-20

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Mucosal Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage IIC Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIA Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIB Melanoma; Stage IIIC Intraocular Melanoma; Stage IIIC Melanoma; Stage IV Intraocular Melanoma; Stage IV Melanoma

  19. Malignant melanoma maxilla

    PubMed Central

    Devi, Seema; Sinha, Richi; Singh, Rakesh Kumar

    2015-01-01

    A malignant melanoma is a highly lethal melanocytic neoplasm. A neoplasm usually affects the skin. Malignant melanomas in the head and neck region are rare, accounting for less than 1% of all melanomas. Malignant melanoma of the nose and paranasal sinuses is an aggressive disease typically presenting at an advanced stage, with a 5-year survival rate ranging 20-30%. Melanomas are tumors arising from melanocytes, which are neuroectodermally derived cells located in the basal layers of the skin. This is a case report of a 35-year-old male, who presented with very aggressive disease and developed liver metastasis. PMID:26668467

  20. Molecular characterization of melanoma cases in Denmark suspected of genetic predisposition.

    PubMed

    Wadt, Karin A W; Aoude, Lauren G; Krogh, Lotte; Sunde, Lone; Bojesen, Anders; Grønskov, Karen; Wartacz, Nine; Ek, Jakob; Tolstrup-Andersen, Morten; Klarskov-Andersen, Mette; Borg, Åke; Heegaard, Steffen; Kiilgaard, Jens F; Hansen, Thomas V O; Klein, Kerenaftali; Jönsson, Göran; Drzewiecki, Krzysztof T; Dunø, Morten; Hayward, Nicholas K; Gerdes, Anne-Marie

    2015-01-01

    Both environmental and host factors influence risk of cutaneous melanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma. PMID:25803691

  1. Prognostic significance of periodic acid-Schiff-positive patterns in primary cutaneous melanoma.

    PubMed

    Warso, M A; Maniotis, A J; Chen, X; Majumdar, D; Patel, M K; Shilkaitis, A; Gupta, T K; Folberg, R

    2001-03-01

    The patterns of periodic acid-Schiff (PAS) staining of extracellular matrix in histological sections of certain melanomas may be predictive of outcome. Recent in vitro and molecular genetic data suggest that the appearance of these patterns in both uveal and cutaneous melanoma is a function of aggressive tumor cells. We studied 96 patients with primary cutaneous melanomas treated at the University of Illinois at Chicago who were monitored for disease-free survival. Survival probabilities were determined by Kaplan-Meier estimates, and prognostic factors were evaluated by multivariate analysis. By univariate analysis, there was a significant decrease in disease-free survival among patients whose tumors contained parallel with cross-linking or network patterns (PXNs; P = 0.0070). Stepwise regression with Cox models that included the combinations of the PAS-positive patterns, tumor thickness, female gender, ulceration, and age yielded a model with thickness and the PAS-positive parallel with cross-linking or networks. Despite the relatively small sample size in this study, the detection of the PAS-positive parallel with cross-linking or networking in cutaneous melanoma was associated with a decrease in disease-free outcome. Additional studies of the prognostic significance of these patterns is warranted on larger data sets. PMID:11297236

  2. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma

    ClinicalTrials.gov

    2016-05-06

    Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

  3. VEGF Trap in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2015-02-02

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage III Melanoma; Stage IV Melanoma

  4. Primary malignant melanoma

    PubMed Central

    Mısır, A. Ferhat; Durmuşlar, Mustafa C.; Zerener, Tamer; Gün, Banu D.

    2016-01-01

    Malignant melanomas (MM) of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period. PMID:27052289

  5. Cutaneous Melanoma in Women

    PubMed Central

    Roh, Mi Ryung; Eliades, Philip; Gupta, Sameer; Tsao, Hensin

    2015-01-01

    The incidence of cutaneous melanoma (CM) continues to increase in the Caucasian population in the United States. In 2014, women only accounted for 42% of the 76,100 new melanoma cases and only 33% of the 9,710 deaths associated with CM in the US.1 These trends are consistently observed in populations around the world. Indeed, gender disparity in melanoma outcome is so consistently observed that gender has been suggested as an important prognostic factor in melanoma, despite not being formerly incorporated in staging algorithms.2 The source of this gender disparity in melanoma remains unclear but likely represents both biological and behavioral etiologies. Herein, we review the current knowledge of how melanoma differs between men and women. PMID:25844396

  6. Concurrent versus sequential application of ferromagnetic hyperthermia and 125I brachytherapy of melanoma in an animal model.

    PubMed Central

    Mieler, W F

    1997-01-01

    OBJECTIVE: To determine the efficacy of concurrent versus sequential ferromagnetic hyperthermia (FMH), combined with Iodine-125 (125I) brachytherapy, in the treatment of uveal melanoma in a rabbit model. MATERIALS AND METHODS: A Greene melanoma cell line was implanted in rabbit eyes to establish a tumor model comparable to a uveal melanoma. Seventy-one tumor-containing rabbit eyes were treated with 125I brachytherapy at 20, 25, 35, 45, or 55 Gray (Gy)(38 eyes), and with either concurrent (15 eyes) or sequential (18 eyes) FMH, delivered at 48.2 degrees C for 1 hour. An additional 13 eyes were treated with FMH alone at 48.2 degrees C, either in a single heat application (5 eyes), or in a repetitive mode (8 eyes). The radiation and heat were delivered via an episcleral plaque. All tumors were followed with indirect ophthalmoscopy and echography. RESULTS: Tumors treated with 125I brachytherapy alone exhibited complete tumor regression in 50% of eyes at 42 Gy with none of the tumors responding to less than 35 Gy. FMH alone at 48.2 degrees C applied in one cycle limited tumor growth in 20% of eyes, while all eyes treated with repetitive heating exhibited complete tumor control. With concurrent application of FMH and 125I, the 50% tumor control rate occurred at 9.5 Gy, thus resulting in a thermal enhancement ratio (TER) of 4.4. With sequential treatment, the 50% tumor control rate was at 30 Gy, with a resultant TER of 1.4. No complications related to 125I brachytherapy were noted in any eyes, while transient retinal whitening was seen with the FMH. CONCLUSION: This study documents the enhanced synergistic interaction of concurrent FMH and 125I brachytherapy, compared to sequential treatment, in this rabbit melanoma model. PMID:9440189

  7. Quantitative proteomic analysis for radiation-induced cell cycle suspension in 92-1 melanoma cell line

    PubMed Central

    Wang, Fengling; Bing, Zhitong; Zhang, Yanan; Ao, Bin; Zhang, Sheng; Ye, Caiyong; He, Jinpeng; Ding, Nan; Ye, Wenling; Xiong, Jie; Sun, Jintu; Furusawa, Yoshiya; Zhou, Guangming; Yang, Lei

    2013-01-01

    Melanoma is a malignant tumor with high invasive and metastatic properties. Though radiation is the major therapy for melanoma, its radio-resistance has been shown to severely influence the clinical outcome. So it is imperative to enhance the sensitivity of uveal melanoma cells to radiotherapy. Previously, we found that the cell cycle of 92-1 uveal melanoma cells was suspended and remained unchanged for up to 5 days after exposure to 10 Gy of X-rays, which might be relevant to the high radio-sensitivity of 92-1 cells. To further investigate the cell cycle suspension-associated proteins, we employed two analyses with stable isotope labeling with amino acids in cell culture technology and two-dimensional liquid chromatography tandem mass spectrometry. Cells were incubated for 15 h or 48 h after irradiation with 10 Gy of X-rays. We identified a total of 737 proteins at 15 h (Group A) and 530 proteins at 48 h post-irradiation (Group B). The gene ontology biological pathway was used to obtain a systems level view of proteome changes in 92-1cells under cell cycle suspension. We further selected the significantly changed proteins for investigation of their potential contribution to cell cycle suspension, growth arrest and cell senescence. These proteins are involved in the cell cycle, stress response, glycolysis and the tricarboxylic acid cycle, etc. Our study expected to reveal potential marker proteins associated with cell suspension induced by irradiation, which might contribute to understanding the mechanism beyond the cell cycle suspension. PMID:23447694

  8. Melanoma in Immunosuppressed Patients

    PubMed Central

    Kubica, Agnieszka W.; Brewer, Jerry D.

    2012-01-01

    The immunogenic characteristics of malignant melanoma are intriguing. To date, multiple studies exist regarding the immunogenicity of melanoma. In this article, we summarize data in the literature on the role of immunosuppression in melanoma and discuss several immunocompromised patient populations in detail. A comprehensive PubMed search was conducted with no date limitation. The following search terms were used: melanoma in combination with immunosuppression, immunocompromised, genetics, antigen processing, UV radiation, organ transplantation, organ transplant recipients, lymphoproliferative disease, lymphoma, CLL, NHL, radiation, and HIV/AIDS. Although no formal criteria were used for inclusion of studies, most pertinent studies on the topic were reviewed, with the exception of smaller case reports and case series. The included studies were generally large (≥1000 patients in organ transplant recipient studies; ≥500 patients in lymphoma studies), with a focus on institutional experiences, or population-based national or international epidemiologic studies. Melanoma-induced immunosuppression, the role of UV radiation in melanoma development, and the epidemiology, clinical course, and prognosis of melanoma in immunocompromised patients are highlighted. Organ transplant recipients, patients with lymphoproliferative disorders, patients with iatrogenic immunosuppression, and patients with human immunodeficiency virus infection/AIDS are also highlighted. Recommendations are proposed for the care and monitoring of immunosuppressed patients with melanoma. With better understanding of the molecular microenvironment and clinical course of melanoma in immunosuppressed patients, novel therapies could be developed and outcomes potentially affected in these patients. PMID:23036673

  9. [{sup 18}F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (PET/CT) Physiologic Imaging of Choroidal Melanoma: Before and After Ophthalmic Plaque Radiation Therapy

    SciTech Connect

    Finger, Paul T.; Chin, Kimberly J.

    2011-01-01

    Purpose: To evaluate changes in [{sup 18}F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) standardized uptake values (SUV) in uveal melanoma before and after plaque brachytherapy. Methods and Materials: A cohort of 217 patients diagnosed with uveal melanoma and eligible for ophthalmic plaque brachytherapy underwent preoperative PET/CT to evaluate their intraocular tumor and screen for metastasis. Subsequent to undergoing plaque brachytherapy, patients' PET/CT SUV were periodically reevaluated over 42 months. Results: In this series, 37 (17%) choroidal melanoma patients were found to have an SUV of >2.0. Of these, 18 patients were able to undergo interval follow-up PET/CT scanning. There were 3 patients with T2, 11 patients with T3, and 4 patients with T4 melanomas according to 7th edition AJCC-UICC criteria. Mean apical thickness was 8.8 mm (range, 3-12.3 mm), and the largest mean tumor diameter was 15.1 mm (range, 12-19.9 mm). The mean initial SUV was 3.7 (range, 2.1-7.3). Patients were followed for a median 16 months (range, 6-42 months). The median time to a tumor SUV of 0 was 8.0 months (range, 6-18 months). There was one case of one interval increase in SUV that diminished after circumferential laser treatment. Conclusions: Intraocular PET/CT imaging provides a physiological assessment of tumor metabolism that can be used to evaluate changes after treatment. In this study, ophthalmic plaque radiation therapy was associated with extinguished tumor PET/CT SUV over time. PET/CT imaging can be used to assess choroidal melanomas for their response to treatment.

  10. Melanoma with gastric metastases.

    PubMed

    Wong, Katherine; Serafi, Sam W; Bhatia, Abhijit S; Ibarra, Irene; Allen, Elizabeth A

    2016-01-01

    An 81-year-old woman with a history of malignant melanoma who presented with dyspnea and fatigue was found to have metastases to the stomach detected on endoscopy. Primary cutaneous malignant melanoma with gastric metastases is a rare occurrence, and it is often not detected until autopsy because of its non-specific manifestations. PMID:27609722

  11. Cutaneous melanoma: uncommon presentations.

    PubMed

    Beyeler, Mirjam; Dummer, Reinhard

    2005-01-01

    Melanoma is the most important nonepithelial skin cancer. The diagnosis is usually made by clinical examination including dermatoscopy and histology. There are, however, variants of melanoma that miss the characteristic signs of pigmented lesions which are easily detectable when using the ABCD rule. PMID:16325067

  12. Genetic epidemiology of melanoma.

    PubMed

    Ribero, Simone; Glass, Dan; Bataille, Veronique

    2016-08-01

    The field of melanoma genetics is moving at great pace with new platforms to investigate single nucleotide polymorphism, genome sequencing, gene expression, and methylation. Melanoma incidence is still rising mainly because of screening campaigns, which has increased the number of reported melanomas. However, mortality due to melanoma is not decreasing. Many cutaneous phenotypic risk factors have been linked to melanoma, but the association with UV radiation is very complex. The level of vitamin D affects both the risk of melanoma and prognosis, but more studies are needed. The genetics of melanoma involves genes involved in pigmentation and naevi, as well as genes involved in the cell cycle and senescence, which have been identified via genome-wide association studies over the last 10 years. One area of research highly relevant to melanoma is telomere biology with further links to reduced senescence. At the somatic level, new gene pathways are being explored with many new therapeutic targets, and boosting immune responses against the tumour appears to offer the best long-term outcome. PMID:27436815

  13. Bilateral Diffuse Uveal Melanocytic Proliferation: Molecular Genetic Analysis of a Case and Review of the Literature

    PubMed Central

    Mittal, Ruchi; Cherepanoff, Svetlana; Thornton, Sophie; Kalirai, Helen; Damato, Bertil; Coupland, Sarah E.

    2015-01-01

    Purpose of the Study To describe the clinicopathological features, mutational and chromosomal copy number analysis, and 8-year follow-up of a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with clear-cell carcinoma of the endometrium. Methods Histological evaluation, multiplex ligation-dependent probe amplification (MLPA) analysis and GNAQ/11 mutational analysis were performed in a 67-year-old female patient with the diagnosis of BDUMP. Results Histological evaluation revealed proliferation of bland spindle cells, diffusely replacing the uveal tract, which showed a proliferation index of less than 1%. There was absence of mutations involving the codon 209 and 183 of GNAQ, and of GNA11. MLPA analysis showed disomy 3 with polysomy 8q for both eyes. The patient died 8 years later of an unrelated condition. Conclusions Although BDUMP is considered to be a benign proliferative disease, copy number alterations of unknown significance may occur in these lesions. PMID:27171825

  14. Main roads to melanoma

    PubMed Central

    Palmieri, Giuseppe; Capone, Mariaelena; Ascierto, Maria Libera; Gentilcore, Giusy; Stroncek, David F; Casula, Milena; Sini, Maria Cristina; Palla, Marco; Mozzillo, Nicola; Ascierto, Paolo A

    2009-01-01

    The characterization of the molecular mechanisms involved in development and progression of melanoma could be helpful to identify the molecular profiles underlying aggressiveness, clinical behavior, and response to therapy as well as to better classify the subsets of melanoma patients with different prognosis and/or clinical outcome. Actually, some aspects regarding the main molecular changes responsible for the onset as well as the progression of melanoma toward a more aggressive phenotype have been described. Genes and molecules which control either cell proliferation, apoptosis, or cell senescence have been implicated. Here we provided an overview of the main molecular changes underlying the pathogenesis of melanoma. All evidence clearly indicates the existence of a complex molecular machinery that provides checks and balances in normal melanocytes. Progression from normal melanocytes to malignant metastatic cells in melanoma patients is the result of a combination of down- or up-regulation of various effectors acting on different molecular pathways. PMID:19828018

  15. Main roads to melanoma.

    PubMed

    Palmieri, Giuseppe; Capone, Mariaelena; Ascierto, Maria Libera; Gentilcore, Giusy; Stroncek, David F; Casula, Milena; Sini, Maria Cristina; Palla, Marco; Mozzillo, Nicola; Ascierto, Paolo A

    2009-01-01

    The characterization of the molecular mechanisms involved in development and progression of melanoma could be helpful to identify the molecular profiles underlying aggressiveness, clinical behavior, and response to therapy as well as to better classify the subsets of melanoma patients with different prognosis and/or clinical outcome. Actually, some aspects regarding the main molecular changes responsible for the onset as well as the progression of melanoma toward a more aggressive phenotype have been described. Genes and molecules which control either cell proliferation, apoptosis, or cell senescence have been implicated. Here we provided an overview of the main molecular changes underlying the pathogenesis of melanoma. All evidence clearly indicates the existence of a complex molecular machinery that provides checks and balances in normal melanocytes. Progression from normal melanocytes to malignant metastatic cells in melanoma patients is the result of a combination of down- or up-regulation of various effectors acting on different molecular pathways. PMID:19828018

  16. Synchronous anorectal melanoma

    PubMed Central

    Balicevic, Drinko; Tomic, Karla; Bekavac-Beslin, Miroslav; Kovacevic, Igor; Mijic, August; Belicza, Mladen; Kruslin, Bozo

    2006-01-01

    Anorectal melanoma is a very rare tumor with poor prognosis. Rectal bleeding is the most frequent symptom and surgical treatment ranges from local excision to radical abdominoperineal resection. We report a case of a 75-years-old male patient who presented with a history of recurrent rectal bleeding, and whose histopathological diagnosis was melanoma. Macroscopically, we found two distinct tumors in anorectal region, 0.5 cm and 1.5 cm from dentate line. The first one was pedunculated, on a thin stalk, measuring 1 cm in greatest diameter, and the second one was sessile and nodular measuring up to 2.8 cm in largest diameter. Microscopic examination and immunohistochemical analysis of both tumors confirmed the diagnosis of melanoma. This case represents multiple synchronous primary melanoma of the anorectal region, with a possibility that one of the lesions is primary melanoma and the second one is a satellite lesion. PMID:16733870

  17. Cutaneous manifestations associated with melanoma.

    PubMed

    Vyas, Ritva; Selph, Jacqueline; Gerstenblith, Meg R

    2016-06-01

    Melanoma is a malignancy most commonly arising from the skin; therefore, primary melanoma characteristics are usually the first cutaneous manifestations of melanoma. Cutaneous metastases, which can occur locally or diffusely, are important to detect in a timely manner as treatments for advanced melanoma that impact survival are now available. Melanoma can be associated with local or diffuse pigmentation changes, including depigmentation associated with the leukodermas and hyperpigmentation associated with diffuse melanosis cutis. The leukodermas occur frequently, illustrate the immunogenic nature of melanoma, and may impact prognosis. Paraneoplastic syndromes in association with melanoma are rare, though can occur. PMID:27178692

  18. Activity of the MEK Inhibitor Trametinib (GSK1120212) in Advanced Melanoma in a Phase I, Dose-escalation Trial

    PubMed Central

    Falchook, Gerald S; Lewis, Karl D; Infante, Jeffrey R; Gordon, Michael S; Vogelzang, Nicholas J; DeMarini, Douglas J; Sun, Peng; Moy, Christopher; Szabo, Stephen A.; Roadcap, Lori T; Peddareddigari, Vijay G R; Lebowitz, Peter F; Le, Ngocdiep T; Burris, Howard A; Messersmith, Wells A; O'Dwyer, Peter J; Kim, Kevin B.; Flaherty, Keith; Bendell, Johanna C.; Gonzalez, Rene; Kurzrock, Razelle; Fecher, Leslie A

    2014-01-01

    Summary Purpose The mitogen-activated extracellular signal-related kinase kinase (MEK) is a member of the RAS/RAF/MEK/ERK signalling cascade, which is commonly activated in melanoma. Direct inhibition of MEK inhibits ERK signalling. Methods We conducted a multicentre, first-in-human, three-part study (dose escalation, cohort expansion, and pharmacodynamic evaluation) to evaluate the oral small-molecule MEK inhibitor trametininb (GSK1120212) in advanced cancer. Intermittent and continuous dosing regimens were evaluated. Safety and efficacy data in patients with melanoma are presented here, with exploratory analyses of available tumour tissues performed on an Illumina genotyping platform. This completed study is registered with ClinicalTrials.gov, number NCT00687622. Findings Ninety-seven melanoma patients, including 81 with cutaneous or unknown primary melanoma (36 BRAF-mutant, 39 BRAF wild-type, six BRAF status unknown) and 16 uveal melanoma patients were enrolled. The most common treatment-related adverse events were rash/dermatitis acneiform (80 out of 97; 82%) and diarrhoea (n=44; 45%), most of which were grade 2 or lower. No cutaneous squamous cell carcinomas were observed. Among the 36 BRAF-mutant patients, 30 were BRAF-inhibitor naïve. Among these 30 patients, 2 complete responses (CRs) and 10 partial responses (PRs) were observed (unconfirmed response rate=40%) including 2 confirmed CRs and 8 confirmed PRs (confirmed response rate=33%); the median progression-free survival was 5·7 months (95% CI, 4·0–7·4). Among the 6 BRAF-mutant patients who received prior BRAF inhibitor therapy, 1 unconfirmed PR was observed. Among 39 patients with BRAF wild-type melanoma, 4 PRs (all confirmed) were observed (confirmed response rate=10%). Conclusions To our knowledge, this is the first demonstration of substantial clinical activity by a MEK inhibitor in melanoma. These data suggest that MEK is a valid therapeutic target. PMID:22805292

  19. Vaccine Therapy With or Without Sargramostim in Treating Patients Who Have Undergone Surgery for Melanoma

    ClinicalTrials.gov

    2015-04-14

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Extraocular Extension Melanoma; Iris Melanoma; Stage IIB Melanoma; Stage IIC Melanoma; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma

  20. Epidemiology of malignant melanoma.

    PubMed

    Liu, T; Soong, S J

    1996-12-01

    Descriptive epidemiology of melanoma indicates increases in both incidence and mortality over the past two to three decades. A moderation in both rates began to emerge in several regions after the 1980s, especially in younger age groups. Recent improvement in survival rates is more likely due to earlier diagnosis than to real improvement in treatment. This suggests the potential effectiveness of secondary prevention. Continued health education efforts to improve awareness about signs and symptoms of melanoma should lead to earlier diagnosis and may increase incidence for a certain period of time. However, reduction in mortality will eventually be achieved owing to thinner melanoma at time of diagnosis. Etiologic studies indicate that the most important environmental risk factor for melanoma is extensive exposure to the sun. Primary prevention efforts should target public education about the risk of sun exposure and the benefit of wearing hats and adequate clothing. Specific prevention and control programs should be implemented among high-risk groups, such as those with light complexions and those sensitive to sunburn. In view of the long latency of melanoma, as much as 10 years, past exposure to the risk factors continues to cause melanoma, and any benefits of preventive efforts do not appear for some time. Although a dramatic decline is not expected in melanoma rates immediately, continuous preventive efforts ultimately should lead to a reduction in incidence and mortality. PMID:8977547

  1. Ciliary body and choroidal melanomas treated by proton beam irradiation. Histopathologic study of eyes

    SciTech Connect

    Seddon, J.M.; Gragoudas, E.S.; Albert, D.M.

    1983-09-01

    Proton beam irradiation resulted in clinical and/or histopathological regression of large ciliary body and choroidal melanomas in three eyes. Enucleations were performed 6 1/2 weeks, five months, and 11 months after irradiation for angle-closure glaucoma from total retinal detachment, increase in retinal detachment, and neovascular glaucoma, respectively. A direct relationship was found between the length of the interval from irradiation to enucleation and the degree of histologic changes. Vascular changes in the tumors included endothelial cell swelling and decreased lumen size, basement membrane thickening, collapse of sinusoidal vessels, and thrombosis of vessels. Although apparently unaltered tumor cells remained, degenerative changes occurred in some melanoma cells, including lipid vacuoles in cytoplasm, pyknotic nuclei, and balloon cell formation. Patchy areas of necrosis and proteinaceous exudate were present. Pigment-laden macrophages were found near tumor vessels and all had a substantial chronic inflammatory infiltrate. The effect of proton beam irradiation on tumor vessels probably plays an important role in uveal melanoma regression.

  2. Low thyroid hormone levels improve survival in murine model for ocular melanoma

    PubMed Central

    Fabian, Ido Didi; Rosner, Mordechai; Fabian, Ina; Vishnevskia-Dai, Vicktoria; Zloto, Ofira; Maman, Elena Shinderman; Cohen, Keren; Ellis, Martin; Lin, Hung-Yun; Hercbergs, Aleck; Davis, Paul J.; Ashur-Fabian, Osnat

    2015-01-01

    Uveal melanoma is highly metastatic, prognosis is poor and there are no effective treatments to extend survival. Accumulating evidence suggests that thyroid hormones have a mitogenic effect via binding to αvβ3 integrin. We aimed to examine the impact of thyroid status on survival in a murine B16F10 model for ocular melanoma, highly expressing the integrin. In two independent experiments oral propylthiouracil (PTU) was used to induce hypothyroidism (n=9), thyroxine to induce hyperthyroidism (n=11) and mice given plain water served as control (n=8). At day 21, the subretinal space was inoculated with 102 B16F10 cells. In non-inoculated mice (n=6 of each group) serum free T4 (FT4) levels were measured and additional non-inoculated mice (3 given PTU and 4 given thyroxine or water) served as internal control to demonstrate the impact of the dissolved substance. The PTU-inoculated mice showed clinical evidence of intraocular tumor growth significantly later than the thyroxine mice (P=0.003) and survival time was significantly longer (P<0.001). FT4 levels differed significantly between groups (P<0.001) and with no signs of illness in the internal control group. Our findings suggest that hyperthyroidism shortens survival, whereas relative hypothyroidism may have a protective role in metastatic ocular melanoma. PMID:25868390

  3. Gnaq and Gna11 in the Endothelin Signaling Pathway and Melanoma

    PubMed Central

    Urtatiz, Oscar; Van Raamsdonk, Catherine D.

    2016-01-01

    In this article, we first briefly outline the function of G protein coupled receptors in cancer, and then specifically examine the roles of the seven transmembrane G protein coupled Endothelin B receptor (Ednrb) and the G proteins, GNAQ and GNA11, in both melanocyte development and melanoma. Ednrb plays an essential role in melanocyte development. GNAQ and GNA11 are oncogenes when mutated in certain types of melanocytic lesions, being extremely frequent in uveal melanoma, which forms from melanocytes located in the eye. Previously, we reported that in mice, Schwann cell precursor derived melanocytes colonize the dermis and hair follicles, while the inter-follicular epidermis is populated by other melanocytes. A pattern has emerged whereby melanocytes whose activities are affected by gain-of-function mutations of the Endothelin 3 ligand and Gαq/11 are the same subset that arise from Schwann cell precursors. Furthermore, the forced expression of the constitutively active human GNAQQ209L oncogene in mouse melanocytes only causes hyper-proliferation in the subset that arise from Schwann cell precursors. This has led us to hypothesize that in Schwann cell precursor derived melanocytes, Ednrb signals through Gαq/11. Ednrb is promiscuous and may signal through other G protein alpha subunits in melanomas located in the inter-follicular epidermis. PMID:27148356

  4. Melanoma and genetics.

    PubMed

    Nelson, Andrew A; Tsao, Hensin

    2009-01-01

    As the incidence of malignant melanoma continues to increase and with the completion of the sequencing of the human genome, there have been increasing efforts to identify the "melanoma gene(s)." Although some patients and families have significantly increased risks due to genetic predisposition, most melanoma cases are sporadic and likely result from low to moderate risk genetic factors. This review focuses on the genes that cover the greatest risk of developing melanoma. It is important to remember that many--if not most--cases of melanoma are the result of undiscovered variants. The strongest genetic risk for the development of melanoma results from heritable alterations in cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, which encodes two separate but related proteins, p16/INK4a and p14/ARF. These proteins help regulate cell division and apoptosis, both of which are necessary to maintain cellular homeostasis. Other important genes include CDK4/6 and retinoblastoma (RB1), which encode downstream proteins in the same pathway as p16/INK4a and p14/ARF. Finally, we discuss the relative importance of the melanocortin 1 receptor (MC1R) gene as a moderate risk factor for melanoma. Although great advances have been made in understanding the molecular basis and genetic predisposition of melanoma, many questions still remain to be answered. Someday soon, it will be possible to predict a patient's risk of melanoma by DNA analysis; however, it is important to reconcile our tremendous technologic capabilities with documented clinical utility. PMID:19095153

  5. [Posterior capsule opacification].

    PubMed

    Milazzo, S; Grenot, M; Benzerroug, M

    2014-12-01

    Posterior capsule opacification (PCO) is the most common complication after cataract surgery, with an incidence of 30%. It tends to be considered a normal event in the natural history of cataract surgery. Better understanding of its pathophysiology and advancement of intraocular lens material and design along with the improvement of phacoemulsification technique have contributed to decrease the incidence of PCO. Although treatment by Nd: YAG laser posterior capsulotomy is quick and non-invasive, the opening of the posterior capsule may be associated with numerous complications. Prevention remains the best measure for controlling this pathology. PMID:25455552

  6. Intraoral malignant melanoma

    PubMed Central

    Babburi, Suresh; Subramanyam, R. V.; Aparna, V.; Sowjanya, P.

    2013-01-01

    Primary oral mucosal melanoma is a rare aggressive neoplasm and accounts for only 0.2-8% of all reported melanomas. It is a malignant neoplasm of melanocytes that may arise from a benign melanocytic lesion or de novo from melanocytes within normal skin or mucosa. It is considered to be the most deadly and biologically unpredictable of all human neoplasms, having the worst prognosis. In this article, we report a case of oral melanoma in a 52-year-old female patient with a chief complaint of black discolouration of the maxillary gingiva and palate. PMID:24249959

  7. Posterior fossa tumor

    MedlinePlus

    ... of the posterior fossa, it can block the flow of spinal fluid and cause increased pressure on the brain and ... the cancer early. A total blockage in the flow of spinal fluid can be life threatening. If tumors are found ...

  8. Posterior Tibial Tendon Dysfunction

    MedlinePlus

    ... when the posterior tibial tendon becomes inflamed or torn. As a result, the tendon may not be ... repetitive use. Once the tendon becomes inflamed or torn, the arch will slowly fall (collapse) over time. ...

  9. Posterior ankle impingement syndrome.

    PubMed

    Maquirriain, Javier

    2005-10-01

    Posterior ankle impingement syndrome is a clinical disorder characterized by posterior ankle pain that occurs in forced plantar flexion. The pain may be acute as a result of trauma or chronic from repetitive stress. Pathology of the os trigonum-talar process is the most common cause of this syndrome, but it also may result from flexor hallucis longus tenosynovitis, ankle osteochondritis, subtalar joint disease, and fracture. Patients usually report chronic or recurrent posterior ankle pain caused or exacerbated by forced plantar flexion or push-off maneuvers, such as may occur during dancing, kicking, or downhill running. Diagnosis of posterior ankle impingement syndrome is based primarily on clinical history and physical examination. Radiography, scintigraphy, computed tomography, and magnetic resonance imaging depict associated bone and soft-tissue abnormalities. Symptoms typically improve with nonsurgical management, but surgery may be required in refractory cases. PMID:16224109

  10. Immunotherapy of Melanoma.

    PubMed

    Snyder, Alexandra; Zamarin, Dmitriy; Wolchok, Jedd D

    2015-01-01

    The history of immunotherapy is rooted in the treatment of melanoma and therapy with immune checkpoint-blocking agents is now a cornerstone for the treatment of metastatic melanoma. The first effective immunotherapies approved by the US Food and Drug Administration in melanoma included interleukin-2 for metastatic disease and interferon alpha in the adjuvant setting. These were followed by a group of new therapies, including checkpoint-blocking antibodies targeting cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1. Therapies intended to 'reeducate' T cells, such as tumor-infiltrating lymphocyte therapy, oncolytic viruses and tumor vaccines, have yielded promising results and are under development. Finally, the integration of the above therapies as well as development of new coinhibitory and costimulatory agents, though in early stages, appear very promising and likely represent the next phase in drug development for the treatment of metastatic melanoma. PMID:26376963

  11. Sunburn and malignant melanoma.

    PubMed Central

    Green, A.; Siskind, V.; Bain, C.; Alexander, J.

    1985-01-01

    We investigated the relationship between cutaneous malignant melanoma and multiple sunburns in the Queensland population. Interview data were gathered from 236 case-control pairs concerning their lifetime experience of severe sunburns, their occupational and recreational sun exposure, and their skin type. Excluding the lentigo maligna melanoma subtype, an association between multiple sunburns and melanoma was evident. After controlling for other major risk factors there was a significant dose-response relationship (P less than 0.05): the estimated relative risk associated with 2-5 sunburns in life was 1.5, and with 6 or more was 2.4. This observation extends the hitherto circumstantial evidence of a causal relationship between exposure to solar ultraviolet radiation and melanoma, and suggests that precautionary measures could prevent the development of this disease in a proportion of cases in fair-skinned populations. PMID:3970815

  12. Melanoma Epidemiology and Prevention.

    PubMed

    Berwick, Marianne; Buller, David B; Cust, Anne; Gallagher, Richard; Lee, Tim K; Meyskens, Frank; Pandey, Shaily; Thomas, Nancy E; Veierød, Marit B; Ward, Sarah

    2016-01-01

    The epidemiology of melanoma is complex, and individual risk depends on sun exposure, host factors, and genetic factors, and in their interactions as well. Sun exposure can be classified as intermittent, chronic, or cumulative (overall) exposure, and each appears to have a different effect on type of melanoma. Other environmental factors, such as chemical exposures-either through occupation, atmosphere, or food-may increase risk for melanoma, and this area warrants further study. Host factors that are well known to be important are the numbers and types of nevi and the skin phenotype. Genetic factors are classified as high-penetrant genes, moderate-risk genes, or low-risk genetic polymorphisms. Subtypes of tumors, such as BRAF-mutated tumors, have different risk factors as well as different therapies. Prevention of melanoma has been attempted using various strategies in specific subpopulations, but to date optimal interventions to reduce incidence have not emerged. PMID:26601858

  13. Drugs Approved for Melanoma

    MedlinePlus

    ... are not listed here. Drugs Approved for Melanoma Aldesleukin Cobimetinib Cotellic (Cobimetinib) Dabrafenib Dacarbazine DTIC-Dome (Dacarbazine) IL-2 (Aldesleukin) Imlygic (Talimogene Laherparepvec) Interleukin-2 (Aldesleukin) Intron A ( ...

