A retrospective review of conjunctival melanoma: Presentation, treatment and evolution | Archivos de la Sociedad Española de Oftalmología (English Edition)

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Curva de supervivencia global para los pacientes con diagnóstico de melanoma conjuntival. La probabilidad de supervivencia a los 5 y 10 años es del 89 y del 69,4%, respectivamente." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "G.E. Pacheco, L. Garcia-Onrubia, C. Garcia-Alvarez, M.F. Muñoz, E. Garcia-Lagarto, D.M. Perez, P. Alonso, M.A. Saornil" "autores" => array:8 [ 0 => array:2 [ "nombre" => "G.E." "apellidos" => "Pacheco" ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Garcia-Onrubia" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Garcia-Alvarez" ] 3 => array:2 [ "nombre" => "M.F." "apellidos" => "Muñoz" ] 4 => array:2 [ "nombre" => "E." "apellidos" => "Garcia-Lagarto" ] 5 => array:2 [ "nombre" => "D.M." "apellidos" => "Perez" ] 6 => array:2 [ "nombre" => "P." 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(a) Retinography: clinical appearance of mushroom-shaped melanoma (red arrow). (b) Ultrasound of mushroom-shaped melanoma: Bruch's membrane rupture and fungiform appearance of MM (red arrow), retinal detachment (blue arrow). (c) T2 MRI coronal plane: mushroom-shaped melanoma (red arrow)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. García Tirado, M. Asencio Durán, J. Peralta Calvo, A. Berjón, E. Ruiz Bravo-Burguillos" "autores" => array:5 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "García Tirado" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Asencio Durán" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Peralta Calvo" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Berjón" ] 4 => array:2 [ "nombre" => "E." 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An epidemiological study: Are resources been used properly?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "211" "paginaFinal" => "217" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Oftalmología de urgencias. Un estudio epidemiológico: ¿se utilizan correctamente los recursos?" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1333 "Ancho" => 2473 "Tamanyo" => 166178 ] ] "descripcion" => array:1 [ "en" => "Evolution of emergencies in the course of the day. Vertical axis refers to the number of consultations." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "F.B. Domínguez-Serrano, P. Molina-Solana, M. Infante-Cossío, J. Sala-Turrens, N. Seva-Silva, E. Rodríguez-de-la-Rúa-Franch" "autores" => array:6 [ 0 => array:2 [ "nombre" => "F.B." "apellidos" => "Domínguez-Serrano" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Molina-Solana" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Infante-Cossío" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Sala-Turrens" ] 4 => array:2 [ "nombre" => "N." "apellidos" => "Seva-Silva" ] 5 => array:2 [ "nombre" => "E." 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Pacheco, L. Garcia-Onrubia, C. Garcia-Alvarez, M.F. Muñoz, E. Garcia-Lagarto, D.M. Perez, P. Alonso, M.A. Saornil" "autores" => array:8 [ 0 => array:4 [ "nombre" => "G.E." "apellidos" => "Pacheco" "email" => array:1 [ 0 => "gabriela.26391@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "L." "apellidos" => "Garcia-Onrubia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "Garcia-Alvarez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "M.F." "apellidos" => "Muñoz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "E." "apellidos" => "Garcia-Lagarto" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "D.M." "apellidos" => "Perez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 6 => array:3 [ "nombre" => "P." "apellidos" => "Alonso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 7 => array:3 [ "nombre" => "M.A." "apellidos" => "Saornil" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Unidad de Tumores del Adulto, Servicio de Oftalmología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Tumores del Adulto, Unidad de Investigación, Hospital Clínico Universitario de Valladolid, Valladolid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Patología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Oncología Radioterápica, Hospital Clínico Universitario de Valladolid, Valladolid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Revisión retrospectiva del melanoma conjuntival: presentación, tratamiento y evolución" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 980 "Ancho" => 1305 "Tamanyo" => 148855 ] ] "descripcion" => array:1 [ "en" => "(a) Nodular conjunctival melanoma (*) in patient with primary acquired melanosis with multicenter pigmentation (**). (b) Ultrasound biomicroscopy showing lesion invading superficial scleral layers, having a base measuring 5.34mm (red line) and a height of 2.27mm (green line). (c) After adjuvant treatment with mitomycin C eyedrops, scleral invasion was treated with episcleral brachytherapy with iodine-125 plate (*). (d) No signs of recurrence were observed 5 years after treatment." ] ] ] "textoCompleto" => "IntroductionConjunctival melanoma (CM) is a rare malign ocular neoplasia with an incidence of 0.2–0.8cases per million inhabitants/year in Caucasian populations, accounting for one-2% of ocular tumours.<a class="elsevierStyleCrossRefs" href="#bib0125">1–3</a> In recent decades the incidence of cutaneous and conjunctival melanoma has increased significantly in the United States and Nordic countries, suggesting increased exposure to solar radiation as a risk factor.<a class="elsevierStyleCrossRefs" href="#bib0140">4–6</a>CM could originate in primary acquired melanosis (PAM) (74%), de novo (19%) and, in smaller percentages, from a pre-existing nevus (7%).<a class="elsevierStyleCrossRef" href="#bib0155">7</a> Clinic presentation is usually a variable pigmentation lesion that could be solitary, multicenter and unilateral in almost all cases.<a class="elsevierStyleCrossRefs" href="#bib0130">2,8,9</a>CM comprises a number of treatment options, including extirpation with safety margins of circumscribed lesions or map biopsy for diffuse or multicenter lesions. Adjuvant therapies could be associated including intra-surgery cryotherapy, topical chemotherapy and/or episcleral brachytherapy. Enucleation or exenteration could be necessary in the case of intraocular and orbital invasion respectively.<a class="elsevierStyleCrossRefs" href="#bib0125">1,3,10</a> Recurrence rates are high, with the absence of adjuvant therapies potentially being a determining factor.<a class="elsevierStyleCrossRefs" href="#bib0175">11–13</a>Metastases are generally regional, systemic or both, disseminating to ipsilateral lymphatic ganglia—cervical, preauricular and submandibular—subsequently extended to the rest of the body, frequently affecting the brain, lung and liver.<a class="elsevierStyleCrossRef" href="#bib0135">3</a> Published mortality rates range between 12 and 20% 5 years after diagnostic, and exceeding 30% after 10years.