Celia Requena

Instituto Valenciano de Oncologia, Valenza, Valencia, Spain

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Publications (150)247.99 Total impact

  • Journal of Cutaneous Pathology 02/2014; 41(2):73-7. · 1.77 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; · 4.91 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 01/2014;
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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 01/2014; 5:3401. · 10.02 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;
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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; · 2.69 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; · 1.77 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. · 3.33 Impact Factor
  • International journal of dermatology 06/2013; 52(6):765-7. · 1.18 Impact Factor
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    ABSTRACT: Background and objectiveAcral lentiginous melanomas —the melanomas most commonly found on the distal portions of the limbs— have usually reached more advanced stages than other types of melanoma when diagnosed. Our aim was to describe the clinical presentation of these tumors.Materials and methodsRetrospective, descriptive, observational study of cases recorded in the database of the Instituto Valenciano de Oncología. In telephone interviews the patients answered a questionnaire on the presenting features of the lesion, on the presence of signs and symptoms included in the Glasgow 7-point checklist and the ABCDEs of melanoma, and on diagnostic delay attributable to patient or physician.ResultsIn the interviews with the 23 patients who responded to the questionnaire, we detected a diagnostic delay of more than 1 year attributable to the patient (delay in seeking care) in 30.4% of the cases. Diagnostic delay of more than 1 year attributable to the physician (failure to suspect the diagnosis) was identified in 20%. The most frequent reasons for consulting a physician about a lesion were changes in size, changes in color, bleeding, or failure to heal. In 20% of the cases the evaluating physician did not order histology for over a year.Conclusions Diagnostic delay is a significant problem in acral lentiginous melanoma and may be attributable either to patients or to physicians’ failure to recognize warning signs. Melanoma prevention campaigns should place more emphasis on the possibility of melanomas appearing on the palms and, particularly, on the soles.
    Actas Dermo-Sifiliográficas 04/2013; 104(3):220–226.
  • Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 03/2013; · 1.19 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVE: Acral lentiginous melanomas-the melanomas most commonly found on the distal portions of the limbs-have usually reached more advanced stages than other types of melanoma when diagnosed. Our aim was to describe the clinical presentation of these tumors. MATERIALS AND METHODS: Retrospective, descriptive, observational study of cases recorded in the database of the Instituto Valenciano de Oncología. In telephone interviews the patients answered a questionnaire on the presenting features of the lesion, on the presence of signs and symptoms included in the Glasgow 7-point checklist and the ABCDEs of melanoma, and on diagnostic delay attributable to patient or physician. RESULTS: In the interviews with the 23 patients who responded to the questionnaire, we detected a diagnostic delay of more than 1 year attributable to the patient (delay in seeking care) in 30.4% of the cases. Diagnostic delay of more than 1 year attributable to the physician (failure to suspect the diagnosis) was identified in 20%. The most frequent reasons for consulting a physician about a lesion were changes in size, changes in color, bleeding, or failure to heal. In 20% of the cases the evaluating physician did not order histology for over a year. CONCLUSIONS: Diagnostic delay is a significant problem in acral lentiginous melanoma and may be attributable either to patients or to physicians' failure to recognize warning signs. Melanoma prevention campaigns should place more emphasis on the possibility of melanomas appearing on the palms and, particularly, on the soles.
    Actas Dermo-Sifiliográficas 03/2013;
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    ABSTRACT: We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 × 10-12, per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanoma-susceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
    Nature Genetics 03/2013; · 35.21 Impact Factor
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    ABSTRACT: Introduction 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. Material and methods 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. Results 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). Conclusions 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 01/2013;
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    ABSTRACT: Erythromelalgia is a rare disorder characterized by 3 major symptoms: warmth, redness, and burning pain. It involves the feet and, to a lesser extent, the hands, head, and ears. We report the case of a 27-year-old man presenting with a 15-year history of episodes with edema, local hyperthermia, and burning pain of both ears.