  14. Melanoma and Hawaii's youth.

    PubMed

    Williams, Laura

    2004-03-01

    Hawaii's sandy beaches, warm crystal waters, and mild climate attract tourists and residents alike to enjoy hours of outdoor activities under the sun. As frequent participants of these sun related activities, Hawaii's youth are exposed to high levels and duration of ultraviolet radiation throughout their early lives. This study aims to define occurrence trends of cutaneous malignant melanoma in Hawaii in correlation to increased childhood ultraviolet exposure. This paper addresses trends in melanoma incidence during 1979-2002 for Hawaii residents < 25 years of age. Data obtained from this review were analyzed by age group and ethnicity. Results show that although the incidence of melanoma is increasing for Hawaii residents over 25 years of age, the rate of melanoma occurrence in Hawaii's youth (< 25 years) is not increasing. PMID:15124743

  15. Melanoma of the eye

    MedlinePlus

    ... modified July 9, 2015. www.cancer.gov/types/eye/hp/intraocular-melanoma-treatment-pdq . Accessed October 7, 2015. Read ... by: Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital, Boston, MA. Also reviewed ...

  16. Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

    ClinicalTrials.gov

    2016-01-13

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  17. Booster Vaccination in Preventing Disease Recurrence in Previously Vaccinated Patients With Melanoma That Has Been Removed By Surgery

    ClinicalTrials.gov

    2015-01-23

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  18. Genetics of melanoma predisposition.

    PubMed

    Lin, J; Hocker, T L; Singh, M; Tsao, H

    2008-08-01

    Over the past 10 years, our understanding of melanoma at the molecular level has blossomed with the advent of genomic technologies. The enormous enthusiasm for the Human Genome Project is slowly being replaced by an even greater excitement for the unravelling of disease genomes, including melanoma. In this review, we will consider some of the clinical implications of these genetic findings for both diagnostics and therapeutics. PMID:18547303

  19. Genetics of melanoma

    PubMed Central

    Wangari-Talbot, Janet; Chen, Suzie

    2013-01-01

    Genomic variation is a trend observed in various human diseases including cancer. Genetic studies have set out to understand how and why these variations result in cancer, why some populations are pre-disposed to the disease, and also how genetics affect drug responses. The melanoma incidence has been increasing at an alarming rate worldwide. The burden posed by melanoma has made it a necessity to understand the fundamental signaling pathways involved in this deadly disease. Signaling cascades such as mitogen-activated protein kinase and PI3K/AKT have been shown to be crucial in the regulation of processes that are commonly dysregulated during cancer development such as aberrant proliferation, loss of cell cycle control, impaired apoptosis, and altered drug metabolism. Understanding how these and other oncogenic pathways are regulated has been integral in our challenge to develop potent anti-melanoma drugs. With advances in technology and especially in next generation sequencing, we have been able to explore melanoma genomes and exomes leading to the identification of previously unknown genes with functions in melanomagenesis such as GRIN2A and PREX2. The therapeutic potential of these novel candidate genes is actively being pursued with some presenting as druggable targets while others serve as indicators of therapeutic responses. In addition, the analysis of the mutational signatures of melanoma tumors continues to cement the causative role of UV exposure in melanoma pathogenesis. It has become distinctly clear that melanomas from sun-exposed skin areas have distinct mutational signatures including C to T transitions indicative of UV-induced damage. It is thus necessary to continue spreading awareness on how to decrease the risk factors of developing the disease while at the same time working for a cure. Given the large amount of information gained from these sequencing studies, it is likely that in the future, treatment of melanoma will follow a highly

  20. Targeted therapy in melanoma.

    PubMed

    Kudchadkar, Ragini R; Smalley, Keiran S M; Glass, L Frank; Trimble, James S; Sondak, Vernon K

    2013-01-01

    Since the discovery of activating mutations in the BRAF oncogene in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. We review the latest developments in our understanding of the role of BRAF/MEK/ERK pathway signaling in melanoma, and the development of inhibitors of this pathway. We also explore alternative mutations seen in melanoma, such as NRAS, KIT, GNAQ, and GNA11, and the drug development that is ongoing based on this biology. Strategies for the management of the vexing clinical problem of BRAF inhibitor resistance, primarily via combination therapy, are outlined. With the recent approval of the BRAF inhibitor vemurafenib for stage IV metastatic melanoma, use of this agent is expanding in the United States. Thus, management of the skin toxicities of this agent, such as squamous cell carcinomas, "acneiform" eruptions, hand-foot syndrome, and panniculitis, will be a growing problem facing dermatologists today. We discuss the toxicities of targeted agents in use for melanoma, in particular the dermatologic effects and the management of these skin toxicities. PMID:23438383

  1. Familial cutaneous melanoma.

    PubMed

    Hansson, Johan

    2010-01-01

    Approximately 5-10 % of all cutaneous melanomas occur in families with hereditary melanoma predisposition. Worldwide, approximately 20-40% of kindreds with familial elanoma harbor germline mutations in the CDKN2A gene, located on chromosome 9p21, which encodes two different proteins, p16INK4 and p14ARF, both involved in regulation of cell cycle progression and induction of senescence. In different populations several recurring CDKN2A founder mutations have been described. The risk of melanoma in CDKN2A mutations carriers varies between populations and is higher in regions with high sun exposure and high incidence of melanoma in the general population. Some CDKN2A mutations have been associated not only with melanoma but also with increased risk of other malignancies--most notably pancreatic carcinoma. A much smaller number of families have germline mutations in the CDK4 gene on chromosome 12q14, encoding a cyclin dependent kinase which normally interacts with p16INK4A. The management of families with hereditary melanoma is discussed. PMID:20687502

  2. Episcleral plaque thermoradiotherapy in patients with choroidal melanoma.

    PubMed

    Petrovich, Z; Astrahan, M A; Luxton, G; Green, R; Langholz, B; Liggett, P

    1992-01-01

    From 1988 to 1991, 21 patients with uveal melanoma were treated in a Phase I study with episcleral plaque radiotherapy (EPRT). This irradiation was combined with localized current field episcleral hyperthermia (LCFHT). Tumor stage was: T3 = 15 (71%) and T2 = 6 (29%). Follow-up ranged from 2 to 42 months (mean 9.2 months). EPRT was given using custom built I-125 gold plaques. Radiation doses to the tumor apex ranged from 13 to 123 Gy (mean dose 70.0 Gy) given at a mean dose rate of 55 cGy/hr. LCFHT was given with 500 KHz frequency for 45 min immediately before EPRT. The temperature was controlled on the scleral surface using four thermocouples. T mean ranged from 42.5 degrees C to 45 degrees C +/- 0.5 degrees C (mean 43.4 degrees C). The study patients showed rapid tumor necrosis. A 25% mean decrease of apical tumor dimension was noted, p = 0.0007. At least ambulatory vision (greater than 5/200) was maintained by 17/21 (81%) patients. Visual acuity was seen to improve greater than 6 months post-plaque therapy in 10 (48%) study patients. This was following an intermediate decrease in visual acuity. Severe complications, including large hemorrhagic retinal detachment and large vitreous hemorrhage, were seen in two (9.5%) of the early study patients. A mean scleral temperature reduction to less than or equal to 44 degrees C +/- 0.5 degrees C resulted in good treatment tolerance and a lack of serious complications in subsequently treated patients. A Phase II prospective randomized trial comparing LCFHT with 60 versus 80 Gy EPRT dose to the tumor apex is currently being activated for patients with choroidal melanoma. PMID:1612961

  3. Bilateral posterior sternoclavicular dislocation.

    PubMed

    Baumann, Matthias; Vogel, Tobias; Weise, Kuno; Muratore, Tim; Trobisch, Per

    2010-07-01

    Posterior sternoclavicular dislocations are a rare injury, representing <5% of all sternoclavicular dislocations and 1 in 1600 shoulder girdle injuries. Proper imaging with computed tomography and prompt diagnosis are essential steps in preventing potentially lethal complications observed in approximately 3% of all posterior sternoclavicular dislocations. Surgical treatment is necessary if closed reduction fails. With the medial clavicular epiphysis being the last to close (between ages 22 and 25), children and adolescents typically present with epiphyseal fractures rather than joint dislocations. If closed reduction fails, open reduction and internal fixation (ORIF) should be considered in fractures, whereas complex reconstructions with tendon graft procedures have been recommended for joint dislocations. This article presents a case of a traumatic bilateral posterior sternoclavicular dislocation due to an epiphyseal fracture in a 15-year-old boy. To our knowledge, this is the first reported case of a bilateral posterior sternoclavicular dislocation. Attempted closed reduction failed with redislocation after 2 days. The patient subsequently required ORIF. This article describes our technique with anterior retraction of the medial clavicle, closure of the posterior periosteum, and ORIF using nonabsorbable sutures. Postoperative shoulder mobilization was started on day 1. At final follow-up, the patient was completely asymptomatic. PMID:20608625

  4. [Histological spectrum of malignant melanoma].

    PubMed

    Brenn, T

    2015-02-01

    The diagnosis of melanocytic tumors is one of the most problematic areas in dermatology and diagnostic pathology. Melanoma is a malignant melanocytic tumor and the risk for metastasis and associated mortality is mainly dependent on tumor thickness and depth of invasion. Early recognition and correct diagnosis is therefore important for successful and effective treatment. The correct diagnosis of melanoma is, however, challenging due to the wide morphological spectrum. Historically, the disease was subdivided into superficial spreading, nodular, lentigo maligna and acral lentiginous melanoma but many more subtypes have subsequently been added. Some of these melanoma variants also show differences relating to the genetic background, clinical presentation, prognosis and treatment and may be associated with a specific differential diagnosis. In this article four of these melanoma variants, desmoplastic melanoma, nevoid melanoma, malignant blue nevus and pigment synthesizing melanoma will be discussed in more detail. PMID:25589353

  5. What Is Melanoma Skin Cancer?

    MedlinePlus

    ... that can become melanoma. They make a brown pigment called melanin , which gives the skin its tan ... to the sun, melanocytes make more of the pigment, causing the skin to tan or darken. Melanoma ...

  6. Tibialis Posterior Tendon Entrapment Within Posterior Malleolar Fracture Fragment.

    PubMed

    Fantry, Amanda; Lareau, Craig; Vopat, Bryan; Blankenhorn, Brad

    2016-01-01

    Management of posterior malleolus fractures continues to be controversial, with respect to both need for fixation and fixation methods. Fixation methods include an open posterior approach to the ankle as well as percutaneous reduction and fixation with or without arthroscopy for visualization of the articular surface. Plain radiographs are unreliable in identifying fracture pattern and intraoperative reduction, making arthroscopy a valuable adjunct to posterior malleolus fracture management. In this article, we report a case of tibialis posterior tendon entrapment within a posterior malleolus fracture, as identified by arthroscopy and managed with open reduction. Tibialis posterior tendon entrapment within a posterior malleolus has not been previously reported. Ankle arthroscopy for posterior malleolus fractures provides an opportunity to identify soft-tissue or tendinous entrapment, articular surface reduction, and articular cartilage injuries unlikely to be identified with fluoroscopy alone and should be considered in reduction and fixation of posterior malleolus fractures. PMID:26991573

  7. Genotyping of cutaneous melanoma

    PubMed Central

    Glitza, Isabella C.; Davies, Michael A.

    2014-01-01

    Until recently, treatment options for patients with metastatic melanoma were very limited. This landscape has evolved dramatically since the discovery of activating mutations in the BRAF gene in ~45% of cutaneous melanomas. Vemurafenib, dabrafenib, and trametinib have all received regulatory approval for the treatment of metastatic melanoma patients with a BRAFV600 mutation. Based on the necessity to document the presence of a BRAFV600 mutation to prescribe these agents, molecular testing is now the standard of care in this disease. However, the options and rationale for testing are evolving rapidly due to an improved understanding of the molecular drivers and heterogeneity of melanoma. Such testing may identify rational combinatorial approaches to prevent or overcome resistance for the approved BRAF inhibitors. In addition, new clinical strategies have been identified for a number of other molecular changes that are detected in this disease, including somatic changes in NRAS, PTEN, CDKN2A, and c-KIT, among others. This review summarizes the current understanding of the genetic landscape of mutations in melanoma, their associations with clinicopathological features, and their implications for clinical testing and treatment. PMID:25632386

  8. Methods of Melanoma Detection.

    PubMed

    Leachman, Sancy A; Cassidy, Pamela B; Chen, Suephy C; Curiel, Clara; Geller, Alan; Gareau, Daniel; Pellacani, Giovanni; Grichnik, James M; Malvehy, Josep; North, Jeffrey; Jacques, Steven L; Petrie, Tracy; Puig, Susana; Swetter, Susan M; Tofte, Susan; Weinstock, Martin A

    2016-01-01

    Detection and removal of melanoma, before it has metastasized, dramatically improves prognosis and survival. The purpose of this chapter is to (1) summarize current methods of melanoma detection and (2) review state-of-the-art detection methods and technologies that have the potential to reduce melanoma mortality. Current strategies for the detection of melanoma range from population-based educational campaigns and screening to the use of algorithm-driven imaging technologies and performance of assays that identify markers of transformation. This chapter will begin by describing state-of-the-art methods for educating and increasing awareness of at-risk individuals and for performing comprehensive screening examinations. Standard and advanced photographic methods designed to improve reliability and reproducibility of the clinical examination will also be reviewed. Devices that magnify and/or enhance malignant features of individual melanocytic lesions (and algorithms that are available to interpret the results obtained from these devices) will be compared and contrasted. In vivo confocal microscopy and other cellular-level in vivo technologies will be compared to traditional tissue biopsy, and the role of a noninvasive "optical biopsy" in the clinical setting will be discussed. Finally, cellular and molecular methods that have been applied to the diagnosis of melanoma, such as comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), will be discussed. PMID:26601859

  9. Melanoma in Black Patients

    PubMed Central

    Smith, Robert J.

    1982-01-01

    Melanoma in black patients is uncommon but not rare. This paper reports six cases seen in one general surgeon's practice in Arkansas during a 14-year period. A review of the current literature regarding melanoma in blacks is given. Characteristically, melanoma in blacks is found on the soles of the feet, palms of the hands, or mucous membranes. The tumor has a deadly potential unless it is treated at an early stage; four of the patients reported have died of metastatic disease. A public health program is needed to make physicians and the public aware of the incidence and location of this tumor. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:7120473

  10. [External ear melanoma].

    PubMed

    Amando García, L; Suárez Nieto, C; Madrigal Rubiales, B; García García, J

    2003-02-01

    Cutaneous melanomas are the tumours that have increased more their incidence in the last fifty years. Melanomas arising from the external auditory canal are extraordinariously unfrequent. These tumours show an aggressive and silent behaviour, and due to this the diagnosis is frequently made in an advanced stage. A male with a malignant melanoma arising from his left external auditory canal was attended in our department, suspecting an epidermoid carcinoma. The clinical findings and the extension of the lesion required a lateral temporal bone resection, parotidectomy and neck dissection to achieve a total resection. We present a review of the literature about this entity and an analysis of the incidence, significance of the lymph node metastases and value of the elective neck dissection. PMID:12802982

  11. Lymphoscintigraphy in malignant melanoma

    SciTech Connect

    Berman, C.G.; Norman, J.; Cruse, C.W.; Reintgen, D.S.; Clark, R.A. )

    1992-01-01

    The development and rationale for the use of lymphoscintigraphy in the preoperative evaluation of patients with malignant melanoma being considered for elective lymph node dissection is reviewed. This overview is updated by an analysis of 135 patients with early stage malignant melanoma involving the head, neck, shoulders, and trunk at Moffitt Cancer Center and Research Institute at the University of South Florida (Tampa, FL). High discordancy rates (overall, 41%) were seen between drainage patterns predicted from historical anatomical guidelines and those revealed by the lymphoscintigraphic examination. The high discordancy rate was most pronounced in the head (64%) and the neck (73%). Surgical management was changed in 33% of the patients, overall. A preoperative lymphoscintigram is recommended for all patients with melanoma with head, neck, and truncal lesions evaluated for elective lymph node dissection as the lymphatic drainage patterns are often unpredictable and variable.

  12. The impact of body area in melanoma self-detection: a retrospective study.

    PubMed

    De Giorgi, Vincenzo; Grazzini, Marta; Savarese, Imma; Gori, Alessia; Papi, Federica; D'Errico, Antonietta; Scarfì, Federica; Gandini, Sara

    2015-07-01

    To assess the patient's capability of performing a correct skin-check examination we investigated the association of melanoma detection pattern with Breslow thickness, by melanoma body area. In this prospective observational study, patients with primary cutaneous melanoma who presented at the Department of Dermatology at the University of Florence between January 2000 and November 2011 were interviewed as part of their clinical data recording procedure at the time of their final histopathological diagnoses of melanoma. With the aim of evaluating a self skin-check, we included patients with melanoma in the anterior part of the trunk (abdomen and chest area), which is generally considered visible in the mirror, and the posterior part of the trunk, which is a more complex area to be self-checked. The treating physician specifically questioned all patients about who had first detected or suspected the lesion that resulted in the histological diagnosis of melanoma in order to compare those who had self-detected (SD) their melanoma with those who had discovered their melanoma during a regular skin-check (RSC) with a dermatologist. A total of 186 melanoma patients were analyzed, with 67% (n=125) of melanomas located on the back and 33% (n=61) in the chest and abdominal area; the majority (55%, n=103) were in the SD group. The median Breslow thickness of the SD group was significantly greater than that of the RSC group: 0.60 versus 0.50 mm (P<0.0001). In the posterior trunk, the frequency of thick melanomas (Breslow≥1.00 mm) was significantly greater in the SD group than in the RSC group (34 vs. 11%; P=0.003), whereas there was no difference in the frequency of thick melanoma by detection patterns in the anterior trunk. Given the influence of the body area in detecting threatening melanoma, we should encourage people to obtain dermatological skin-checks more often. Skin self-examinations cannot be sufficiently accurate. PMID:25325306

  13. Vitamins and Melanoma

    PubMed Central

    Russo, Irene; Caroppo, Francesca; Alaibac, Mauro

    2015-01-01

    A tremendous amount of information was published over the past decades in relation to the role of vitamins in various neoplastic diseases. In particular, several studies showed an inverse relationship between selected vitamins intake and cancer risk. In this review we will focus on the role played by vitamins in melanoma with particular regard to vitamin A, D, K, E and C. Given that vitamin supplementation is easy, convenient, and readily accepted by patients, in the future the use of vitamins in chemoprevention and therapy of melanoma could be encouraged if supported by pre-clinical and clinical evidence. PMID:26213971

  14. Melanoma of the Foot.

    PubMed

    Bristow, Ivan; Bower, Chris

    2016-07-01

    Melanoma is a rare form of skin cancer that is responsible for most skin cancer deaths globally. Tumors arising on the foot continue to be a particular challenge. Patients present later and lesions are frequently misdiagnosed, leading to more advanced disease with an overall poorer prognosis then melanoma elsewhere. In order to improve early recognition, this article reviews the clinical features of the disease along with published algorithms. Emerging assessment techniques such as dermoscopy are also discussed as tools to improve clinical decision making. Contemporary drug therapies in the treatment of advanced disease are also discussed. PMID:27215160

  15. Pathology of melanoma.

    PubMed

    Elder, David E

    2015-04-01

    The pathology of melanoma is discussed in relation to surgical diagnosis and management. Pitfalls that may result in problems of clinicopathologic communication are emphasized. A compelling vision for the future is that all tumors will be characterized by their driving oncogenes, suppressor genes, and other genomic factors. The success of targeted therapy directed against individual oncogenes, despite its limitations, suggests that a repertoire of targeted agents will be developed that can be used against a variety of different tumors, depending on the results of genetic testing. Nevertheless, histopathologic diagnosis and surgical therapy will remain mainstays of management for melanoma. PMID:25769708

  16. Angiogenesis and Melanoma

    PubMed Central

    Ribatti, Domenico; Annese, Tiziana; Longo, Vito

    2010-01-01

    Angiogenesis occurs in pathological conditions, such as tumors, where a specific critical point in tumor progression is the transition from the avascular to the vascular phase. Tumor angiogenesis depends mainly on the release by neoplastic cells of growth factors specific for endothelial cells, which are able to stimulate the growth of the host’s blood vessels. This article summarizes the literature concerning the relationship between angiogenesis and human melanoma progression. The recent applications of antiangiogenic agents which interfere with melanoma progression are also described. PMID:24281035

  17. Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type

    PubMed Central

    Torres-Cabala, Carlos A; Wang, Wei-Lien; Trent, Jonathan; Yang, Dan; Chen, Su; Galbincea, John; Kim, Kevin B; Woodman, Scott; Davies, Michael; Plaza, Jose A; Nash, JW; Prieto, Victor G; Lazar, Alexander J; Ivan, Doina

    2014-01-01

    The role of immunohistochemistry in the assessment of KIT status in melanomas, especially acral lentiginous/mucosal, is not well established. Although the reported prevalence of KIT mutations in acral lentiginous/ mucosal melanomas is relatively low, detection of mutations in KIT can have profound therapeutic implications. We evaluated the efficacy of immunohistochemistry to predict mutations in KIT. One hundred seventy-three tumors, comprising primary and metastatic melanomas (141 acral lentiginous/mucosal, 5 nodular, 4 lentigo maligna, 3 superficial spreading, 2 uveal, 1 melanoma of soft parts, 8 metastases from unclassified primaries, and 9 metastases from unknown primaries) were studied. Immunohistochemical expression of KIT using an anti-CD117 antibody and KIT mutational analysis by gene sequencing of exons 11, 13, and 17 were performed. Eighty-one percent of acral lentiginous/mucosal melanomas, primary and metastatic, showed KIT expression by at least 5% of the tumor cells. The overall frequency of activating KIT gene mutations in acral lentiginous/ mucosal melanomas was 15% (14 out of 91 cases), being the L576P mutation in exon 11 the most frequently detected (4 of 14 cases). Cases showing less than 10% positive tumor cells were negative for KIT mutations. Eighty-two percent (12 of 14) of cases positive for KIT mutation showed KIT expression in more than 50% of the cells. An association between immunohistochemical expression of KIT and mutation status was found (P= 0.007). Immunohistochemical expression of KIT in less than 10% of the cells of the invasive component of acral lentiginous/mucosal melanomas appears to be a strong negative predictor of KIT mutation and therefore can potentially be used to triage cases for additional KIT genotyping. PMID:19718013

  18. Basic and clinical aspects of malignant melanoma

    SciTech Connect

    Nathanson, L. )

    1987-01-01

    This book contains the following 10 chapters: The role of oncogenes in the pathogenesis of malignant melanoma; Laminin and fibronectin modulate the metastatic activity of melanoma cells; Structure, function and biosynthesis of ganglioside antigens associated with human tumors derived from the neuroectoderm; Epidemiology of ocular melanoma; Malignant melanoma: Prognostic factors; Endocrine influences on the natural history of human malignant melanoma; Psychosocial factors associated with prognostic indicators, progression, psychophysiology, and tumor-host response in cutaneous malignant melanoma; Central nervous system metastases in malignant melanoma; Interferon trials in the management of malignant melanoma and other neoplasms: an overview; and The treatment of malignant melanoma by fast neutrons.

  19. Raman spectroscopy detects melanoma and the tissue surrounding melanoma using tissue-engineered melanoma models

    PubMed Central

    Yorucu, Ceyla; Lau, Katherine; Mittar, Shweta; Green, Nicola H.; Raza, Ahtasham; Rehman, Ihtesham Ur; MacNeil, Sheila

    2016-01-01

    ABSTRACT Invasion of melanoma cells from the primary tumor involves interaction with adjacent tissues and extracellular matrix. The extent of this interaction is not fully understood. In this study Raman spectroscopy was applied to cryo-sections of established 3D models of melanoma in human skin. Principal component analysis was used to investigate differences between the tumor and normal tissue and between the peri-tumor area and the normal skin. Two human melanoma cells lines A375SM and C8161 were investigated and compared in 3D melanoma models. Changes were found in protein conformations and tryptophan configurations across the entire melanoma samples, in tyrosine orientation and in more fluid lipid packing only in tumor dense areas, and in increased glycogen content in the peri-tumor areas of melanoma. Raman spectroscopy revealed changes around the perimeter of a melanoma tumor as well as detecting differences between the tumor and the normal tissue. PMID:27158185

  20. Melanoma of the Skin

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 76,380 % of All New Cancer Cases 4.5% Estimated Deaths in 2016 10,130 % of All Cancer ... of This Cancer : In 2013, there were an estimated 1,034,460 people living with melanoma of ...

  1. Radiotherapy of malignant melanoma

    SciTech Connect

    Cooper, J.S.

    1985-04-01

    The role of radiotherapy in the treatment of malignant melanoma is limited, and surgery generally forms the mainstay of medical practice. However, there are some circumstances in which radiotherapy should be considered the treatment of choice. Symptomatic metastatic lesions in bone or brain can effectively be palliated in a substantial proportion of instances. At the current stage of our knowledge, conventionally fractionated treatment of such lesions forms the standard against which other treatments should be measured. In contrast, metastatic lesions to skin or lymph nodes that do not overlie critical normal structures probably are better treated by high-dose-per-fraction techniques. Radiotherapy may play a definitive role in the treatment of lentigo maligna. The precise optimal energy of the beam to be used remains to be defined. Slightly more penetrating radiation appears to be required for lentigo maligna melanomas. Here, too, the optimal energy remains to be defined. The treatment of nonlentigenous melanomas primarily by radiotherapy is unproved in my opinion. Certainly, the data from the Princess Margaret Hospital is exciting, but I believe it must be corroborated by a well-designed trial before it can be accepted without question. Future directions in treatment of malignant melanoma are likely to include further trials of unconventional fractionation and the use of radiosensitizing agents in conjunction with radiotherapy. The time for dermatologists and radiation therapists to cooperate in such studies is at hand.

  2. Melanoma Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing melanoma cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  3. Spice Blocks Melanoma Growth

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Curcumin, the pungent yellow spice found in both turmeric and curry powders, blocks a key biological pathway needed for development of melanoma and other cancers, according to a study that appears in the journal Cancer. Researchers from The University of Texas M. D. Anderson Cancer Center demonstrate how curcumin stops laboratory strains of…

  4. Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile.

    PubMed

    Larsen, Ann-Cathrine

    2016-05-01

    Conjunctival malignant melanoma is a rare disease associated with considerable mortality. Most published data have been based on case reports or series of referred patients. In addition, very little is known about the genetic and epigenetic profile of conjunctival melanoma and the resemblance to uveal, cutaneous and mucosal melanoma. The aim was to determine the incidence rate of conjunctival melanoma, and to relate clinicopathological features and treatment to prognosis. A further aim was to determine the prevalence of BRAF mutations in conjunctival melanoma, to determine whether BRAF mutations are early events in pathogenesis, and relate clinicopathological features and prognosis to BRAF-mutation status. Finally, we wanted to identify tumour-specific and prognostic microRNAs in conjunctival melanoma, and to compare these with the microRNA expression of other melanoma subtypes. In order to investigate these rare tumours, we studied all the conjunctival melanomas that had been surgically removed in Denmark over a period of 52 years (1960-2012). Tissue samples, clinical files, pathology reports and follow-up data were collected and re-evaluated. Using droplet digital polymerase chain reaction and immunohistochemistry, we investigated BRAF mutations; and using microRNA expression profiling, we investigated differentially expressed microRNAs. The overall incidence of conjunctival melanoma was 0.5/1 000 000/year, and it increased in Denmark over 52 years. The increase was mainly caused by an increase in older patients (>65 years) and bulbar lesions. Clinicopathological features significantly associated with a poor prognosis were extrabulbar location, involvement of adjacent tissue structures, tumour thickness exceeding 2 mm and local tumour recurrence. Patients undergoing incisional biopsy and/or treatment involving excision without adjuvant therapy fared worse than patients treated with excision and any type of adjuvant treatment. We found that 35% (39/110) of

  5. A case of giant nodular posterior scleritis mimicking choroidal malignancy

    PubMed Central

    Liu, Andrea T; Luk, Fiona O; Chan, Carmen K

    2015-01-01

    To report a case of giant nodular posterior scleritis mimicking a choroidal tumor. A 42-year-old lady with systemic hypertension presented with a 1-week history of unilateral visual loss, pain and redness in her left eye. Examination showed sectoral anterior episcleritis in her left eye as well as a dome-shaped choroidal mass at the inferior-temporal periphery, associated with retinal hemorrhages and subretinal fluid. Systemic evaluation and imaging of the choroidal mass were performed and could not rule out amelanotic choroidal melanoma. At the same time, she was prescribed a 2-week course of oral nonsteroidal anti-inflammatory drug (NSAID) for her sectoral anterior episcleritis. The choroidal mass was found to have resolved completely right before her scheduled fine needle biospy. Diagnosis of nodular posterior scleritis and a trial of oral NSAID can be considered in patients presenting with a choroidal mass before any invasive procedure. PMID:26862098

  6. Dabrafenib Alone and in Combination With Trametinib Before Surgery in Treating Patients With Locally or Regionally Advanced Melanoma That Can Be Removed By Surgery

    ClinicalTrials.gov

    2013-03-29

    Recurrent Melanoma; Stage IIB Melanoma (Locally Advanced); Stage IIC Melanoma (Locally Advanced); Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma (Limited, Resectable)

  7. Molecular Pathogenesis of Sporadic Melanoma and Melanoma-Initiating Cells

    PubMed Central

    Kong, Yunyi; Kumar, Suresh M.; Xu, Xiaowei

    2014-01-01

    Recent advances in molecular genetics and cancer stem cell biology have shed some light on the molecular basis of melanomagenesis. In this review, we will focus on major genetic alterations in the melanoma, particularly pathways involved in cell proliferation, apoptosis, and tumor suppression. The potential role of melanoma-initiating cells during melanomagenesis and progression will also be discussed. Understanding pathogenesis of melanoma may uncover new diagnostic clues and therapeutic targets for this increasingly prevalent disease. PMID:21128770

  8. Unfolding the mutational landscape of human melanoma.

    PubMed

    Davar, Diwakar; Lin, Yan; Kirkwood, John M

    2015-03-01

    Over the preceding two decades, sophisticated sequencing techniques have been used to characterize the genetic drivers of adult melanoma. However, our understanding of pediatric melanomas is still rudimentary. In this report, we comment on a thorough multi-platform analysis of common pediatric melanoma subsets, including pediatric conventional melanoma (CM), congenital nevus-derived melanoma (CNM), and Spitzoid melanoma (SM), contributed by Lu et al. PMID:25666674

  9. Melanoma Treatments: Advances and Mechanisms.

    PubMed

    Marzuka, Alexander; Huang, Laura; Theodosakis, Nicholas; Bosenberg, Marcus

    2015-11-01

    Advances in the understanding of the molecular pathogenesis of melanoma and in cancer immunology have led to the rational design and recent clinical implementation of a variety of novel therapies for metastatic melanoma. BRAF and MEK inhibitors that target the MAPK pathway have high rates of clinical response in BRAF-mutant melanoma. Therapies that modulate the immune response to melanoma, including monoclonal antibodies that interfere with pathways that inhibit T-cell function, have been shown to be effective in melanoma. Lessons learned from these encouraging results are driving the development of new treatments for melanoma and other cancers. This review will focus on the science and clinical findings related to targeted therapies that inhibit BRAF or MEK as well as the immunotherapies that block the CTLA-4 or PD-1 pathways. Other experimental and combinatorial therapeutic approaches will also be discussed. PMID:25899612

  10. New Diagnostic Aides for Melanoma

    PubMed Central

    Ferris, Laura K.; Harris, Ryan J.

    2012-01-01

    Synopsis Detection of melanoma at an early stage is crucial to improving survival rates in melanoma. Accurate diagnosis by current techniques including dermatoscopy remains difficult, and new tools are needed to improve our diagnostic abilities. This article discusses recent advances in diagnostic techniques including confocal scanning laser microscopy, MelaFind, Siascopy, noninvasive genomic detection, as well as other future possibilities to aid in diagnosing melanoma. Advantages and barriers to implementation of the various technologies are discussed as well. PMID:22800557

  11. AZD2171 in Treating Patients With Recurrent or Stage IV Melanoma

    ClinicalTrials.gov

    2015-06-01

    Acral Lentiginous Malignant Melanoma; Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Intraocular Melanoma; Iris Melanoma; Lentigo Maligna Malignant Melanoma; Recurrent Melanoma; Stage, Intraocular Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

  12. Melanomas Associated With Blue Nevi or Mimicking Cellular Blue Nevi: Clinical, Pathologic, and Molecular Study of 11 Cases Displaying a High Frequency of GNA11 Mutations, BAP1 Expression Loss, and a Predilection for the Scalp.

    PubMed

    Costa, Sebastian; Byrne, Michelle; Pissaloux, Daniel; Haddad, Veronique; Paindavoine, Sandrine; Thomas, Luc; Aubin, Francois; Lesimple, Thierry; Grange, Florent; Bonniaud, Bertille; Mortier, Laurent; Mateus, Christine; Dreno, Brigitte; Balme, Brigitte; Vergier, Beatrice; de la Fouchardiere, Arnaud

    2016-03-01

    Melanomas associated with blue nevi (MABN) or mimicking cellular blue nevi (MMCBN) represent exceptional variants of malignant cutaneous melanocytic tumors. Uveal and leptomeningeal melanomas frequently have somatic mutations of GNAQ or GNA11, which are believed to be early driver mutations. In uveal melanomas, monosomy 3, linked to the BAP1 gene, is an adverse prognostic factor. We have studied the clinical, histologic, BAP1 expression profile, and molecular data of 11 cases of MABN/MMCBN and 24 cellular blue nevi. Most of the cases of MABN/MMCBN occurred on the scalps of adult patients and presented as rapidly growing nodules, typically >1 cm, often arising at the site of a preexisting melanocytic lesion. The MABN/MMCBN were composed of dense nests of large dermal atypical melanocytes, in some cases lying adjacent to a blue nevus. Four patients developed metastatic disease, and 2 died from their disease. A GNA11 mutation was found in 8/11 cases and a GNAQ mutation in 1 case. Seven of 11 cases showed loss of nuclear BAP1 immunohistochemical (IHC) expression in the malignant component, sparing the adjacent nevus. Array comparative genomic hybridization revealed recurrent deletions of chromosomes 1p, 3p, 4q, 6q, 8p, 16q, and 17q and recurrent gains of chromosomes 6p, 8q, and 21q. The 24 cases of cellular blue nevi frequently occurred on the sacrum, had GNAQ mutations, and showed normal positive IHC staining for BAP1. These results underscore overlapping features in all blue-like malignant melanocytic tumors. Loss of BAP1 IHC expression was restricted to melanomas, including all metastatic cases. PMID:26645730

  13. Posterior Tibial Tendon Transfer.

    PubMed

    Shane, Amber M; Reeves, Christopher L; Cameron, Jordan D; Vazales, Ryan

    2016-01-01

    When performed correctly with the right patient population, a tibialis posterior muscle/tendon transfer is an effective procedure. Many different methods have been established for fixating the tendon, each of which has its' own indications. Passing through the interosseous membrane is the preferred and recommended method and should be used unless this is not possible. Good surgical planning based on patient needs and expectations, along with excellent postoperative care including early range of motion and physical therapy minimizes risk of complications and allows for the optimal outcome to be achieved. PMID:26590722

  14. Posterior Urethral Strictures

    PubMed Central

    Gelman, Joel; Wisenbaugh, Eric S.