<a class="elsevierStyleCrossRefs" href="#bib0135">3,11,12,14</a>The purpose of the present study is to review presentation forms, treatment and evolution of patients with conjunctival melanoma treated at the Tumour Unit of the University Clinic Hospital of Valladolid during 25years, in order to make recommendations for the diagnostic, treatment and follow-up of said patients on the basis of the authors’ experience and a review of the literature.Material and methodsDesign of the study and inclusion criteriaA retrospective study of consecutive patients registered at the database of the Ocular Tumour Unit with a confirmed CM histopathological diagnosis between January 1992 and December 2017. The study also included patients with a previously histologically confirmed diagnostic in other hospitals with or without previous treatment as well as cases referred due to recurrence.Diagnostic and treatment protocolThe Tumour Unit protocol consists in performing complete anamnesis, investigating presentation form, evolution time and previous treatments. After anterior pole biomicroscopy, the location, extension and circumscribed or multicenter form are registered. When suspecting the intraocular and/or orbital extension, ultrasound biomicroscopy and/or magnetic resonance are carried out.Biopsy is taken as a diagnostic measure. In the case of circumscribed lesions (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), excisional biopsy with 3mm safety margins could be the treatment if the edges are free of the disease, but in the case of extended lesions incisional biopsy is performed. Upon histopathological confirmation, adjuvant therapies are subsequently applied. In the case of multi-centre lesions, map biopsy is performed extirpating the areas suspected of invasive melanoma with subsequent indication of adjuvant therapies. In the presence of intraocular invasion, enucleation is performed and, in the presence of extensive or multiple orbital invasion, orbital exenteration is performed. In the event that the patient declines exenteration and/or exhibits systemic extension, palliative surgery and/or external radiotherapy can be performed. Extension diagnostic is based on head and neck computerized tomography to identify compromised lymphatic ganglia (locoregional extension) and thoracoabdominal tomography to identify systemic extension.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Adjuvant therapies are associated when suspecting residual disease due to compromise of biopsy edges. If epithelial residual disease is confirmed in circumscribed or multicenter cases (primary acquired melanosis with or without atypia), 0.02% topical mitomycin eyedrops are prescribed at a rate of one drop every 6h during one week, alternating with an additional week of artificial tears until the residual lesion has disappeared. In the absence of clinically detectable disease, 2 cycles of mitomycin eyedrops are applied as above. In the case of deep edge compromise and/or suspected invasion of external scleral layers, episcleral brachytherapy is indicated with 85Gy doses at a depth of 2mm, generally with ruthenium 106 plates.After confirming diagnostic and carrying out treatment, the patient is followed up at 3-month intervals during the first year and at 6-month intervals the following 2–5years (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), looking for local relapses and palpation of regional ganglia as well as requesting head and neck computerized tomography. In the presence of locoregional metastases, compromised cervical nodes lymphadenectomy is performed followed by adjuvant radiotherapy. In the case of the systemic extension, the patient is referred to the Oncology Department for assessment and treatment.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Data recordalData were recorded in a Microsoft Access database designed for the study. Collected information included demographic data of patients, clinic examination, clinic and histopathological diagnostic, presence of regional or systemic extension, biopsy type (excisional, map or incisional) and type of administered treatment. Relapses were also included, together with the appearance of locoregional and systemic metastases and cause of demise, if applicable.Statistical analysisQuantitative variables are presented with mean and typical deviation, while qualitative variables are presented as per frequency distribution. Survival was analyzed with the Kaplan–Meier analysis and mortality tables. The comparison test was the generalized Wilcoxon test. Data were analyzed with the IBM SPSS Statistics application, version 24.0 for Windows.ResultsClinic presentationOut of 462 patients with conjunctival tumour diagnosis between January 1992 and December 2017, 252 cases (54.5%) exhibited melanocytic origin. Of these, 27 were conjunctival melanoma which accounted for 5.8% of all conjunctival tumours. Clinic characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The mean age at diagnostic was 59.2 (16–88) years, 59% were females and laterality predominance was for the right eye (74%). In none of the cases melanoma was suspected in a routine examination, with the main reason for the diagnostic being lesion growths in 25 cases (93%) and inflammatory symptoms in 2 cases (7%).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Out of the total number of 27 patients, 11 (41%) had been previously treated before being referred, of which 2 had multiple previous treatment and relapses. In 12 cases, the lesions were extirpated without suspecting the existence of melanoma.The most frequent location was bulbar conjunctiva in 22 cases (81%), and the most frequent lesion type was multicenter in 52% of cases. In what concerns extension, 12 patients (44%) exhibited over 3 compromised quadrants. Only one patient exhibited intraocular invasion, having exhibited multiple relapses in the 5 previous years that were treated at different hospitals.According to clinic diagnostic, 2 cases were diagnosed as suspicious nevus due to growth (11%) and 10 cases of PAM (37%). Biopsies showed the existence of invasive melanoma. In the remaining 55% (15 cases) clinic melanoma diagnostic was histopathologically confirmed.According to origin, 16 cases (59%) arose from PAM, 7 cases (26%) from nevus and 4 patients (15%) had de novo origins.TreatmentExcisional biopsy with security margin was performed on 13 patients with circumscribed lesions (48%), while map (44.5%) or incisional (7.5%) biopsy was performed on the rest of patients. Adjuvant chemotherapy was prescribed with topical mitomycin C according to the above-described regime in 15 patients with suspected epithelial residual disease or histopathological PAM diagnostic with atypia (55%), and brachytherapy for 5 patients (18.5%) with confirmed histopathological edge in depth and sclera superficial layers compromise, 4 cases were treated with ruthenium 106 and one with iodine-125 plate.Enucleation was carried out in 3 cases who had undergone previous treatments in other hospitals before being referred to the authors’ practice. One enucleation was after the fourth relapse of a tumour involving more than 2 quadrants and with invasion demonstrated