Celia Requena

Instituto Valenciano de Oncologia, Valenza, Valencia, Spain

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Publications (162)275.91 Total impact

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    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.
    European journal of cancer (Oxford, England: 1990) 06/2015; 370. DOI:10.1016/j.ejca.2015.05.023 · 4.82 Impact Factor
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    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.
    05/2015; DOI:10.1684/ejd.2015.2557
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    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.
    Journal of Cutaneous Pathology 05/2015; DOI:10.1111/cup.12519 · 1.56 Impact Factor
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    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.
    International journal of dermatology 03/2015; DOI:10.1111/ijd.12496 · 1.23 Impact Factor
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    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.
    American Journal of Dermatopathology 01/2015; 37(5). DOI:10.1097/DAD.0000000000000249 · 1.43 Impact Factor
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    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.
    Journal of Cancer Education 12/2014; DOI:10.1007/s13187-014-0766-z · 1.05 Impact Factor
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    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.
    Actas Dermo-Sifiliográficas 09/2014; DOI:10.1016/j.ad.2013.11.007
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    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.
    British Journal of Dermatology 09/2014; 172(5). DOI:10.1111/bjd.13417 · 4.10 Impact Factor
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    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.
    Nature Communications 07/2014; 5:3401. DOI:10.1038/ncomms4401 · 10.74 Impact Factor
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    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.
    JAMA Dermatology 06/2014; 150(8). DOI:10.1001/jamadermatol.2013.9856 · 4.30 Impact Factor
  • Journal of the European Academy of Dermatology and Venereology 05/2014; DOI:10.1111/jdv.12539 · 3.11 Impact Factor
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    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.
    Journal of the European Academy of Dermatology and Venereology 04/2014; 29(5). DOI:10.1111/jdv.12522 · 3.11 Impact Factor
  • Journal of Cutaneous Pathology 02/2014; 41(2):73-7. DOI:10.1111/cup.12290 · 1.56 Impact Factor
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    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.
    Actas Dermo-Sifiliográficas 01/2014;
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    ABSTRACT: BRAF mutations are frequent in melanoma but their prognostic significance remains unclear. We sought to further evaluate the prognostic value of BRAF mutations in localized cutaneous melanoma. We undertook an observational retrospective study of 147 patients with localized invasive (stages I and II) cutaneous melanomas to determine the prognostic value of BRAF mutation status. After a median follow-up of 48 months, patients with localized melanomas with BRAF-mutant melanomas exhibited poorer disease-free survival than those with BRAF-wt genotype (hazard ratio 2.2, 95% confidence interval 1.1-4.3) even after adjustment for Breslow thickness, tumor ulceration, location, age, sex, and tumor mitotic rate. The retrospective design and the small number of events are limitations. Our findings suggest that reappraisal of clinical treatment approaches for patients with localized melanoma harboring tumors with BRAF mutation might be warranted.
    Journal of the American Academy of Dermatology 01/2014; 70(5). DOI:10.1016/j.jaad.2013.10.064 · 5.00 Impact Factor
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    ABSTRACT: Patients with cutaneous melanoma who are carriers of polymorphisms in the melanocortin 1 receptor gene (MC1R) have distinctive clinical characteristics. The objective of this study was to determine the clinical characteristics associated with differing degrees of functional impairment of the melanocortin 1 receptor, as determined by the number and type (R and r) of MC1R polymorphisms. In total, 1044 consecutive patients with melanoma diagnosed in our hospital after January 2000 were selected from the melanoma database. These patients were divided into 3 groups according to a score based on nonsynonymous MC1R polymorphisms. The frequencies of epidemiologic, phenotypic, and histologic variables and personal and family history of cancer were compared. Patients with a score of 3 or more were more likely to develop melanoma before the age of 50 years (odds ratio [OR]=1.47), have a tumor on the head or neck (OR=3.04), have a history of basal cell carcinoma or cutaneous squamous cell carcinoma (OR=1.70), have atypical nevi (OR=1.74), and have nevi associated with the melanoma (OR=1.87). The use of a scoring system for MC1R polymorphisms allowed us to identify associations between the degree of functional impairment of the melanogenesis pathway and the clinical characteristics of the patients and melanoma presentation.