    2015-01-01

    Pelvic fracture urethral injuries are typically partial and more often complete disruptions of the most proximal bulbar and distal membranous urethra. Emergency management includes suprapubic tube placement. Subsequent primary realignment to place a urethral catheter remains a controversial topic, but what is not controversial is that when there is the development of a stricture (which is usually obliterative with a distraction defect) after suprapubic tube placement or urethral catheter removal, the standard of care is delayed urethral reconstruction with excision and primary anastomosis. This paper reviews the management of patients who suffer pelvic fracture urethral injuries and the techniques of preoperative urethral imaging and subsequent posterior urethroplasty. PMID:26691883

  15. Posterior Urethral Strictures.

    PubMed

    Gelman, Joel; Wisenbaugh, Eric S

    2015-01-01

    Pelvic fracture urethral injuries are typically partial and more often complete disruptions of the most proximal bulbar and distal membranous urethra. Emergency management includes suprapubic tube placement. Subsequent primary realignment to place a urethral catheter remains a controversial topic, but what is not controversial is that when there is the development of a stricture (which is usually obliterative with a distraction defect) after suprapubic tube placement or urethral catheter removal, the standard of care is delayed urethral reconstruction with excision and primary anastomosis. This paper reviews the management of patients who suffer pelvic fracture urethral injuries and the techniques of preoperative urethral imaging and subsequent posterior urethroplasty. PMID:26691883

  16. Targeted Therapy for Melanoma.

    PubMed

    Wong, Deborah J L; Ribas, Antoni

    2016-01-01

    Vemurafenib and dabrafenib, two potent tyrosine kinase inhibitors (TKIs) of the BRAF(V600E) kinase, are highly effective in the treatment of a BRAF (V600) -mutant metastatic melanoma. These are selective type I inhibitors (functional against the active conformation of the kinase) of the RAF kinases, which are key players in the mitogen-activated protein kinase (MAPK) pathway. BRAF (V600) mutations are present in approximately 7 % of all cancers, including high frequencies of mutations reported in 50 % of advanced melanomas and 100 % of hairy cell leukemias. As with most targeted therapies, resistance to BRAF inhibitors is an issue, and mechanisms of resistance are varied. Combining BRAF inhibitors with MEK inhibitors such as trametinib delays the development of resistance. Rationally combining targeted therapies to address the mechanism of resistance or combining BRAF inhibitors with other effective therapies such as immunotherapy may result in further improvement in outcomes for patients. PMID:26601866

  17. [Treatment of melanoma].

    PubMed

    Dréno, Brigitte; Wallon-Dumont, Gwénaëlle

    2003-01-11

    At the stage of primary tumour and lymph node extension, the treatment of melanoma is mainly surgical. Interferon alpha has obtained marketing authorisation to be used as adjuvant therapy at different doses in the treatment of these two stages of the disease and must therefore be discussed with the patient. At the metastatic stage, no real progress in chemotherapy has been noted for more than 20 years. Combined therapy with chemotherapy and cytokines (interferon alpha or interleukine 2) increases the percentage of response but without increasing the overall survival. THREE IMMUNOTHERAPY TECHNIQUES: Cellular immunotherapy represents the main hope of these future years in the treatment of melanoma, with the injection of in vitro expanded cytotoxic T cells, vaccination and dendritic cells. Although clinical results are starting to be published, cellular immunotherapy remains in the field of clinical research, within the framework of clinical trials. PMID:12610396

  18. Posterior Cortical Atrophy

    PubMed Central

    Crutch, Sebastian J; Lehmann, Manja; Schott, Jonathan M; Rabinovici, Gil D; Rossor, Martin N; Fox, Nick C

    2013-01-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome that is characterized by a progressive decline in visuospatial, visuoperceptual, literacy and praxic skills. The progressive neurodegeneration affecting parietal, occipital and occipito-temporal cortices which underlies PCA is attributable to Alzheimer's disease (AD) in the majority of patients. However, alternative underlying aetiologies including Dementia with Lewy Bodies (DLB), corticobasal degeneration (CBD) and prion disease have also been identified, and not all PCA patients have atrophy on clinical imaging. This heterogeneity has led to diagnostic and terminological inconsistencies, caused difficulty comparing studies from different centres, and limited the generalizability of clinical trials and investigations of factors driving phenotypic variability. Significant challenges remain in identifying the factors associated with both the selective vulnerability of posterior cortical regions and the young age of onset seen in PCA. Greater awareness of the syndrome and agreement over the correspondence between syndrome-and disease-level classifications are required in order to improve diagnostic accuracy, research study design and clinical management. PMID:22265212

  19. Tumor vascularity and hematogenous metastasis in experimental murine intraocular melanoma.

    PubMed Central

    Grossniklaus, H E

    1998-01-01

    PURPOSE: The purpose of this study is to test the hypothesis that primary tumor vascularity in a murine model of intraocular melanoma positively correlates with the development and hematogenous spread of metastasis. METHODS: Forty 12-week-old C57BL6 mice were inoculated in either the anterior chamber (AC) or posterior compartment (PC) of 1 eye with 5 x 10(5) cells/microL of Queens tissue culture melanoma cells. The inoculated eye was enucleated at 2 weeks; the mice were sacrificed at 4 weeks postinoculation, and necropsies were performed. The enucleated eyes were examined for histologic and ultrastructural features, including relationship of tumor cells to tumor vascular channels, vascular pattern, and mean vascular density. RESULTS: Melanoma grew and was confined to the eye in 12 of 20 AC eyes and 10 of 20 PC eyes. Histologic and electron microscopic examination showed tumor invasion into vascular channels. Five of 12 AC tumors (42%) and 8 of 10 PC tumors (80%) metastasized. All of the AC tumors, but none of the PC tumors, that distantly metastasized also metastasized to ipsilateral cervical lymph nodes (P = .00535). There was no statistically significant difference of vascular pattern between the melanomas that did and did not metastasize to lungs in the PC group (P = .24), although there was a significant difference in the AC group (P = .02). Tumors with high-grade vascular patterns were more likely to metastasize than tumors with low-grade vascular patterns in the AC group. The mean vascular density positively correlated with the presence and number of metastases in both groups (P = .0000 and P < .001, respectively). There was no statistically significant difference of vascular pattern and mean vascular density for AC versus PC melanoma (P = .97). CONCLUSIONS: The rate of metastasis in this murine intraocular melanoma model positively correlates with primary tumor vascularity. The melanoma metastasizes via invasion of tumor vascular channels. AC melanoma also

  20. Desmoplastic Melanoma: A Review

    PubMed Central

    Chen, Lucy L.; Jaimes, Natalia; Barker, Christopher A.; Busam, Klaus J.; Marghoob, Ashfaq A.

    2015-01-01

    Desmoplastic melanoma (DM) is a variant of spindle cell melanoma typically found on chronically sun-damaged skin of older individuals. Early diagnosis can be challenging because it is often amelanotic and has a predominantly dermal component. DM can be difficult to diagnose not only clinically but also histologically, and can be mistaken for a variety of benign and malignant non-melanocytic spindle cell tumors when viewed on prepared histopathology slides. Pathologists have observed that DMs can manifest significant variation with respect to the extent of intratumoral cellularity, fibrosis and/or perineural invasion. Furthermore, some tumors present with a pure desmoplastic invasive component (>90%) while other tumors display mixed features of desmoplastic and non-desmoplastic melanoma. This has lead to the separation of DM into two histologic subtypes, pure and mixed. With a focus on the distinction between pure and mixed DM, this review will detail what is currently known about the diagnostic features of DM, discuss risk and prognostic factors and examine the current literature on disease progression and management. PMID:23267722

  1. Evaluating Biomarkers in Melanoma

    PubMed Central

    Karagiannis, Panagiotis; Fittall, Matthew; Karagiannis, Sophia N.

    2015-01-01

    The incidence of cutaneous melanoma has more than doubled over the last decades making it one of the fastest rising cancers worldwide. Improved awareness and early detection of malignant moles now permit earlier diagnosis aiming to decrease the likelihood of recurrence. However, it is difficult to identify those patients initially diagnosed with localized melanoma who subsequently develop metastatic disease. For this group, prognosis remains poor and clinical outcomes are variable and challenging to predict. Considerable efforts have focused on the search for novel prognostic tools, with numerous markers evaluated in the circulation and in tumor lesions. The most reliable predictors of patient outcome are the clinical and histological features of the primary tumor such as Breslow thickness, ulceration status, and mitotic rate. Elevated serum levels of the enzyme lactate dehydrogenase, likely to indicate active metastatic disease, are also routinely used to monitor patients. The emergence of novel immune and checkpoint antibody treatments for melanoma and increasing appreciation of key roles of the immune system in promoting or halting cancer progression have focused attention to immunological biomarkers. Validation of the most promising of these may have clinical applications in assisting prognosis, assessing endpoints in therapy, and monitoring responses during treatment. PMID:25667918

  2. Principles of Melanoma Staging.

    PubMed

    Boland, Genevieve M; Gershenwald, Jeffrey E

    2016-01-01

    Although now commonplace in contemporary cancer care, the systematic approach to classification of disease-specific cancers into a formalized staging system is a relatively modern concept. Overall, the goals of cancer staging are to characterize the status of cancer at a specific moment in time, risk stratify, facilitate prognostication, and inform clinical decision making. The revisions to the American Joint Committee on Cancer (AJCC) melanoma staging system over time reflect changes in our understanding of the biology of the disease. Since the 1st edition, where tumor thickness was defined anatomically by its relationship to the reticular or papillary dermis (Clark level) as well as tumor thickness (Breslow thickness), there have been significant strides in our use of clinicopathological variables to stratify low- versus high-risk patients. Management of the regional nodal basin has also changed dramatically over time, impacted by techniques such as lymphatic mapping and sentinel lymph node biopsy (SLNB) and changes in pathological evaluation of the regional lymph nodes. Additionally, stratification of distant metastases has evolved as survival outcomes have been shown to vary based upon anatomic site of metastases and serum lactate dehydrogenase levels. The variables in use in the current (7th edition) AJCC staging system are surrogate markers of biology with validated impact of survival outcomes. Going forward, it is likely that these and additional clinicopathological factors will be integrated with molecular and other correlates of melanoma tumor biology to further refine and personalize melanoma staging. PMID:26601861

  3. Biomarkers in melanoma.

    PubMed

    Griewank, Klaus G

    2016-01-01

    Malignant melanoma remains the skin cancer with the highest number of mortalities worldwide. While early diagnosis and complete surgical excision remain the best possibility for curing disease, prognosis at the stage of metastasis is still poor. Recent years have brought about considerable advances in terms of understanding the pathogenesis of melanoma and treating advanced disease. The discovery of activating BRAF mutations in around 50% of tumors has led to the introduction of targeted therapies downregulating BRAF signaling output. These have been further refined as combination therapies, which by targeting multiple targets have further improved the clinical outcome. A comparable, potentially even superior therapeutic alternative has been the introduction of immunotherapeutic approaches, including PD-1 and CTLA-4 checkpoint blockade therapies. Despite all genetic knowledge acquired in recent years, a clearly applicable prognostic signature of clinical value has not been established. General prognostic assessment of cutaneous melanoma remains based on clinical and pathological criteria (most importantly tumor thickness). The main challenges lying ahead are to establish a reliable prognostic test effectively determining which tumors will metastasize. Additionally establishing biomarkers which will allow patients to be stratified according to the most promising systemic therapy (immunotherapies and/or BRAF inhibitor therapies) is of utmost importance for patients with metastasized disease. Identifying serum biomarkers enabling disease to be monitored as well as determining tumor properties (i.e. resistance) would also be of great value. While initial results have proven promising, there remains much work to be done. PMID:27467728

  4. Heterogeneity in Melanoma.

    PubMed

    Shannan, Batool; Perego, Michela; Somasundaram, Rajasekharan; Herlyn, Meenhard

    2016-01-01

    Melanoma is among the most aggressive and therapy-resistant human cancers. While great strides in therapy have generated enthusiasm, many challenges remain. Heterogeneity is the most pressing issue for all types of therapy. This chapter summarizes the clinical classification of melanoma, of which the research community now adds additional layers of classifications for better diagnosis and prediction of therapy response. As the search for new biomarkers increases, we expect that biomarker analyses will be essential for all clinical trials to better select patient populations for optimal therapy. While individualized therapy that is based on extensive biomarker analyses is an option, we expect in the future genetic and biologic biomarkers will allow grouping of melanomas in such a way that we can predict therapy outcome. At this time, tumor heterogeneity continues to be the major challenge leading inevitably to relapse. To address heterogeneity therapeutically, we need to develop complex therapies that eliminate the bulk of the tumor and, at the same time, the critical subpopulations. PMID:26601857

  5. Adjuvant Therapy: Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad; Kirkwood, John M.

    2011-01-01

    With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway. PMID:22220281

  6. Adjuvant Therapy for Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad A.

    2012-01-01

    Estimates from the U.S. Surveillance, Epidemiology, and End Results (SEER) registry suggest that melanoma incidence will reach 70,230 in 2011, of which 8,790 will die. The rising incidence and predilection for young individuals makes this tumor a leading source of lost productive years in the society. High-dose interferon-α2b is the only agent approved for adjuvant therapy of melanoma; the improvement in relapse-free survival has been observed across nearly all published studies and meta-analyses. However toxicity affects compliance and current research is focusing upon biomarkers that may allow selection of patients with greater likelihood of response, and exploring new agents either singly or in combination that may improve upon the benefit of IFN. In this article, we review the data for the adjuvant therapy of malignant melanoma - focusing on the results obtained with various regimens testing the several formulations of interferon-α2, and the adjuvant studies of vaccines and radiotherapy. Recent advances in the treatment of metastatic disease have established a role for CTLA-4 blockade and BRAF-inhibition, and raising hopes that these agents may have a role in the adjuvant setting. At present, several trials investigating combinations of novel agents with existing immunomodulators are underway. PMID:22453021

  7. Malignant uveal schwannoma with peripheral nerve extension in a 12-week-old color-dilute Labrador Retriever.

    PubMed

    Duke, F D; Teixeira, L B C; Galle, L E; Green, N; Dubielzig, R R

    2015-01-01

    The formalin-fixed, amber-colored right globe from a 12-week-old female silver Labrador Retriever dog was submitted to the Comparative Ocular Pathology Laboratory of Wisconsin for light microscopic evaluation. The clinical history described a collapsed anterior chamber and multifocal nodular lesions in the peripheral iris. Histologically, immunohistochemically, and ultrastructurally, the uveal mass was consistent with a malignant schwannoma; there was extension along peripheral nerves within the sclera. The signalment and behavior of the neoplasm distinguish it from the uveal schwannoma of blue-eyed dogs and bear some resemblance to the ocular lesions in human neurofibromatosis. The dilute color mutation may contribute to the cause. Six weeks later, the dog did not develop any additional masses. PMID:24513800

  8. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    SciTech Connect

    Ungerer, Christopher; Doberstein, Kai; Boehm, Beate; Pfeilschifter, Josef; Mihic-Probst, Daniela; Gutwein, Paul

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  9. Novel posterior fixation keratoprosthesis

    NASA Astrophysics Data System (ADS)

    Lacombe, Emmanuel

    1992-08-01

    The keratoprosthesis is the last solution for corneally blind patients that cannot benefit from corneal transplants. Keratoprostheses that have been designed to be affixed anteriorly usually necessitate multi-step surgical procedures and are continuously subjected to the extrusion forces generated by the positive intraocular pressure; therefore, clinical results in patients prove inconsistent. We proposed a novel keratoprosthesis concept that utilizes posterior corneal fixation which `a priori' minimizes the risk of aqueous leakage and expulsion. This prosthesis is implanted in a single procedure thereby reducing the number of surgical complications normally associated with anterior fixation devices. In addition, its novel design makes this keratoprosthesis implantable in phakic eyes. With an average follow-up of 13 months (range 3 to 25 months), our results on 21 cases are encouraging. Half of the keratoprostheses were implanted in severe burn cases, with the remainder in cases of pseudo- pemphigus. Good visual results and cosmetic appearance were obtained in 14 of 21 eyes.

  10. Malignant Melanoma of the Foot

    MedlinePlus

    ... If a biopsy is performed and it reveals melanoma, the surgeon will discuss a treatment plan. Prevention and Early Detection Everyone should practice strategies that can help prevent melanoma—or at least aid in early detection, so ... treatment can be undertaken. Precautions to avoid getting melanoma ...

  11. Immunobiology of primary murine melanomas.

    PubMed

    Donawho, C; Evans, R; Kripke, M L

    1992-10-01

    Primary cutaneous melanomas can be induced in inbred mice by applying a dose of dimethylbenz[a]anthracene to the skin of 4-day-old mice, and then applying repeated doses of a tumor promoter to the same site over a long period of time. Preliminary experiments suggest that the final incidence of melanomas is strongly influenced by the age at which the initiating dose of carcinogen is applied. Melanomas induced by this method in C3H mice are immunogenic and exhibit a high degree of cross-reactivity when tested by immunization and challenge in vivo. Exposing the mice to ultraviolet (UV) radiation during carcinogenesis dramatically accelerates the appearance of melanoma. We are attempting to determine how UV radiation potentiates melanoma induction by studying the growth of melanoma cells transplanted into UV-irradiated skin. Our studies suggest that UV irradiation accelerates the outgrowth of melanoma cells by means of a local, immunosuppressive effect on the skin. However, this effect is distinct from the ability of UV irradiation to alter epidermal Langerhans cells and interfere with the induction of contact hypersensitivity responses. We postulate that UV irradiation augments melanoma development by interfering with the efferent arm of the immune response in the UV-irradiated site. PMID:1445809

  12. Keeping a watch on melanoma.

    PubMed

    Casparian, J Michael; Rodewald, Erin J

    2002-05-01

    When performing a total body skin examination, we discovered a melanoma in situ when a patient took off her wristwatch. This case illustrates the importance of removing jewelry when performing a complete skin examination. Furthermore, the location of this lesion highlights the association between malignant melanoma and intermittent sun exposure. PMID:12041820

  13. Primary Desmoplastic Melanoma of the Penis.

    PubMed

    Chu, Julia T; Liss, Michael A; Wu, William W; Dash, Atreya; Lu, Di

    2015-01-01

    Desmoplastic melanomas are rare amelanotic melanomas that usually occur on skin with sun exposure. In this report, we present a 72-year-old man who presented with a desmoplastic melanoma of the penis. To our knowledge this represents the first reported case of primary desmoplastic melanoma of the penis. We discuss the pathologic differential and histologic evaluation. PMID:26613063

  14. Primary Desmoplastic Melanoma of the Penis

    PubMed Central

    Chu, Julia T.; Liss, Michael A.; Wu, William W.; Dash, Atreya; Lu, Di

    2015-01-01

    Desmoplastic melanomas are rare amelanotic melanomas that usually occur on skin with sun exposure. In this report, we present a 72-year-old man who presented with a desmoplastic melanoma of the penis. To our knowledge this represents the first reported case of primary desmoplastic melanoma of the penis. We discuss the pathologic differential and histologic evaluation. PMID:26613063

  15. Ric-8A gene deletion or phorbol ester suppresses tumorigenesis in a mouse model of GNAQ(Q209L)-driven melanoma.

    PubMed

    Patel, B R; Tall, G G

    2016-01-01

    The heterotrimeric G protein α subunit oncogenes GNAQ or GNA11 carry Q209X or R183X activating mutations and are present with ~90% frequency in human uveal melanomas. Forced expression of GNAQ/11(Q209L) in melanocytes is sufficient to drive metastatic melanoma in immune-compromised mice. No known drugs directly target these oncogenic G proteins. Ric-8A is the molecular chaperone that selectively folds Gαq/i/13 subunits. Targeting Ric-8A serves as a rational, yet unexplored approach to reduce the functional abundance of oncogenic Gαq/11 in order to blunt cancer signaling. Here, using mouse melanocyte cell graft tumorigenesis models, we determined that Ric-8A genetic ablation attenuated the abundance and melanoma-driving potential of Gαq-Q209L. A new conditional Ric-8A(Flox/Flox); Rosa-CreER(+/)(-) mouse strain was derived and used as a tissue source to culture an immortalized, tamoxifen-inducible Ric-8A knockout melanocyte cell line that required 12-O-tetradecanoylphorbol-13-acetate (TPA, phorbol ester) for growth. The cell line failed to grow tumors when grafted into immune-compromised mice regardless of Ric-8A expression. Stable expression of human GNAQ(Q209L), but not GNAQ(WT) in the cell line promoted TPA-independent cell proliferation, and upon cell grafting in mice, the initiation and robust growth of darkly-pigmented melanoma tumors. Deletion of Ric-8A in GNAQ(Q209L) cells restored TPA-dependent growth, reduced Gαq-Q209L below detectable levels and completely mitigated tumorigenesis from primary or secondary cell line grafts. Interestingly, TPA treatment of cultured GNAQ(Q209L) cells or host animals grafted with GNAQ(Q209L) cells also sharply reduced Gαq-Q209L abundance and tumorigenic capacity. Finally, tumorigenesis initiated from GNAQ(Q209L) cell grafts, followed by host mouse systemic tamoxifen treatment to delete Ric-8A in the grafted cells completely abrogated GNAQ(Q209L)-driven tumor progression unless a stable human RIC-8A transgene was used to

  16. Ric-8A gene deletion or phorbol ester suppresses tumorigenesis in a mouse model of GNAQQ209L-driven melanoma

    PubMed Central

    Patel, B R; Tall, G G

    2016-01-01

    The heterotrimeric G protein α subunit oncogenes GNAQ or GNA11 carry Q209X or R183X activating mutations and are present with ~90% frequency in human uveal melanomas. Forced expression of GNAQ/11Q209L in melanocytes is sufficient to drive metastatic melanoma in immune-compromised mice. No known drugs directly target these oncogenic G proteins. Ric-8A is the molecular chaperone that selectively folds Gαq/i/13 subunits. Targeting Ric-8A serves as a rational, yet unexplored approach to reduce the functional abundance of oncogenic Gαq/11 in order to blunt cancer signaling. Here, using mouse melanocyte cell graft tumorigenesis models, we determined that Ric-8A genetic ablation attenuated the abundance and melanoma-driving potential of Gαq-Q209L. A new conditional Ric-8AFlox/Flox; Rosa-CreER+/− mouse strain was derived and used as a tissue source to culture an immortalized, tamoxifen-inducible Ric-8A knockout melanocyte cell line that required 12-O-tetradecanoylphorbol-13-acetate (TPA, phorbol ester) for growth. The cell line failed to grow tumors when grafted into immune-compromised mice regardless of Ric-8A expression. Stable expression of human GNAQQ209L, but not GNAQWT in the cell line promoted TPA-independent cell proliferation, and upon cell grafting in mice, the initiation and robust growth of darkly-pigmented melanoma tumors. Deletion of Ric-8A in GNAQQ209L cells restored TPA-dependent growth, reduced Gαq-Q209L below detectable levels and completely mitigated tumorigenesis from primary or secondary cell line grafts. Interestingly, TPA treatment of cultured GNAQQ209L cells or host animals grafted with GNAQQ209L cells also sharply reduced Gαq-Q209L abundance and tumorigenic capacity. Finally, tumorigenesis initiated from GNAQQ209L cell grafts, followed by host mouse systemic tamoxifen treatment to delete Ric-8A in the grafted cells completely abrogated GNAQQ209L-driven tumor progression unless a stable human RIC-8A transgene was used to rescue the floxed

  17. Oral Amelanotic Melanoma of the Maxilla

    PubMed Central

    Saghravanian, Nasrollah; Pazouki, Mahdi; Zamanzadeh, Maryam

    2014-01-01

    Amelanotic melanoma is a variant of malignant melanoma comprising 2% to 8% of all malignant melanomas. The amelanotic presentation of melanoma in the oral cavity is extremely rare and has been reported only occasionally in the literature. Moreover, the lack of melanin makes these tumors difficult to diagnose than that of pigmented lesions and the prognosis tends to be poorer. Herein, we report an amelanotic melanoma involving the oral mucosa of the maxilla in a 27 year-old male. PMID:25628704

  18. Recurrent inactivating RASA2 mutations in melanoma

    PubMed Central

    Arafeh, Rand; Qutob, Nouar; Emmanuel, Rafi; Keren-Paz, Alona; Madore, Jason; Elkahloun, Abdel; Wilmott, James S.; Gartner, Jared J.; Di Pizio, Antonella; Winograd-Katz, Sabina; Sindiri, Sivasish; Rotkopf, Ron; Dutton-Regester, Ken; Johansson, Peter; Pritchard, Antonia; Waddell, Nicola; Hill, Victoria K.; Lin, Jimmy C.; Hevroni, Yael; Rosenberg, Steven A.; Khan, Javed; Ben-Dor, Shifra; Niv, Masha Y.; Ulitsky, Igor; Mann, Graham J; Scolyer, Richard A.; Hayward, Nicholas K.; Samuels, Yardena

    2016-01-01

    Analysis of 501 melanoma exomes revealed RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas. Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration. RASA2 expression was lost in ≥30% of human melanomas and was associated with reduced patient survival. These findings reveal RASA2 inactivation as a melanoma driver and highlight the importance of Ras GAPs in cancer. PMID:26502337

  19. Proteomic Findings in Melanoma

    PubMed Central

    Sengupta, Deepanwita; Tackett, Alan J

    2016-01-01

    Although the emergence of proteomics as an independent branch of science is fairly recent, within a short period of time it has contributed substantially in various disciplines. The tool of mass spectrometry has become indispensable in the analysis of complex biological samples. Clinical applications of proteomics include detection of predictive and diagnostic markers, understanding mechanism of action of drugs as well as resistance mechanisms against them and assessment of therapeutic efficacy and toxicity of drugs in patients. Here, we have summarized the major contributions of proteomics towards the study of melanoma, which is a deadly variety of skin cancer with a high mortality rate. PMID:27274624

  20. Xenovaccinotherapy for melanoma.

    PubMed

    Seledtsov, Victor I; Shishkov, Alexey A; Surovtseva, Mariya A; Samarin, Denis M; Seledtsova, Galina V; Niza, Natalya A; Seledtsov, Dmitriy V

    2006-01-01

    The objectives of this phase I-II trial were to assess the toxicity, immunological and clinical responses induced in stage III/IV melanoma patients by the subcutaneous administration of xenogenic polyantigenic vaccine (XPV) prepared from disrupted murine melanoma (B16) and carcinoma (LLC) cells. An inducing course of vaccinotherapy consisted of ten immunizations (five at weekly and five at fortnight intervals). Twenty-four hours following each of the first five vaccinations, the patient was subcutaneously given a low dose of the recombinant interleukin-2 (IL-2). A consolidating course of the vaccinotherapy consisted of monthly vaccinations. Grade 3 or 4 toxicities, as well as laboratory and clinical signs of developing autoimmune disorders, were recorded in none of the 40 XPV-treated evaluable patients. A significant increase in delayed-type hypersensitivity (DTH) skin reaction to vaccinal B16, but not to LLC antigens (Ags), occurred in patients after inducing vaccinations. At the same time, those patients demonstrated a marked augmentation of blood lymphocyte proliferation responses not only to B16 but also to LLC Ags. Vaccinations also led to increased cell-mediated reactivity to murine non-tumor, spleen cell (SC)-associated Ags, which, however, was not as significant as that to tumor-associated antigens (TAAs). Of great importance was the fact that XPV administration resulted in increased blood lymphocyte proliferative reactivity of patients to human melanoma-associated Ags, while not affecting their reactivity to the control alloantigens. With immunotherapy, concentrations of both interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were elevated in patients' sera, suggesting an intensification of the T helper1/ T helper 2-mediated responses in the XPV-treated patients. The average survival of the 32 stage IV melanoma XPV-treated evaluable patients was noticeably higher than that of the 32 clinically comparable control patients (13 vs. 5 months). The overall 3

  1. Gossypiboma mimicking posterior urethral stricture

    PubMed Central

    Kumar, Bindey; Kumar, Prem; Sinha, Sanjay Kumar; Sinha, Neelam; Hasan, Zaheer; Thakur, Vinit Kumar; Anand, Utpal; Priyadarshi, Rajiv Nayan; Mandal, Manish

    2013-01-01

    INTRODUCTION Foreign bodies in the urogenital tract are not uncommon. Hairpins, glass rods, umbilical tapes, ball point pen are described in lower urogenital tract. Retained gauze piece (gossypiboma) in posterior urethra may cause diagnostic dilemma. Symptoms and investigations may mimic stricture of posterior urethra. PRESENTATION OF CASE Two cases of retained gauze pieces in the urethra are described here. The micturating cystourethrogram was suggestive of posterior urethral stricture. DISCUSSION Two cases described here had retained gauze piece as a cause of filling defect and abnormal appearance in the micturating cystourethrogram. Gossypiboma may be a possibility where posterior urethral stricture are seen after previous surgery in paediatric age group. CONCLUSION In the setting of previous urogenital surgery gossypiboma should be kept in the differential diagnosis where posterior urethral stricture are seen in the paediatric age group. PMID:23500749

  2. [Posterior reversible encephalopathy syndrome].

    PubMed

    Fischer, M; Schmutzhard, E

    2016-06-01

    Posterior reversible encephalopathy syndrome refers to a neurological disorder characterized by headache, disorders of consciousness, visual disturbances, epileptic seizures, and subcortical vasogenic edema. About two thirds of patients develop neurological symptoms, which are associated with blood pressure fluctuations. One hypothesis is that hypertensive episodes cause autoregulatory failure, and values above the upper limit of cerebral autoregulation result in a breakthrough followed by hyperperfusion and blood-brain barrier dysfunction. In another hypothesis, endothelial dysfunction triggered by numerous factors including preeclampsia, immunosuppressive agents, chemotherapeutics, sepsis, or autoimmune disorders is thought to be the key pathomechanism. Endo- or exogenic toxic agents including pharmacological substances, cytokines, or bacterial toxins are supposed to trigger endothelial activation and dysfunction resulting in the release of vasoconstrictors, pro-inflammatory mediators, and vascular leakage. Diagnosis is usually based on clinical and neuroimaging findings that frequently show a bilateral, symmetric, and parietooccipital pattern. However, the diagnosis can often only be confirmed during the course of disease after excluding important differential diagnoses. Currently, there is no specific treatment available. Lowering of arterial blood pressure and eliminating the underlying cause usually leads to an improvement of clinical and neuroradiological findings. Admission to a critical care unit is required in about 40 % of patients due to complicating conditions including status epilepticus, cerebral vasoconstriction, ischemia, or intracerebral hemorrhage. Prognosis is favorable; in the majority of patients neurological deficits and imaging findings resolve completely. PMID:27272329

  3. Melanoma immunotherapy dominates the field.

    PubMed

    Diamantopoulos, Panagiotis; Gogas, Helen

    2016-07-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:27563656

  4. Melanoma immunotherapy dominates the field

    PubMed Central

    Diamantopoulos, Panagiotis

    2016-01-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:27563656

  5. Targeted Radionuclide Therapy of Melanoma.

    PubMed

    Norain, Abdullah; Dadachova, Ekaterina

    2016-05-01

    An estimated 60,000 individuals in the United States and 132,000 worldwide are yearly diagnosed with melanoma. Until recently, treatment options for patients with stages III-IV metastatic disease were limited and offered marginal, if any, improvement in overall survival. The situation changed with the introduction of B-RAF inhibitors and anti-cytotoxic T-lymphocyte antigen 4 and anti-programmed cell death protein 1 immunotherapies into the clinical practice. With only some patients responding well to the immune therapies and with very serious side effects and high costs of immunotherapy, there is still room for other approaches for the treatment of metastatic melanoma. Targeted radionuclide therapy of melanoma could be divided into the domains of radioimmunotherapy (RIT), radiolabeled peptides, and radiolabeled small molecules. RIT of melanoma is currently experiencing a renaissance with the clinical trials of alpha-emitter (213)Bi-labeled and beta-emitter (188)Rhenium-labeled monoclonal antibodies in patients with metastatic melanoma producing encouraging results. The investigation of the mechanism of efficacy of melanoma RIT points at killing of melanoma stem cells by RIT and involvement of immune system such as complement-dependent cytotoxicity. The domain of radiolabeled peptides for targeted melanoma therapy has been preclinical so far, with work concentrated on radiolabeled peptide analogues of melanocyte-stimulating hormone receptor and on melanin-binding peptides. The field of radiolabeled small molecule produced radioiodinated benzamides that cross the cellular membrane and bind to the intracellular melanin. The recent clinical trial demonstrated measurable antitumor effects and no acute or midterm toxicities. We are hopeful that the targeted radionuclide therapy of metastatic melanoma would become a clinical reality as a stand-alone therapy or in combination with the immunotherapies such as anti-PD1 programmed cell death protein 1 monoclonal antibodies

  6. Simulants of Malignant Melanoma

    PubMed Central

    Piérard-Franchimont, Claudine; Delvenne, Philippe

    2015-01-01

    During the recent period, dermoscopy has yielded improvement in the early disclosure of various atypical melanocytic neoplasms (AMN) of the skin. Beyond this clinical procedure, AMN histopathology remains mandatory for establishing their precise diagnosis. Of note, panels of experts in AMN merely report moderate agreement in various puzzling cases. Divergences in opinion and misdiagnosis are likely increased when histopathological criteria are not fine-tuned and when facing a diversity of AMN types. Furthermore, some AMN have been differently named in the literature including atypical Spitz tumor, metastasizing Spitz tumor, borderline and intermediate melanocytic tumor, malignant Spitz nevus, pigmented epithelioid melanocytoma or animal-type melanoma. Some acronyms have been further suggested such as MELTUMP (after melanocytic tumor of uncertain malignant potential) and STUMP (after Spitzoid melanocytic tumor of uncertain malignant potential). In this review, such AMN at the exclusion of cutaneous malignant melanoma (MM) variants, are grouped under the tentative broad heading skin melanocytoma. Such set of AMN frequently follows an indolent course, although they exhibit atypical and sometimes worrisome patterns or cytological atypia. Rare cases of skin melanocytomas progress to loco regional clusters of lesions (agminate melanocytomas), and even to regional lymph nodes. At times, the distinction between a skin melanocytoma and MM remains puzzling. However, multipronged immunohistochemistry and emerging molecular biology help profiling any malignancy risk if present. PMID:26779311

  7. Morphogenesis of early stage melanoma

    NASA Astrophysics Data System (ADS)

    Chatelain, Clément; Amar, Martine Ben

    2015-08-01

    Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

  8. What's New in Research and Treatment of Melanoma Skin Cancer?

    MedlinePlus

    ... Topic Additional resources for melanoma skin cancer What’s new in melanoma skin cancer research? Research into the ... Melanoma Talking With Your Doctor After Treatment What`s New in Skin Cancer - Melanoma Research? Other Resources and ...