through ultrasound biomicroscopy and magnetic resonance covering over 80% of scleral thickness. The other 2 cases had also received previous treatment including mitomycin, topically and in the bed of the lesion, with side effects on the ocular surface (corneal ulceration, limbic insufficiency) that did not allow conservative treatment due to the occurrence of a new epibulbar relapse. Only one patient was administered palliative external radiotherapy due to CM with orbital invasion and systemic extension at diagnostic.Follow-up, extension and survivalMean follow-up was 6.1±6.8years. Relapses arose in 9 patients (33%); in 7, originated after PAM while locoregional extension was diagnosed in 8. Ipsilateral cervical ganglia extraction with subsequent external local radiotherapy was performed in one case, 5 developed systemic disease and 4 patients died due to melanoma.Mean survival of all patients was 18years (IC 95%: 13.7–22.2), with a 5 and 10 year survival probability of 89 and 69.4% respectively (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). In patients with recurrence, survival probability at 5 and 10 years was 88.9 and 61%, in comparison with those who did not exhibit recurrence who had 93.1% at 5 and 10years (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). Patients exhibiting recurrence had 2 years less mean survival in comparison to those who did not.<elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>DiscussionCM accounted for only 5.8% of all conjunctival tumours diagnosed at the Ocular Tumour Unit of the authors’ hospital, a percentage that was lower when compared to a similar review by Shields et al., <a class="elsevierStyleCrossRef" href="#bib0195">15</a> where CM represented 12% of 5002 conjunctival tumour cases. However, the statistics of the present study could be biased due to being a reference unit.Mean age at CM diagnostic is generally in the area of 60,<a class="elsevierStyleCrossRef" href="#bib0200">16</a> being rare in children.<a class="elsevierStyleCrossRefs" href="#bib0205">17,18</a> The present study found similar data, with the mean age at diagnostic being 59.2years. None of the patients were diagnosed in a routine examination and the most frequent reason for consultation was the growth of a pre-existing lesion. The presence of inflammatory symptoms was even less frequent. Eleven cases were referred from other centres with previous treatments, generally without following standardized criteria. According to Shields et al.,<a class="elsevierStyleCrossRef" href="#bib0180">12</a> in a retrospective study (1974–1997) carried out in Philadelphia with 254 cases of CM, the most frequent symptoms or signs were the appearance and growth of a conjunctival spot and the presence of an raised lesion. One of the reasons for belated diagnostic is the variability of clinic presentation, for which reason evaluations and expert follow-up are of paramount importance when suspecting a conjunctival melanocytic lesion.Intraocular and orbital local extension of CM is a rare finding.<a class="elsevierStyleCrossRef" href="#bib0215">19</a> It was detected in only 2 cases who had undergone incomplete previous treatment and were referred after several relapses. One of said cases exhibited metastasis at diagnostic. A study by Yousef and Finger<a class="elsevierStyleCrossRef" href="#bib0220">20</a> in the Ocular Cancer Center of New York found that only 5 out of 42 patients with CM exhibited orbital invasion with a recurrence rate of 80%.CM diagnosis is based on biopsy (excisional or map). Histopathological confirmation is essential to establish adequate treatment and provide grounds for indicating adjuvant therapies.<a class="elsevierStyleCrossRef" href="#bib0200">16</a> It is known that patients referred to centres specialized on intraocular tumours after undergoing surgery in other hospitals are at high risk of relapses<a class="elsevierStyleCrossRef" href="#bib0200">16</a> and that inadequate surgical treatment could increase the risk of recurrence and metastasis. For these reasons it is recommendable to diagnose and treat early and fully in one procedure.The majority of the patients of this study were treated with excisional or PAMA biopsy with added adjuvants treatment, topical chemotherapy with 0.02% mitomycin C being the most frequent, leaving brachytherapy with a smaller percentage. A study carried out by Brouwer et al.<a class="elsevierStyleCrossRef" href="#bib0225">21</a> in Holland on 70 patients with CM described that the initial treatment was excisional biopsy with adjuvant therapy, with ruthenium plate brachytherapy being most frequent. Current studies advise against excisional biopsy without adjuvant treatment due to being related with increased rates of recurrence, metastasis and mortality related to melanoma.<a class="elsevierStyleCrossRefs" href="#bib0180">12,16</a>Recurrent disease generally appears in 50% of cases.<a class="elsevierStyleCrossRef" href="#bib0230">22</a> Brouwer et al.<a class="elsevierStyleCrossRef" href="#bib0225">21</a> described a recurrence rate of 29% at 5 years while other studies reported ranges between 26 and 61%.<a class="elsevierStyleCrossRefs" href="#bib0135">3,11</a> The present study found a recurrence rate of 33%, most of them originating in PAM. For patients without recurrence, the probability of survival at 5 and 10 years was 93.1%, while patients with relapses had a survival rate of 89.9 and 61% respectively. Relapses are more frequent in melanoma arising from PAM and accordingly this type of patient must be followed up in a thorough, regular and permanent manner with locoregional and systemic extension tests in the event of recurrence as these are at the highest risk of exhibiting extension and higher mortality.<a class="elsevierStyleCrossRef" href="#bib0225">21</a>Conjunctival melanoma is one of the few ocular surface tumours that could be life-threatening for patients, with survival ranging between 68 and 93%.<a class="elsevierStyleCrossRefs" href="#bib0175">11,21</a> At 5 years, survival probability ranges between 74 and 86.3% while at 10years it diminishes to 41–77.7%.<a class="elsevierStyleCrossRefs" href="#bib0235">23,24</a> The results of the present study (89 and 69.4% at 5 and 10 years, respectively) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>) match those of previously published studies.Melanoma-related mortality at the end of the follow-up was 15%. Similar studies reported CM-related mortality at the end of follow-up at 13%,<a class="elsevierStyleCrossRef" href="#bib0230">22</a> being after 5 and 10years post-diagnosis of 14 and 30% respectively.<a class="elsevierStyleCrossRef" href="#bib0135">3</a> Several risk factors are associated to higher mortality, i.e., palpebral conjunctival location, caruncle, fornix, tumour thickness, substance invasion, epitheloid cell type, nodular pattern growth, lymphatic invasion and local disease recurrence.