    Dermatology online journal 01/2013; 19(2):16.
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    ABSTRACT: Merkel cell carcinoma is a malignant skin tumor with a poor prognosis that primarily affects photoexposed areas of elderly patients. Tumor size is a very strong prognostic factor, with much better outcomes associated with small lesions, measuring less than 1cm. However, such lesions are rarely seen in the clinic in view of the rapid growth of this tumor. We report 2 cases of incipient Merkel cell carcinoma. Both cases of incipient Merkel cell carcinoma measured approximately 5mm in diameter. One tumor was confined to the epidermis and papillary dermis on the nose of a 79-year-old man and the other was located in the deep dermis, almost in the hypodermis, on the buttock of an 82-year-old woman. In both cases, the lesions had appeared weeks earlier. The first tumor seemed to originate in the dermoepidermal junction whereas the second originated almost in the hypodermis. Although the lesions were at a similar disease stage and had a similar size, their different locations within the dermis highlight once again the controversy about which cells give rise to Merkel cell carcinoma. The precursor cells could feasibly be Merkel cells in the first case but not in the second.
    Actas Dermo-Sifiliográficas 12/2012;
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    ABSTRACT: Objectives  The frequency and clinicopathologic characteristics of cutaneous lesions in sepsis are not well known. This study aimed to analyze cutaneous lesions in bacterial septic vasculopathy. Methods  The study population comprised 32 patients with bacterial sepsis, cutaneous lesions, and skin biopsy-proven septic vasculopathy. The clinical and histologic characteristics of the lesions were analyzed. Findings in non-immunosuppressed patients (NISPs) and immunosuppressed patients (ISPs) were compared. Results  Nine of 32 patients were immunosuppressed. The foci of sepsis were variable; in 17 patients, the focus was not identified. Although Neisseria meningitidis was the most common causal agent, several microorganisms were identified. Cutaneous manifestations were an early event in 90.6% of patients. The most common skin signs were purpuric lesions and petechiae. Overall mortality was 28.1%; 65.5% of patients survived without sequelae. Skin biopsies showed thrombi in 100% of cases. Other common findings were inflammatory infiltrate, blood extravasation, and epidermal involvement. Bacteria within the vascular wall were seen in 21.9% of cases and fibrinoid necrosis in 25%. A comparison of ISPs with NISPs disclosed that meningococcemia was more common in the latter group, and the presence of pustules was more common in the former. Histopathology testing revealed that fibrinoid necrosis and bacterial invasion of the vessel wall were more common in ISPs than in NISPs. Conclusions  Several microorganisms can cause septic vasculopathy. Clinical presentation is variable and does not depend on the microorganism or the pathogenic mechanism. Histopathologically, septic vasculopathy is a thrombo-occlusive vasculopathy with variable morphology. Cutaneous lesions are an early event and allow for rapid diagnosis.
    International journal of dermatology 12/2012; · 1.18 Impact Factor
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    ABSTRACT: Malignant chondroid syringoma is a very rare type of malignant sweat gland tumor. Diagnosis is based on pathologic features but is complicated by the low frequency of this tumor. The authors report a new case of malignant chondroid syringoma, initially misdiagnosed as basal cell carcinoma, that exhibited very aggressive local behavior and was located on the face, a rare site for this tumor. The authors describe its histopathologic appearance and highlight the importance of including adenoid cystic carcinoma in the differential diagnosis.
    The American Journal of dermatopathology 10/2012; · 1.30 Impact Factor
  • The Journal of Dermatology 09/2012; · 1.77 Impact Factor

Publication Stats

551 Citations
247.99 Total Impact Points

Institutions

  • 2003–2014
    • Instituto Valenciano de Oncologia
      Valenza, Valencia, Spain
  • 2012
    • German Cancer Research Center
      • Division of Molecular Genetic Epidemiology
      Heidelberg, Baden-Wuerttemberg, Germany
    • Instituto Valenciano de la Edificación
      Valenza, Valencia, Spain
  • 2011
    • Hospital Universitari i Politècnic la Fe
      Valenza, Valencia, Spain
  • 2001–2010
    • Universidad Autónoma de Madrid
      • Department of Pathology
      Madrid, Madrid, Spain
    • Fundación Jiménez Díaz
      Madrid, Madrid, Spain
  • 2009
    • University of Valencia
      • Departamento de Patología
      Valencia, Valencia, Spain
  • 2005
    • Hospital Clínico Universitario de Valencia
      Valenza, Valencia, Spain
  • 2002
    • Hospital del Niño Jesús
      Madrid, Madrid, Spain
    • Consorcio Hospital General Universitario de Valencia
      • Departamento de Dermatología
      Valencia, Valencia, Spain