  9. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients

    PubMed Central

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H.T.; Aarntzen, Erik H.J.G.; Schreibelt, Gerty; Creemers, Jeroen H.A.; Punt, Cornelis J.A.; Figdor, Carl G.; Gerritsen, Winald R.; Bol, Kalijn F.

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8+ T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  10. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients.

    PubMed

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H T; Aarntzen, Erik H J G; Schreibelt, Gerty; Creemers, Jeroen H A; Punt, Cornelis J A; Figdor, Carl G; de Vries, I Jolanda M; Gerritsen, Winald R; Bol, Kalijn F

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8 T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  11. What Does Melanoma Look Like?

    MedlinePlus

    ... that begins in melanocytes ( cells that make the pigment melanin ). Below are photos of melanoma that formed ... often ragged, notched, or blurred in outline. The pigment may spread into the surrounding skin. Color that ...

  12. A Case of Uveal Colobomas Showing Marked Left-Right Difference in Diabetic Retinopathy

    PubMed Central

    Moriya, Takeshi; Ochi, Ryosuke; Imagawa, Yukihiro; Sato, Bumpei; Morishita, Seita; Tonari, Masahiro; Fukumoto, Masanori; Suzuki, Hiroyuki; Kobayashi, Takatoshi; Kida, Teruyo; Ikeda, Tsunehiko

    2016-01-01

    Purpose Congenital uveal colobomas, including inferior iris and choroidal colobomas, are associated with microcornea and microphthalmia and often show left-right differences (laterality). The purpose of this study was to report a case of choroidal coloboma associated with left-right differences in diabetic retinopathy (DR). Case This study reports a 59-year-old male with bilateral iris and choroidal colobomas. The colobomatous area in the patient's right eye extended to the macula, and his right eye had been amblyopic since birth. The colobomatous area in his left eye was less extensive and did not involve the macula. Examination of the patient's left eye revealed multiple hemorrhages and hard exudates in the macula due to DR, but examination of his right eye showed almost no changes in DR, thus revealing a marked left-right difference. Optical coherence tomography showed more extensive retinal thinning in the patient's right eye than in his left eye. Fluorescein fundus angiography revealed a retinal nonperfusion area only in the left eye, and panretinal photocoagulation was subsequently performed. Conclusion Our findings show that the reason for the left-right difference in DR was attributed to the more severe choroidal coloboma and retinal thinning in the patient's right eye compared to his left eye, thus reducing oxygen demand, as is also seen in eyes with severe myopia. PMID:27099608

  13. Melanoma Cell Colony Expansion Parameters Revealed by Approximate Bayesian Computation

    PubMed Central

    Vo, Brenda N.; Drovandi, Christopher C.; Pettitt, Anthony N.; Pettet, Graeme J.

    2015-01-01

    In vitro studies and mathematical models are now being widely used to study the underlying mechanisms driving the expansion of cell colonies. This can improve our understanding of cancer formation and progression. Although much progress has been made in terms of developing and analysing mathematical models, far less progress has been made in terms of understanding how to estimate model parameters using experimental in vitro image-based data. To address this issue, a new approximate Bayesian computation (ABC) algorithm is proposed to estimate key parameters governing the expansion of melanoma cell (MM127) colonies, including cell diffusivity, D, cell proliferation rate, λ, and cell-to-cell adhesion, q, in two experimental scenarios, namely with and without a chemical treatment to suppress cell proliferation. Even when little prior biological knowledge about the parameters is assumed, all parameters are precisely inferred with a small posterior coefficient of variation, approximately 2–12%. The ABC analyses reveal that the posterior distributions of D and q depend on the experimental elapsed time, whereas the posterior distribution of λ does not. The posterior mean values of D and q are in the ranges 226–268 µm2h−1, 311–351 µm2h−1 and 0.23–0.39, 0.32–0.61 for the experimental periods of 0–24 h and 24–48 h, respectively. Furthermore, we found that the posterior distribution of q also depends on the initial cell density, whereas the posterior distributions of D and λ do not. The ABC approach also enables information from the two experiments to be combined, resulting in greater precision for all estimates of D and λ. PMID:26642072

  14. Melanoma Cell Colony Expansion Parameters Revealed by Approximate Bayesian Computation.

    PubMed

    Vo, Brenda N; Drovandi, Christopher C; Pettitt, Anthony N; Pettet, Graeme J

    2015-12-01

    In vitro studies and mathematical models are now being widely used to study the underlying mechanisms driving the expansion of cell colonies. This can improve our understanding of cancer formation and progression. Although much progress has been made in terms of developing and analysing mathematical models, far less progress has been made in terms of understanding how to estimate model parameters using experimental in vitro image-based data. To address this issue, a new approximate Bayesian computation (ABC) algorithm is proposed to estimate key parameters governing the expansion of melanoma cell (MM127) colonies, including cell diffusivity, D, cell proliferation rate, λ, and cell-to-cell adhesion, q, in two experimental scenarios, namely with and without a chemical treatment to suppress cell proliferation. Even when little prior biological knowledge about the parameters is assumed, all parameters are precisely inferred with a small posterior coefficient of variation, approximately 2-12%. The ABC analyses reveal that the posterior distributions of D and q depend on the experimental elapsed time, whereas the posterior distribution of λ does not. The posterior mean values of D and q are in the ranges 226-268 µm2h-1, 311-351 µm2h-1 and 0.23-0.39, 0.32-0.61 for the experimental periods of 0-24 h and 24-48 h, respectively. Furthermore, we found that the posterior distribution of q also depends on the initial cell density, whereas the posterior distributions of D and λ do not. The ABC approach also enables information from the two experiments to be combined, resulting in greater precision for all estimates of D and λ. PMID:26642072

  15. Diagnostic Challenge of Desmoplastic Melanoma.

    PubMed

    Andreevscaia, Olga; Theate, Ivan; Goossens, Cathy; Vanhooteghem, Olivier

    2016-03-21

    Desmoplastic melanoma (DM) is a rare variant of spindle-cell malignant melanoma. DM is easily misdiagnosed at an early stage because it can be confused with benign entities. Histological analysis, including careful attention to the presence of atypical spindle cells, as well as to lymphocytic aggregates in an abundant fibrotic stroma in the dermis, provides clues for diagnosis. The adjunction of an immunohistochemical panel, and particularly testing for S-100 protein, is needed for the final diagnosis. PMID:27134705

  16. Diagnostic Challenge of Desmoplastic Melanoma

    PubMed Central

    Andreevscaia, Olga; Theate, Ivan; Goossens, Cathy; Vanhooteghem, Olivier

    2016-01-01

    Desmoplastic melanoma (DM) is a rare variant of spindle-cell malignant melanoma. DM is easily misdiagnosed at an early stage because it can be confused with benign entities. Histological analysis, including careful attention to the presence of atypical spindle cells, as well as to lymphocytic aggregates in an abundant fibrotic stroma in the dermis, provides clues for diagnosis. The adjunction of an immunohistochemical panel, and particularly testing for S-100 protein, is needed for the final diagnosis. PMID:27134705

  17. Delay in cutaneous melanoma diagnosis

    PubMed Central

    Xavier, Marcus H.S.B.; Drummond-Lage, Ana P.; Baeta, Cyntia; Rocha, Lorena; Almeida, Alessandra M.; Wainstein, Alberto J.A.

    2016-01-01

    Abstract Advanced melanoma is an incurable disease with complex and expensive treatments. The best approach to prevent melanoma at advanced stages is an early diagnosis. A knowledge of factors associated with the process of detecting cutaneous melanomas and the reasons for delays in diagnosis is essential for the improvement of the secondary prevention of the disease. Identify sociodemographic, individual, and medical aspects related to cutaneous melanoma diagnosis delay. Interviews evaluated the knowledge of melanoma, signals, symptoms, persons who were suspected, delays in seeking medical attention, physician's deferrals, and related factors of 211 patients. Melanomas were self-discovered in 41.7% of the patients; healthcare providers detected 29.9% of patients and others detected 27%. The main component in delay was patient-related. Only 31.3% of the patients knew that melanoma was a serious skin cancer, and most thought that the pigmented lesion was not important, causing a delay in seeking medical assistance. Patients (36.4%) reported a wait interval of more than 6 months from the onset of an observed change in a pigmented lesion to the first visit to a physician. The delay interval from the first physician visit to a histopathological diagnosis was shorter (<1 month) in 55.5% of patients. Improper treatments without a histopathological confirmation occurred in 14.7% of patients. A professional delay was related to both inappropriate treatments performed without histopathological confirmation (P = 0.003) and long requirements for medical referrals (P < 0.001). A deficient knowledge in the population regarding melanoma and physicians’ misdiagnoses regarding suspicious lesions contributed to delays in diagnosis. PMID:27495055

  18. An unusual case of desmoplastic malignant melanoma.

    PubMed

    Javabal, Pandiaraja; Subramanian, Viswanathan

    2015-01-01

    Desmoplastic malignant melanoma is a rare variant of spindle cell melanoma, commonly seen in older adults, on sun-exposed areas. It accounts for 1-4% of all cases of cutaneous melanoma. The common location of the desmoplastic melanoma is the head and neck region, whereas, other sites are less common. Regional lymph node involvement is reported in 0 to 13.7% of the cases, which is less frequent than other cutaneous melanomas. A 75-year-old male presented with an ulceroproliferative growth on the left foot that was diagnosed as desmoplastic melanoma with regional lymph node metastasis and in transit metastasis, with extensive pulmonary metastasis. PMID:25949027

  19. Aldesleukin and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

    ClinicalTrials.gov

    2016-04-21

    Metastatic Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck

  20. Tool to Distinguish Moles from Melanoma

    Cancer.gov

    “Moles to Melanoma: Recognizing the ABCDE Features” presents photos that show changes in individual pigmented lesions over time, and describes the different appearances of moles, dysplastic nevi, and melanomas.

  1. Modeling Melanoma In Vitro and In Vivo

    PubMed Central

    Beaumont, Kimberley A.; Mohana-Kumaran, Nethia; Haass, Nikolas K.

    2013-01-01

    The behavior of melanoma cells has traditionally been studied in vitro in two-dimensional cell culture with cells adhering to plastic dishes. However, in order to mimic the three-dimensional architecture of a melanoma, as well as its interactions with the tumor microenvironment, there has been the need for more physiologically relevant models. This has been achieved by designing 3D in vitro models of melanoma, such as melanoma spheroids embedded in extracellular matrix or organotypic skin reconstructs. In vivo melanoma models have typically relied on the growth of tumor xenografts in immunocompromised mice. Several genetically engineered mouse models have now been developed which allow the generation of spontaneous melanoma. Melanoma models have also been established in other species such as zebrafish, which are more conducive to imaging and high throughput studies. We will discuss these models as well as novel techniques that are relevant to the study of the molecular mechanisms underlying melanoma progression.

  2. Molecular probes for malignant melanoma imaging.

    PubMed

    Ren, Gang; Pan, Ying; Cheng, Zhen

    2010-09-01

    Malignant melanoma represents a serious public health problem and is a deadly disease when it is diagnosed at late stage. Though (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) has been widely used clinically for melanoma imaging, other approaches to specifically identify, characterize, monitor and guide therapeutics for malignant melanoma are still needed. Consequently, many probes targeting general molecular events including metabolism, angiogenesis, hypoxia and apoptosis in melanoma have been successfully developed. Furthermore, probes targeting melanoma associated targets such as melanocortin receptor 1 (MC1R), melanin, etc. have undergone active investigation and have demonstrated high melanoma specificity. In this review, these molecular probes targeting diverse melanoma biomarkers have been summarized. Some of them may eventually contribute to the improvement of personalized management of malignant melanoma. PMID:20497118

  3. Melanoma Cancer Stem Cells: Markers and Functions

    PubMed Central

    Parmiani, Giorgio

    2016-01-01

    The discovery of cancer stem cells (CSCs) in human solid tumors has allowed a better understanding of the biology and neoplastic transformation of normal melanocytes, and the possible mechanisms by which melanoma cells acquire tumorigenicity. In this review I summarize the literature findings on the potential biomarkers of melanoma CSCs, their presence in the melanoma cell populations, the interaction with the immune system (with both T and NK cells) and the role of melanoma CSCs in the clinics. Given the extraordinary progress in the therapy of melanoma caused by immune checkpoint antibodies blockade, I discuss how these antibodies can work by the activation of melanoma infiltrating T cells specifically recognizing neo-antigens expressed even by melanoma CSCs. This is the mechanism that can induce a regression of the metastatic melanomas. PMID:26978405

  4. When narrative medicine helps in the diagnosis of conjunctival melanoma – an exceptional case report

    PubMed Central

    Nunes, Ana Teresa; Almeida, Leonor; Crujo, Conceição; Monteiro-Grillo, Manuel

    2012-01-01

    Introduction: Conjunctival melanoma is a relatively rare ocular malignancy with substantial associated morbidity and mortality. It can arise in previously unblemished and unpigmented regions (approximately 10% of cases), from a preexisting nevus (approximately 20% of cases), or from the flat, spreading pigmentation of primary acquired melanosis with atypia (60–70% of cases), actually called conjunctival melanocytic intraepithelial neoplasia (C-MIN) with atypia (histopathologically more accurately term). Purpose: The authors describe an extremely rare case of malignant conjunctival melanoma, with a long evolution, in a young black woman. Results: Until now the patient has not shown any sign of relapse of this melanoma, after local excision. Conclusion: Conjunctival melanoma is a condition of concern because of its rarity and lethal potential. Advances in the understanding and management of this neoplasm have markedly reduced the mortality and possibly the morbidity associated with this malignancy. We observe that there are some cases of conjunctival melanoma that might be cured with only a local excision with posterior cryotherapy without more aggressive methods. The practice of narrative medicine brings new possibilities in the diagnosis and collection of classical history.

  5. Features of Cutaneous Malignant Melanoma Metastatic to the Retina and Vitreous

    PubMed Central

    Breazzano, Mark P.; Barker-Griffith, Ann E.

    2015-01-01

    Background/Aims To report a case of cutaneous malignant melanoma with cerebral metastasis found to have vitreoretinal metastasis upon referral for neovascular glaucoma. Methods The clinical history and ocular examination findings, including histologic, cytologic, genetic, and immunohistochemical features of the vitreoretinal metastatic tumor, were reviewed. Additionally, the histologic and immunohistochemical features of the primary skin tumor and brain metastasis were also assessed. Results A 62-year-old woman with cutaneous malignant melanoma metastatic to the right frontal lobe (BRAF V600E negative) was evaluated for blurred vision in the right eye. Neovascular glaucoma, iritis, and posterior synechiae with no view of the retina or vitreous were evident on examination. Vitreoretinal biopsy and enucleation specimen both showed widespread neoplastic involvement of the retina and residual vitreous strands after vitrectomy. Choroid, trabeculum, and other intraocular structures were devoid of tumor burden. Diagnosis of cutaneous malignant melanoma metastatic to the retina and vitreous was confirmed, and the patient expired shortly thereafter. Conclusion Cutaneous malignant melanoma metastatic to the eye has a relatively greater preference for the retina and frequently presents with uveitis and glaucoma. Neovascular glaucoma in these cases may likely be attributable to unusually increased vascular endothelial growth factor production by the intraocular melanoma tumor cells. PMID:27172390

  6. Photoprotection and prevention of melanoma.

    PubMed

    Marks, R

    1999-01-01

    This article summarizes the current position on primary prevention of melanoma, including what is the evidence relating sunlight exposure to the development of melanoma, what forms of photoprotection there are and what are their relative values. There have been increasing incidence and mortality rates due to melanoma in most countries where they are being recorded. The initial approach in many countries has been to develop some form of early detection program in an attempt to diagnose and treat at a curable stage the melanomas that are occurring now. Primary prevention of melanoma is the more long term approach to the problem which many countries are now considering and a number are actively pursuing. Recent concern about stratospheric ozone depletion has contributed to the desire for the primary prevention approach. There are epidemiological data associating the risk of melanoma with increased exposure to sunlight in people with fair skin. They show that it is sunlight exposure in childhood and in doses sufficient to cause sunburn remembered many years later, that is particularly associated with risk of melanoma in adulthood. The exact spectrum of radiation in sunlight which is responsible for these tumours is not known, although the ultraviolet range is believed to be most important, particularly UVB but probably also UVA. The approach to photoprotection is a reduction in the overall exposure to sunlight, not just a single component of it. The natural protection of shade, clothing and hats is promoted as the best protection. Sunscreens have assumed a major component of primary prevention programs based on their convenience of use and also on their widespread promotion by those people who have a commercial interest in them. These products protect predominantly in the UVB range for which there is a sun protection factor (SPF) grading, as well as having some activity in the UVA range (for which there is not yet a satisfactory grading method). PMID:10417449

  7. Polypoid melanoma and superficial spreading melanoma different subtypes in the same lesion.

    PubMed

    Hikawa, Renato Shintani; Kanehisa, Eliza Sayuri; Enokihara, Mílvia Maria Simões e Silva; Enokihara, Mauro Yoshiaki; Hirata, Sérgio Henrique

    2014-01-01

    Melanoma is a malignant melanocytic neoplasm with high mortality rate, and steadily and universally increasing incidence rates. Polypoid melanoma is considered an exophytic variant of the nodular subtype. The incidence of polypoid melanoma is extremely variable, most likely because of the different criteria used for its characterization. We presented a rare case of polypoid melanoma and superficial spreading melanoma in the same lesion. PMID:25054761

  8. Primary malignant achromic melanoma of the lung

    PubMed Central

    Lazarou, Ilias; Purek, Lesek; Duc, Christophe; Licker, Marc-Joseph; Spiliopoulos, Anastase; Tschopp, Jean-Marie

    2014-01-01

    Currently, less than thirty cases of primary malignant melanoma of the lung have been reported in the literature. Thus, strict criteria for diagnosis have been published and include: malignant melanoma associated with bronchial epithelial changes; a solitary lung tumor; no prior history of skin, mucous membrane, intestinal or ocular melanoma; and absence of any other detectable tumor at the time of diagnosis. In this article we present a case of melanoma of the lung without evidence of extra-pulmonary disease. PMID:26766979

  9. Primary malignant achromic melanoma of the lung.

    PubMed

    Lazarou, Ilias; Purek, Lesek; Duc, Christophe; Licker, Marc-Joseph; Spiliopoulos, Anastase; Tschopp, Jean-Marie

    2014-01-01

    Currently, less than thirty cases of primary malignant melanoma of the lung have been reported in the literature. Thus, strict criteria for diagnosis have been published and include: malignant melanoma associated with bronchial epithelial changes; a solitary lung tumor; no prior history of skin, mucous membrane, intestinal or ocular melanoma; and absence of any other detectable tumor at the time of diagnosis. In this article we present a case of melanoma of the lung without evidence of extra-pulmonary disease. PMID:26766979

  10. Isolated Posterior Fossa Involvement in Posterior Reversible Encephalopathy Syndrome

    PubMed Central

    Shimizu, Yukie; Tha, Khin Khin; Iguchi, Akihiro; Cho, Yuko; Yoshida, Atsushi; Fujima, Noriyuki; Tsukahara, Akiko; Shirato, Hiroki; Terae, Satoshi

    2013-01-01

    Summary Posterior reversible encephalopathy syndrome (PRES) is characterized by reversible vasogenic edema affecting the subcortical white matter of bilateral occipital and parietal lobes. We describe a case of isolated posterior fossa involvement of PRES which occurred during remission induction chemotherapy for T-cell acute lymphoblastic leukemia. Both the brainstem and cerebellum were extensively involved, but the supratentorial structures were completely spared. The follow-up magnetic resonance images revealed reversibility of most lesions. The knowledge of atypical radiological features of PRES is essential for prompt diagnosis. PMID:24199811

  11. Current concepts of metastasis in melanoma

    PubMed Central

    Zbytek, Blazej; Carlson, J Andrew; Granese, Jacqueline; Ross, Jeffrey; Mihm, Martin C; Slominski, Andrzej

    2008-01-01

    The main cause of death in melanoma patients is widespread metastases. Staging of melanoma is based on the primary tumor thickness, ulceration, lymph node and distant metastases. Metastases develop in regional lymph nodes, as satellite or in-transit lesions, or in distant organs. Lymph flow and chemotaxis is responsible for the homing of melanoma cells to different sites. Standard pathologic evaluation of sentinel lymph nodes fails to find occult melanoma in a significant proportion of cases. Detection of small numbers of malignant melanoma cells in these and other sites, such as adjacent to the primary site, bone marrow or the systemic circulation, may be enhanced by immunohistochemistry, reverse transcription PCR, evaluation of lymphatic vessel invasion and proteomics. In the organs to which melanoma cells metastasize, extravasation of melanoma cells is regulated by adhesion molecules, matrix metalloproteases, chemokines and growth factors. Melanoma cells may travel along external vessel lattices. After settling in the metastatic sites, melanoma cells develop mechanisms that protect them against the attack of the immune system. It is thought that one of the reasons why melanoma cells are especially resistant to killing is the fact that melanocytes (cells from which melanoma cells derive) are resistant to such noxious factors as ultraviolet light and reactive oxygen species. Targeted melanoma therapies are, so far, largely unsuccessful, and new ones, such as adjuvant inhibition of melanogenesis, are under development. PMID:19649148

  12. Melanoma at LLNL: An update

    SciTech Connect

    Moore, D.H. II; Schneider, J.S.; Bennett, D.E.; Patterson, H.W.

    1994-03-01

    From 1972 to 1977, the Laboratory experienced a diagnosis rate of malignant melanoma among its employees that was three to four times higher than expected based on rates for the surrounding Alameda and Contra Costa counties in the Bay Area. In 1984, Austin and Reynolds from the California Department of Health Services reported the results of their study comparing individuals diagnosed with melanoma and otherwise healthy controls from the Laboratory. These researchers concluded that five occupational factors were [open quotes]casually associated[close quotes] with melanoma risk at LLNL. The factors were exposure to radioactive materials, exposure to volatile photographic chemicals, work at Site 300, visits to the Pacific Test Site, and duties as a chemist. In recent years, the rate of diagnosis of the more lethal form of melanoma among LLNL workers, which was previously elevated, has returned to that of the surrounding geographical area where most employees live. If our program of employee awareness about melanoma, enhanced surveillance, and early diagnosis continues to lead to decreased mortality from this disease, then such an approach may have important public health implications for the broader community.

  13. Other targeted drugs in melanoma

    PubMed Central

    Rodón, Jordi; Karachaliou, Niki; Sánchez, Jesús; Santarpia, Mariacarmela; Viteri, Santiago; Pilotto, Sara; Teixidó, Cristina; Riso, Aldo; Rosell, Rafael

    2015-01-01

    Targeted therapy drugs are developed against specific molecular alterations on cancer cells. Because they are “targeted” to the tumor, these therapies are more effective and better tolerated than conventional therapies such as chemotherapy. In the last decade, great advances have been made in understanding of melanoma biology and identification of molecular mechanisms involved in malignant transformation of cells. The identification of oncogenic mutated kinases involved in this process provides an opportunity for development of new target therapies. The dependence of melanoma on BRAF-mutant kinase has provided an opportunity for development of mutation-specific inhibitors with high activity and excellent tolerance that are now being used in clinical practice. This marked a new era in the treatment of metastatic melanoma and much research is now ongoing to identify other “druggable” kinases and transduction signaling networking. It is expected that in the near future the spectrum of target drugs for melanoma treatment will increase. Herein, we review the most relevant potential novel drugs for melanoma treatment based on preclinical data and the results of early clinical trials. PMID:26605312

  14. [Gastric melanoma--clinical case].

    PubMed

    Doran, H; Pătraşcu, Tr; Catrina, E; Mihalache, O; Degeratu, D; Predescu, G

    2009-01-01

    Malignant melanomas of the gastrointestinal tract and particulary of the stomach are very rare intra-operative findings. The majority of such melanomas are metastatic from a cutaneous primary. We present the clinical case of a 69-years-old woman with malignant melanoma of the left pectoral region resected in 1988, presented with epigastric pain, weight loss and anaemia. Endoscopy and CT-scan suggested the diagnosis of malignant tumor of the large curvature of the stomach. Explorative laparotomy revealed a large ulcerated tumor of the fornix, with spleno-pancreatic invasion. We also found several pigmented satellite nodules. The surgical solution consisted in a total gastrectomy and distal spleno-pancreatectomy. Histology revealed the tumor and the satellite nodules to be composed of nests of epithelioid cells with melanin pigment. After 3 months, the evolution was favorable. There are some articles in medical literature which present cases of primary gastric melanomas. According to these scientific criterias from the literature, we discussed the nature of this melanoma - a primary or a metastatic one. PMID:19943569

  15. Posterior polar cataract: A review

    PubMed Central

    Kalantan, Hatem

    2011-01-01

    Posterior polar cataract is a rare form of congenital cataract. It is usually inherited as an autosomal dominant disease, yet it can be sporadic. Five genes have been attributed to the formation of this disease. It is highly associated with complications during surgery, such as posterior capsule rupture and nucleus drop. The reason for this high complication rate is the strong adherence of the opacity to the weak posterior capsule. Different surgical strategies were described for the handling of this challenging entity, most of which emphasized the need for gentle maneuvering in dealing with these cases. It has a unique clinical appearance that should not be missed in order to anticipate, avoid, and minimize the impact of the complications associated with it. PMID:23960967

  16. Rethinking "posterior" tongue-tie.

    PubMed

    Douglas, Pamela Sylvia

    2013-12-01

    Currently, many clinicians who help with breastfeeding problems are diagnosing "posterior" tongue-tie in infants and performing or referring for frenotomy. In this "Speaking Out" article, I argue that the diagnosis of "posterior" tongue-tie has successfully raised awareness of the importance of impaired tongue function in breastfeeding difficulty. However, the diagnosis of "posterior" tongue-tie also applies a reductionist, medicalized theoretical frame to the complex problem of impaired tongue function, risking unintended outcomes. Impaired tongue function arises out of multiple interacting and co-evolving factors, including the interplay between social behaviors concerning breastfeeding and mother-infant biology. Consideration of theoretical frames is vital if we are to build an evidence base through efficient use of the scarce resources available for clinical breastfeeding research and minimize unintended outcomes. PMID:24143939

  17. Ocular Inflammation in Uveal Tract in Aged Obese Type 2 Diabetic Rats (Spontaneously Diabetic Torii Fatty Rats)

    PubMed Central

    Kemmochi, Yusuke; Miyajima, Katsuhiro; Ohta, Takeshi; Yasui, Yuzo; Toyoda, Kaoru; Kakimoto, Kochi; Shoda, Toshiyuki

    2014-01-01

    We report uveitis observed in an obese type 2 diabetes rat model, Spontaneously Diabetic Torii Leprfa (SDT fatty) rats aged over 50 weeks. The eyes of SDT fatty rats (16 animals: 7 males and 9 females with 50 or 60 weeks of age) were examined histopathologically. Infiltration of inflammatory cells in the uveal tract was observed in 13 of 16 animals. One female showed severe inflammation affecting the entire uveal tract including the iris, ciliary body, and choroid with a variety of inflammatory cells (neutrophils, lymphocytes, and macrophages). Those changes clinically mimic the findings of diabetic iridocyclitis in diabetic patients. Uveitis associated with diabetes can occur in diabetic patients but the pathogenesis still remains unknown. Since increased extramedullary hematopoiesis in the spleen and abscess in the genital and lower urinary tracts were observed in some SDT fatty rats, increased susceptibility to infection, prolongation of inflammatory states, and disorders of the immune system were considered to be possible factors of the uveitis in aged SDT fatty rats. There have been few reports on how diabetes has influence on the development of uveitis associated with bacterial infection. The SDT fatty rat can be an animal model to investigate diabetes-associated uveitis. PMID:25295283

  18. Surgical management of melanoma: an EORTC Melanoma Group survey

    PubMed Central

    Testori, A; Soteldo, J; Powell, B; Sales, F; Borgognoni, L; Rutkowski, P; Lejeune, F; van Leeuwen, PAM; Eggermont, A

    2013-01-01

    Objectives: The objective of the article is to explore the surgical practices and views in the treatment of melanoma within members and non-members of the EORTC Melanoma Group (MG) during the years 2003–2005. Methods: An e-mail questionnaire (see appendix) developed within the EORTC MG was sent to all melanoma units (MUs) of the EORTC (180) and to selected international centres between 2003 and 2005. The questionnaire investigated the different practices regarding surgical management of melanoma patients at all stages. Results: A total of 75 questionnaires were returned from centres in Europe (70), Israel (3), Australia (1) and the United States (1). Resection margins on primary melanoma vary according to AJCC 2002 staging. Sixty three of 75 MUs perform Sentinel node biopsy. Modified radical neck dissection is performed in 82% of MUs for macrometastases and in 80% of MUs for micrometastases. Most MUs surveyed perform all three levels of Berg axillary dissection whether for macrometastases (79%) or micrometastases (62%). An ilio inguinal-obturator dissection is proposed with macrometastases (41% of MUs), whereas 33% of MUs perform a pelvic dissection only if the Cloquet node is positive. Twenty five of 75 MUs perform an isolated limb perfusion with a therapeutic indication; three also as an adjuvant. The majority of MUs perform surgery for distant metastases including superficial (53 of 75 [71%]) or solitary visceral metastases (52 of 75[69%]) or for palliation (58 of 75[77%]). Conclusion: The adequacy of surgery appears to be the most important milestone in the therapeutic approach of melanoma. Even if surgery is fundamental in the different stages of the disease, there is quite a variability concerning the extension of the surgical treatment related to primary and lymphnodal disease. Phase III randomised trials have shown that wide margins, elective lymph node dissections, and prophylactic isolated limb perfusions have not improved survival and cannot be

  19. Melanoma: etiology, treatment, and dental implications.

    PubMed

    Little, James W

    2006-01-01

    Melanoma is one of the most serious skin cancers. It arises from neural crest-derived melanocytes located in the epidermis or dermis of the skin. Melanoma also can arise from melanocytes located in other regions of the body such as the eye, meninges, digestive tract, mucosal surfaces, or lymph nodes. There are no proven causes of melanoma but the most commonly associated factor is episodic exposure to the sun. Melanoma is a common cancer that has been increasing in incidence for the last 35 years. The median age at the time of diagnosis is 53 years. It is much more common in whites than in people of color. Five-year survival rates for melanoma of the skin have been increasing since 1976. There are four types of melanoma: superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lintiginous melanoma. Clinical signs indicating possible melanoma are asymmetry, border irregularity, color variation, increase in diameter, elevation, ulceration, and bleeding of pigmented lesions. Histopathologic findings (tumor thickness, tumor invasion), surface ulceration, spread to lymph nodes, and distant metastases are used to project patient prognosis. Treatment consists of surgical excision, lymph node dissection, limb perfusion, regional chemotherapy infusion, radiation, intralesional immunotherapy, systemic chemotherapy, and/or interferon-alpha, depending on the staging of the melanoma. Oral melanomas are rare; however, approximately 20% of all melanomas are found in the head and neck region. The role of the dentist is to be alert for changes in pigmented lesions of the oral mucosa and skin of the head and neck. Lesions suspected of melanoma must be biopsied, which usually involves referral of the patient. PMID:16494125

  20. Hyperspectral imaging for melanoma screening

    NASA Astrophysics Data System (ADS)

    Martin, Justin; Krueger, James; Gareau, Daniel

    2014-03-01

    The 5-year survival rate for patients diagnosed with Melanoma, a deadly form of skin cancer, in its latest stages is about 15%, compared to over 90% for early detection and treatment. We present an imaging system and algorithm that can be used to automatically generate a melanoma risk score to aid clinicians in the early identification of this form of skin cancer. Our system images the patient's skin at a series of different wavelengths and then analyzes several key dermoscopic features to generate this risk score. We have found that shorter wavelengths of light are sensitive to information in the superficial areas of the skin while longer wavelengths can be used to gather information at greater depths. This accompanying diagnostic computer algorithm has demonstrated much higher sensitivity and specificity than the currently commercialized system in preliminary trials and has the potential to improve the early detection of melanoma.