    Actas Dermo-Sifiliográficas 11/2013; 105(2). DOI:10.1016/j.ad.2013.10.001
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    ABSTRACT: Dermatofibrosarcoma protuberans (DFSP) is characterized by unpredictable subclinical extension, meaning that positive margins are frequently detected following conventional surgical excision. To study the presence or absence of residual tumour in DFSP with positive margins after conventional surgery and identify possible predictors of residual tumour or clear margins following a single Mohs micrographic surgery (MMS) stage. A retrospective study of patients with DFSP and positive margins following conventional excision referred for MMS was performed. We studied gender, age, tumour site, time from presentation to diagnosis, and affected margins. We studied 58 cases, 35 (60.3%) of which had histological evidence of residual tumour. Tumours of the head and neck were significantly associated with the persistence of tumour. A single MMS stage was sufficient to achieve clearance in the majority of cases (n = 46). All tumours with lateral involvement only were resolved with a single Mohs stage. DFSPs with positive margins after conventional surgical excision should undergo re-excision because the majority have histologic evidence of residual tumour. Re-excision with 1-cm margins beyond the scar could be an option in certain tumour sites, particularly when it is known which margins are involved.
    Journal of the European Academy of Dermatology and Venereology 08/2013; 28(8). DOI:10.1111/jdv.12235 · 3.11 Impact Factor
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    ABSTRACT: Dermatofibrosarcoma protuberans (DFSP) was recently shown to express nestin, a marker that has been associated with poorer prognosis when present in high levels in certain tumors. The objective of this study is to explore the association between high nestin expression and deep invasion. We performed a retrospective, observational study in which we evaluated the degree of nestin expression in 71 DFSP. The odds of fascial involvement was calculated before and after adjusting for the following confounders: age, sex, tumor size, time to diagnosis, tumor site, the presence of fibrosarcomatous areas, pleomorphism, number of mitotic figures and predominant histopathologic pattern. We also calculated the Spearman Rho correlation coefficient between nestin staining intensity and depth of invasion. Nestin immunopositivity was found in 98.6% of the tumors, and high expression levels were significantly associated with invasion of the fascia. The odds of fascial involvement in tumors with strong nestin staining was 6.56 (p = 0.001) before adjustment for confounders and 14.86 after adjustment (p = 0.007). The Spearman rho correlation coefficient between nestin expression and deep invasion was 0.287 (p = 0.015). High inmunohistochemical nestin expression appears to be associated with deeper invasion in DFSP.
    Journal of Cutaneous Pathology 07/2013; DOI:10.1111/cup.12203 · 1.56 Impact Factor
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    ABSTRACT: The influence of variants at the 9p21 locus on melanoma risk has been reported through investigation of CDKN2A variants through candidate gene approach as well as by genome wide association studies (GWAS). In the present study we genotyped, 25 SNPs that tag 273 variants on chromosome 9p21 in 837 melanoma cases and 1154 controls from Spain. Ten SNPs were selected based on previous associations, reported in GWAS, with either melanocytic nevi or melanoma risk or both. The other 15 SNPs were selected to fine map the CDKN2A gene region. All the 10 variants selected from the GWAS showed statistically significant association with melanoma risk. Statistically significant association with melanoma risk was also observed for the carriers of the variant T-allele of rs3088440 (540 C>T) at the 3' UTR of CDKN2A gene with an OR 1.52 (95% CI 1.14-2.04). Interaction analysis between risk associated polymorphisms and previously genotyped MC1R variants, in the present study, did not show any statistically significant association. Statistical significant association was observed for the interaction between phototypes and the rs10811629 (located in intron 5 of MTAP). The strongest association was observed between the homozygous carrier of the A--allele and phototype II with an OR of 15.93 (95% CI 5.34-47.54) CONCLUSIONS: Our data confirmed the association of different variants at chromosome 9p21 with melanoma risk and we also found an association of a variant with skin phototypes.
    BMC Cancer 07/2013; 13(1):325. DOI:10.1186/1471-2407-13-325 · 3.32 Impact Factor
  • International journal of dermatology 06/2013; 52(6):765-7. DOI:10.1111/j.1365-4632.2011.05038.x · 1.23 Impact Factor

Publication Stats

1k Citations
275.91 Total Impact Points

Institutions

  • 2001–2015
    • Instituto Valenciano de Oncologia
      Valenza, Valencia, Spain
    • Fundación Jiménez Díaz
      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
  • 2002
    • Hospital del Niño Jesús
      Madrid, Madrid, Spain