<a class="elsevierStyleCrossRef" href="#bib0240">24</a>In conclusion, CM is an aggressive and rare neoplasia that could be undervalued, thus leading to insufficient and late treatment. Differential diagnostic between precancerous and malign lesions could be difficult, for which reason experts biopsy is essential for diagnostic confirmation. Diagnosis and adequate and full treatments with adjuvant therapies for the initial lesion are essential for preventing recurrences and systemic extension with the aim of preserving the visual acuity as well as the life of the patient.FundingNo funding was received for carrying out the present study.Conflict of interestsNo commercial interests were involved in the present study." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1184802" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1104913" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1184803" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1104912" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Design of the study and inclusion criteria" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Diagnostic and treatment protocol" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Data recordal" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Clinic presentation" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Treatment" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Follow-up, extension and survival" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-11-06" "fechaAceptado" => "2019-01-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1104913" "palabras" => array:4 [ 0 => "Conjunctiva" 1 => "Conjunctival tumour" 2 => "Conjunctival melanoma" 3 => "Primary acquired melanosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1104912" "palabras" => array:4 [ 0 => "Conjuntiva" 1 => "Tumor de conjuntiva" 2 => "Melanoma conjuntival" 3 => "Melanosis adquirida primaria" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveThe purpose of the present study is to describe the clinical characteristics and outcomes of patients diagnosed and treated for conjunctival melanoma in the Ocular Oncology Unit of the University Hospital Clinic of Valladolid. MethodsA retrospective observational case series study was conducted on patients diagnosed with conjunctival melanoma in the Ocular Oncology Unit of University Hospital Clinic of Valladolid, from January 1992 to December 2017. Demographic information and tumour features were recorded in a Microsoft Access database. ResultsAmong a total of 462 consecutive patients, the tumour was classified as melanocytic in 252 cases (54.5%), with 27 patients having the pathological diagnosis of conjunctival melanoma. The mean age at diagnosis was 59.2years (16–88), and there were 41% males and 59% females, with a mean follow-up of 6.1±6.8years. As regards the origin of conjunctival melanoma, 16 cases (59%) arose from primary acquired melanosis, 26% from nevus, and 15% developed de novo. The treatment performed was incisional or excisional biopsy in all patients, local adjuvant chemotherapy in 15 cases (56%) and brachytherapy in 5 patients (18%). The median survival was 18years and the probability of survival at 5 and 10years was 89% and 69%, respectively. ConclusionsConjunctival melanoma is a rare disease, usually undervalued by the patient as well as being underdiagnosed, leading to insufficient and delayed treatment. Early diagnosis and treatment are essential to prevent recurrences and systemic extension, as well as to preserve vision and life." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoDescribir las características clínicas y la evolución de los pacientes diagnosticados y tratados de melanoma conjuntival en la Unidad de Tumores del Hospital Clínico Universitario de Valladolid. MétodosEstudio retrospectivo; se incluyeron pacientes diagnosticados consecutivamente de melanoma conjuntival desde enero de 1992 hasta diciembre de 2017. La información demográfica y las características del tumor fueron registradas en una base de datos en Microsoft Access. ResultadosDe un total de 462 pacientes con diagnóstico de tumor conjuntival, 252 casos (54,5%) fueron de origen melanocítico, y de estos, 27 casos fueron melanomas de conjuntiva. La edad media fue de 59,2 (16-88) años; 41% hombres y 59% mujeres, con un seguimiento medio de 6,1±6,8 años. Según el origen del melanoma conjuntival, 16 casos (59%) surgieron a partir de melanosis adquirida primaria, el 26% de nevus y el 15% de novo. Se realizó biopsia incisional o escisional en todos los pacientes, quimioterapia local adyuvante en 15casos (56%) y braquiterapia en 5pacientes (18%). La supervivencia media fue de 18años (IC95%) y la probabilidad de supervivencia a los 5 y 10años fue del 89 y del 69%, respectivamente. ConclusionesEl melanoma conjuntival es una enfermedad rara que se suele infravalorar en estadios iniciales, lo que lleva a un tratamiento insuficiente y tardío. El diagnóstico y el tratamiento precoces son esenciales para prevenir las recurrencias y la extensión sistémica y para preservar la visión y la vida del paciente." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Pacheco GE, Garcia-Onrubia L, Garcia-Alvarez C, Muñoz MF, Garcia-Lagarto E, Perez DM, et al. Revisión retrospectiva del melanoma conjuntival: presentación, tratamiento y evolución. Arch Soc Esp Oftalmol. 2019;94:218–224." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 568 "Ancho" => 755 "Tamanyo" => 58131 ] ] "descripcion" => array:1 [ "en" => "Circumscribed conjunctival melanoma (black arrow) in upper nasal area invading the corner limbus, treated with excisional biopsy with safety margin." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 980 "Ancho" => 1305 "Tamanyo" => 148855 ] ] "descripcion" => array:1 [ "en" => "(a) Nodular conjunctival melanoma (*) in patient with primary acquired melanosis with multicenter pigmentation (**). (b) Ultrasound biomicroscopy showing lesion invading superficial scleral layers, having a base measuring 5.34mm (red line) and a height of 2.27mm (green line). (c) After adjuvant treatment with mitomycin C eyedrops, scleral invasion was treated with episcleral brachytherapy with iodine-125 plate (*). (d) No signs of recurrence were observed 5 years after treatment." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1488 "Ancho" => 1536 "Tamanyo" => 97822 ] ] "descripcion" => array:1 [ "en" => "Kaplan–Meier analysis. Overall survival curve for patients with conjunctival melanoma diagnostic. Survival probability at 5 and 10 years is 89 and 69.4%, respectively." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1509 "Ancho" => 1514 "Tamanyo" => 129172 ] ] "descripcion" => array:1 [ "en" => "Kaplan–Meier analysis and generalized Wilcoxon comparison test. In patients without recurrences, the survival probability at 5 and 10 years is of 93.1%, in contrast with those who had recurrences, with a survival probability of 88.9 and 61%, respectively." ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">n=27 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Sex</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Laterality</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Initial consultation reason</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Routine checkup \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inflammation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Growth \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">93 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Previous treatments \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Location</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Epibulbar</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bulbar \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">81 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Limbar \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Corneal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Not epibulbar</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fornix \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tarsal conjuntiva \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Caruncle \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Form</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Circunscribed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Multicenter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Extension in quadrants</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Q1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Q2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Q3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Q4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Local extension</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Intraocular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Orbital \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Clinic diagnostic</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nevus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PAM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Origin of melanoma</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PAM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nevus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">De novo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Treatment</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Biopsy</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Excisional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Incisional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Map \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Topical chemotherapy (0.02% MCM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Brachytherapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Enucleation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">External radiotherapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Recurrences \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1R \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2R \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3R \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Extension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Locoregional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Specific mortality due to melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2019728.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of patients and tumours." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib0125" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Conjunctival tumors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.A. Saornil" 1 => "E. 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A retrospective review of conjunctival melanoma: Presentation, treatment and evolution

Revisión retrospectiva del melanoma conjuntival: presentación, tratamiento y evolución

G.E. Pachecoa,

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gabriela.26391@gmail.com

Corresponding author.

, L. Garcia-Onrubiaa, C. Garcia-Alvareza, M.F. Muñozb, E. Garcia-Lagartoc, D.M. Perezd, P. Alonsod, M.A. Saornila

a Unidad de Tumores del Adulto, Servicio de Oftalmología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain

b Unidad de Tumores del Adulto, Unidad de Investigación, Hospital Clínico Universitario de Valladolid, Valladolid, Spain

c Servicio de Patología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain

d Servicio de Oncología Radioterápica, Hospital Clínico Universitario de Valladolid, Valladolid, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Conjunctival melanoma &#40;CM&#41; is a rare malign ocular neoplasia with an incidence of 0&#46;2&#8211;0&#46;8<span class="elsevierStyleHsp" style=""></span>cases per million inhabitants&#47;year in Caucasian populations&#44; accounting for one-2&#37; of ocular tumours&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">1&#8211;3</span></a> In recent decades the incidence of cutaneous and conjunctival melanoma has increased significantly in the United States and Nordic countries&#44; suggesting increased exposure to solar radiation as a risk factor&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">4&#8211;6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">CM could originate in primary acquired melanosis &#40;PAM&#41; &#40;74&#37;&#41;&#44; <span class="elsevierStyleItalic">de novo</span> &#40;19&#37;&#41; and&#44; in smaller percentages&#44; from a pre-existing nevus &#40;7&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a> Clinic presentation is usually a variable pigmentation lesion that could be solitary&#44; multicenter and unilateral in almost all cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">2&#44;8&#44;9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">CM comprises a number of treatment options&#44; including extirpation with safety margins of circumscribed lesions or map biopsy for diffuse or multicenter lesions&#46; Adjuvant therapies could be associated including intra-surgery cryotherapy&#44; topical chemotherapy and&#47;or episcleral brachytherapy&#46; Enucleation or exenteration could be necessary in the case of intraocular and orbital invasion respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">1&#44;3&#44;10</span></a> Recurrence rates are high&#44; with the absence of adjuvant therapies potentially being a determining factor&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">11&#8211;13</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Metastases are generally regional&#44; systemic or both&#44; disseminating to ipsilateral lymphatic ganglia&#8212;cervical&#44; preauricular and submandibular&#8212;subsequently extended to the rest of the body&#44; frequently affecting the brain&#44; lung and liver&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a> Published mortality rates range between 12 and 20&#37; 5 years after diagnostic&#44; and exceeding 30&#37; after 10<span class="elsevierStyleHsp" style=""></span>years&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">3&#44;11&#44;12&#44;14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The purpose of the present study is to review presentation forms&#44; treatment and evolution of patients with conjunctival melanoma treated at the Tumour Unit of the University Clinic Hospital of Valladolid during 25<span