  1. Metastatic melanoma to the heart.

    PubMed

    Allen, Brian C; Mohammed, Tan Lucien; Tan, Carmela D; Miller, Dylan V; Williamson, Eric E; Kirsch, Jacobo S

    2012-01-01

    Melanoma is a common neoplasm with a propensity to metastasize to the heart. Although cardiac metastasis is rarely diagnosed ante mortem, using a multimodality approach, several imaging findings may be seen. Echocardiography is often the initial imaging method used to detect cardiac metastases and their complications. On computed tomography, intraluminal filling defects and myocardial/pericardial nodules may be seen. On magnetic resonance imaging, metastatic melanoma is classically hyperintense on T1 images and hypointense on T2 images, a result of the T1 shortening of melanin; however, this is seen in a minority of cases. As melanoma metastases are fluorine-18-fluorodeoxyglucose avid, fluorine-18-fluorodeoxyglucose positron emission tomography may also be used to detect cardiac metastases. PMID:22818836

  2. Cell Cycle Regulation and Melanoma.

    PubMed

    Xu, Wen; McArthur, Grant

    2016-06-01

    Dysregulation of cell cycle control is a hallmark of melanomagenesis. Agents targeting the G1-S and G2-M checkpoints, as well as direct anti-mitotic agents, have all shown promising preclinical activity in melanoma. However, in vivo, standalone single agents targeting cell cycle regulation have only demonstrated modest efficacy in unselected patients. The advent of specific CDK 4/6 inhibitors targeting the G1-S transition, with an improved therapeutic index, is a significant step forward. Potential synergy exists with the combination of CDK4/6 inhibitors with existing therapies targeting the MAPK pathway, particularly in subsets of metastatic melanomas such as NRAS and BRAF mutants. This reviews summaries of the latest developments in both preclinical and clinical data with cell cycle-targeted therapies in melanoma. PMID:27106898

  3. Melanoma: oncogenic drivers and the immune system

    PubMed Central

    Karachaliou, Niki; Pilotto, Sara; Teixidó, Cristina; Viteri, Santiago; González-Cao, María; Riso, Aldo; Morales-Espinosa, Daniela; Molina, Miguel Angel; Chaib, Imane; Santarpia, Mariacarmela; Richardet, Eduardo; Bria, Emilio

    2015-01-01

    Advances and in-depth understanding of the biology of melanoma over the past 30 years have contributed to a change in the consideration of melanoma as one of the most therapy-resistant malignancies. The finding that oncogenic BRAF mutations drive tumor growth in up to 50% of melanomas led to a molecular therapy revolution for unresectable and metastatic disease. Moving beyond BRAF, inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided targets for cancer immunotherapy. In this review, we discuss the molecular biology of melanoma and we focus on the recent advances of molecularly targeted and immunotherapeutic approaches. PMID:26605311

  4. Cross-species models of human melanoma.

    PubMed

    van der Weyden, Louise; Patton, E Elizabeth; Wood, Geoffrey A; Foote, Alastair K; Brenn, Thomas; Arends, Mark J; Adams, David J

    2016-01-01

    Although transformation of melanocytes to melanoma is rare, the rapid growth, systemic spread, as well as the chemoresistance of melanoma present significant challenges for patient care. Here we review animal models of melanoma, including murine, canine, equine, and zebrafish models, and detail the immense contribution these models have made to our knowledge of human melanoma development, and to melanocyte biology. We also highlight the opportunities for cross-species comparative genomic studies of melanoma to identify the key molecular events that drive this complex disease. PMID:26354726

  5. NF-κB activation in melanoma

    PubMed Central

    Ueda, Yukiko; Richmond, Ann

    2009-01-01

    Summary Metastatic melanoma is an aggressive skin cancer that is notoriously resistant to current cancer therapies. In human melanoma, nuclear factor-kappa B (NF-κB) is upregulated, leading to the deregulation of gene transcription. In this review, we discuss (i) the relationship between gene alteration in melanoma and upregulation of NF-κB, (ii) mechanisms by which activated NF-κB switch from pro-apoptotic to anti-apoptotic functions in melanoma and (iii) autocrine mechanisms that promote constitutive activation of NF-κB in metastatic melanoma. PMID:16524427

  6. Recurrent inactivating RASA2 mutations in melanoma.

    PubMed

    Arafeh, Rand; Qutob, Nouar; Emmanuel, Rafi; Keren-Paz, Alona; Madore, Jason; Elkahloun, Abdel; Wilmott, James S; Gartner, Jared J; Di Pizio, Antonella; Winograd-Katz, Sabina; Sindiri, Sivasish; Rotkopf, Ron; Dutton-Regester, Ken; Johansson, Peter; Pritchard, Antonia L; Waddell, Nicola; Hill, Victoria K; Lin, Jimmy C; Hevroni, Yael; Rosenberg, Steven A; Khan, Javed; Ben-Dor, Shifra; Niv, Masha Y; Ulitsky, Igor; Mann, Graham J; Scolyer, Richard A; Hayward, Nicholas K; Samuels, Yardena

    2015-12-01

    Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas. Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration. RASA2 expression was lost in ≥30% of human melanomas and was associated with reduced patient survival. These findings identify RASA2 inactivation as a melanoma driver and highlight the importance of RasGAPs in cancer. PMID:26502337

  7. Local tumor control after {sup 106}Ru brachytherapy of choroidal melanoma

    SciTech Connect

    Damato, Bertil . E-mail: Bertil@damato.co.uk; Patel, Imran; Campbell, Ian R.; Mayles, Helen M.; Errington, R. Douglas

    2005-10-01

    Purpose To report on local tumor control after {sup 106}Ru brachytherapy for choroidal melanoma. Methods and Materials A total of 458 patients with choroidal melanoma were treated at a single institution between January 1993 and December 2001. The tumors had a median longest basal dimension of 10.6 mm and a median height of 3.2 mm. The brachytherapy was administered using a 15- or 20-mm plaque. For posterior tumors, the plaque was positioned eccentrically with its posterior edge aligned with the posterior tumor margin to reduce the radiation dose to the optic disk and fovea. A minimal scleral dose sufficient to cause visible choroidal atrophy provided a permanent ophthalmoscopic record of the distribution of choroidal irradiation. If radiotherapy to the posterior tumor was uncertain, adjunctive transpupillary thermotherapy was administered 6 months postoperatively. Results The actuarial rates of tumor recurrence were 1%, 2%, and 3% at 2, 5, and 7 years, respectively. Local tumor recurrence correlated with the longest basal tumor dimension (Cox univariate analysis, p = 0.02, risk ratio 1.41, 95% confidence interval 1.06-1.88). Seven of the nine eyes with recurrent tumor were salvaged with additional conservative therapy. Conclusion The low rate of local tumor recurrence suggests that ruthenium plaque radiotherapy is effective with good case selection and if special measures are taken to ensure that the plaque is positioned correctly.

  8. [Laboratory markers of melanoma progression].

    PubMed

    Bánfalvi, Teodóra; Edesné, Mariann B; Gergye, Mária; Udvarhelyi, Nóra; Orosz, Zsolt; Gilde, Katalin; Kremmer, Tibor; Ottó, Szabolcs; Tímár, József

    2003-01-01

    Extracellular tumour markers may have potential role in the follow-up of patients with malignant melanoma, in therapy monitoring and in prediction of prognosis. In our article circulating tumour markers in melanoma (melanoma inhibitory activity, lipid bound sialic acid, neuron specific enolase, TA90 immune complex, S-100B protein, 5-S-cysteinyldopa, tyrosinase, cytokines, metalloproteinases, LDH) were reviewed. Among laboratory melanoma markers the S-100B protein is the most investigated. S-100B protein has high specificity, appropriate sensitivity and proved to be significant prognostic factor independent from stages. High serum values are associated with shorter survival. However, before S-100B monitoring immunohistochemistry for the detection of S-100B is required. In the case of malignant melanomas with low expression serum S-100B monitoring may not be sensitive enough to follow disease progression. Although the serum concentration of 5-S-cysteinyldopa did not prove to be independent prognostic factor in our previous studies comprising the highest patient number in the literature, the marker was suggested for therapy monitoring. The survival analysis indicated that the elevated 5-S-cysteinyldopa level predicts shorter survival. In spite of the calculated low correlation between the two markers, parallel elevation of S-100B protein and 5-S-cysteinyldopa indicated shorter survival. On the basis of the literature LDH is the most appropriate tumour marker in stage IV to predict prognosis, but its sensitivity and specificity could not achieve that of S-100B protein. S-100B and LDH proved to be similarly reliable in respect to the clinical outcome. Determination of serum concentration of MIA and tyrosinase are also reliable markers in malignant melanoma. The other investigated markers are not well known yet or do not provide useful information to the clinicians. PMID:12704461

  9. Histological types of polypoid cutaneous melanoma II.

    PubMed

    Knezević, Fabijan; Duancić, Vjekoslav; Sitić, Sanda; Horvat-Knezević, Anica; Benković, Vesna; Ramić, Snjezana; Kostović, Kresimir; Ramljak, Vesna; Vrdoljak, Danko Velemir; Stanec, Mladen; Bozović, Angelina

    2007-12-01

    The aim of this study was to ascertain which histological types of melanoma can clinically and morphologically appear as polypoid melanomas. In 645 cases of primary cutaneous melanoma we have analyzed criteria for diagnosis of polypoid cutaneous melanoma and afterwards we have analyzed growth phase in each polypoid melanoma, histological type of atypical melanocytes, the number of epidermal ridges which are occupied by atypical melanocytes, and distribution according to age, sex and location, as well as the disease free survival. According to the criteria for polypoid melanomas we have found 147 (22.8%) polypoid cutaneous melanomas. Analyzing the growth phases, histological types of atypical melanocytes and the number of affected epidermal ridges in the group of polypoid melanomas we have ascertained 2 (1.4%) ALMs, 4 (2.8%) LMMs, 42 (28.6%) SSMs and 99 (67.2%) NMs. Our conclusion is that polypoid cutaneous melanomas are morphological forms of various histological melanoma types (ALM, LMM, SSM and NM) and they can all display polypoid morphological form. Polypoid cutaneous melanomas are most often of nodular histological type. PMID:18217457

  10. Posterior Tibial Tendon Dysfunction (PTTD)

    MedlinePlus

    ... ACFAS | Información en Español Advanced Search Home » Foot & Ankle Conditions » Posterior Tibial Tendon Dysfunction (PTTD) Text Size ... the arch, and an inward rolling of the ankle. As the condition progresses, the symptoms will change. ...

  11. Stereolithography for Posterior Fossa Cranioplasty

    PubMed Central

    Agner, Celso; Dujovny, Manuel; Evenhouse, Raymond; Charbel, Fady T.; Sadler, Lewis

    1998-01-01

    Posterior fossa cranioplasty has been suggested for improvement of neurological symptoms following craniectomy. However, there is no particular recommendation in the literature about techniques for prosthesis manufacture and implantation. We report our experience using rapid prototyping technology and stereolithography for pre-surgical implant design and production of cranioplasties. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:17171056

  12. Desmoplastic melanoma of the eyelid and conjunctival melanoma in neurofibromatosis type 1: a clinical pathological correlation.

    PubMed

    Rubinstein, Tal J; Plesec, Thomas P; Singh, Arun D

    2015-01-01

    A 56-year-old woman with neurofibromatosis type 1 (NF1) presented with a left upper eyelid amelanotic nodule with adjacent eyelid margin hyperpigmentation. Physical examination additionally revealed primary acquired melanosis (PAM) on the palpebral conjunctiva of the same eyelid. Full thickness eyelid excision and conjunctival map biopsy identified desmoplastic melanoma of the eyelid in addition to invasive conjunctival melanoma and conjunctival melanoma in situ. Sentinel lymph node biopsy was negative for metastasis. She was treated with surgical excision for the eyelid melanoma and topical mitomycin C for the conjunctival melanoma. We discuss the rare entity of desmoplastic melanoma of the eyelid and its possible association with NF1. PMID:25233828

  13. Prevalence of Germline BAP1, CDKN2A, and CDK4 Mutations in an Australian Population-Based Sample of Cutaneous Melanoma Cases.

    PubMed

    Aoude, Lauren G; Gartside, Michael; Johansson, Peter; Palmer, Jane M; Symmons, Judith; Martin, Nicholas G; Montgomery, Grant W; Hayward, Nicholas K

    2015-04-01

    Mutations in Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A) and Cyclin-Dependent Kinase 4 (CDK4) contribute to susceptibility in approximately 40% of high-density cutaneous melanoma (CMM) families and about 2% of unselected CMM cases. BRCA-1 associated protein-1 (BAP1) has been more recently shown to predispose to CMM and uveal melanoma (UMM) in some families; however, its contribution to CMM development in the general population is unreported. We sought to determine the contribution of these genes to CMM susceptibility in a population-based sample of cases from Australia. We genotyped 1,109 probands from Queensland families and found that approximately 1.31% harbored mutations in CDKN2A, including some with novel missense mutations (p.R22W, p.G35R and p.I49F). BAP1 missense variants occurred in 0.63% of cases but no CDK4 variants were observed in the sample. This is the first estimate of the contribution of BAP1 and CDK4 to a population-based sample of CMM and supports the previously reported estimate of CDKN2A germline mutation prevalence. PMID:25787093

  14. Cutaneous melanoma: A current overview.

    PubMed

    Wick, Mark R

    2016-07-01

    Cutaneous melanoma continues to increase in frequency, for unknown reasons, and it can pose considerable diagnostic challenges to clinician and pathologists alike. This review considers current concepts pertaining to that tumor, including those concerning epidemiology, clinical diagnosis, histologic findings, adjunctive diagnostic studies, and prognosis. PMID:27229301

  15. [Endocrine factors influencing melanoma progression].

    PubMed

    Dobos, Judit

    2009-03-01

    According to recent findings that beside cancers traditionally considered as hormone-dependent, several other tumor types show different behavior in the two sexes, indicating the possible role of endocrine factors in the course of these diseases. The possibility that endocrine factors may influence the clinical course of human malignant melanoma is suggested by the higher survival rate in premenopausal vs. postmenopausal women or men of any ages. However, investigations on the sex hormone receptor status of human cutaneous melanomas and experiments attempting to support the epidemiological results yielded conflicting results. In our human melanoma cell lines we failed to detect steroid receptors at protein level, while quantitative PCR demonstrated that their mRNA expression level was orders of magnitude lower compared to the positive control cell lines. Sex hormones did not influence the in vitro features of the human melanoma cells considerably. On the other hand, glucocorticoid receptor was present both at mRNA and protein level, although dexamethasone was effective in vitro only at high doses. Our previous experiments showed that intrasplenic injection of human melanoma cells resulted in a significantly higher number of liver colonies in male than in female SCID mice. We now show that this difference evolves during the first day. After injection into the tail vein we did not observe gender-dependent difference in the efficiency of pulmonary colonization. Examining the pattern of metastasis formation after intracardiac injection, we have found differences between the two sexes in the incidence or number of colonies only in the case of the liver but not in other organs. We concluded that the observed phenomenon is specific to the liver; therefore we investigated the effects of 2-methoxyestradiol, an endogenous metabolite of estradiol produced mainly in the liver, with an estrogen receptor-independent antitumor activity. 2ME2 effectively inhibited melanoma cell

  16. Isolation of tumorigenic circulating melanoma cells

    PubMed Central

    Ma, Jie; Lin, Jennifer Y.; Alloo, Allireza; Wilson, Brian J.; Schatton, Tobias; Zhan, Qian; Murphy, George F.; Waaga-Gasser, Ana-Maria; Gasser, Martin; Hodi, F. Stephen; Frank, Natasha Y.; Frank, Markus H.

    2010-01-01

    Circulating tumor cells (CTC) have been identified in several human malignancies, including malignant melanoma. However, whether melanoma CTC are tumorigenic and cause metastatic progression is currently unknown. Here we isolate for the first time viable tumorigenic melanoma CTC and demonstrate that this cell population is capable of metastasis formation in human-to-mouse xenotransplantation experiments. The presence of CTC among peripheral blood mononuclear cells (PBMC) of murine recipients of subcutaneous (s.c.) human melanoma xenografts could be detected based on mRNA expression for human GAPDH and/or ATP-binding cassette subfamily B member 5 (ABCB5), a marker of malignant melanoma-initiating cells previously shown to be associated with metastatic disease progression in human patients. ABCB5 expression could also be detected in PBMC preparations from human stage IV melanoma patients but not healthy controls. The detection of melanoma CTC in human-to-mouse s.c. tumor xenotransplantation models correlated significantly with pulmonary metastasis formation. Moreover, prospectively isolated CTC from murine recipients of s.c. melanoma xenografts were capable of primary tumor initiation and caused metastasis formation upon xenotransplantation to secondary murine NOD-scid IL2Rγnull recipients. Our results provide initial evidence that melanoma CTC are tumorigenic and demonstrate that CTC are capable of causing metastatic tumor progression. These findings suggest a need for CTC eradication to inhibit metastatic progression and provide a rationale for assessment of therapeutic responses of this tumorigenic cell population to promising emerging melanoma treatment modalities. PMID:20977885

  17. Primary mucosal melanomas: a comprehensive review

    PubMed Central

    Mihajlovic, Marija; Vlajkovic, Slobodan; Jovanovic, Predrag; Stefanovic, Vladisav

    2012-01-01

    Primary mucosal melanomas arise from melanocytes located in mucosal membranes lining respiratory, gastrointestinal and urogenital tract. Although a majority of mucosal melanomas originate from the mucosa of the nasal cavity and accessory sinuses, oral cavity, anorectum, vulva and vagina, they can arise in almost any part of mucosal membranes. Most of mucosal melanomas occur in occult sites, which together with the lack of early and specific signs contribute to late diagnosis, and poor prognosis. Because of their rareness the knowledge about their pathogenesis and risk factors is insufficient, and also there are not well established protocols for staging and treatment of mucosal melanomas. Surgery is the mainstay of treatment, with trends toward more conservative treatment since radical surgery did not show an advantage for survival. Radiotherapy can provide better local control in some locations, but did not show improvement in survival. There is no effective systemic therapy for these aggressive tumors. Compared with cutaneous and ocular melanoma, mucosal melanomas have lowest percent of five-year survival. Recently revealed molecular changes underlying mucosal melanomas offer new hope for development of more effective systemic therapy for mucosal melanomas. Herein we presented a comprehensive review of various locations of primary melanoma along mucosal membranes, their epidemiological and clinical features, and treatment options. We also gave a short comparison of some characteristics of cutaneous and mucosal melanomas. PMID:23071856

  18. Cutaneous melanoma in solid organ transplant patients.

    PubMed

    Russo, I; Piaserico, S; Belloni-Fortina, A; Alaibac, M

    2014-08-01

    Solid organ transplant patients are at greatly increased risk of developing a wide variety of skin cancers, particularly epithelial skin cancers. On the other hand, it is well known that an intact immune system limits the development of benign melanocytic lesions. The eruptive nevi phenomenon, which we can observe in solid organ transplant recipients, is indicative of the relationship between melanocyte proliferation and immune system. Regression of melanocytic nevi after restoration of complete immune responsiveness is a further clinical example the role of immunosurveillance on melanocyte proliferation. However, melanoma incidence in organ transplant recipients appears only 2-3 folds higher than in general population. To this regard, organ transplant recipients who develop de novo melanomas thicker than 2mm seem to have a significantly worse outcome with a greatly increased risk of dying of metastatic melanoma, whereas those who develop a ≤2 mm thickness melanoma seem to have a prognosis similar to that of the general population. Furthermore, there is no evidence supporting an increased risk of melanoma recurrences after transplant in patients with a history of low-risk melanoma. Melanoma is also one of the most frequent and lethal donor-derived malignancies suggesting that a history of invasive melanoma should be considered an absolute contraindication to donation. The aim of this review is to investigate the relationship between immunosuppression and melanoma and to discuss its clinical implications for the management of transplant-associated melanoma. PMID:25068225

  19. Posterior cruciate ligament of the knee (image)

    MedlinePlus

    The posterior cruciate ligament (PCL) is a powerful ligament extending from the top-rear surface of the tibia to the bottom-front surface of the femur. The ligament prevents the knee joint from posterior instability.

  20. Bilateral posterior cerebral artery infarction.

    PubMed

    Ryan, Davinia; Murphy, Sinead M; Hennessey, Michael J

    2010-01-01

    We report the case of a 70-year-old man who presented with short-term memory impairment and a homonymous left inferior quadrantanopia secondary to simultaneous bilateral posterior cerebral artery (PCA) territory infarction. As in more than a quarter of cases of PCA infarction, no aetiological cause was identified. Unlike the transient nature of symptoms in some cases following unilateral infarction, his deficits persisted on 2-month follow-up. PMID:22798298

  1. Spinal hemianesthesia: Unilateral and posterior

    PubMed Central

    Imbelloni, Luiz Eduardo

    2014-01-01

    The injection of a non-isobaric local anesthetic should induce a unilateral spinal anesthesia in patients in a lateral decubitus position. The posterior spinal hemianesthesia only be obtained with hypobaric solutions injected in the jackknife position. The most important factors to be considered when performing a spinal hemianesthesia are: type and gauge of the needle, density of the local anesthetic relative to the CSF, position of the patient, speed of administration of the solution, time of stay in position, and dose/concentration/volume of the anesthetic solution. The distance between the spinal roots on the right-left sides and anterior-posterior is, approximately, 10-15 mm. This distance allows performing unilateral spinal anesthesia or posterior spinal anesthesia. The great advantage of obtaining spinal hemianesthesia is the reduction of cardiovascular changes. Likewise, both the dorsal and unilateral sensory block predominates in relation to the motor block. Because of the numerous advantages of producing spinal hemianesthesia, anesthesiologists should apply this technique more often. This review considers the factors which are relevant, plausible and proven to obtain spinal hemianesthesia. PMID:25886320

  2. Use of imiquimod for residual acral melanoma.

    PubMed

    Sue, Gloria R; Hanlon, Allison; Lazova, Rossitza; Narayan, Deepak

    2014-01-01

    Recent reports suggest that topical imiquimod cream is an effective treatment option for certain types of melanomas. No reports exist on the efficacy of using imiquimod cream to treat melanoma located on the plantar surface of the foot. We present two patients with a melanoma of the foot who had residual melanoma following surgical excision with acceptable margins. The patients were then treated with topical imiquimod for 8 weeks after which a repeat biopsy of the affected region showed no evidence of residual melanoma in situ. The use of topical imiquimod cream should be considered in the management of residual melanoma in situ of the plantar surface of the foot. PMID:25188932

  3. Melanoma biomarkers: Vox clamantis in deserto (Review)

    PubMed Central

    AL-SHAER, MAYS; GOLLAPUDI, DIVYA; PAPAGEORGIO, CHRIS

    2010-01-01

    Detecting malignant melanoma at an early stage, monitoring therapy, predicting recurrence and identifying patients at risk for metastasis continue to be a challenging and demanding objective. The last two decades have witnessed innovations in the field of melanoma biomarkers. However, global agreement concerning monitoring and early detection has yet to be reached. This is a review of the current literature regarding melanoma biomarkers including demographic, clinical, pathological and molecular biomarkers that are produced by melanoma or non-melanoma cells. A number of these biomarkers demonstrate promising results as possible methods for early detection, predicting recurrence and monitoring therapy. Other biomarkers appear to be promising for identifying patients at risk for metastasis. We reviewed the most pertinent information in the field thus far and how this knowledge can impact, or not, the management of melanoma patients prognostically and therapeutically. PMID:22966315

  4. Melanoma biomarkers: Vox clamantis in deserto (Review).

    PubMed

    Al-Shaer, Mays; Gollapudi, Divya; Papageorgio, Chris

    2010-05-01

    Detecting malignant melanoma at an early stage, monitoring therapy, predicting recurrence and identifying patients at risk for metastasis continue to be a challenging and demanding objective. The last two decades have witnessed innovations in the field of melanoma biomarkers. However, global agreement concerning monitoring and early detection has yet to be reached. This is a review of the current literature regarding melanoma biomarkers including demographic, clinical, pathological and molecular biomarkers that are produced by melanoma or non-melanoma cells. A number of these biomarkers demonstrate promising results as possible methods for early detection, predicting recurrence and monitoring therapy. Other biomarkers appear to be promising for identifying patients at risk for metastasis. We reviewed the most pertinent information in the field thus far and how this knowledge can impact, or not, the management of melanoma patients prognostically and therapeutically. PMID:22966315

  5. The genomic landscape of cutaneous melanoma.

    PubMed

    Zhang, Tongwu; Dutton-Regester, Ken; Brown, Kevin M; Hayward, Nicholas K

    2016-05-01

    Somatic mutation analysis of melanoma has been performed at the single gene level extensively over the past several decades. This has provided considerable insight into the critical pathways controlling melanoma initiation and progression. During the last 5 yr, next-generation sequencing (NGS) has enabled even more comprehensive mutational screening at the level of multigene panels, exomes and genomes. These studies have uncovered many new and unexpected players in melanoma development. The recent landmark study from The Cancer Genome Atlas (TCGA) consortium describing the genomic architecture of 333 cutaneous melanomas provides the largest and broadest analysis to date on the somatic aberrations underlying melanoma genesis. It thus seems timely to review the mutational landscape of melanoma and highlight the key genes and cellular pathways that appear to drive this cancer. PMID:26833684

  6. Enucleation versus plaque irradiation for choroidal melanoma

    SciTech Connect

    Straatsma, B.R.; Fine, S.L.; Earle, J.D.; Hawkins, B.S.; Diener-West, M.; McLaughlin, J.A.

    1988-07-01

    The Collaborative Ocular Melanoma Study (COMS) is an international, multicenter-controlled study. The organization includes an Executive Committee, Steering Committee, 6 Central Units, 32 Clinical Centers, and a Data and Safety Monitoring Committee. Scientifically, the COMS consists of (1) a randomized trial of patients with medium choroidal melanoma treated with enucleation versus iodine-125 plaque irradiation, (2) a randomized trial of patients with large choroidal melanoma treated with enucleation versus preenucleation external beam irradiation and enucleation, and (3) a prospective observational study of patients with small choroidal melanoma to determine whether a randomized trial of treatment is appropriate. In design and conduct of the COMS, special consideration is given to biostatistics and sample size considerations, iodine-125 plaque irradiation of choroidal melanoma, and coordinated ocular melanoma research. Recruitment is in progress. However, the pool of eligible patients is limited and the COMS needs the continued support and cooperation of ophthalmologists throughout the United States and Canada.

  7. Genetic and environmental melanoma models in fish

    PubMed Central

    Patton, E Elizabeth; Mitchell, David L; Nairn, Rodney S

    2010-01-01

    Experimental animal models are extremely valuable for the study of human diseases, especially those with underlying genetic components. The exploitation of various animal models, from fruitflies to mice, has led to major advances in our understanding of the etiologies of many diseases, including cancer. Cutaneous malignant melanoma is a form of cancer for which both environmental insult (i.e., UV) and hereditary predisposition are major causative factors. Fish melanoma models have been used in studies of both spontaneous and induced melanoma formation. Genetic hybrids between platyfish and swordtails, different species of the genus Xiphophorus, have been studied since the 1920s to identify genetic determinants of pigmentation and melanoma formation. Recently, transgenesis has been used to develop zebrafish and medaka models for melanoma research. This review will provide a historical perspective on the use of fish models in melanoma research, and an updated summary of current and prospective studies using these unique experimental systems. PMID:20230482

  8. Primary extramedullary spinal melanoma mimicking spinal meningioma: A case report and literature review

    PubMed Central

    LI, YU-PING; ZHANG, HENG-ZHU; SHE, LEI; WANG, XIAO-DONG; DONG, LUN; XU, ENXI; WANG, XING-DONG

    2014-01-01

    Primary spinal melanoma is a rare lesion, which occurs throughout the cranial and spinal regions, however, is primarily observed in the middle or lower thoracic spine. The clinical features of primary spinal melanoma are complex and unspecific, resulting in a high misdiagnosis rate. In the present case report, a rare case of spinal melanoma exhibiting the dural tail sign and mimicking spinal meningioma is reported. The initial diagnosis, using magnetic resonance imaging (MRI), was unclear. Thus, melanin-containing tumors and spinal meningioma should have been considered in the differential diagnosis. The tumor was completely resected using a standard posterior midline approach, which was followed by chemotherapy. Subsequent to the surgery, the patient was discharged with improved motor capacity and a follow-up MRI scan showed no recurrence after six months. The present study demonstrates that it is critical for neurosurgeons to focus on increasing the accuracy of initial diagnoses in order to make informed decisions regarding the requirement for surgical resection. The present case report presents the clinical, radiological and pathological features of primary extramedullary spinal melanoma mimicking spinal meningioma to emphasize the importance of early identification and diagnosis. PMID:24959273

  9. Melanoma-specific marker expression in skin biopsy tissues as a tool to facilitate melanoma diagnosis.

    PubMed

    Alexandrescu, Doru T; Kauffman, C Lisa; Jatkoe, Timothy A; Hartmann, Dan P; Vener, Tatiana; Wang, Haiying; Derecho, Carlo; Rajpurohit, Yashoda; Wang, Yixin; Palma, John F

    2010-07-01

    Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed. PMID:20357814

  10. Primary malignant melanoma of the esophagus

    PubMed Central

    Jora, Charu; Pankaj, Promila; Verma, Ritu; Jain, Anjali; Belho, Ethel S.

    2015-01-01

    Primary malignant melanoma most commonly originates from the skin; other less common extra cutaneous sites include squamous mucous membranes, uvea, retina, leptomeninges, genitourinary tract, digestive tract, biliary tract, and upper respiratory tract. Primary melanoma of the gastrointestinal tract is exceedingly rare. We are reporting a histo-pathologically proven rare case of primary malignant melanoma of the esophagus and its findings on fluorodeoxyglucose positron emission tomography and computed tomography. PMID:25829739

  11. Primary malignant melanoma of the esophagus.

    PubMed

    Jora, Charu; Pankaj, Promila; Verma, Ritu; Jain, Anjali; Belho, Ethel S

    2015-01-01

    Primary malignant melanoma most commonly originates from the skin; other less common extra cutaneous sites include squamous mucous membranes, uvea, retina, leptomeninges, genitourinary tract, digestive tract, biliary tract, and upper respiratory tract. Primary melanoma of the gastrointestinal tract is exceedingly rare. We are reporting a histo-pathologically proven rare case of primary malignant melanoma of the esophagus and its findings on fluorodeoxyglucose positron emission tomography and computed tomography. PMID:25829739

  12. A Case of Amelanotic Subungual Melanoma

    PubMed Central

    Kim, Sun Ji; Park, Hyun Jeong; Lee, Jun Young

    2008-01-01

    Amelanotic subungual melanoma is a rare dermatosis, and it is frequently misdiagnosed probably because of its nonspecific clinical features. We herein report on a case of amelanotic subungual melanoma extended to the adjacent skin in a 36-year-old Korean woman. This case is interesting in that clinically, it needed differentiation from Bowen's disease, lichen planus, sarcoidosis, etc. and very early invading features of the melanoma were observed on the histopathologic section. PMID:27303154

  13. Clinicopathological characterization of mouse models of melanoma.

    PubMed

    Ferguson, Blake; Soyer, H Peter; Walker, Graeme J

    2015-01-01

    Mouse models of melanoma have proven invaluable in the delineation of key molecular events involved in disease progression in humans and provide potential preclinical models for therapeutic testing (Damsky and Bosenberg, Pigment Cell Melanoma Res 25(4):404-405, 2012; Walker et al., Pigment Cell Melanoma Res 24(6):1158-1176, 2011). Here we concentrate on the clinicopathological analysis of melanocytic tumors. PMID:25636472

  14. Dermoscopic and clinical features of trunk melanomas

    PubMed Central

    Emiroglu, Nazan; Hofmann-Wellenhof, Rainer

    2014-01-01

    Introduction Malignant melanomas account for 5% of all skin cancers and usually have a fatal clinical course. Additionally, the incidence of melanoma increases more rapidly than in any other cancer, and this has been attributed to the development of highly sensitive diagnostic techniques, mainly dermoscopy, which allows for early diagnosis. The phenotypic manifestations of gene/environment interactions, environmental factor and genetic factors may determine subtypes and anatomic localization of melanoma. Histopathologic subtypes, risk factors, and thickness of the skin are different in trunk melanomas. Aim To determine the frequency of dermatoscopic features in trunk melanomas. This study also investigates dermoscopic features according to the diameter of lesions. Material and methods Seventy-one trunk melanomas were included. Their dermoscopic and clinical images, histopathological and clinical data were assessed. The relations between the diameter, Breslow thickness and dermoscopic characteristics were evaluated. Results The most common dermoscopic findings of trunk melanomas were the multicomponent pattern (55 patients, 77.5%), asymmetry (62 patients; 87.3%), blue-gray veil (59 patients, 83.1%), and color variety (56 patients, 78.8%). When dermoscopic findings were compared, a multicomponent pattern (p = 0.03), milky-red areas (p = 0.001), blue-gray veils (p = 0.023), and regression structures (p = 0.037) were more common in large melanomas than in small melanomas. Conclusions The most common dermoscopic findings of trunk melanomas were the multicomponent pattern, asymmetry and blue-gray veil, color variety. The multicomponent pattern, milky-red areas, blue-gray veils, regression structures were statistically significant dermoscopic features in a group of large-diameter melanomas, compared to small melanomas. PMID:25610350

  15. Histone variants and melanoma: facts and hypotheses.

    PubMed

    Konstantinov, Nikifor K; Ulff-Møller, Constance J; Dimitrov, Stefan

    2016-07-01

    Melanoma is the most aggressive form of skin cancer with rising incidence and morbidity. Despite advances in treatment, the 10-yr survival for patients with metastatic disease is less than 10%. During the past few years, ongoing research on different epigenomic aberrations in melanoma has catalyzed better understanding of its pathogenesis and identification of new therapeutics. In our review, we will focus on the role of histone variants, key epigenetic players in melanoma initiation and progression. Specifically, incorporation of histone variants enables additional layers of chromatin structure, and here, we will describe how alterations in this epigenetic behavior impact melanoma. PMID:26909678

  16. Emerging phytochemicals for prevention of melanoma invasion

    PubMed Central

    Jones, Virginia; Katiyar, Santosh K.

    2013-01-01

    Cutaneous malignant melanoma is the leading cause of death from skin diseases due to its propensity to metastasize. Once diagnosed with metastatic melanoma, most patients will die of their disease within 2 years. As suppression of metastases requires long-term interventions, potential anti-metastatic agents must not only be efficacious but also have low toxicity. Many phytochemicals used in traditional medicine have low toxicity and recent studies suggest that some are promising candidates for the prevention or treatment of metastatic melanoma. Here, we review the recent literature regarding phytochemicals that have shown inhibitory effects on melanoma cell migration or invasion. PMID:23474498

  17. Emerging targets for combination therapy in melanomas.

    PubMed

    Saito, Renata de Freitas; Tortelli, Tharcísio Citrângulo; Jacomassi, Mayara D'Auria; Otake, Andréia Hanada; Chammas, Roger

    2015-11-14

    Cutaneous melanomas are often difficult to treat when diagnosed in advanced stages. Melanoma cells adapt to survive in extreme environmental conditions and are among the tumors with larger genomic instability. Here we discuss some intrinsic and extrinsic mechanisms of resistance of melanoma cells to both conventional and target therapies, such as autophagy, adaptation to endoplasmic reticulum stress, metabolic reprogramming, mechanisms of tumor repopulation and the role of extracellular vesicles in this later phenomenon. These biological processes are potentially targetable and thus provide a platform for research and discovery of new drugs for combination therapy to manage melanoma patient treatment. PMID:26450371

  18. Genetic testing for melanoma predisposition: current challenges.

    PubMed

    Gerstenblith, Meg R; Goldstein, Alisa M; Tucker, Margaret A; Fraser, Mary C

    2007-01-01

    A complex interaction of genetic, host, and environmental factors results in cutaneous malignant melanoma, the fifth most common cancer among men and the sixth among women in the United States. Mortality rates for cutaneous malignant melanoma depend on stage at diagnosis; thus, efforts are aimed at early detection and identification of risk factors for melanoma to distinguish those individuals requiring close surveillance. Melanoma susceptibility genes CDKN2A and CDK4 play a role in the development of melanoma, especially among some familial melanoma kindreds. The functions of CDKN2A and CDK4 in melanoma development, however, are currently incompletely understood. Therefore, at this time, predictive genetic testing for CDKN2A mutations outside of defined research protocols is not recommended because of the low likelihood of detecting mutations even in high-risk groups, the present inadequacy of interpreting a test result due to variations in penetrance and unclear associations with other cancers, and the minimal influence knowledge of mutation status currently has on medical management. Oncology nurses have an important role in identifying individuals at high risk for melanoma regardless of CDKN2A mutation status, encouraging enrollment in skin surveillance programs, and providing patient education regarding sun protection, prevention and early detection of melanoma. PMID:18025917

  19. Desmoplastic melanoma: a diagnostic dilemma.

    PubMed

    Alva, Ashwin K; K V, Rajeshwara; Udaykumar

    2013-06-01

    Desmoplastic melanoma (DM) is an uncommonly encountered type of melanoma. A pigmentation is frequently absent, although a lentigo or lentigomaligna-like discolouration, adjacent to the nodule, is not uncommon. Hence, the clinical impression at presentation may vary from those of basal cell or squamous cell carcinomas, dermatofibromas or sarcomas to cysts and indurated plaque-like lesions which resemble scars. Making a cinical diagnosis of this tumour is difficult and it may very often mislead the physician. The clinical appearance of DM may be highly variable and the diagnosis of the tumour is difficult. We are reporting a case of DM which was diagnosed histopathologically and confirmed by immunohistochemistry (IHC), for its rarity and unique presentation. PMID:23905132

  20. Neutron capture therapy for melanoma

    SciTech Connect

    Coderre, J.A.; Glass, J.D.; Micca, P.; Fairchild, R.G.

