Celia Requena

Instituto Valenciano de Oncologia, Valenza, Valencia, Spain

Are you Celia Requena?

Claim your profile

Publications (186)315.66 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. Methods: CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. Results: Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. Conclusion: The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med advance online publication 17 December 2015Genetics in Medicine (2015); doi:10.1038/gim.2015.160.
    Full-text · Article · Dec 2015 · Genetics in medicine: official journal of the American College of Medical Genetics
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Melanoma survivors are at an increased risk of developing other malignancies, including keratinocyte skin cancer (KSC). While it is known that many risk factors for melanoma also impact risk of KSC in the general population, no previous study has investigated risk factors for KSC development in melanoma patients. Objective: We assessed associations of personal and clinical characteristics, including skin phenotype and variations in the melanocortin 1 receptor (MC1R) gene, with KSC risk in melanoma patients. Patients and methods: We used prospective follow-up information on 1200 patients treated for melanoma at the Instituto Valenciano de Oncología, Spain, between 2000 and 2011. We computed hazard ratios and 95% confidence intervals (CIs) for the association of clinical, personal and genetic characteristics with risk of KSC, squamous cell carcinoma (SCC), or basal cell carcinoma (BCC) from Cox proportional hazard models. Five-year cumulative incidence based on competing risk models of SCC, BCC or KSC overall was computed using multivariate subdistribution hazard models. To assess predictive performance of the models, we computed areas under the receiver-operating characteristic curves (AUCs, discriminatory power) using cross-validation. Results: Median follow-up was 57.2 months; a KSC was detected in 163 patients (13.6%). In multivariable Cox models, age, sex, sunburns, chronic sun exposure, past personal history of non-melanoma skin cancer or other non-cutaneous neoplasia, and the MC1R variants p.D294H and p.R163Q were significantly associated with KSC risk. A cumulative incidence model including age, sex, personal history of KSC, and of other non-cutaneous neoplasia had an AUC of 0.76 (95% CI: 0.71-0.80). When p.D294H and p.R163Q variants were added to the model, the AUC increased to 0.81 (95% CI: 0.77-0.84) (p-value for difference <0.0001). Conclusions: In addition to age, sex, skin characteristics, and sun exposure, p.R163Q and p.D294H MC1R variants significantly increased KSC risk among melanoma patients. Our findings may help identify patients who could benefit most from preventive measures.
    No preview · Article · Dec 2015 · European Journal of Cancer
  • [Show abstract] [Hide abstract]
    ABSTRACT: Melanoma tumors are known to exhibit uneven growth. In about 70-80% the growth rate can be calculated based on Breslow thickness and the information that patients provide about the time of lesion development (Martorell-Calatayud et al., 2011). In one third of those cases where growth can be measured, tumors grow at a rate of at least 0.5 millimeters per month, which constitute so-called fast growing melanoma. Fast growing melanomas are considered as a probable reason for the lack of decrease in absolute incidence of thick melanomas. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · Pigment Cell & Melanoma Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Locoregional cutaneous metastases of melanoma (LCMM) represent a therapeutic challenge. Many treatment options are available with varying results. The combination of cryotherapy and imiquimod, two treatments with a possible synergistic effect, has not yet been described for treating this disease. In this paper, we aimed to show the response of LCMM to cryotherapy combined with topical imiquimod 5%. A retrospective review of 20 patients diagnosed with LCMM and treated with cryotherapy combined with topical imiquimod 5% between November 2000 and May 2014 at three institutions was performed. The locoregional cutaneous response was evaluated. After a mean of five sessions, 13 patients (65%) responded to treatment, eight (40%) of these completely and five (25%) partially. Systemic disease progressed in 16 (80%) patients. Cryotherapy followed by topical imiquimod 5% is simple to apply, has minimal adverse effects and provides response rates similar to other, more complex treatment options.
    No preview · Article · Nov 2015 · The Journal of Dermatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Treatment of oral erosive lichen planus is considered a therapeutic challenge. Various systemic and topical agents aimed at controlling the symptoms, rather than curing the lesions, have been used with varying results. Objective: To evaluate the response to treatment with antimalarial drugs in patients with oral erosive lichen planus. Methods: Eight patients diagnosed with oral erosive lichen planus were treated with antimalarial agents. The first clinical evaluation was made after a month of treatment and then every 2-3 months. Baseline ophthalmologic examinations were performed, and laboratory values were monitored before and during treatment. Results: All studied patients who had previously been resistant to other treatments responded favorably. Pain relief and reduced erythema and erosions were observed after of a mean of 2.4 months. Conclusion: Antimalarials may be useful for the treatment of oral erosive lichen planus. They are easily administered and affordable, with few adverse effects.