class="elsevierStyleHsp" style=""></span>years&#44; in order to make recommendations for the diagnostic&#44; treatment and follow-up of said patients on the basis of the authors&#8217; experience and a review of the literature&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design of the study and inclusion criteria</span><p id="par0030" class="elsevierStylePara elsevierViewall">A retrospective study of consecutive patients registered at the database of the Ocular Tumour Unit with a confirmed CM histopathological diagnosis between January 1992 and December 2017&#46; The study also included patients with a previously histologically confirmed diagnostic in other hospitals with or without previous treatment as well as cases referred due to recurrence&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Diagnostic and treatment protocol</span><p id="par0035" class="elsevierStylePara elsevierViewall">The Tumour Unit protocol consists in performing complete anamnesis&#44; investigating presentation form&#44; evolution time and previous treatments&#46; After anterior pole biomicroscopy&#44; the location&#44; extension and circumscribed or multicenter form are registered&#46; When suspecting the intraocular and&#47;or orbital extension&#44; ultrasound biomicroscopy and&#47;or magnetic resonance are carried out&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Biopsy is taken as a diagnostic measure&#46; In the case of circumscribed lesions &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; excisional biopsy with 3<span class="elsevierStyleHsp" style=""></span>mm safety margins could be the treatment if the edges are free of the disease&#44; but in the case of extended lesions incisional biopsy is performed&#46; Upon histopathological confirmation&#44; adjuvant therapies are subsequently applied&#46; In the case of multi-centre lesions&#44; map biopsy is performed extirpating the areas suspected of invasive melanoma with subsequent indication of adjuvant therapies&#46; In the presence of intraocular invasion&#44; enucleation is performed and&#44; in the presence of extensive or multiple orbital invasion&#44; orbital exenteration is performed&#46; In the event that the patient declines exenteration and&#47;or exhibits systemic extension&#44; palliative surgery and&#47;or external radiotherapy can be performed&#46; Extension diagnostic is based on head and neck computerized tomography to identify compromised lymphatic ganglia &#40;locoregional extension&#41; and thoracoabdominal tomography to identify systemic extension&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Adjuvant therapies are associated when suspecting residual disease due to compromise of biopsy edges&#46; If epithelial residual disease is confirmed in circumscribed or multicenter cases &#40;primary acquired melanosis with or without atypia&#41;&#44; 0&#46;02&#37; topical mitomycin eyedrops are prescribed at a rate of one drop every 6<span class="elsevierStyleHsp" style=""></span>h during one week&#44; alternating with an additional week of artificial tears until the residual lesion has disappeared&#46; In the absence of clinically detectable disease&#44; 2 cycles of mitomycin eyedrops are applied as above&#46; In the case of deep edge compromise and&#47;or suspected invasion of external scleral layers&#44; episcleral brachytherapy is indicated with 85<span class="elsevierStyleHsp" style=""></span>Gy doses at a depth of 2<span class="elsevierStyleHsp" style=""></span>mm&#44; generally with ruthenium 106 plates&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">After confirming diagnostic and carrying out treatment&#44; the patient is followed up at 3-month intervals during the first year and at 6-month intervals the following 2&#8211;5<span class="elsevierStyleHsp" style=""></span>years &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; looking for local relapses and palpation of regional ganglia as well as requesting head and neck computerized tomography&#46; In the presence of locoregional metastases&#44; compromised cervical nodes lymphadenectomy is performed followed by adjuvant radiotherapy&#46; In the case of the systemic extension&#44; the patient is referred to the Oncology Department for assessment and treatment&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Data recordal</span><p id="par0055" class="elsevierStylePara elsevierViewall">Data were recorded in a Microsoft Access database designed for the study&#46; Collected information included demographic data of patients&#44; clinic examination&#44; clinic and histopathological diagnostic&#44; presence of regional or systemic extension&#44; biopsy type &#40;excisional&#44; map or incisional&#41; and type of administered treatment&#46; Relapses were also included&#44; together with the appearance of locoregional and systemic metastases and cause of demise&#44; if applicable&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Quantitative variables are presented with mean and typical deviation&#44; while qualitative variables are presented as per frequency distribution&#46; Survival was analyzed with the Kaplan&#8211;Meier analysis and mortality tables&#46; The comparison test was the generalized Wilcoxon test&#46; Data were analyzed with the IBM SPSS Statistics application&#44; version 24&#46;0 for Windows&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Clinic presentation</span><p id="par0065" class="elsevierStylePara elsevierViewall">Out of 462 patients with conjunctival tumour diagnosis between January 1992 and December 2017&#44; 252 cases &#40;54&#46;5&#37;&#41; exhibited melanocytic origin&#46; Of these&#44; 27 were conjunctival melanoma which accounted for 5&#46;8&#37; of all conjunctival tumours&#46; Clinic characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The mean age at diagnostic was 59&#46;2 &#40;16&#8211;88&#41; years&#44; 59&#37; were females and laterality predominance was for the right eye &#40;74&#37;&#41;&#46; In none of the cases melanoma was suspected in a routine examination&#44; with the main reason for the diagnostic being lesion growths in 25 cases &#40;93&#37;&#41; and inflammatory symptoms in 2 cases &#40;7&#37;&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Out of the total number of 27 patients&#44; 11 &#40;41&#37;&#41; had been previously treated before being referred&#44; of which 2 had multiple previous treatment and relapses&#46; In 12 cases&#44; the lesions were extirpated without suspecting the existence of melanoma&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The most frequent location was bulbar conjunctiva in 22 cases &#40;81&#37;&#41;&#44; and the most frequent lesion type was multicenter in 52&#37; of cases&#46; In what concerns extension&#44; 12 patients &#40;44&#37;&#41; exhibited over 3 compromised quadrants&#46; Only one patient exhibited intraocular invasion&#44; having exhibited multiple relapses in the 5 previous years that were treated at different hospitals&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">According to clinic diagnostic&#44; 2 cases were diagnosed as suspicious nevus due to growth &#40;11&#37;&#41; and 10 cases of PAM &#40;37&#37;&#41;&#46; Biopsies showed the existence of invasive melanoma&#46; In the remaining 55&#37; &#40;15 cases&#41; clinic melanoma diagnostic was histopathologically confirmed&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">According to origin&#44; 16 cases &#40;59&#37;&#41; arose from PAM&#44; 7 cases &#40;26&#37;&#41; from nevus and 4 patients &#40;15&#37;&#41; had <span class="elsevierStyleItalic">de novo</span> origins&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Treatment</span><p id="par0090" class="elsevierStylePara elsevierViewall">Excisional biopsy with security margin was performed on 13 patients with circumscribed lesions &#40;48&#37;&#41;&#44; while map &#40;44&#46;5&#37;&#41; or incisional &#40;7&#46;5&#37;&#41; biopsy was performed on the rest of patients&#46; Adjuvant chemotherapy was prescribed with topical mitomycin C according to the above-described regime in 15 patients with suspected epithelial residual disease or histopathological PAM diagnostic with atypia &#40;55&#37;&#41;&#44; and brachytherapy for 5 patients &#40;18&#46;5&#37;&#41; with confirmed histopathological edge in depth and sclera superficial layers compromise&#44; 4 cases were treated with ruthenium 106 and one with iodine-125 plate&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Enucleation was carried out in 3 cases who had undergone previous treatments in other hospitals before being referred to the authors&#8217; practice&#46; One enucleation was after the fourth relapse of a tumour involving more than 2 quadrants and with invasion demonstrated through ultrasound biomicroscopy and magnetic resonance covering over 80&#37; of scleral thickness&#46; The other 2 cases had also received previous treatment including mitomycin&#44; topically and in the bed of the lesion&#44; with side effects on the ocular surface &#40;corneal ulceration&#44; limbic insufficiency&#41; that did not allow conservative treatment due to the occurrence of a new epibulbar relapse&#46; Only one patient was administered palliative external radiotherapy due to CM with orbital invasion and systemic extension at diagnostic&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Follow-up&#44; extension and survival</span><p id="par0100" class="elsevierStylePara elsevierViewall">Mean follow-up was 6&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;8<span class="elsevierStyleHsp" style=""></span>years&#46; Relapses arose in 9 patients &#40;33&#37;&#41;&#59; in 7&#44; originated after PAM while locoregional extension was diagnosed in 8&#46; Ipsilateral cervical ganglia extraction with subsequent external local radiotherapy was performed in one case&#44; 5 developed systemic disease and 4 patients died due to melanoma&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Mean survival of all patients was 18<span class="elsevierStyleHsp" style=""></span>years &#40;IC 95&#37;&#58; 13&#46;7&#8211;22&#46;2&#41;&#44; with a 5 and 10 year survival probability of 89 and 69&#46;4&#37; respectively &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; In patients with recurrence&#44; survival probability at 5 and 10 years was 88&#46;9 and 61&#37;&#44; in comparison with those who did not exhibit recurrence who had 93&#46;1&#37; at 5 and 10<span class="elsevierStyleHsp" style=""></span>years &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; Patients exhibiting recurrence had 2 years less mean survival in comparison to those who did not&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">CM accounted for only 5&#46;8&#37; of all conjunctival tumours diagnosed at the Ocular Tumour Unit of the authors&#8217; hospital&#44; a percentage that was lower when compared to a similar review by Shields et al&#46;&#44; <a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">15</span></a> where CM represented 12&#37; of 5002 conjunctival tumour cases&#46; However&#44; the statistics of the present study could be biased due to being a reference unit&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Mean age at CM diagnostic is generally in the area of 60&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">16</span></a> being rare in children&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">17&#44;18</span></a> The present study found similar data&#44; with the mean age at diagnostic being 59&#46;2<span class="elsevierStyleHsp" style=""></span>years&#46; None of the patients were diagnosed in a routine examination and the most frequent reason for consultation was the growth of a pre-existing lesion&#46; The presence of inflammatory symptoms was even less frequent&#46; Eleven cases were referred from other centres with previous treatments&#44; generally without following standardized criteria&#46; According to Shields et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a> in a retrospective study &#40;1974&#8211;1997&#41; carried out in Philadelphia with 254 cases of CM&#44; the most frequent symptoms or signs were the appearance and growth of a conjunctival spot and the presence of an raised lesion&#46; One of the reasons for belated diagnostic is the variability of clinic presentation&#44; for which reason evaluations and expert follow-up are of paramount importance when suspecting a conjunctival melanocytic lesion&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Intraocular and orbital local extension of CM is a rare finding&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> It was detected in only 2 cases who had undergone incomplete previous treatment and were referred after several relapses&#46; One of said cases exhibited metastasis at diagnostic&#46; A study by Yousef and Finger<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a> in the Ocular Cancer Center of New York found that only 5 out of 42 patients with CM exhibited orbital invasion with a recurrence rate of 80&#37;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">CM diagnosis is based on biopsy &#40;excisional or map&#41;&#46; Histopathological confirmation is essential to establish adequate treatment and provide grounds for indicating adjuvant therapies&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">16</span></a> It is known that patients referred to centres specialized on intraocular tumours after undergoing surgery in other hospitals are at high risk of relapses<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">16</span></a> and that inadequate surgical treatment could increase the risk of recurrence and metastasis&#46; For these reasons it is recommendable to diagnose and treat early and fully in one procedure&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The majority of the patients of this study were treated with excisional or PAMA biopsy with added adjuvants treatment&#44; topical chemotherapy with 0&#46;02&#37; mitomycin C being the most frequent&#44; leaving brachytherapy with a smaller percentage&#46; A study carried out by Brouwer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a> in Holland on 70 patients with CM described that the initial treatment was excisional