    1988-01-01

    The development of boron-containing compounds which localize selectively in tumor may require a tumor-by-tumor type of approach that exploits any metabolic pathways unique to the particular type of tumor. Melanin-producing melanomas actively transport and metabolize aromatic amino acids for use as precursors in the synthesis of the pigment melanin. It has been shown that the boron-containing amino acid analog p-borono-phenylalanine (BPA) is selectively accumulated in melanoma tissue, producing boron concentrations in tumor that are within the range estimated to be necessary for successful boron neutron capture therapy (BNCT). We report here the results of therapy experiments carried out at the Brookhaven Medical Research Reactor (BMRR). 21 refs., 5 figs., 3 tabs.

  1. Melanoma of the glans penis.

    PubMed

    Betti, Roberto; Menni, Silvano; Crosti, Carlo

    2005-01-01

    The authors describe the case of a 64-year old man who presented with an asymptomatic brown macula on his glans penis that had appeared about 18 months earlier. Dermoscopy analysis demonstrated a prominent, wide and irregular pigment network, which stopped abruptly at the periphery of the lesion. A diagnostic biopsy showed the characteristics of a melanoma in situ . The patient was referred for partial surgical excision of the glans. No recurrence or metastasis occurred during the two years after the operation. Melanoma in situ of the penis is very rare in dermatologic literature. Early diagnosis is of paramount importance because its prognosis is very poor. Early systematic use of dermoscopy may be useful for the differential diagnosis of pigmented mucosal lesions, which include mucosal melanosis and other benign melanoses of genitalia. PMID:15757826

  2. A Rare and Extensive Case of Oral Malignant Melanoma involving Mandibular Gingiva.

    PubMed

    Rathore, Rajendrasinh S; Phulari, Rashmi Gs; Vasavada, Dharmesh G; Patel, Dipen K

    2016-02-01

    Oral malignant melanoma is an infrequent but an aggressive neoplasm of unknown etiology, seen most commonly in middle age male patients and is more frequently seen at the hard palate and gingiva. The tumor tends to metastasize or locally invade tissue more readily than other malignant tumors in the oral region. In this article, we report a rare case of extensive oral melanoma in a 55-year-old male patient, with a chief complaint of painless growth in mandibular anterior gingiva measuring about 2.6 X 1.7 X 0.8 cm and extending bilaterally till posterior mandibular gingiva and unilaterally to right buccal mucosa. The most common site being hard palate and maxillary gingiva, it is extremely rare in mandibular gingiva (less than 7%) and hence, this rare occurrence in mandibular gingiva is reported, the diagnosis of which was confirmed by histopathology and immunohistochemistry. PMID:27042595

  3. A Rare and Extensive Case of Oral Malignant Melanoma involving Mandibular Gingiva

    PubMed Central

    Rathore, Rajendrasinh S; Vasavada, Dharmesh G; Patel, Dipen K

    2016-01-01

    Oral malignant melanoma is an infrequent but an aggressive neoplasm of unknown etiology, seen most commonly in middle age male patients and is more frequently seen at the hard palate and gingiva. The tumor tends to metastasize or locally invade tissue more readily than other malignant tumors in the oral region. In this article, we report a rare case of extensive oral melanoma in a 55-year-old male patient, with a chief complaint of painless growth in mandibular anterior gingiva measuring about 2.6 X 1.7 X 0.8 cm and extending bilaterally till posterior mandibular gingiva and unilaterally to right buccal mucosa. The most common site being hard palate and maxillary gingiva, it is extremely rare in mandibular gingiva (less than 7%) and hence, this rare occurrence in mandibular gingiva is reported, the diagnosis of which was confirmed by histopathology and immunohistochemistry. PMID:27042595

  4. Biology of Human Cutaneous Melanoma

    PubMed Central

    Elias, Elias G.; Hasskamp, Joanne H.; Sharma, Bhuvnesh K.

    2010-01-01

    A review of the natural behavior of cutaneous melanoma, clinical and pathological factors, prognostic indicators, some basic research and the present and possible futuristic strategies in the management of this disease are presented. While surgery remains to be the most effective therapeutic approach in the management of early primary lesions, there is no standard adjuvant therapy after surgical resection, or for metastatic disease. PMID:24281039

  5. Choroidal Metastases From Cutaneous Melanoma.

    PubMed

    Mercado, Carmel L; Toy, Brian C; Kistler, Henry B; Moshfeghi, Darius M

    2016-05-01

    A 92-year-old man presented with months of progressive blurry vision, worsening acutely in his right eye. He denied pain, diplopia, or photopsias. His history was significant for multiple myeloma, prostate cancer, and malignant melanoma of his right shoulder treated with local excision. He had local recurrence with hepatic metastasis of the melanoma treated with radiation and chemotherapy. On examination, his visual acuity was counting fingers in the right eye and 20/60 in the left eye. Amsler grid testing demonstrated metamorphopsia in the right eye. Fundus exam of the right and left eyes revealed multiple, elevated, pigmented choroidal lesions, with associated subretinal fluid in the right macula. This appearance is consistent with hematogenous metastasis of cutaneous malignant melanoma to the choroid and associated serous fluid-causing metamorphopsia. The patient was enrolled in a clinical trial combining plasmid IL-12 with pembrolizumab (Keytruda; Merck, Whitehouse Station, NJ). He passed away 2 months after initial presentation to our clinic. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:497.]. PMID:27183558

  6. Melanoma arising after imiquimod use.

    PubMed

    Paul, Sharad P

    2014-01-01

    Imiquimod belongs to the class of 1H-imidazo-[4,5-c]quinolones-drugs originally developed as nucleoside analogues with the aim of finding new potential antiviral agents (Harrison et al., 1988). Indeed, Imiquimod was first released as treatment for genital warts before its actions against skin cancer were studied. Imiquimod is a relatively small sized molecule (Mr = 240.3) and is hydrophobic, allowing it to penetrate the skin epidermal barrier and therefore making it suitable for topical formulations (Gerster et al., 2005). Imiquimod has shown itself effective against skin cancers and precancerous lesions, especially basal cell cancers and actinic keratosis (Salasche et al., 2002, Beutner et al., 1999). There have been reports of Imiquimod being used as topical treatment against cutaneous metastases of melanoma and some authors have reported its use as first-line therapy against melanoma in situ (Smyth et al., 2011, Gagnon, 2011). We report a case of an invasive malignant melanoma arising de novo at the specific site of application of Imiquimod (Aldara cream 5%) for a biopsy-proven superficial BCC. Therefore while Imiquimod has added to our topical armamentarium against skin cancer, care must be exercised in prescribing this treatment and it is especially important to follow up patients regularly. PMID:25431597

  7. Genomic Classification of Cutaneous Melanoma.

    PubMed

    2015-06-18

    We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making. PMID:26091043

  8. Melanoma: from mutations to medicine

    PubMed Central

    Tsao, Hensin; Chin, Lynda; Garraway, Levi A.; Fisher, David E.

    2012-01-01

    Melanoma is often considered one of the most aggressive and treatment-resistant human cancers. It is a disease that, due to the presence of melanin pigment, was accurately diagnosed earlier than most other malignancies and that has been subjected to countless therapeutic strategies. Aside from early surgical resection, no therapeutic modality has been found to afford a high likelihood of curative outcome. However, discoveries reported in recent years have revealed a near avalanche of breakthroughs in the melanoma field—breakthroughs that span fundamental understanding of the molecular basis of the disease all the way to new therapeutic strategies that produce unquestionable clinical benefit. These discoveries have been born from the successful fruits of numerous researchers working in many—sometimes-related, although also distinct—biomedical disciplines. Discoveries of frequent mutations involving BRAF(V600E), developmental and oncogenic roles for the microphthalmia-associated transcription factor (MITF) pathway, clinical efficacy of BRAF-targeted small molecules, and emerging mechanisms underlying resistance to targeted therapeutics represent just a sample of the findings that have created a striking inflection in the quest for clinically meaningful progress in the melanoma field. PMID:22661227

  9. Immune based therapy for melanoma

    PubMed Central

    Ancuceanu, Robert; Neagu, Monica

    2016-01-01

    A few years ago therapeutic options in advanced melanoma were very limited and the prognosis was somber. Although recent progresses are far from providing a cure for advanced melanoma, yet these have kindled new hopes and searching for a cure does not seem unreasonable. Seven new medicines have been authorized in various regions of the world in the recent past in the therapy of advanced melanoma, over half of them acting by mechanisms involving the immune system of the host. The anti-CTLA-4 (cytotoxic T lymphocyte associated protein-4) ipilimumab has been followed by anti-PD1 (programmed death1) inhibitors, more effective and safer. Very recently, the first oncolytic immunotherapy, talimogene laherparepvec (T-VEC) has been authorized for placing on the market and a variety of combinations of the new therapies are currently being evaluated or considered. Besides, a plethora of other molecules and approaches, especially monoclonal antibodies, are in the preliminary phases of clinical investigation and are likely to bring new benefits for the treatment of this potentially fatal form of cancer. PMID:27121512

  10. Isolated posterior cruciate ligament calcification.

    PubMed

    Koukoulias, Nikolaos E; Papastergiou, Stergios G

    2011-01-01

    The authors present a case of calcified posterior cruciate ligament (PCL). A 61-year-old female presented in our department reporting 12 months history of knee pain that was getting worse during the night. The patient was under medication for epileptic seizure, osteoporosis and hyperthyroidism. X-rays demonstrated calcification of the PCL. CT and MRI excluded any other intra-articular and extra-articular pathology. Arthroscopic debridement of the calcium deposits was performed and the symptoms resolved immediately, while the postoperative x-rays were normal. Histological examination confirmed the calcium nature of the lesion. Two years postoperatively the patient remains asymptomatic. PMID:22669889

  11. Isolated posterior cruciate ligament calcification

    PubMed Central

    Koukoulias, Nikolaos E; Papastergiou, Stergios G

    2011-01-01

    The authors present a case of calcified posterior cruciate ligament (PCL). A 61-year-old female presented in our department reporting 12 months history of knee pain that was getting worse during the night. The patient was under medication for epileptic seizure, osteoporosis and hyperthyroidism. X-rays demonstrated calcification of the PCL. CT and MRI excluded any other intra-articular and extra-articular pathology. Arthroscopic debridement of the calcium deposits was performed and the symptoms resolved immediately, while the postoperative x-rays were normal. Histological examination confirmed the calcium nature of the lesion. Two years postoperatively the patient remains asymptomatic. PMID:22669889

  12. Posterior ankyloglossia: a case report.

    PubMed

    Chu, Michael W; Bloom, David C

    2009-06-01

    Ankyloglossia, or tongue-tie, refers to an abnormally short lingual frenulum. Ankyloglossia is a recognized but poorly defined condition and has been reported to cause feeding difficulties, dysarthria, dyspnea, and social or mechanical problems. In infants, the most concerning symptoms are feeding difficulties and inability to breastfeed. While a recent trend toward breastfeeding has brought frenulectomy back into favor, the literature regarding treatment remains inconclusive. We report a case of posterior ankyloglossia with anterior mucosal hooding and a simple, safe, and effective way to treat it to improve breastfeeding. PMID:19303646

  13. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey.

    PubMed

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian; Drzewiecki, Krzysztof T; Prause, Jan U; Heegaard, Steffen

    2016-06-01

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma). PMID:27004972

  14. Gab2-Mediated Signaling Promotes Melanoma Metastasis

    PubMed Central

    Horst, Basil; Gruvberger-Saal, Sofia K.; Hopkins, Benjamin D.; Bordone, Lindsey; Yang, Ying; Chernoff, Karen A.; Uzoma, Ijeoma; Schwipper, Volker; Liebau, Jutta; Nowak, Norma J.; Brunner, Georg; Owens, David; Rimm, David L.; Parsons, Ramon; Celebi, Julide Tok

    2009-01-01

    Metastatic melanoma is a disease with a poor prognosis that currently lacks effective treatments. Critical biological features of metastasis include acquisition of migratory competence, growth factor independence, and invasive potential. In an attempt to identify genes that contribute to melanoma pathogenesis, a genome-wide search using bacterial artificial chromosome array comparative genomic hybridization and single nucleotide polymorphism arrays in a series of 64 metastatic melanoma samples and 20 melanoma cell lines identified increased copy numbers of Gab2 located on 11q14.1. Gab2 is an adaptor protein that potentiates the activation of the Ras-Erk and PI3K-Akt pathways and has recently been implicated in human cancer; however, its role in melanoma has not been explored. In this study, we found that Gab2 was either amplified (∼11%) and/or overexpressed (∼50%) in melanoma. Gab2 protein expression correlated with clinical melanoma progression, and higher levels of expression were seen in metastatic melanomas compared with primary melanoma and melanocytic nevi. We found that overexpression of Gab2 potentiates, whereas silencing of Gab2 reduces, migration and invasion of melanoma cells. Gab2 mediated the hyperactivation of Akt signaling in the absence of growth factors, whereas inhibition of the PI3K-Akt pathway decreased Gab2-mediated tumor cell migration and invasive potential. Gab2 overexpression resulted in enhanced tumor growth and metastatic potential in vivo. These studies demonstrate a previously undefined role for Gab2 in melanoma tumor progression and metastasis. PMID:19342374

  15. Longevity of Posterior Composite Restorations

    PubMed Central

    Opdam, N.J.M.; van de Sande, F.H.; Bronkhorst, E.; Cenci, M.S.; Bottenberg, P.; Pallesen, U.; Gaengler, P.; Lindberg, A.; Huysmans, M.C.D.N.J.M.; van Dijken, J.W.

    2014-01-01

    The aim of this meta-analysis, based on individual participant data from several studies, was to investigate the influence of patient-, materials-, and tooth-related variables on the survival of posterior resin composite restorations. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a search resulting in 12 longitudinal studies of direct posterior resin composite restorations with at least 5 years’ follow-up. Original datasets were still available, including placement/failure/censoring of restorations, restored surfaces, materials used, reasons for clinical failure, and caries-risk status. A database including all restorations was constructed, and a multivariate Cox regression method was used to analyze variables of interest [patient (age; gender; caries-risk status), jaw (upper; lower), number of restored surfaces, resin composite and adhesive materials, and use of glass-ionomer cement as base/liner (present or absent)]. The hazard ratios with respective 95% confidence intervals were determined, and annual failure rates were calculated for subgroups. Of all restorations, 2,816 (2,585 Class II and 231 Class I) were included in the analysis, of which 569 failed during the observation period. Main reasons for failure were caries and fracture. The regression analyses showed a significantly higher risk of failure for restorations in high-caries-risk individuals and those with a higher number of restored surfaces. PMID:25048250

  16. Huge interparietal posterior fontanel meningohydroencephalocele

    PubMed Central

    Dos Santos, Manuel Filipe Dias; de Santa Barbara, Rita de Cassia

    2015-01-01

    Congenital encephalocele is a neural tube defect characterized by a sac-like protrusion of the brain, meninges, and other intracranial structures through the skull, which is caused by an embryonic development abnormality. The most common location is at the occipital bone, and its incidence varies according to different world regions. We report a case of an 1-month and 7-day-old male child with a huge interparietal-posterior fontanel meningohydroencephalocele, a rare occurrence. Physical examination and volumetric computed tomography were diagnostic. The encephalocele was surgically resected. Intradural and extradural approaches were performed; the bone defect was not primarily closed. Two days after surgery, the patient developed hydrocephaly requiring ventriculoperitoneal shunting. The surgical treatment of the meningohydroencephalocele of the interparietal-posterior fontanel may be accompanied by technical challenges and followed by complications due to the presence of large blood vessels under the overlying skin. In these cases, huge sacs herniate through large bone defects including meninges, brain, and blood vessels. The latter present communication with the superior sagittal sinus and ventricular system. A favorable surgical outcome generally follows an accurate strategy taking into account individual features of the lesion. PMID:26484324

  17. Treatment of malignant melanoma by selective thermal neutron capture therapy using melanoma-seeking compound

    SciTech Connect

    Mishima, Y.; Ichihashi, M.; Tsuji, M.; Hatta, S.; Ueda, M.; Honda, C.; Suzuki, T.

    1989-05-01

    As pigment cells undergo melanoma genesis, accentuated melanogenesis concurrently occurs in principle. Subsequent to the understanding of intrinsic factors controlling both processes, we found our selective melanoma neutron capture therapy (NCT) using 10B-dopa (melanin substrate) analogue, 10B1-p-boronophenylalanine (10B1-BPA), followed by 10B(n, alpha)7Li reaction, induced by essentially harmless thermal neutrons, which releases energy of 2.33 MeV to 14 mu, the diameter of melanoma cells. In vitro/in vivo radiobiological analysis revealed the highly enhanced melanoma killing effect of 10B1-BPA. Chemical and prompt gamma ray spectrometry assays of 10B accumulated within melanoma cells after 10B1-BPA administration in vitro and in vivo show high affinity, e.g., 10B melanoma/blood ratio of 11.5. After successfully eradicating melanoma transplanted into hamsters with NCT, we advanced to preclinical studies using spontaneously occurring melanoma in Duroc pig skin. We cured three melanoma cases, 4.6 to 12 cm in diameter, by single neutron capture treatment. Complete disappearance of melanoma was obtained without substantial side effects. Acute and subacute toxicity as well as pharmacodynamics of 10B1-BPA have been studied in relation to therapeutic dosage requirements. Clinical radiation dosimetry using human phantom has been carried out. Further preclinical studies using human melanoma transplanted into nude mouse have been a useful model for obtaining optimal results for each melanoma type. We recently treated the first human melanoma patient with our NCT, using essentially the method for Duroc pig melanoma, and obtained similar regression time course leading to cure.

  18. Herramienta para distinguir lunares de melanoma.

    Cancer.gov

    “De lunares a melanoma: reconocimiento de las características ABCDE” presenta fotos que muestran cambios en lesions individuales pigmentadas con el tiempo, y describe las diferentes apariencias de lunares, de nevos displásicos y de melanomas.

  19. Malignant melanoma at a scientific laboratory

    SciTech Connect

    Shy, C.M.; Checkoway, H.; Marshall, E.G.

    1985-11-15

    The general consensus of the seven reviewers is that occupational exposures at Lawrence Livermore National Laboratory have not been established as a causal factor for the observed excess of malignant melanoma. Several observations support the impression that some or all of the observed melanoma excess may be attributable to intense surveillance and enhanced detection of early stage melanoma lesions. Since the incidence of melanomas among Laboratory employees has not diminished, an early harvesting effect is unlikely. This suggests the distinct possibility that localized, in situ melanomas that would normally not be detected are being reported, and that in the absence of this enhanced detection, many of these early stage lesions would show little or no clinical progression. This phenomenon would explain the continued high incidence of melanomas in the absence of a physical or chemical inciting cause. A key point in this reasoning is the issue of the rate of growth of early stage melanomas, and this point remains a key question for study. Even if the observed excess cannot be explained by detection bias, the reviewers agree that the Austin and Reynolds' study does not make a convincing case for occupational factors being a cause of the high melanoma incidence. 6 refs.

  20. Update in genetic susceptibility in melanoma.

    PubMed

    Potrony, Miriam; Badenas, Celia; Aguilera, Paula; Puig-Butille, Joan Anton; Carrera, Cristina; Malvehy, Josep; Puig, Susana

    2015-09-01

    Melanoma is the most deadly of the common skin cancers and its incidence is rapidly increasing. Approximately 10% of cases occur in a familial context. To date, cyclin-dependent kinase inhibitor 2A (CDKN2A), which was identified as the first melanoma susceptibility gene more than 20 years ago, is the main high-risk gene for melanoma. A few years later cyclin-dependent kinase 4 (CDK4) was also identified as a melanoma susceptibility gene. The technologic advances have allowed the identification of new genes involved in melanoma susceptibility: Breast cancer 1 (BRCA1) associated protein 1 (BAP1), CXC genes, telomerase reverse transcriptase (TERT), protection of telomeres 1 (POT1), ACD and TERF2IP, the latter four being involved in telomere maintenance. Furthermore variants in melanocortin 1 receptor (MC1R) and microphthalmia-associated transcription factor (MITF) give a moderately increased risk to develop melanoma. Melanoma genetic counseling is offered to families in order to better understand the disease and the genetic susceptibility of developing it. Genetic counseling often implies genetic testing, although patients can benefit from genetic counseling even when they do not fulfill the criteria for these tests. Genetic testing for melanoma predisposition mutations can be used in clinical practice under adequate selection criteria and giving a valid test interpretation and genetic counseling to the individual. PMID:26488006

  1. Update in genetic susceptibility in melanoma

    PubMed Central

    Potrony, Miriam; Badenas, Celia; Aguilera, Paula; Puig-Butille, Joan Anton; Carrera, Cristina; Malvehy, Josep

    2015-01-01

    Melanoma is the most deadly of the common skin cancers and its incidence is rapidly increasing. Approximately 10% of cases occur in a familial context. To date, cyclin-dependent kinase inhibitor 2A (CDKN2A), which was identified as the first melanoma susceptibility gene more than 20 years ago, is the main high-risk gene for melanoma. A few years later cyclin-dependent kinase 4 (CDK4) was also identified as a melanoma susceptibility gene. The technologic advances have allowed the identification of new genes involved in melanoma susceptibility: Breast cancer 1 (BRCA1) associated protein 1 (BAP1), CXC genes, telomerase reverse transcriptase (TERT), protection of telomeres 1 (POT1), ACD and TERF2IP, the latter four being involved in telomere maintenance. Furthermore variants in melanocortin 1 receptor (MC1R) and microphthalmia-associated transcription factor (MITF) give a moderately increased risk to develop melanoma. Melanoma genetic counseling is offered to families in order to better understand the disease and the genetic susceptibility of developing it. Genetic counseling often implies genetic testing, although patients can benefit from genetic counseling even when they do not fulfill the criteria for these tests. Genetic testing for melanoma predisposition mutations can be used in clinical practice under adequate selection criteria and giving a valid test interpretation and genetic counseling to the individual. PMID:26488006

  2. Mechanisms of Melanoma Promotion by Ultraviolet Radiation.

    PubMed

    Rünger, Thomas M

    2016-09-01

    The mutagenic properties of ultraviolet radiation drive the initiation of melanoma. Induction of matrix metalloproteinases in melanoma cells by longwave UVA radiation, possibly via a Warburg-like effect, promotes melanoma invasiveness. This is one of several mechanisms by which ultraviolet radiation also promotes further growth of previously established melanomas. PMID:27542295

  3. Beyond BRAF: where next for melanoma therapy?

    PubMed Central

    Fedorenko, I V; Gibney, G T; Sondak, V K; Smalley, K S M

    2015-01-01

    In recent years, melanoma has become a poster-child for the development of oncogene-directed targeted therapies. This approach, which has been exemplified by the development of small-molecule BRAF inhibitors and the BRAF/MEK inhibitor combination for BRAF-mutant melanoma, has brought new hope to patients. Despite these successes, treatment failure seems near inevitable in the majority of cases—even in individuals treated with the BRAF/MEK inhibitor doublet. In the current review, we discuss the future of combination strategies for patients with BRAF-mutant melanoma as well as the emerging therapeutic options for patients with NRAS-mutant and BRAF/NRAS-wild-type melanoma. We also outline some of the newest developments in the in-depth personalisation of therapy that should allow melanoma treatment to continue shaping the field precision cancer medicine. PMID:25180764

  4. From Melanocyte to Metastatic Malignant Melanoma

    PubMed Central

    Bandarchi, Bizhan; Ma, Linglei; Navab, Roya; Seth, Arun; Rasty, Golnar

    2010-01-01

    Malignant melanoma is one of the most aggressive malignancies in human and is responsible for almost 60% of lethal skin tumors. Its incidence has been increasing in white population in the past two decades. There is a complex interaction of environmental (exogenous) and endogenous, including genetic, risk factors in developing malignant melanoma. 8–12% of familial melanomas occur in a familial setting related to mutation of the CDKN2A gene that encodes p16. The aim of this is to briefly review the microanatomy and physiology of the melanocytes, epidemiology, risk factors, clinical presentation, historical classification and histopathology and, more in details, the most recent discoveries in biology and genetics of malignant melanoma. At the end, the final version of 2009 AJCC malignant melanoma staging and classification is presented. PMID:20936153

  5. Primary hepatic malignant melanoma: a case report.

    PubMed

    Du, Fangjuan; Yang, Maowu; Fang, Jingzhong; Jing, Changchun

    2015-01-01

    Primary hepatic malignant melanoma is a very rare disease. In order to provide clues concerning diagnosis, differential diagnosis and pathogenesis of the disease, a case of a 49 year-old female patient with primary hepatic malignant melanoma is presented. B-mode ultrasound and Contrast-enhanced abdominal computerized tomography (CT) examinations revealed that nodules of varying sizes are diffusely distributed in her enlarged liver. Pathological examination revealed that tumor cells with poor differentiation were located in nests with prominent melanin deposition. Immuno-histochemical staining showed that the tumor cells were positive for HMB-45 and S-100 protein. No evidence for primary malignant melanoma of other sites had been found by comprehensive examinations. Therefore, the patient was diagnosed with primary malignant melanoma of liver. Our case showed that primary malignant melanoma of liver is of histological heterogeneity, and immunohistochemical staining may aid in differential diagnosis between it and other hepatic neoplasms. PMID:25973128

  6. Clinical and morphological characteristics of cutaneous melanoma.

    PubMed

    Balaban, Jagoda; Ninković Baroš, Djuka; Grujić, Dragana; Starović, Dragana; Ćelić, Milanka

    2014-01-01

    The incidence of cutaneous melanoma has increased significantly worldwide over the last several decades. The aim of this study is to determine clinical and morphology characteristics of primary melanoma, since some of them are important prognostic factors. This retrospective study included 172 patients. The data were collected by the Consulting team for malignant skin tumors in the Banja Luka Clinical Centre from 2009 to 2011. We did not use dermoscopy as a diagnostic tool in our investigation. We determined that melanoma occurs equally commonly in both sexes, in women in the sixth decade and the seventh in men. The most common sub-type was nodular melanoma (59.5%, P<0.05), followed by superficial spreading (27.8%) and acral lentiginous melanoma (11.4%). The most common localization was on the back in men (34.3%) and on the legs in women (P<0.05). More than half of our patients (55.8%) had melanoma thickness from 1.0 to 4.0 mm, and 38% had a melanoma thicker than 4.0 mm. The average Breslow thickness is 4.6 mm. More women than men had melanoma thicker than 4 mm (P<0.05). Spread of the primary tumor localization was found in 31.4% of patients, more frequently in men than in women (P<0.05). In most cases it was abstraction of lymph nodes (P<0.05). The average thickness of the melanoma in our patients is much higher than the average in the world and the countries of Europe. The results of this study indicate a need for better unique regional registry in this part of Bosnia and Herzegovina and improvement of preventive measures in the early diagnosis of melanoma. PMID:25580786

  7. Minimally invasive posterior hamstring harvest.

    PubMed

    Wilson, Trent J; Lubowitz, James H

    2013-01-01

    Autogenous hamstring harvesting for knee ligament reconstruction is a well-established standard. Minimally invasive posterior hamstring harvest is a simple, efficient, reproducible technique for harvest of the semitendinosus or gracilis tendon or both medial hamstring tendons. A 2- to 3-cm longitudinal incision from the popliteal crease proximally, in line with the semitendinosus tendon, is sufficient. The deep fascia is bluntly penetrated, and the tendon or tendons are identified. Adhesions are dissected. Then, an open tendon stripper is used to release the tendon or tendons proximally; a closed, sharp tendon stripper is used to release the tendon or tendons from the pes. Layered, absorbable skin closure is performed, and the skin is covered with a skin sealant, bolster dressing, and plastic adhesive bandage for 2 weeks. PMID:24266003

  8. Primary Burkitt lymphoma in the posterior mediastinum.

    PubMed

    Chaari, Zied; Charfi, Slim; Hentati, Abdessalem; Ayadi, Ines; Abid, Hanene; Frikha, Imed

    2015-11-01

    A 13-year-old boy was admitted to our hospital with complaints of posterior chest pain and dyspnea. Computed tomography and magnetic resonance imaging of the chest revealed a mass in the posterior mediastinum, extending from T8 to T11 with intraspinal involvement. A percutaneous core needle biopsy confirmed the diagnosis of Burkitt lymphoma. He was treated according to the Lymphoma Malignancy B protocol 2001 arm C3, but he presented with liver and brain relapses and died 7.5 months after admission. Although lymphoma is rarely localized in the posterior mediastinum, it should be considered in the differential diagnosis of posterior mediastinal masses in children. PMID:26038605

  9. Fas-mediated apoptosis of melanoma cells and infiltrating lymphocytes in human malignant melanomas.

    PubMed

    Shukuwa, Tetsuo; Katayama, Ichiro; Koji, Takehiko

    2002-04-01

    In a rodent system, melanoma cells expressing Fas ligand (FasL) could kill Fas-positive lymphocytes, suggesting that FasL expression was an essential factor for melanoma cell survival in vivo. These findings led us to investigate apoptosis, and to histochemically analyze involvement of Fas and FasL in the induction of apoptosis, in human malignant melanoma tissues. The percentages of terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end-labeling (TUNEL)-positive melanoma cells and of proliferating cell nuclear antigen (PCNA)-positive melanoma cells in melanoma tissues (n = 22) were greater than those in melanocytes in uninvolved skin (n = 6) and nevus cells in nevi tissues (n = 9). The infiltrating lymphocytes around melanomas were also TUNEL positive. Immunohistochemistry revealed expression of Fas and FasL in melanoma cells and lymphocytes, whereas no Fas or FasL expression was detected in normal skin melanocytes and nevus cells. There was significant correlation between Fas-positive indices and TUNEL indices in melanoma tissues. Moreover, TUNEL-, Fas-, and FasL-positive indices of melanoma cells from patients with Stage 3 melanomas were significantly lower than those with Stage 2 melanomas. The PCNA index of Stage 1 melanoma was significantly lower than that of the other stages, although the difference of PCNA index was insignificant among Stages 2 to 4. Among Stages 1 to 4, there was no difference in the PCNA, TUNEL-, and Fas-positive indices of lymphocytes, although the FasL-positive index of lymphocytes from Stage 3 melanomas was significantly lower than in that from Stage 2. These data reveal that melanoma cells and infiltrating lymphocytes have the potential to induce their own apoptosis regulated by Fas and FasL in an autocrine and/or paracrine fashion and that the decline of Fas-mediated apoptosis of melanoma cells, rather than the apoptosis of infiltrating lymphocytes, may affect the prognosis of melanoma patients, possibly through the

  10. Characteristics and Treatment of Cutaneous Melanoma of the Foot

    PubMed Central

    Nam, Kyung Wook; Nam, Soo Bong; Kim, Joo Hyung; Kim, Hoon Soo; Choi, Young Jin

    2016-01-01

    Background In East Asia, the foot is the most common site of cutaneous melanoma. The purpose of this study was to investigate the differences between cutaneous melanoma of the foot and melanomas of other sites. Methods We studied 52 patients who underwent surgical treatment for cutaneous melanoma of the foot from September 2000 to January 2015. Through a retrospective review of their medical records, we collected data relating to their sex, age, histopathological subtype, Clark level, tumor thickness, lymph node involvement, stage, and survival rate, and we compared these parameters to those of 61 patients treated for melanoma of other sites. Moreover, we analyzed the surgical procedures, complications, and mortality rates associated with cutaneous melanoma on various parts of the foot. Results Melanoma of the foot differed from other melanomas only in the histopathological subtype. Other clinical features, including survival rate, did not differ significantly between the two groups heel was the most common site of melanoma of the foot (22 cases, 42.3%). The method of reconstruction varied depending on the region involved. Conclusions A comparison of melanoma of the foot to other melanomas showed that melanoma of the foot was associated with a significantly different distribution of histological subtypes. Consistent with previous findings, we found that the acral lentiginous subtype was the most common among melanomas of the foot. Furthermore, in contrast with previous studies, we did not find a worse prognosis or lower survival rate for melanoma of the foot in comparison with other melanomas. PMID:26848447

  11. Nevus count associations with pigmentary phenotype, histopathological melanoma characteristics and survival from melanoma.