    No preview · Article · Oct 2015 · Dermatology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent reports suggested frequent occurrence of cancer associated somatic mutations within regulatory elements of the genome. Based on initial exome sequencing of 21 melanomas, we report frequent somatic mutations in skin cancers in a bidirectional promoter of diphthamide biosynthesis 3 (DPH3) and oxidoreductase NAD-binding domain containing 1 (OXNAD1) genes. The UV-signature mutations occurred at sites adjacent and within a binding motif for E-twenty six/ternary complex factors (Ets/TCF), at -8 and -9 bp from DPH3 transcription start site. Follow up screening of 586 different skin lesions showed that the DPH3 promoter mutations were present in melanocytic nevi (2/114; 2%), melanoma (30/304; 10%), basal cell carcinoma of skin (BCC; 57/137; 42%) and squamous cell carcinoma of skin (SCC; 12/31; 39%). Reporter assays carried out in one melanoma cell line for DPH3 and OXNAD1 orientations showed statistically significant increased promoter activity due to -8/-9CC > TT tandem mutations; although, no effect of the mutations on DPH3 and OXNAD1 transcription in tumors was observed. The results from this study show occurrence of frequent somatic non-coding mutations adjacent to a pre-existing binding site for Ets transcription factors within the directional promoter of DPH3 and OXNAD1 genes in three major skin cancers. The detected mutations displayed typical UV signature; however, the functionality of the mutations remains to be determined.
    Full-text · Article · Sep 2015 · Oncotarget
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In patients with primary cutaneous melanoma, there is generally a delay between excisional biopsy of the primary tumour and sentinel-node biopsy. The objective of this study is to analyse the prognostic implications of this delay. This was an observational, retrospective, cohort study in four tertiary referral hospitals. A total of 1963 patients were included. The factor of interest was the interval between the date of the excisional biopsy of the primary melanoma and the date of the sentinel-node biopsy (delay time) in the prognosis. The primary outcome was melanoma-specific survival and disease-free survival. A delay time of 40days or less (hazard ratio (HR), 1.7; confidence interval (CI), 1.2-2.5) increased Breslow thickness (Breslow ⩾2mm, HR, >3.7; CI, 1.4-10.7), ulceration (HR, 1.6; CI, 1.1-2.3), sentinel-node metastasis (HR, 2.9; CI, 1.9-4.2), and primary melanoma localised in the head or neck were independently associated with worse melanoma-specific survival (all P<0.03). The stratified analysis showed that the effect of delay time was at the expense of the patients with a negative sentinel-node biopsy and without regression. Early sentinel-node biopsy is associated with worse survival in patients with cutaneous melanoma. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jun 2015 · European journal of cancer (Oxford, England: 1990)
  • [Show abstract] [Hide abstract]
    ABSTRACT: Among melanoma patients, women have a better prognosis than men but the differences might be due to a different presentation of melanoma. The aim of this study was to identify differences in clinical presentation and survival in cutaneous melanoma between men and women in a Spanish population stratified by age. In total, 1,607 consecutive patients with localized cutaneous melanoma and complete clinical and pathological information were evaluated. Average follow-up was 5 years. Patients were stratified by age into three groups: ≤45 years, 46-60 years, and >60 years. Disease-free survival, overall-survival and disease-specific survival were generated using the Kaplan-Meier method. Multivariate survival analyses were evaluated using Cox modelling. Melanoma presented more frequently in the trunk in male patients and in the lower extremities and acral location in female patients. Men presented thicker tumors than women. However, for histological type, mitotic rate and ulceration there were no significant differences between the sexes. In the univariate survival analyses, women showed better disease-free, overall and disease-specific survival in the younger age group, compared with males of the same group. After adjusting for anatomical site, Breslow thickness, mitotic rate and presence of ulceration, there were no differences between males and females in any of the three age groups. The superior survival for women over men did not persist after adjusting for multiple prognostic variables such as anatomical site, Breslow thickness, mitotic rate and ulceration.
    No preview · Article · May 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Atypical Spitz tumor with loss of BAP1 or Wiesner nevus is a peculiar variant of intradermal spitzoid melanocytic neoplasm composed of epithelioid melanocytes with a sheet-like growth pattern, abundant infiltrating lymphocytes, and rare or absent mitotic activity. This subset of atypical spitzoid tumors is characterized by the BRAF(V600E) mutation and loss of BAP1 expression. Recognition of these lesions is important because they can be a marker for a hereditary BAP1-associated cancer syndrome. We present an unusual case of sporadic Wiesner nevus that had typical histopathologic features and a BAP1 but not a BRAF mutation. The biological significance of Wiesner nevus is controversial, and little is known about prognosis, particularly in atypical cases like this one. This article is protected by copyright. All rights reserved.