    PubMed

    Taylor, Nicholas J; Thomas, Nancy E; Anton-Culver, Hoda; Armstrong, Bruce K; Begg, Colin B; Busam, Klaus J; Cust, Anne E; Dwyer, Terence; From, Lynn; Gallagher, Richard P; Gruber, Stephen B; Nishri, Diane E; Orlow, Irene; Rosso, Stefano; Venn, Alison J; Zanetti, Roberto; Berwick, Marianne; Kanetsky, Peter A

    2016-09-15

    Although nevus count is an established risk factor for melanoma, relationships between nevus number and patient and tumor characteristics have not been well studied and the influence of nevus count on melanoma-specific survival is equivocal. Using data from the Genes, Environment and Melanoma (GEM) study, a large population-based study of primary cutaneous melanoma, we evaluated associations between number of nevi and patient features, including sun-sensitivity summarized in a phenotypic index, and tumor characteristics. We also assessed the association of nevus count with melanoma-specific survival. Higher nevus counts were independently and positively associated with male gender and younger age at diagnosis, and they were inversely associated with lentigo maligna histology. We observed a borderline significant trend of poorer melanoma-specific survival with increasing quartile of nevus count, but little or no association between number of nevi and pigmentary phenotypic characteristics or prognostic tumor features. PMID:27101944

  12. A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation.

    PubMed

    Kaufman, Charles K; Mosimann, Christian; Fan, Zi Peng; Yang, Song; Thomas, Andrew J; Ablain, Julien; Tan, Justin L; Fogley, Rachel D; van Rooijen, Ellen; Hagedorn, Elliott J; Ciarlo, Christie; White, Richard M; Matos, Dominick A; Puller, Ann-Christin; Santoriello, Cristina; Liao, Eric C; Young, Richard A; Zon, Leonard I

    2016-01-29

    The "cancerized field" concept posits that cancer-prone cells in a given tissue share an oncogenic mutation, but only discreet clones within the field initiate tumors. Most benign nevi carry oncogenic BRAF(V600E) mutations but rarely become melanoma. The zebrafish crestin gene is expressed embryonically in neural crest progenitors (NCPs) and specifically reexpressed in melanoma. Live imaging of transgenic zebrafish crestin reporters shows that within a cancerized field (BRAF(V600E)-mutant; p53-deficient), a single melanocyte reactivates the NCP state, revealing a fate change at melanoma initiation in this model. NCP transcription factors, including sox10, regulate crestin expression. Forced sox10 overexpression in melanocytes accelerated melanoma formation, which is consistent with activation of NCP genes and super-enhancers leading to melanoma. Our work highlights NCP state reemergence as a key event in melanoma initiation. PMID:26823433

  13. Automatic differentiation of melanoma from dysplastic nevi.

    PubMed

    Rastgoo, Mojdeh; Garcia, Rafael; Morel, Olivier; Marzani, Franck

    2015-07-01

    Malignant melanoma causes the majority of deaths related to skin cancer. Nevertheless, it is the most treatable one, depending on its early diagnosis. The early prognosis is a challenging task for both clinicians and dermatologist, due to the characteristic similarities of melanoma with other skin lesions such as dysplastic nevi. In the past decades, several computerized lesion analysis algorithms have been proposed by the research community for detection of melanoma. These algorithms mostly focus on differentiating melanoma from benign lesions and few have considered the case of melanoma against dysplastic nevi. In this paper, we consider the most challenging task and propose an automatic framework for differentiation of melanoma from dysplastic nevi. The proposed framework also considers combination and comparison of several texture features beside the well used colour and shape features based on "ABCD" clinical rule in the literature. Focusing on dermoscopy images, we evaluate the performance of the framework using two feature extraction approaches, global and local (bag of words) and three classifiers such as support vector machine, gradient boosting and random forest. Our evaluation revealed the potential of texture features and random forest as an almost independent classifier. Using texture features and random forest for differentiation of melanoma and dysplastic nevi, the framework achieved the highest sensitivity of 98% and specificity of 70%. PMID:25797605

  14. Wavelengths Effective in Induction of Malignant Melanoma

    NASA Astrophysics Data System (ADS)

    Setlow, Richard B.; Grist, Eleanor; Thompson, Keith; Woodhead, Avril D.

    1993-07-01

    It is generally agreed that sunlight exposure is one of the etiologic agents in malignant melanoma of fair-skinned individuals. However, the wavelengths responsible for tumorigenesis are not known, although DNA is assumed to be the target because individuals defective in the repair of UV damage to DNA are several thousandfold more prone to the disease than the average population. Heavily pigmented backcross hybrids of the genus Xiphophorus (platyfish and swordtails) are very sensitive to melanoma induction by single exposures to UV. We irradiated groups of five 6-day-old fish with narrow wavelength bands at 302, 313, 365, 405, and 436 nm and scored the irradiated animals for melanomas 4 months later. We used several exposures at each wavelength to obtain estimates of the sensitivity for melanoma induction as a function of exposure and wavelength. The action spectrum (sensitivity per incident photon as a function of wavelength) for melanoma induction shows appreciable sensitivity at 365, 405, and probably 436 nm, suggesting that wavelengths not absorbed directly in DNA are effective in induction. We interpret the results as indicating that light energy absorbed in melanin is effective in inducing melanomas in this animal model and that, in natural sunlight, 90-95% of melanoma induction may be attributed to wavelengths > 320 nm-the UV-A and visible spectral regions.

  15. Wavelengths effective in induction of malignant melanoma

    SciTech Connect

    Setlow, R.B.; Grist, E.; Thompson, K.; Woodhead, A.D. )

    1993-07-15

    It is generally agreed that sunlight exposure is one of the etiologic agents in malignant melanoma of fair-skinned individuals. However, the wavelengths responsible for tumorigenesis are not known, although DNA is assumed to be the target because individuals defective in the repair of UV damage to DNA are several thousandfold more prone to the disease than the average population. Heavily pigmented back-cross hybrids of the genus Xiphophorus (platyfish and swordtails) are very sensitive to melanoma induction by single exposures to UV. The authors irradiated groups of five 6-day-old fish with narrow wavelength bands at 302, 313, 365, 405, and 436 nm and score the irradiated animals for melanomas 4 months later. They used several exposures at each wavelength to obtain estimates of the sensitivity for melanoma induction as a function of exposure and wavelength. The action spectrum (sensitivity per incident photon as a function of wavelength) for melanoma induction shows appreciable sensitivity at 365, 405, and probably 436 nm, suggesting that wavelengths not absorbed directly in DNA are effective in induction. They interpret the results as indicating that light energy absorbed in melanin is effective in inducing melanomas in this animal model and that, in natural sunlight, 90-95% of melanoma induction may be attributed to wavelengths >320 nm-the UV-A and visible spectral regions. 25 refs., 4 figs., 1 tab.

  16. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine.

    PubMed

    Kircher, David A; Silvis, Mark R; Cho, Joseph H; Holmen, Sheri L

    2016-01-01

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases. PMID:27598148

  17. Pseudoaneurysm of the Posterior Tibial Artery After Posterior Tibial Tendon Transfer.

    PubMed

    Elabdi, Monsef; Roukhsi, Redouane; Tijani, Youssef; Chtata, Hassan; Jaafar, Abdeloihab

    2016-01-01

    Pseudoaneurysm of the posterior tibial artery is an uncommon condition that, left untreated, can lead to hemorrhage, thrombosis, or emboli. We present the case of a 54-year-old male who developed pseudoaneurysm of the posterior tibial artery 4 months after undergoing tibialis posterior tendon transfer for management of peroneal nerve palsy, which had developed as a complication of hip arthroplasty. PMID:26972754

  18. Whole Body Melanoma Transcriptome Response in Medaka

    PubMed Central

    Schartl, Manfred; Shen, Yingjia; Maurus, Katja; Walter, Ron; Tomlinson, Chad; Wilson, Richard K.; Postlethwait, John; Warren, Wesley C.

    2015-01-01

    The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model. PMID

  19. Stage-specific prognostic biomarkers in melanoma.

    PubMed

    Cheng, Yabin; Lu, Jing; Chen, Guangdi; Ardekani, Gholamreza Safaee; Rotte, Anand; Martinka, Magdalena; Xu, Xuezhu; McElwee, Kevin J; Zhang, Guohong; Zhou, Youwen

    2015-02-28

    The melanoma staging system proposed by the American Joint Committee on Cancer (AJCC) (which classifies melanoma patients into four clinical stages) is currently the most widely used tool for melanoma prognostication, and clinical management decision making by clinicians. However, multiple studies have shown that melanomas within specific AJCC Stages can exhibit varying progression and clinical outcomes. Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression. Having previously found six independent prognostic biomarkers in melanoma, including BRAF, MMP2, p27, Dicer, Fbw7 and Tip60, our group has gone on to investigate if these markers are useful in risk stratification of melanoma patients in individual AJCC stages. First, we performed Kaplan-Meier survival and Cox proportional multivariate analyses comparing prognostication power of these markers in 254 melanoma patients for whom the expression levels were known, identifying the best performing markers as candidates for stage-specific melanoma markers. We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients). Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test). Thus, our study has identified stage-specific biomarkers in melanoma, a finding which may assist clinicians in designing improved personalized therapeutic modalities. PMID:25784655

  20. Whole Body Melanoma Transcriptome Response in Medaka.

    PubMed

    Schartl, Manfred; Shen, Yingjia; Maurus, Katja; Walter, Ron; Tomlinson, Chad; Wilson, Richard K; Postlethwait, John; Warren, Wesley C

    2015-01-01

    The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model. PMID

  1. Malignant melanoma--a genetic overview.

    PubMed

    Bloethner, S; Scherer, D; Drechsel, M; Hemminki, K; Kumar, R

    2009-11-01

    Malignant melanoma, a potentially lethal skin neoplasm, is characterized by a complex and heterogeneous etiology. Both incidences and deaths associated with melanoma are increasing in Caucasian populations. While exposure to ultraviolet radiation through sun-exposure is the major risk factor; the host factors including skin type and number of moles are critical in predisposition. The CDKN2A is a high penetrance melanoma susceptibility gene as carriers of the mutations are predisposed to the disease within familial settings. The gene is also somatically altered to varying degrees in sporadic melanoma. The CDK4 gene due to occurrence of activation mutations in a few families worldwide represents another melanoma susceptibility locus. The variants within the melanocortin receptor 1 (MC1R) gene, which encodes a melanocyte specific surface receptor with a key role in pigmentation, are associated with high risk phenotypes and increased risk of melanoma. Melanoma tumors are characterized by activation of the RAS-RAF-MEK-ERK pathway through either autocrine growth factor stimulation or oncogenic mutations in the B-RAF or N-RAS genes. Somatic mutations in the B-RAF gene are complemented by those in the N-RAS gene and represent the major genetic alterations. The mutations in the B-RAF gene in melanoma due to occurrence in melanocytic nevi represent early events that additionally require loss of cell cycle inhibitors like CDKN2A for melanoma progression and development. The sequence of events points to the cooperative collaboration between different genetic pathways in tumor development that can be and are being used as targets for developing specific therapeutic agents. PMID:20096196

  2. [Melanoma brain metastases : Treatment options].

    PubMed

    Rauschenberg, R; Tabatabai, G; Troost, E G C; Garzarolli, M; Beissert, S; Meier, F

    2016-07-01

    The majority of patients with metastatic melanoma will develop brain metastases, which are the most common cause of death. Until recently, local therapies (e. g., neurosurgery, radiotherapy) were the only options for brain metastases; however, effective systemic treatment options are now available. Upon suspicion of brain metastases, diagnostic staging with brain MRI and a neurological investigation are indicated. Prognostic factors such as number of cerebral metastases and symptoms, serum lactate dehydrogenase and S‑100 levels, extracerebral metastases, and ECOG status are considered during therapeutic planning. Treatment planning and therapeutic interventions should be based on an interdisciplinary and multimodal approach. Established treatments for singular brain metastases are neurosurgical resection and stereotactic radiotherapy, which can prolong survival. In patients with asymptomatic BRAF V600E-mutant brain metastases, the BRAF inhibitors dabrafenib, vemurafenib, and immunotherapy with ipilimumab are used. In the case of multiple symptomatic brain metastases, palliative whole-brain radiotherapy is used for treatment, although it has failed to show an overall survival benefit. Increased intracranial pressure and epileptic seizures are addressed with corticosteroids and anticonvulsants. Current clinical studies for melanoma patients with brain metastases are investigating new treatment options such as PD-1 antibodies, combined ipilimumab and nivolumab, combined BRAF inhibitors and MEK inhibitors, and stereotactic radiation in combination with immunotherapy or targeted therapy. PMID:27206449

  3. Coping strategies in melanoma patients.

    PubMed

    Trapp, Michael; Trapp, Eva-Maria; Richtig, Erika; Egger, Josef Wilhelm; Zampetti, Anna; Sampogna, Francesca; Rohrer, Peter Michael; Komericki, Peter; Strimitzer, Tanja; Linder, Michael Dennis

    2012-11-01

    An observational, questionnaire-based, cross-sectional study was performed to assess whether differences in coping behaviour (positive and negative strategies) between patients with either a recent diagnosis of malignant melanoma (MM) or with benign dermatological disease, were predictive of the diagnosis. Coping strategies were assessed with the German version of the stress-coping questionnaire (SVF 120) in 46 inpatients for whom surgery was planned at the Department of Dermatology, Medical University of Graz, Austria. Subjects were divided into two groups: patients with non-metastatic MM, and patients with benign dermatological diseases (controls). The risk for the diagnosis "melanoma" decreased with higher values of "situation control" (p = 0.007) and increased with higher values of resignation (p = 0.035) and trivialisation (p = 0.039). More-over, the risk for having a MM with thickness > 1 mm decreased in patients with higher values in positive coping strategies (p < 0.34). These results suggest differences in coping behaviour between patients with MM and those with benign skin diseases and, amidst patients with MM, between patients with different MM thickness; the results may hence lead to earlier, more specific and more effective psychological interventions to improve coping in patients with MM, as differences in coping behaviour seem to appear even in the non-metastatic stage of the disease. PMID:22772950

  4. Posterior Cervical Foraminotomy: Indications, Technique, and Outcomes.

    PubMed

    Dodwad, Shah-Jahan M; Dodwad, Shah-Nawaz M; Prasarn, Mark L; Savage, Jason W; Patel, Alpesh A; Hsu, Wellington K

    2016-06-01

    Cervical radiculopathy presents with upper extremity pain, decreased sensation, and decreased strength caused by irritation of specific nerve root(s). After failure of conservative management, surgical options include anterior cervical decompression and fusion, disk arthroplasty, and posterior cervical foraminotomy. In this review, we discuss indications, techniques, and outcomes of posterior cervical laminoforaminotomy. PMID:27187617

  5. Consistently inconsistent, the posterior vaginal wall.

    PubMed

    Hale, Douglass S; Fenner, Dee

    2016-03-01

    Posterior vaginal wall prolapse is one of the most common prolapses encountered by gynecological surgeons. What appears to be a straightforward condition to diagnose and treat surgically for physicians has proven to be frustratingly unpredictable with regard to symptom relief for patients. Functional disorders such as dyssynergic defecation and constipation are often attributed to posterior vaginal wall prolapse. Little scientific evidence supports this assumption, emphasizing that structure and function are not synonymous when treating posterior vaginal wall prolapse. Rectoceles, enteroceles, sigmoidoceles, peritoneoceles, rectal and intraanal intussusception, rectal prolapse, and descending perineal syndrome are all conditions that have an impact on the posterior vaginal wall. All too often these different anatomic conditions are treated with the same surgical approach, addressing a posterior vaginal wall bulge with a traditional posterior colporrhaphy. Studies that examine the correlation between stage of posterior wall prolapse and patient symptoms have failed to reliably do so. Surgical outcomes measured by prolapse staging appear successful, yet patient expectations are often not met. As increasing attention is being placed on patient satisfaction outcomes concerning surgical treatments, this fact will need to be addressed. Surgeons will have to clearly communicate what can and what cannot be expected with surgical repair of posterior vaginal wall prolapse. PMID:26348375

  6. Desmoplastic Melanoma: Clinical Behavior and Management Implications

    PubMed Central

    Kapil, Jyoti P.; Wolfe, Luke G.; Kaplan, Brian J.; Neifeld, James P.

    2016-01-01

    Introduction: Desmoplastic melanoma is a rare variant of melanoma that has been reported to demonstrate unique clinical behavior when compared with other histological subtypes. In this study, we present the clinical course of patients with this unusual diagnosis. We hypothesized that desmoplastic melanoma would differ from nondesmoplastic melanoma with regard to its presentation, rate of regional metastasis, and recurrence pattern. Methods: After institutional review board approval, a retrospective chart review was performed on all patients with a diagnosis of desmoplastic melanoma since 1998. The following data were collected: patient demographics, histopathological details of the lesion, initial treatment, and clinical course. In addition, the available slides were reviewed by a dermatopathologist. Results: Twenty-eight patient charts were reviewed. Mean age at diagnosis was 65 years. Fifty-seven percent of patients were men, and 67% of the lesions originated from the head and neck. Of the 28 patients, 11 had pathology slides that were adequate for evaluation. Pure desmoplastic melanoma, defined by more than 90% of the specimen demonstrating desmoplastic features, was found in only 3 patients. Taking into account all cases, the mean Breslow thickness was 5.09 mm and ulceration was present in 12.5% of lesions. Regional disease was discovered in 18% of patients. The mean follow-up time was 43 months, and the overall recurrence rate was 32%. 66.7% of first recurrences were local. Two of 3 patients with pure desmoplastic melanoma developed regional metastasis. Conclusions: Our data largely support previous studies that suggest desmoplastic melanoma behaves differently compared with other histological subtypes. However, the incidence of regional disease among patients with pure desmoplastic melanoma appears to be higher in our study than in previous reports. Although this rare variant typically presents with advanced local disease, the rate of regional metastasis is

  7. [Treatment of BRAF-mutated metastatic melanoma].

    PubMed

    Boyles, Tessa Bystrup; Svane, Inge Marie; Bastholt, Lars; Schmidt, Henrik

    2016-08-29

    Melanoma is an aggressive form of skin cancer which is the cause of a great number of skin cancer-related deaths worldwide and about 300 deaths in Denmark. After several years of failure of treatment of metastatic melanoma, the development of BRAF- and later MEK inhibitors was considered revolutionary. Treatment with BRAF inhibitors alone and especially in combination with a MEK inhibitor improves outcome for patients with BRAF V600-mutated metastatic melanoma. However, even when treated with the combination of the inhibitors, many patients develop acquired resistance within a year. PMID:27592869

  8. Epithelial Inclusion Cyst in Conjunctival Melanoma.

    PubMed

    Esposito, Evangelina; Zoroquiain, Pablo; Mastromonaco, Christina; Morales, Melina C; Belfort Neto, Rubens; Burnier, Miguel

    2016-09-01

    Conjunctival melanoma is the second most common conjunctival malignancy. Its differential diagnosis with other conjunctival melanocytic neoplasms is inherently difficult. The presence of epithelial cysts is a useful feature in conjunctival tumors and favors a benign lesion. Herein 2 cases of conjunctival melanoma with cysts are presented. To the best of our knowledge, this is the first series of conjunctival melanoma with epithelial inclusion cysts. This series emphasizes the importance of considering several malignant features when reviewing conjunctival melanocytic lesions, as malignancy can exist even in the presence of epithelial inclusion cysts. PMID:27160434

  9. Vitreous histocytology of primary choroidal malignant melanoma.

    PubMed

    Traboulsi, E I; Jalkh, A E; Frangieh, G T; Tomb, J

    1987-02-01

    The cytomorphologic findings of a vitrectomy specimen from the right eye of an 80-year-old woman with an unsuspected primary choroidal malignant melanoma are described. The patient had undergone a closed vitrectomy because of chronic vitreous hemorrhage. Histocytology of the vitreous fluid specimens revealed melanoma cells of variable shape and size (from 30-150 microns) with eccentric nuclei. Many of these cells were binucleated or multinucleated with small, uniform, evenly dispersed intracytoplasmic melanin granules. The histocytologic findings together with the postoperative tumor characteristics by ultrasonography and fluorescein angiography suggested the diagnosis of choroidal malignant melanoma. PMID:3566022

  10. Socioeconomic status, sunlight exposure, and risk of malignant melanoma: the Western Canada Melanoma Study.

    PubMed

    Gallagher, R P; Elwood, J M; Threlfall, W J; Spinelli, J J; Fincham, S; Hill, G B

    1987-10-01

    In a study of 261 male melanoma patients and age-and sex-matched controls, a strong positive univariate association between socioeconomic status, as determined by usual occupation, and risk of melanoma was detected. This association, however, was substantially explained by host constitutional factors and occupational, recreational, and vacation sunlight exposure. The study demonstrated an increased risk of melanoma in draftsmen and surveyors and a reduced risk of melanoma in construction workers and individuals employed in the finance, insurance, and real estate industry even after control for the effect of host factors and sunlight exposure. PMID:3116308

  11. Intraepidermal epidermotropic metastatic melanoma: a clinical and histopathological mimicker of melanoma in situ occurring in multiplicity.

    PubMed

    Lestre, Sara; João, Alexandre; Ponte, Pedro; Peixoto, Ana; Vieira, Joana; Teixeira, Manuel R; Fidalgo, Ana

    2011-06-01

    The distinction between primary melanoma and melanoma metastatic to the skin has major prognostic implications. We report a case of a 67-year-old male with a diagnosis of a superficial spreading melanoma (stage IB) rendered 6 years earlier who presented clinically with an atypical nevus on his left thigh. Histopathological examination showed an intraepidermal melanocytic proliferation that was interpreted as melanoma in situ. Subsequently, 45 additional pigmented macules appeared in crops over a 9-month period. Clinically and dermoscopically, these lesions were extremely polymorphic. Histopathological findings were compatible with melanoma in situ, as each lesion consisted of a wholly intraepidermal proliferation of markedly atypical melanocytes arranged singly and in nests. A complete gastrointestinal study showed multiple pigmented metastatic lesions throughout the stomach and small bowel, which supported a diagnosis of metastatic melanoma with gastrointestinal and epidermotropic skin involvement. Monosomy of chromosome 9 and a BRAF V600E mutation were detected in the primary tumor sample and in macro-dissected secondary lesions. No CDKN2A or CDK4 germline mutations were found. Intraepidermal epidermotropic metastases of melanoma have been rarely described in literature. In this case, histopathology alone was insufficient to distinguish metastatic melanoma from multiple in situ melanomas. The recognition of epidermotropic metastases should be based on the correlation between clinical, dermoscopic, histopathological and molecular findings. PMID:21352266

  12. Melanoma risk perception and prevention behavior among African-Americans: the minority melanoma paradox

    PubMed Central

    Goldenberg, Alina; Vujic, Igor; Sanlorenzo, Martina; Ortiz-Urda, Susana

    2015-01-01

    Introduction Melanoma is the most deadly type of skin cancer with 75% of all skin cancer deaths within the US attributed to it. Risk factors for melanoma include ultraviolet exposure, genetic predisposition, and phenotypic characteristics (eg, fair skin and blond hair). Whites have a 27-fold higher incidence of melanoma than African-Americans (AA), but the 5-year survival is 17.8% lower for AA than Whites. It is reported continuously that AA have more advanced melanomas at diagnosis, and overall lower survival rates. This minority melanoma paradox is not well understood or studied. Objective To explore further, the possible explanations for the difference in melanoma severity and survival in AA within the US. Methods Qualitative review of the literature. Results Lack of minority-targeted public education campaigns, low self-risk perception, low self-skin examinations, intrinsic virulence, vitamin D differences, and physician mistrust may play a role in the melanoma survival disparity among AA. Conclusion Increases in public awareness of melanoma risk among AA through physician and media-guided education, higher index of suspicion among individuals and physicians, and policy changes can help to improve early detection and close the melanoma disparity gap in the future. PMID:26346576

  13. Promotion of melanoma growth by the metabolic hormone leptin.

    PubMed

    Ellerhorst, Julie A; Diwan, A H; Dang, Shyam M; Uffort, Deon G; Johnson, Marilyn K; Cooke, Carolyn P; Grimm, Elizabeth A

    2010-04-01

    We have previously shown that melanoma cells proliferate in response to the metabolic hormones TRH and TSH. The objective of the present study was to test the hypothesis that a third metabolic hormone, leptin, serves as a growth factor for melanoma. Using western blotting, indirect immunofluorescence, and RT-PCR, leptin receptors were found to be expressed by human melanoma cells. In contrast, cultured melanocytes expressed message for the receptor without detectable protein. Melanoma cells responded to treatment with leptin by activating the MAPK pathway and proliferating. Melanoma cells but not melanocytes, also expressed leptin protein, creating a potential autocrine loop. Examination of human melanoma tumors by immunohistochemistry revealed that melanomas and nevi expressed leptin at a high frequency. Melanomas also strongly expressed the leptin receptor, whereas nevi expressed this receptor to a much lesser degree. We conclude that leptin is a melanoma growth factor and that a leptin autocrine-loop may contribute to the uncontrolled proliferation of these cells. PMID:20204272

  14. Melanoma cell galectin-1 ligands functionally correlate with malignant potential*

    PubMed Central

    Yazawa, Erika M.; Geddes-Sweeney, Jenna E.; Cedeno-Laurent, Filiberto; Walley, Kempland C.; Barthel, Steven R.; Opperman, Matthew J.; Liang, Jennifer; Lin, Jennifer Y.; Schatton, Tobias; Laga, Alvaro C.; Mihm, Martin C.; Qureshi, Abrar A.; Widlund, Hans R.; Murphy, George F.; Dimitroff, Charles J.

    2015-01-01

    Galectin-1 (Gal-1)-binding to Gal-1 ligands on immune and endothelial cells can influence melanoma development through dampening anti-tumor immune responses and promoting angiogenesis. However, whether Gal-1 ligands are functionally expressed on melanoma cells to help control intrinsic malignant features remains poorly understood. Here, we analyzed expression, identity and function of Gal-1 ligands in melanoma progression. Immunofluorescent analysis of benign and malignant human melanocytic neoplasms revealed that Gal-1 ligands were abundant in severely-dysplastic nevi as well as in primary and metastatic melanomas. Biochemical assessments indicated that melanoma cell adhesion molecule (MCAM) was a major Gal-1 ligand on melanoma cells that was largely dependent on its N-glycans. Other melanoma cell Gal-1 ligand activity conferred by O-glycans was negatively regulated by α2,6 sialyltransferase ST6GalNAc2. In Gal-1-deficient mice, MCAM-silenced (MCAMKD) or ST6GalNAc2-overexpressing (ST6O/E) melanoma cells exhibited slower growth rates, underscoring a key role for melanoma cell Gal-1 ligands and host Gal-1 in melanoma growth. Further analysis of MCAMKD or ST6O/E melanoma cells in cell migration assays indicated that Gal-1 ligand-dependent melanoma cell migration was severely inhibited. These findings provide a refined perspective on Gal-1 – melanoma cell Gal-1 ligand interactions as contributors to melanoma malignancy. PMID:25756799

  15. Case report of nodular melanoma within congenital melanocytic nevus- primary closure challenge

    PubMed Central

    Eljuga, Domagoj; Milas, Ivan; Kirac, Iva; Stanec, Mladen; Vrdoljak, Danko Velimir

    2016-01-01

    Introduction Congenital melanocytic nevi (CMN) are present in 1–2% of newborn infants. The size of CMN defines the risk of developing melanoma which is estimated from 5–10%, especially in lesions that are located across the spine. Presentation of case Herein we report a case where nodular melanoma was discovered on the periphery of medium sized CMN in a high risk patient. After complete excision, the defect was reconstructed with random pattern, triple rhomboid flap. Discussion Melanoma that arose within medium sized CMN would leave a complex posterior lower trunk defect. We used a triple Limberg flap which was proven to be straightforward and simple method when large defects are to be covered with vital tissue. We have also showed that this type of reconstruction is suitable for high risk patients that could not withstand any complex procedures. Conclusion In our case, the method we choose to reconstruct the defect proved to be simple, safe and easy, especially when surgery is performed in a high risk patient. PMID:26826932

  16. Desmoplastic melanoma: recent advances and persisting challenges.

    PubMed

    Wood, Benjamin A

    2013-08-01

    Desmoplastic melanoma is an uncommon variant of melanoma which presents significant challenges to the clinician and histopathologist. In particular, many cases show a bland 'fibroblastic' appearance, mimicking scar and a range of other benign proliferations. This diagnosis can be particularly problematic in small biopsy specimens, a difficulty exacerbated by an immunoprofile which is typically negative for a number of conventional melanocytic markers. The clinical and histological features of desmoplastic melanoma are reviewed, as are the differential diagnoses and some newer techniques which may contribute to assessment of these lesions. In recent years it has become clear that subclassification of desmoplastic melanoma into pure and mixed variants has clinical significance and it is suggested that this classification be employed in routine practice. PMID:23811805

  17. How Is Melanoma Skin Cancer Diagnosed?

    MedlinePlus

    ... medicine doctor injects a small amount of a radioactive substance into the area of the melanoma. After ... one or more sentinel lymph nodes. Once the radioactive area has been marked, the patient is taken ...

  18. Updates in Therapy for Advanced Melanoma

    PubMed Central

    Singh, Bhavana P.; Salama, April K. S.

    2016-01-01

    Cutaneous melanoma is one of the most aggressive forms of skin cancer, and is correlated with a large proportion of skin cancer-related deaths. Therapy for cutaneous melanoma has advanced greatly through careful identification of therapeutic targets and the development of novel immunotherapeutic approaches. The identification of BRAF as well as other driver mutations, have allowed for a specialized approach to treatment. In addition, immune checkpoint inhibition has dramatically changed the treatment landscape over the past 5–10 years. The successful targeting of CTLA-4, as well as PD-1/PD-L1, has been translated into meaningful clinical benefit for patients, with multiple other potential agents in development. Systemic therapy for cutaneous melanoma is becoming more nuanced and often takes a multifaceted strategy. This review aims to discuss the benefits and limitations of current therapies in systemic melanoma treatment as well as areas of future development. PMID:26784231

  19. Pembrolizumab for Ipilimumab-Resistant Melanoma

    Cancer.gov

    KEYNOTE-002 was designed to test the safety and efficacy of two doses of pembrolizumab compared with chemotherapy in patients with ipilimumab-resistant melanoma; interim results show that pembrolizumab improves progression-free survival for these patients

  20. Four cases of rituximab-associated melanoma.

    PubMed

    Velter, Charles; Pagès, Cécile; Schneider, Pierre; Osio, Amélie; Brice, Pauline; Lebbé, Céleste

    2014-08-01

    Biological agents have transformed the management of inflammatory and proliferative disorders. Safety issues have been raised, particularly the increased risk of opportunistic infections and secondary cancers. We report four cases of melanoma worsening or occurring after rituximab treatment for associated B-cell lymphoma, and discuss the accountability of the molecule in this process. In three cases, melanoma was diagnosed before or at the same time as a B-cell lymphoma treated with rituximab associated with chemotherapy and we observed rapid metastatic progression. In the last case, melanoma appeared after 5 years treatment with rituximab for a follicular lymphoma. Although it is premature to conclude on the role of rituximab in melanoma, careful follow-up and registration of such cases are important to gain further insight on this topic. PMID:24743053

  1. [Combined chemotherapy of disseminated skin melanoma].

    PubMed

    Dement'eva, N P; Voznyĭ, E K; Koroleva, L A

    1978-01-01

    The author's experience with nitrosomethylurea+prospidine treatment in 37 patients having disseminated melanoma is described. The mentioned scheme of the combination therapy is proved to be effective. PMID:741699

  2. Mucosal malignant melanoma of the maxillary sinus.

    PubMed

    Norhafizah, M; Mustafa, W M B W; Sabariah, A R; Shiran, M S; Pathmanathan, R

    2010-09-01

    Mucosal malignant melanoma (MMM) is an aggressive tumour occurring in the upper respiratory tract. It is rare compared to malignant melanoma of the skin. We report a case of a 53-year-old man with left paranasal swelling. A biopsy showed high-grade spindle cell tumour. Subsequently a subtotal maxillectomy was performed. Histopathological examination revealed a hypercellular tumour composed of mixed spindle and epitheloid cells with very occasional intracytoplasmic melanin pigment. The malignant cells were immunopositive for vimentin, S-100 protein and HMB-45. It was diagnosed as mucosal malignant melanoma (MMM). This article illustrates a rare case of MMM where the diagnosis may be missed or delayed without proper histopathological examination that include meticulous search for melanin pigment and appropriate immunohistochemical stains to confirm the diagnosis. Malignant melanoma can mimic many other types of high-grade malignancy and should be considered as a differential diagnosis in many of these instances. PMID:21939172

  3. Evolving treatment options for melanoma brain metastases.

    PubMed

    Ajithkumar, Thankamma; Parkinson, Christine; Fife, Kate; Corrie, Pippa; Jefferies, Sarah

    2015-10-01

    Melanoma is a leading cause of lost productivity due to premature cancer mortality. Melanoma frequently spreads to the brain and is associated with rapid deterioration in quality and quantity of life. Until now, treatment options have been restricted to surgery and radiotherapy, although neither modality has been well studied in clinical trials. However, the new immune checkpoint inhibitors and molecularly targeted agents that have been introduced for treatment of metastatic melanoma are active against brain metastases and offer new opportunities to improve disease outcomes. New challenges arise, including how to integrate or sequence multiple treatment modalities, and current practice varies widely. In this Review, we summarise evidence for the treatment of melanoma brain metastases, and discuss the rationale and evidence for combination modalities, highlighting areas for future research. PMID:26433822

  4. The state of melanoma: challenges and opportunities.

    PubMed

    Merlino, Glenn; Herlyn, Meenhard; Fisher, David E; Bastian, Boris C; Flaherty, Keith T; Davies, Michael A; Wargo, Jennifer A; Curiel-Lewandrowski, Clara; Weber, Michael J; Leachman, Sancy A; Soengas, Maria S; McMahon, Martin; Harbour, J William; Swetter, Susan M; Aplin, Andrew E; Atkins, Michael B; Bosenberg, Marcus W; Dummer, Reinhard; Gershenwald, Jeffrey E; Halpern, Allan C; Herlyn, Dorothee; Karakousis, Giorgos C; Kirkwood, John M; Krauthammer, Michael; Lo, Roger S; Long, Georgina V; McArthur, Grant; Ribas, Antoni; Schuchter, Lynn; Sosman, Jeffrey A; Smalley, Keiran S; Steeg, Patricia; Thomas, Nancy E; Tsao, Hensin; Tueting, Thomas; Weeraratna, Ashani; Xu, George; Lomax, Randy; Martin, Alison; Silverstein, Steve; Turnham, Tim; Ronai, Ze'ev A

    2016-07-01

    The Melanoma Research Foundation (MRF) has charted a comprehensive assessment of the current state of melanoma research and care. Intensive discussions among members of the MRF Scientific Advisory Council and Breakthrough Consortium, a group that included clinicians and scientists, focused on four thematic areas - diagnosis/early detection, prevention, tumor cell dormancy (including metastasis), and therapy (response and resistance). These discussions extended over the course of 2015 and culminated at the Society of Melanoma Research 2015 International Congress in November. Each of the four groups has outlined their thoughts as per the current status, challenges, and opportunities in the four respective areas. The current state and immediate and long-term needs of the melanoma field, from basic research to clinical management, are presented in the following report. PMID:27087480

  5. Melanoma: Clinical Features and Genomic Insights

    PubMed Central

    Hawryluk, Elena B.; Tsao, Hensin

    2014-01-01

    Recent efforts in genomic research have enabled the characterization of molecular mechanisms underlying many types of cancers, ushering novel approaches for diagnosis and therapeutics. Melanoma is a molecularly heterogeneous disease, as many genetic alterations have been identified and the clinical features can vary. Although discoveries of frequent mutations including BRAF have already made clinically significant impact on patient care, there is a growing body of literature suggesting a role for additional mutations, driver and passenger types, in disease pathophysiology. Although some mutations have been strongly associated with clinical phenotypes of melanomas (such as physical distribution or morphologic subtype), the function or implications of many of the recently identified mutations remains less clear. The phenotypic and clinical impact of genomic mutations in melanoma remains a promising opportunity for progress in the care of melanoma patients. PMID:25183853

  6. Cutaneous Melanoma: A Population Health Problem.

    PubMed

    Warren, Hermine

    2015-01-01

    Cutaneous melanoma (CM), generally referred to as melanoma, has been identified as an overall population health problem. Examination of evidence-based research revealed a strong correlation between CM and tanning bed usage, specifically by young females. For these reasons, a preliminary research question/hypothesis was structured that proposed examining different geographical locations, and whether the relationship between melanoma and tanning bed exposure by young females would be affected. Epidemiologic principles will be utilized to provide guidelines and tools for comprehensively examining this health issue and how it might affect morbidity and mortality within the populations where occurrences are identified. Furthermore, to understand some of the contributing factors of this disease, melanoma was discussed in terms of person, place, time, and how tanning bed exposure may significantly heighten CM as a potentially fatal health problem. PMID:26605821

  7. [Molecular alterations in melanoma and targeted therapies].