    No preview · Article · May 2015 · Journal of Cutaneous Pathology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Melanoma is considered a heterogeneous tumor with genetic and environmental factors involved in its pathogenesis. The impact of these factors varies depending on age.Objective The aim of this study was to characterize the epidemiological, phenotypic, and histological features of patients with melanoma according to three age groups: ≤40, 41–65, and >65 years.MethodsA total of 1122 consecutive patients with invasive melanoma definitively treated in our institution since January 2000 were selected from our melanoma database. Epidemiological, phenotypic, and histological data were retrieved and analyzed as a function of age.ResultsFemale patients predominated in the younger age group. The location of cutaneous malignant melanoma differed with age. In the younger and middle age groups, tumors presented mainly on the trunk, while in the older group they were mainly found on the head/neck. Signs of actinic damage such as actinic keratoses, solar lentigines, or other skin tumors increased with age, while genetic factors such as family history of melanoma or a high number of common melanocytic nevi were more frequent in the younger group.Conclusion Our results suggest that melanoma development in younger patients is the result of genetic factors, particularly related to multiple nevi, whereas in older patients environmental factors such as severe chronic sun exposure play a major role.
    No preview · Article · Mar 2015 · International journal of dermatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: : We report the unique association of primary cutaneous marginal zone B-cell lymphoma and Rosai-Dorfman disease (RDD)-type histiocytic infiltrates involving the same lesions. The patient was an 82-year-old woman with 3 long-standing, well-circumscribed firm erythematous to brownish plaques on her left arm, right scapular area, and lumbosacral area. Histopathologic examination disclosed a dermal and subcutaneous nodular lymphoplasmacytic infiltrate with evidence of germinal center colonization and light-chain restriction and sheets of S-100 CD68-positive histiocytes with ample pale cytoplasm and occasional emperipolesis of lymphocytes. The neoplastic plasma cells expressed immunoglobulin (Ig) G4. A review of 14 examples of cutaneous RDD showed a substantial number of IgG4-positive cells in only 3 of them, and a review of 8 primary cutaneous marginal zone B-cell lymphomas disclosed only 2 with significant IgG4 expression. The coexistence of lymphomas and RDD has been rarely reported in the literature but only seldom involving the same lymph node and-to the best of our knowledge-never in the skin.
    No preview · Article · Jan 2015 · American Journal of Dermatopathology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Melanoma is potentially curable if diagnosed at its earliest stages and treated properly. The best approaches for reducing deaths due to melanoma are primary and secondary prevention. The objective of this study is to evaluate patient awareness of the risk factors for developing melanoma and attitudes toward its prevention. Also, this study aims to assess observance of recommended preventive measures and to identify possible factors associated with a low adoption of these measures. This cross-sectional study based on an online questionnaire included 185 consecutively enrolled subjects at risk of developing melanoma monitored in a pigmented lesion unit in Valencia (Spain). Level of knowledge, attitude, and observance of preventive measures were evaluated. Statistical analysis was carried out using contingency tables, chi-squared test, and Spearman correlation. Out of those who reported practicing skin self-examination, only 24.1 % performed it in the optimal way. A better attitude was observed in low-risk patients (r = -0.28, p < 0.01). Being female (p < 0.01), aged 18-35 (p = 0.02), fair-haired (p = 0.02), having skin phototype I-II (p < 0.01), and a suitable attitude (p = 0.05) and knowledge (p < 0.01) were related to a better use of sunscreens and avoidance of sun exposure. Knowledge was inversely associated with age (p = 0.01). Despite the high level of knowledge and positive attitude, inadequate practice of compliance with recommended primary and secondary preventive measures was observed in our risk population.
    No preview · Article · Dec 2014 · Journal of Cancer Education
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction and objectives Adult dermatomyositis presents as a paraneoplastic syndrome in up to 25% of cases, but no clinical, histologic, or laboratory markers completely specific for paraneoplastic disease in dermatomyositis have been identified to date. Furthermore, studies on adult dermatomyositis do not usually report the frequency of cutaneous features of dermatomyositis in patients with associated cancer. Our aim was to review the characteristics of paraneoplastic dermatomyositis in patients seen at our hospital. Material and methods We studied 12 cases of paraneoplastic dermatomyositis and recorded patient age and sex, associated cancer, time between onset of dermatomyositis and cancer, emergent cutaneous manifestations, muscle involvement, dysphagia, lung disease, and levels of creatine phosphokinase and circulating autoantibodies. Results The mean age of the patients was 61 years and the 2 most common malignancies were ovarian cancer and bladder cancer. The mean time between the diagnosis of cancer and dermatomyositis was 7 months and in most cases, the cancer was diagnosed first. Seven patients had amyopathic dermatomyositis. The most common cutaneous signs were a violaceous photodistributed rash sparing the interscapular area and a heliotrope rash, followed by Gottron papules and cuticle involvement. Superficial cutaneous necrosis was observed in 3 cases. Myositis-specific autoantibodies were not detected in any of the 6 patients who underwent this test. Conclusions Paraneoplastic dermatomyositis is often amyopathic. There are no specific cutaneous markers for malignancy in dermatomyositis. Myositis-specific antibodies are not associated with paraneoplastic dermatomyositis.
    No preview · Article · Sep 2014 · Actas Dermo-Sifiliográficas
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Dermatofibrosarcoma protuberans (DFSP) is an uncommon skin tumour with aggressive local growth. Whether DFSP should be treated with conventional surgery (CS) or Mohs micrographic surgery (MMS) has long been a topic of debate.Objective To calculate in a large series of DFSP treated by MMS the minimum margin that would have been needed to achieve complete clearance by CS as well as the percentage of healthy tissue that was preserved by MMS rather than CS with 2- and 3-cm margins.Methods The minimum margin was calculated by measuring the largest distance from the visible edge of the tumour to the edge of the definitive surgical defect. Tumour and surgical defect areas for hypothetical CS with 2- and 3-cm margins were calculated using AutoCAD for Windows.ResultsA mean minimum margin of 1.34 cm was required to achieve complete clearance for the 74 tumours analyzed. The mean percentage of skin spared using MMS rather than CS with 2- and 3-cm margins was 49.4% and 67.9% respectively.ConclusionMMS can achieve tumour clearance with smaller margins and greater preservation of healthy tissue compared with CS.This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2014 · British Journal of Dermatology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We previously reported a disease segregating causal germline mutation in a melanoma family and recurrent somatic mutations in metastasized tumours from unrelated patients in the core promoter region of the telomerase reverse transcriptase (TERT) gene. Here we show that the TERT promoter mutations, besides causing an increased gene expression, associate with increased patient age, increased Breslow thickness and tumour ulceration in 287 primary melanomas. The mutations are more frequent at both intermittently and chronically sun-exposed sites than non-exposed sites and tend to co-occur with BRAF and CDKN2A alterations. The association with parameters generally connected with poor outcome, coupled with high recurrence and mechanistic relevance, raises the possibility of the eventual use of TERT promoter mutations in the disease management.
    Full-text · Article · Jul 2014 · Nature Communications
  • [Show abstract] [Hide abstract]
    ABSTRACT: Importance The influence of regression on the status of the sentinel node (SN) is controversial. In many centers, the presence of regression in thin melanomas supports the performance of an SN biopsy.Objective To identify whether regression in primary melanoma has any influence on SN involvement.Design, Setting, and Participants Retrospective study of melanomas with a Breslow thickness greater than 0.75 mm and undergoing SN biopsy from January 1, 2003, through December 31, 2010, at Instituto Valenciano de Oncología, which receives melanoma patients from regional hospitals and dermatology practices. Only cases with paraffin blocks or histologic slides representative of the primary tumor and available for review were included in the study. Melanomas from 201 patients met these criteria and constitute the core of this study.Exposures Sentinel node biopsy in melanoma.Main Outcomes and Measures Presence or absence of regression in the primary melanoma, type (early vs late), and extension were correlated with the presence or absence of metastasis in the SNs. In addition, the main clinical and histologic characteristics of the primary melanoma were correlated with the status of SN and the regression features.Results Regression was found in 52 melanomas (25.9%). Regression did not show a statistically significant association with SN status. When melanomas were subdivided by Breslow thickness into 4 groups, those with regression had a lower frequency of positive SNs in 3 of the 4 groups (≤1.00, 1.01-2.00, and >4.00 mm), although differences did not reach statistical significance in any group. We found no influence by type of regression or its extension on the SN status. Regression was found more frequently in thin melanomas (≤1.00 mm), melanomas located on an axial site, and superficial spreading or lentigo maligna melanoma types (P = .02, P < .001, and P = .03, respectively).Conclusions and Relevance Regression of the primary melanoma is not associated with a higher proportion of positive SNs. These data do not support the practice of performing SN biopsy in thin melanomas with regression in the absence of additional adverse prognostic characteristics.
    No preview · Article · Jun 2014 · JAMA Dermatology