    PubMed

    Mourah, Samia; Lebbé, Céleste

    2014-12-01

    Melanoma is a skin cancer whose incidence is increasing steadily. The recent discovery of frequent and recurrent genetic alterations in cutaneous melanoma allowed a molecular classification of tumors into distinct subgroups, and paved the way for targeted therapy. Several signaling pathways are involved in the progression of this disease with oncogenic mutations affecting signaling pathways: MAPK, PI3K, cAMP and cyclin D1/CDK4. In each of these pathways, several potential therapeutic targets have been identified and specific inhibitors have already been developed and have shown clinical efficacy. The use of these inhibitors is often conditioned by tumors genotyping. In France, melanomas genotyping is supported by the platforms of the National Cancer Institute (INCA), which implemented a national program ensuring access to innovation for personalized medicine. The identification of new targets in melanoma supplies a very active dynamic development of innovative molecules contributing to changing the therapeutic landscape of this pathology. PMID:25776766

  8. Nivolumab-Based Treatments for Advanced Melanoma

    Cancer.gov

    A summary of results from an international, double-blind, randomized phase III trial testing the combination of nivolumab (Opdivo®) and ipilimumab (Yervoy®) against nivolumab alone and ipilimumab alone in patients with advanced melanoma.

  9. Congenital basis of posterior fossa anomalies

    PubMed Central

    Cotes, Claudia; Bonfante, Eliana; Lazor, Jillian; Jadhav, Siddharth; Caldas, Maria; Swischuk, Leonard

    2015-01-01

    The classification of posterior fossa congenital anomalies has been a controversial topic. Advances in genetics and imaging have allowed a better understanding of the embryologic development of these abnormalities. A new classification schema correlates the embryologic, morphologic, and genetic bases of these anomalies in order to better distinguish and describe them. Although they provide a better understanding of the clinical aspects and genetics of these disorders, it is crucial for the radiologist to be able to diagnose the congenital posterior fossa anomalies based on their morphology, since neuroimaging is usually the initial step when these disorders are suspected. We divide the most common posterior fossa congenital anomalies into two groups: 1) hindbrain malformations, including diseases with cerebellar or vermian agenesis, aplasia or hypoplasia and cystic posterior fossa anomalies; and 2) cranial vault malformations. In addition, we will review the embryologic development of the posterior fossa and, from the perspective of embryonic development, will describe the imaging appearance of congenital posterior fossa anomalies. Knowledge of the developmental bases of these malformations facilitates detection of the morphological changes identified on imaging, allowing accurate differentiation and diagnosis of congenital posterior fossa anomalies. PMID:26246090

  10. Mutational Heterogeneity in Melanoma: An Inconvenient Truth.

    PubMed

    Chang, Gregory A; Polsky, David

    2015-12-01

    Identification of oncogenic BRAF mutations in primary and metastatic melanomas supports a linear model of clonal evolution in cancer. Some mutational studies, however, have failed to identify BRAF mutations in metastatic tumors from patients with BRAFmutant primary melanomas. Using a combination of methods, Riveiro-Falkenbach et al. (2015) assert that technical issues, and not clonal heterogeneity, may explain prior discordant mutational results. PMID:26569584

  11. Peptide-targeted radionuclide therapy for melanoma.

    PubMed

    Miao, Yubin; Quinn, Thomas P

    2008-09-01

    Melanocortin-1 receptor (MC1-R) and melanin are two attractive melanoma-specific targets for peptide-targeted radionuclide therapy for melanoma. Radiolabeled peptides targeting MC1-R/melanin can selectively and specifically target cytotoxic radiation generated from therapeutic radionuclides to melanoma cells for cell killing, while sparing the normal tissues and organs. This review highlights the recent advances of peptide-targeted radionuclide therapy of melanoma targeting MC1-R and melanin. The promising therapeutic efficacies of 188Re-(Arg(11))CCMSH (188Re-[Cys(3,4,10), D-Phe(7),Arg(11)]-alpha-MSH(3-13)), 177Lu- and 212Pb-labeled DOTA-Re(Arg(11))CCMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[ReO-(Cys(3,4,10), D-Phe(7), Arg(11))]-alpha-MSH(3-13)) and 188Re-HYNIC-4B4 (188Re-hydrazinonicotinamide-Tyr-Glu-Arg-Lys-Phe-Trp-His-Gly-Arg-His) in preclinical melanoma-bearing models demonstrate an optimistic outlook for peptide-targeted radionuclide therapy for melanoma. Peptide-targeted radionuclide therapy for melanoma will likely contribute in an adjuvant setting, once the primary tumor has been surgically removed, to treat metastatic deposits and for treatment of end-stage disease. The lack of effective treatments for metastatic melanoma and end-stage disease underscores the necessity to develop and implement new treatment strategies, such as peptide-targeted radionuclide therapy. PMID:18387816

  12. TERT promoter mutations in melanoma survival.

    PubMed

    Nagore, Eduardo; Heidenreich, Barbara; Rachakonda, Sívaramakrishna; Garcia-Casado, Zaida; Requena, Celia; Soriano, Virtudes; Frank, Christoph; Traves, Victor; Quecedo, Esther; Sanjuan-Gimenez, Josefa; Hemminki, Kari; Landi, Maria Teresa; Kumar, Rajiv

    2016-07-01

    Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at-risk primary melanoma patients. In this study, we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. Tumors from 300 patients with stage I/II melanoma were sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression-free and melanoma-specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease-free and melanoma-specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease-free survival was 2.3 (95% CI 1.2-4.4) and for melanoma-specific survival 5.8 (95% CI 1.9-18.3). The effect of the mutations on melanoma-specific survival in noncarriers of variant allele of the polymorphism was significant (HR 4.5, 95% CI 1.4-15.2) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.3, 95% CI 0.1-0.9). The data in this study provide preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter. PMID:26875008

  13. Immunotherapy in a rare case of primary pelvic retroperitoneal melanoma.

    PubMed

    Talag, Maria Monica; Alsharedi, Mohamed; Bou Zgheib, Nadim; Lebowicz, Yehuda

    2016-01-01

    Recent advances in novel immunotherapeutic and targeted therapeutic agents have increased treatment options in patients with advanced metastatic melanoma. However, evidence in the literature on whether or not extracutaneous melanoma will acquire an equivalent advantage from these therapies is very scarce. In general, extracutaneous melanomas are rare and aggressive melanomas, which are clinically and biologically unique, with higher incidence of metastatic disease and poor prognosis. In this case report, we present a very rare case of a 54-year-old woman with primary pelvic retroperitoneal melanoma treated with an anti-PD-1 antibody, pembrolizumab. Furthermore, we explore the role of novel immunotherapies in the treatment of advanced melanoma. PMID:27624447

  14. Inflammation-Induced Plasticity in Melanoma Therapy and Metastasis.

    PubMed

    Hölzel, Michael; Tüting, Thomas

    2016-06-01

    Phenotype switching contributes to nongenomic heterogeneity in melanoma and other cancers. These dynamic and in part reversible phenotype changes impose diagnostic and therapeutic challenges. Understanding the reciprocal coevolution of melanoma and immune cell phenotypes during disease progression and in response to therapy is a prerequisite to improve current treatment strategies. Here we discuss how proinflammatory signals promote melanoma cell plasticity and govern interactions of melanoma and immune cells in the tumor microenvironment. We examine phenotypic plasticity and heterogeneity in different melanoma mouse models with respect to their utility for translational research and emphasize the interplay between melanoma cells and neutrophils as a critical driver of metastasis. PMID:27151281

  15. High-Dose Recombinant Interferon Alfa-2B, Ipilimumab, or Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery

    ClinicalTrials.gov

    2016-09-14

    Metastatic Non-Cutaneous Melanoma; Non-Cutaneous Melanoma; Recurrent Melanoma of the Skin; Recurrent Non-Cutaneous Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck

  16. Thigmotropism of malignant melanoma cells.

    PubMed

    Quatresooz, Pascale; Piérard-Franchimont, Claudine; Noël, Fanchon; Piérard, Gérald E

    2012-01-01

    During malignant melanoma (MM) progression including incipient metastasis, neoplastic cells follow some specific migration paths inside the skin. In particular, they progress along the dermoepidermal basement membrane, the hair follicles, the sweat gland apparatus, nerves, and the near perivascular space. These features evoke the thigmotropism phenomenon defined as a contact-sensing growth of cells. This process is likely connected to modulation in cell tensegrity (control of the cell shape). These specifically located paucicellular aggregates of MM cells do not appear to be involved in the tumorigenic growth phase, but rather they participate in the so-called "accretive" growth model. These MM cell collections are often part of the primary neoplasm, but they may, however, correspond to MM micrometastases and predict further local overt metastasis spread. PMID:22203839

  17. Non-melanoma skin cancer.

    PubMed

    Griffin, Liezel L; Ali, Faisal Rehman; Lear, John T

    2016-02-01

    Non-melanoma skin cancer (NMSC) comprises basal cell carcinoma (BCC) and squamous cell carcinoma, together with a host of rare tumours. NMSC is the commonest malignancy among Caucasians and its incidence continues to rise annually. Exposure to UV radiation initiates approximately 90% of NMSC, causing malignant transformation of keratinocytes and suppression of the inflammatory response. Risk factors include sun exposure and immunosuppression. There are several subtypes of BCC, although histological overlap is common. Surgery has traditionally been regarded as the 'gold-standard' treatment, offering excellent cure rates and cosmetic results. Other treatment modalities include physical destruction (radiotherapy, curettage and cautery, and cryotherapy), chemical destruction (photodynamic therapy and topical 5-flurouracil) and immunomodulatory therapy (topical imiquimod). The recent development of novel hedgehog pathway inhibitors for high-risk BCC (including oral vismodegib and sonidegib) may represent a paradigm shift towards medical management of NMSC. PMID:26833519

  18. Anorectal malignant melanomas: experience of Uludag University.

    PubMed

    Aytac, Berna; Adim, Saduman Balaban; Yerci, Omer; Yilmazlar, Tuncay

    2010-12-01

    Anorectal melanomas represent a group of mucosal melanomas with unknown etiology and poor prognosis. The lesions can be misdiagnosed as hemorrhoids during clinical examination. We reviewed the morphological and clinical features of 14 anorectal melanomas, and discuss the treatment modalities of this entity. Fourteen patients who were diagnosed with anorectal malignant melanoma between 1997 and 2004 were evaluated with regard to age, sex, size, morphology, lymph node or distant metastasis, treatment modality and survival. Eight patients were female and six were male, and their mean age was 58 years. The size of melanoma ranged from 3 cm to 8 cm. Pathological evaluation revealed epithelioid and spindle cell type tumor in seven and two patients, respectively, whereas, in the remaining seven patients, the tumor was composed of both types. Pigmentation was apparent in all tumors. There was lymph node metastasis in 11 patients and distant metastasis in all patients. Eleven patients underwent abdominoperineal resection and three were treated by local excision. Mean survival was 8.7 months. Prognosis of anorectal melanoma remains poor. Awareness of the diverse clinicopathological features of these lesions, both on the part of the clinicians and pathologists, is crucial for their early detection and proper treatment. PMID:21186014

  19. Phytochemicals for the Management of Melanoma

    PubMed Central

    Pal, Harish Chandra; Hunt, Katherine Marchiony; Diamond, Ariana; Elmets, Craig A.; Afaq, Farrukh

    2016-01-01

    Melanoma claims approximately 80% of skin cancer-related deaths. Its life-threatening nature is primarily due to a propensity to metastasize. The prognosis for melanoma patients with distal metastasis is bleak, with median survival of six months even with the latest available treatments. The most commonly mutated oncogenes in melanoma are BRAF and NRAS accounting approximately 60% and 20% of cases, respectively. In malignant melanoma, accumulating evidence suggests that multiple signaling pathways are constitutively activated and play an important role in cell proliferation, cell survival, epithelial to mesenchymal transition, metastasis and resistance to therapeutic regimens. Phytochemicals are gaining considerable attention because of their low toxicity, low cost, and public acceptance as dietary supplements. Cell culture and animals studies have elucidated several cellular and molecular mechanisms by which phytochemicals act in the prevention and treatment of metastatic melanoma. Several promising phytochemicals, such as, fisetin, epigallocatechin-3-gallate, resveratrol, curcumin, proanthocyanidins, silymarin, apigenin, capsaicin, genistein, indole-3-carbinol, and luteolin are gaining considerable attention and found in a variety of fresh fruits, vegetables, roots, and herbs. In this review, we will discuss the preventive potential, therapeutic effects, bioavailability and structure activity relationship of these selected phytochemicals for the management of melanoma. PMID:26864554

  20. Two cases of subungual melanoma in situ.

    PubMed

    Imakado, Sumihisa; Sato, Hiroyuki; Hamada, Kazutoshi

    2008-11-01

    Melanonychia, which is characterized by brown or black pigmentation within the nail plate, includes heterogeneous conditions such as pigmented nevus, subungual melanoma and lentigo. We treated two cases of subungual melanoma in situ. One case was a 58-year-old woman who suffered from a malignant melanoma in situ of the left third fingernail, who had also suffered from melanonychia of the fingers for more than 30 years. She had a past history of carcinoma of the uterine cervix. The other patient was a 42-year-old man, who suffered from a malignant melanoma in situ of the right fifth fingernail. He had a past history of carcinoma of the stomach for which he had undergone surgery 2 years earlier. Both cases were accompanied by Hutchinson's sign on the fingertip skin, and the presence of this sign led to the correct diagnosis of subungual melanoma in situ. Judging from previously reported cases, it is unlikely that patients with malignant melanoma have an increased risk of carcinoma of the uterine cervix or of the stomach. PMID:19120774

  1. Melanoma resistance to photodynamic therapy: new insights

    PubMed Central

    Huang, Ying-Ying; Vecchio, Daniela; Avci, Pinar; Yin, Rui; Garcia-Diaz, Maria; Hamblin, Michael R.

    2012-01-01

    Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. Melanoma is highly resistant to traditional chemotherapy and radiotherapy, although modern targeted therapies such as BRAF inhibitors are showing some promise. Photodynamic therapy (PDT, the combination of photosensitizing dyes and visible light) has been tested for melanoma with some promising results, but melanoma is generally considered to also be resistant to PDT. Optical interference by the highly-pigmented melanin, the anti-oxidant effect of melanin, the sequestration of photosensitizers inside melanosomes, defects in apoptotic pathways, and the efflux of photosensitizers by ATP-binding cassette (ABC) transporters have all been implicated in melanoma resistance to PDT. Approaches to overcoming melanoma resistance to PDT include: the discovery of highly active photosensitizers absorbing in the 700–800-nm near infrared spectral region; interventions that can temporarily reduce the amount or the pigmentation of the melanin; compounds that can reverse apoptotic defects or inhibit drug-efflux of photosensitizers; and immunotherapy approaches that can take advantage of the ability of PDT to activate the host immune system to the treated tumor. PMID:23152406

  2. Role of TRPM in melanocytes and melanoma

    PubMed Central

    Guo, Huazhang; Carlson, J. Andrew; Slominski, Andrzej

    2012-01-01

    Transient receptor potential (TRP) cation channel superfamily plays important roles in variety cellular processes including polymodal cellular sensing, cell adhesion, cell polarity, proliferation, differentiation, and apoptosis. One of its subfamilies are TRPM channels. mRNA expression of its founding member, TRPM1 (melastatin), correlates with terminal melanocytic differentiation and loss of its expression has been identified as an important diagnostic and prognostic marker for primary cutaneous melanoma. Because TRPM1 gene codes two transcripts: TRPM1 channel protein in its exons, and miR-211 in one of its introns, we propose a dual role for TRPM1 gene where the loss of TRPM1 channel protein is an excellent marker of melanoma aggressiveness, while the expression of miR-211 is linked to the tumor suppressor function of TRPM1. In addition, three other members of this subfamily, TRPM 2, 7 and 8 are implicated in regulation of melanocytic behavior. TRPM2 is capable of inducing melanoma apoptosis and necrosis. TRPM7 can be a protector and detoxifier in both melanocytes and melanoma cells. TRPM8 can mediate agonist-induced melanoma cell death. Therefore, we propose that TRPM1, TRPM2, TRPM7, and TRPM8 play crucial roles in melanocyte physiology and melanoma oncology, and are excellent diagnostic markers and theraputic targets. PMID:22897572

  3. Gallbladder melanoma mimicking acute acalculous cholecystitis.

    PubMed

    De Simone, P; Mainente, P; Bedin, N

    2000-06-01

    Gallbladder (GB) melanoma is a rare entity with a dismal prognosis. Its primary or secondary status is difficult to establish in the absence of an overt cutaneous localization. We report herein the case of a misdiagnosed GB melanoma mimicking acute acalculous cholecystitis that was treated by means of laparoscopic cholecystectomy (LC). A 54-year-old man was referred to our institution for acute cholecystitis. Apart from the ablation of some nevocytic nevi 7 years before admission, the patient's medical history was unremarkable. The ultrasound (US) examination showed a slightly enlarged acalculous gallbladder with thickened walls and a well-circumscribed polypoid mass in the fundus. The patient was treated medically and referred to LC. At surgery, some satellite nodules were visualized in the GB hepatic bed. The GB was removed, and two hepatic nodules were excised. Histology showed a pT3 melanoma. The patient underwent an open hepatic wedge resection 3 weeks after laparoscopy. No recurrence was observed at 6-month follow-up. To date, only one case of melanoma of the gallbladder treated with LC has been reported. GB melanoma is a diagnostic challenge when there is no evidence of a primary lesion. However, the occurrence of acalculous cholecystitis and a GB polyp in patients with a positive history of mole ablation should alert surgeons to the possibility of a melanoma. PMID:11265063

  4. Generation and analysis of zebrafish melanoma models.

    PubMed

    Wojciechowska, S; van Rooijen, E; Ceol, C; Patton, E E; White, R M

    2016-01-01

    The rapid emergence of the zebrafish as a cancer model has been aided by advances in genetic, chemical, and imaging technologies. Melanoma in particular highlights both the power and challenges associated with cancer modeling in zebrafish. This chapter focuses on the lessons that have emerged from the melanoma models as paradigmatic of what will apply to nearly all cancer models in the zebrafish system. We specifically focus on methodologies related to germline and mosaic transgenic melanoma generation, and how these can be used to deeply interrogate additional cooperating oncogenes or tumor suppressors. These transgenic tumors can in turn be used to generate zebrafish-specific, stable melanoma cell lines which can be fluorescently labeled, modified by cDNA/CRISPR techniques, and used for detailed in vivo imaging of cancer progression in real time. These zebrafish melanoma models are beginning to elucidate both cell intrinsic and microenvironmental factors in melanoma that have broader implications for human disease. We envision that nearly all of the techniques described here can be applied to other zebrafish cancer models, and likely expanded beyond what we describe here. PMID:27312504

  5. Sickle cell disease and posterior reversible leukoencephalopathy.

    PubMed

    Geevasinga, Nimeshan; Cole, Catherine; Herkes, Geoffrey K; Barnett, Yael; Lin, Jamie; Needham, Merrilee

    2014-08-01

    Sickle cell disease can present with neurological manifestations. One such presentation is with posterior reversible leukoencephalopathy also known as reversible posterior leukoencephalopathy. The condition is classically described as reversible over time; it commonly presents with oedematous changes involving the white matter of the occipital and parietal regions. Only a few patients with the association between sickle cell disease and posterior reversible leukoencephalopathy have been described in the adult literature. We present two patients from our institutions to emphasise the association between the two conditions and summarise the published cases in the literature. PMID:24656986

  6. Desmoplastic melanoma with sarcomatoid dedifferentiation.

    PubMed

    Kiuru, Maija; McDermott, Gregory; Berger, Michael; Halpern, Allan C; Busam, Klaus J

    2014-06-01

    Desmoplastic melanoma (DM) is a variant of melanoma, which typically affects chronically sun-damaged skin of elderly patients. Pure DM displays a low density of fusiform melanocytes in a collagen-rich matrix. In mixed DM, tumor cell density is higher, and parts of the tumor lack abundant stromal fibrosis. Both pure and mixed DMs usually express S100 protein homogenously. We report herein an unusual biphenotypic tumor characterized by the association of a pure DM with an undifferentiated solid spindle cell nodule. It occurred on the scalp of a 66-year-old man. A biopsy of the undifferentiated spindle cell nodule was initially interpreted at a commercial laboratory as atypical fibroxanthoma. The pure DM was seen only in the excisional specimen. All cells of the pure DM stained for S100 protein and SOX10. The adjacent solid sarcomatoid spindle cell nodule lacked expression of S100 protein, SOX10, as well as melan-A, gp100, and microphthalmia-associated transcription factor in >95% of its tumor cells. Although focal expression of melanocyte differentiation antigens in the solid tumor component made us favor a combined DM with sarcomatoid dedifferentiation, we also considered the possibility of a collision scenario, that is, a pleomorphic dermal sarcoma incidentally colliding with a DM. To further assess a possible relationship of the sarcomatoid nodule with the DM, we performed next-generation sequencing analysis on each component separately. The analysis revealed shared chromosomal copy number changes and a high number of common mutations, thereby supporting the concept of a DM with a dedifferentiated sarcomatoid component. An interesting finding is the presence of mutations of the neurofibromin 1 (NF1) gene in both tumor components. PMID:24618614

  7. Imaging of ocular melanoma metastasis.

    PubMed

    Balasubramanya, Rashmi; Selvarajan, Santosh Kumar; Cox, Mougnyan; Joshi, Ganesh; Deshmukh, Sandeep; Mitchell, Donald G; O'Kane, Patrick

    2016-09-01

    Ocular melanoma is the most common adult primary intraocular tumour. Although <1% of patients have metastatic disease at the time of initial diagnosis, most will develop metastasis at varying lengths of time. Metastasis surveillance is therefore critical in the follow-up of patients with ocular melanoma. Liver is the most common site of metastasis and prognosis is based on the treatment of liver metastasis. Hence, imaging of liver metastasis is vital. MRI is the most specific modality for imaging liver metastasis and is at least as sensitive as CT. Extrahepatic metastasis such as retroperitoneal nodules and bone metastases are also better evaluated on MRI. Gadolinium-based contrast agents are extremely helpful for detecting liver lesions. In particular, newer hepatobiliary contrast agents which offer an additional hepatobiliary phase of excretion help in the detection of even tiny liver metastases. Diffusion-weighted imaging is helpful when an i.v. contrast cannot be administered. Treated lesions are also better evaluated with MRI. CT is useful for evaluating lung nodules, large liver metastasis or in patients in whom MRI is medically contraindicated. The disadvantage lies in its inability to detect small liver metastasis and the radiation dose involved. The lesions treated with iodized oil as part of chemoembolization procedures can be followed on CT. Ultrasound can be used only for detecting hepatic metastases. However, it is heavily operator dependent, technically challenging and time consuming especially in patients who are large. Extrahepatic metastasis cannot be seen on ultrasound. Its utility is primarily for the biopsy of liver lesions. Positron emission tomography (PET)-CT can detect lung nodules and large liver lesions but is insensitive to small liver lesions. Moreover, the high radiation dose is a major disadvantage. PMID:27168029

  8. Hereditary melanoma: Update on syndromes and management: Genetics of familial atypical multiple mole melanoma syndrome.

    PubMed

    Soura, Efthymia; Eliades, Philip J; Shannon, Kristen; Stratigos, Alexander J; Tsao, Hensin

    2016-03-01

    Malignant melanoma is considered the most lethal skin cancer if it is not detected and treated during its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (ie, unilateral lineage, multigenerational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. These patients have a high risk of developing multiple primary melanomas and internal organ malignancies, especially pancreatic cancer; therefore, a multidisciplinary approach is necessary in many cases. The value of dermoscopic examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first-degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. This must be performed with care, however, and only by qualified individuals trained in cancer risk analysis. PMID:26892650

  9. High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma.

    PubMed

    Guo, Hongwei; Cheng, Yabin; Martinka, Magdalena; McElwee, Kevin

    2015-09-22

    Increased or decreased expression of LIF receptor (LIFr) has been reported in several human cancers, including skin cancer, but its role in melanoma is unknown. In this study, we investigated the expression pattern of LIFr in melanoma and assessed its prognostic value. Using tissue microarrays consisting of 441 melanomas and 96 nevi, we found that no normal nevi showed high LIFr expression. LIFr staining was significantly increased in primary melanoma compared to dysplastic nevi (P = 0.0003) and further increased in metastatic melanoma (P = 0.0000). Kaplan-Meier survival curve and univariate Cox regression analyses showed that increased expression of LIFr was correlated with poorer 5-year patient survival (overall survival, P = 0.0000; disease-specific survival, P = 0.0000). Multivariate Cox regression analyses indicated that increased LIFr expression was an independent prognostic marker for primary melanoma (P = 0.036). LIFr knockdown inhibited melanoma cell migration in wound healing assays and reduced stress fiber formation. LIFr knockdown correlated with STAT3 suppression, but not YAP, suggesting that LIFr activation might stimulate melanoma cell migration through the STAT3 pathway. Our data indicate that strong LIFr expression identifies potentially highly malignant melanocytic lesions at an early stage and LIFr may be a potential target for the development of early intervention therapeutics. PMID:26329521

  10. Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma

    PubMed Central

    Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M

    2014-01-01

    Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. PMID:24128326

  11. High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma

    PubMed Central

    Guo, Hongwei; Cheng, Yabin; Martinka, Magdalena; McElwee, Kevin

    2015-01-01

    Increased or decreased expression of LIF receptor (LIFr) has been reported in several human cancers, including skin cancer, but its role in melanoma is unknown. In this study, we investigated the expression pattern of LIFr in melanoma and assessed its prognostic value. Using tissue microarrays consisting of 441 melanomas and 96 nevi, we found that no normal nevi showed high LIFr expression. LIFr staining was significantly increased in primary melanoma compared to dysplastic nevi (P = 0.0003) and further increased in metastatic melanoma (P = 0.0000). Kaplan–Meier survival curve and univariate Cox regression analyses showed that increased expression of LIFr was correlated with poorer 5-year patient survival (overall survival, P = 0.0000; disease-specific survival, P = 0.0000). Multivariate Cox regression analyses indicated that increased LIFr expression was an independent prognostic marker for primary melanoma (P = 0.036). LIFr knockdown inhibited melanoma cell migration in wound healing assays and reduced stress fiber formation. LIFr knockdown correlated with STAT3 suppression, but not YAP, suggesting that LIFr activation might stimulate melanoma cell migration through the STAT3 pathway. Our data indicate that strong LIFr expression identifies potentially highly malignant melanocytic lesions at an early stage and LIFr may be a potential target for the development of early intervention therapeutics. PMID:26329521

  12. [ Spectrum of oncogene mutations is different in melanoma subtypes].

    PubMed

    Mazurenko, N N; Tsyganova, I V; Lushnikova, A A; Ponkratova, D A; Anurova, O A; Cheremushkin, E A; Mikhailova, I N; Demidov, L V

    2015-01-01

    Melanoma is the most lethal malignancy of skin, which is comprised of clinically relevant molecular subsets defined by specific "driver" mutations in BRAF, NRAS, and KIT genes. Recently, the better results in melanoma treatment were obtained with the mutation-specific inhibitors that have been developed for clinical use and target only patients with particular tumor genotypes. The aim of the study was to characterize the spectrum of "driver" mutations in melanoma subtypes from 137 patients with skin melanoma and 14 patients with mucosal melanoma. In total 151 melanoma cases, the frequency of BRAF, NRAS, KIT, PDGFRA, and KRAS mutations was 55.0, 10.6, 4.0, 0.7, and 0.7%, respectively. BRAF mutations were found in 69% of cutaneous melanoma without UV exposure and in 43% of cutaneous melanoma with chronic UV exposure (p=0.045), rarely in acral and mucosal melanomas. Most of melanomas containing BRAF mutations, V600E (92%) and V600K (6.0%) were potentially sensitive to inhibitors vemurafenib and dabrafenib. NRAS mutations were more common in cutaneous melanoma with chronic UV exposure (26.0%), in acral and mucosal melanomas; the dominant mutations being Q61R/K/L (87.5%). KIT mutations were found in cutaneous melanoma with chronic UV exposure (8.7%) and mucosal one (28.6%), but not in acral melanoma. Most of KIT mutations were identified in exon 11; these tumors being sensitive to tyrosine kinase inhibitors. This is the first monitoring of BRAF, NRAS, KIT, PDGFRA, and KRAS hotspot mutations in different subtypes of melanoma for Russian population. On the base of data obtained, one can suppose that at the molecular level melanomas are heterogeneous tumors that should be tested for "driver" mutations in the each case for evaluation of the potential sensitivity to target therapy. The obtained results were used for treatment of melanoma patients. PMID:26710785

  13. Melanoma--clinical, dermatoscopical, and histopathological morphological characteristics.

    PubMed

    Situm, Mirna; Buljan, Marija; Kolić, Maja; Vučić, Majda

    2014-01-01

    Melanoma is one of the most malignant skin tumors with constantly rising incidence worldwide, especially in fair-skinned populations. Melanoma is usually diagnosed at the average age 50, but, nowadays is also diagnosed more frequently in younger adults, and very rarely in childhood. There is no unique or specific clinical presentation of a melanoma. The clinical presentation of melanomas varies depending on the anatomic localization and the type of growth, i.e., the histopathological type of the cancer. There are four major histopathological types of melanoma--superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma. Although dermatoscopy is a very useful tool in early melanoma detection, dermatoscopical features of melanomas are also variable. Therefore, experience and education in dermatoscopy is crucial in the evaluation of skin tumors. Differential diagnosis of melanomas includes a wide range of benign and malignant skin lesions, due to their clinical presentation and resemblance to various dermatological entities. In this review we present the most important aspects of clinical, dermatoscopical, and histopathological features of melanomas. PMID:24813835

  14. Melanoma

    MedlinePlus

    ... m. and 4 p.m. Try to avoid sun exposure during these hours. Protect your skin by wearing ... following tips can also help: Apply high-quality sunscreen with a sun protection factor (SPF) rating of ...

  15. Melanoma

    MedlinePlus

    ... are essential for reducing exposure to harmful ultraviolet (UV) light. These protective measures are especially important in children because 80% of our lifetime exposure to UV light occurs before age 18. Once a month, you ...

  16. Melanoma

    MedlinePlus

    ... Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español Making a Change – Your Personal Plan Hot Topics Meningitis Choosing Your Mood Prescription Drug Abuse Healthy School Lunch Planner How Can I ...

  17. Standard melanoma-associated markers do not identify the MM127 metastatic melanoma cell line

    PubMed Central

    Haridas, Parvathi; McGovern, Jacqui A.; Kashyap, Abhishek S.; McElwain, D. L. Sean; Simpson, Matthew J.

    2016-01-01

    Reliable identification of different melanoma cell lines is important for many aspects of melanoma research. Common markers used to identify melanoma cell lines include: S100; HMB-45; and Melan-A. We explore the expression of these three markers in four different melanoma cell lines: WM35; WM793; SK-MEL-28; and MM127. The expression of these markers is examined at both the mRNA and protein level. Our results show that the metastatic cell line, MM127, cannot be detected using any of the commonly used melanoma-associated markers. This implies that it would be very difficult to identify this particular cell line in a heterogeneous sample, and as a result this cell line should be used with care. PMID:27087056

  18. Standard melanoma-associated markers do not identify the MM127 metastatic melanoma cell line.

    PubMed

    Haridas, Parvathi; McGovern, Jacqui A; Kashyap, Abhishek S; McElwain, D L Sean; Simpson, Matthew J

    2016-01-01

    Reliable identification of different melanoma cell lines is important for many aspects of melanoma research. Common markers used to identify melanoma cell lines include: S100; HMB-45; and Melan-A. We explore the expression of these three markers in four different melanoma cell lines: WM35; WM793; SK-MEL-28; and MM127. The expression of these markers is examined at both the mRNA and protein level. Our results show that the metastatic cell line, MM127, cannot be detected using any of the commonly used melanoma-associated markers. This implies that it would be very difficult to identify this particular cell line in a heterogeneous sample, and as a result this cell line should be used with care. PMID:27087056

  19. Posterior Reversible Encephalopathy Syndrome in ALL.

    PubMed

    Millichap, J Gordon

    2015-07-01

    Investigators from Soochow University, Suzhou, China, studied the possible pathogenetic mechanisms and treatment of posterior reversible encephalopathy syndrome (PRES) observed in 11 cases of pediatric acute lymphoblastic leukemia (ALL) after induction chemotherapy. PMID:26933594

  20. Posterior cruciate ligament (PCL) injury - aftercare

    MedlinePlus

    ... posterior cruciate ligament (PCL) is located inside your knee joint and connects the bones of your upper and ... such as a knee dislocation , you will need knee surgery to repair the joint. For milder injuries, you may not need surgery. ...