  • No preview · Article · May 2014 · Journal of the European Academy of Dermatology and Venereology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Granulomatous reactions to silicone facial fillers are well described in the literature. Clinically, these reactions present as nodules or pseudotumors that are frequently described as silicone granulomas or siliconomas.Objective We want to report a peculiar form of granulomatous reaction to injected silicone characterized by recurrent episodes of facial edema.Methods We collected silicone infiltrated patients with a similar clinical picture consisting of asymptomatic episodes of unilateral facial edema that had been recurring for months or years.ResultsWe found four women with recurrent episodes of facial edema. They had been infiltrated with silicone in the face. Histology showed silicone deposits and a granulomatous infiltrate in all 4 cases.Conclusion We describe and illustrate a new type of adverse reaction to injected silicone simulating orofacial granulomatosis. The reaction presents as recurrent, unilateral, asymmetric facial edema of the cheek in patients who have been injected with silicone in the face. Familiarity with this adverse reaction will help to prevent erroneous diagnoses such as idiopathic angioedema, Melkersson Rosenthal syndrome, and orofacial granulomatosis.
    No preview · Article · Apr 2014 · Journal of the European Academy of Dermatology and Venereology

  • No preview · Article · Feb 2014 · Journal of Cutaneous Pathology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adult dermatomyositis presents as a paraneoplastic syndrome in up to 25% of cases, but no clinical, histologic, or laboratory markers completely specific for paraneoplastic disease in dermatomyositis have been identified to date. Furthermore, studies on adult dermatomyositis do not usually report the frequency of cutaneous features of dermatomyositis in patients with associated cancer. Our aim was to review the characteristics of paraneoplastic dermatomyositis in patients seen at our hospital. We studied 12 cases of paraneoplastic dermatomyositis and recorded patient age and sex, associated cancer, time between onset of dermatomyositis and cancer, emergent cutaneous manifestations, muscle involvement, dysphagia, lung disease, and levels of creatine phosphokinase and circulating autoantibodies. The mean age of the patients was 61 years and the 2 most common malignancies were ovarian cancer and bladder cancer. The mean time between the diagnosis of cancer and dermatomyositis was 7 months and in most cases, the cancer was diagnosed first. Seven patients had amyopathic dermatomyositis. The most common cutaneous signs were a violaceous photodistributed rash sparing the interscapular area and a heliotrope rash, followed by Gottron papules and cuticle involvement. Superficial cutaneous necrosis was observed in 3 cases. Myositis-specific autoantibodies were not detected in any of the 6 patients who underwent this test. Paraneoplastic dermatomyositis is often amyopathic. There are no specific cutaneous markers for malignancy in dermatomyositis. Myositis-specific antibodies are not associated with paraneoplastic dermatomyositis.
    No preview · Article · Jan 2014 · Actas Dermo-Sifiliográficas

Publication Stats

2k Citations
315.66 Total Impact Points

Institutions

  • 2001-2015
    • Instituto Valenciano de Oncologia
      Valenza, Valencia, Spain
  • 2012
    • Instituto Valenciano de la Edificación
      Valenza, Valencia, Spain
  • 2002-2012
    • Fundación Jiménez Díaz
      Madrid, Madrid, Spain
    • Hospital del Niño Jesús
      Madrid, Madrid, Spain
    • Universidad Autónoma de Madrid
      • Department of Pathology
      Madrid, Madrid, Spain
  • 2000-2012
    • Consorcio Hospital General Universitario de Valencia
      • Departamento de Dermatología
      Valenza, Valencia, Spain
  • 2011
    • Universidad Católica de Ávila
      Valenza, Valencia, Spain
  • 2009
    • University of Valencia
      Valenza, Valencia, Spain
  • 2003-2004
    • Hospital de Cabueñes, Gijon
      Gijón, Asturias, Spain
  • 1990
    • Hospital Clínico San Carlos
      Madrid, Madrid, Spain
  • 1986
    • Hospital Central de la Defensa Gómez Ulla
      Madrid, Madrid, Spain