biopsy with adjuvant therapy&#44; with ruthenium plate brachytherapy being most frequent&#46; Current studies advise against excisional biopsy without adjuvant treatment due to being related with increased rates of recurrence&#44; metastasis and mortality related to melanoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">12&#44;16</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Recurrent disease generally appears in 50&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">22</span></a> Brouwer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a> described a recurrence rate of 29&#37; at 5 years while other studies reported ranges between 26 and 61&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">3&#44;11</span></a> The present study found a recurrence rate of 33&#37;&#44; most of them originating in PAM&#46; For patients without recurrence&#44; the probability of survival at 5 and 10 years was 93&#46;1&#37;&#44; while patients with relapses had a survival rate of 89&#46;9 and 61&#37; respectively&#46; Relapses are more frequent in melanoma arising from PAM and accordingly this type of patient must be followed up in a thorough&#44; regular and permanent manner with locoregional and systemic extension tests in the event of recurrence as these are at the highest risk of exhibiting extension and higher mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Conjunctival melanoma is one of the few ocular surface tumours that could be life-threatening for patients&#44; with survival ranging between 68 and 93&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">11&#44;21</span></a> At 5 years&#44; survival probability ranges between 74 and 86&#46;3&#37; while at 10<span class="elsevierStyleHsp" style=""></span>years it diminishes to 41&#8211;77&#46;7&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">23&#44;24</span></a> The results of the present study &#40;89 and 69&#46;4&#37; at 5 and 10 years&#44; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; match those of previously published studies&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Melanoma-related mortality at the end of the follow-up was 15&#37;&#46; Similar studies reported CM-related mortality at the end of follow-up at 13&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">22</span></a> being after 5 and 10<span class="elsevierStyleHsp" style=""></span>years post-diagnosis of 14 and 30&#37; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a> Several risk factors are associated to higher mortality&#44; <span class="elsevierStyleItalic">i&#46;e&#46;</span>&#44; palpebral conjunctival location&#44; caruncle&#44; fornix&#44; tumour thickness&#44; substance invasion&#44; epitheloid cell type&#44; nodular pattern growth&#44; lymphatic invasion and local disease recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">In conclusion&#44; CM is an aggressive and rare neoplasia that could be undervalued&#44; thus leading to insufficient and late treatment&#46; Differential diagnostic between precancerous and malign lesions could be difficult&#44; for which reason experts biopsy is essential for diagnostic confirmation&#46; Diagnosis and adequate and full treatments with adjuvant therapies for the initial lesion are essential for preventing recurrences and systemic extension with the aim of preserving the visual acuity as well as the life of the patient&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Funding</span><p id="par0155" class="elsevierStylePara elsevierViewall">No funding was received for carrying out the present study&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interests</span><p id="par0160" class="elsevierStylePara elsevierViewall">No commercial interests were involved in the present study&#46;</p></span></span>"
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            3 => "Primary acquired melanosis"
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            0 => "Conjuntiva"
            1 => "Tumor de conjuntiva"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The purpose of the present study is to describe the clinical characteristics and outcomes of patients diagnosed and treated for conjunctival melanoma in the Ocular Oncology Unit of the University Hospital Clinic of Valladolid&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A retrospective observational case series study was conducted on patients diagnosed with conjunctival melanoma in the Ocular Oncology Unit of University Hospital Clinic of Valladolid&#44; from January 1992 to December 2017&#46; Demographic information and tumour features were recorded in a Microsoft Access database&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Among a total of 462 consecutive patients&#44; the tumour was classified as melanocytic in 252 cases &#40;54&#46;5&#37;&#41;&#44; with 27 patients having the pathological diagnosis of conjunctival melanoma&#46; The mean age at diagnosis was 59&#46;2<span class="elsevierStyleHsp" style=""></span>years &#40;16&#8211;88&#41;&#44; and there were 41&#37; males and 59&#37; females&#44; with a mean follow-up of 6&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;8<span class="elsevierStyleHsp" style=""></span>years&#46; As regards the origin of conjunctival melanoma&#44; 16 cases &#40;59&#37;&#41; arose from primary acquired melanosis&#44; 26&#37; from nevus&#44; and 15&#37; developed <span class="elsevierStyleItalic">de novo</span>&#46; The treatment performed was incisional or excisional biopsy in all patients&#44; local adjuvant chemotherapy in 15 cases &#40;56&#37;&#41; and brachytherapy in 5 patients &#40;18&#37;&#41;&#46; The median survival was 18<span class="elsevierStyleHsp" style=""></span>years and the probability of survival at 5 and 10<span class="elsevierStyleHsp" style=""></span>years was 89&#37; and 69&#37;&#44; respectively&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Conjunctival melanoma is a rare disease&#44; usually undervalued by the patient as well as being underdiagnosed&#44; leading to insufficient and delayed treatment&#46; Early diagnosis and treatment are essential to prevent recurrences and systemic extension&#44; as well as to preserve vision and life&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Describir las caracter&#237;sticas cl&#237;nicas y la evoluci&#243;n de los pacientes diagnosticados y tratados de melanoma conjuntival en la Unidad de Tumores del Hospital Cl&#237;nico Universitario de Valladolid&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo&#59; se incluyeron pacientes diagnosticados consecutivamente de melanoma conjuntival desde enero de 1992 hasta diciembre de 2017&#46; La informaci&#243;n demogr&#225;fica y las caracter&#237;sticas del tumor fueron registradas en una base de datos en <span class="elsevierStyleItalic">Microsoft Access</span>&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">De un total de 462 pacientes con diagn&#243;stico de tumor conjuntival&#44; 252 casos &#40;54&#44;5&#37;&#41; fueron de origen melanoc&#237;tico&#44; y de estos&#44; 27 casos fueron melanomas de conjuntiva&#46; La edad media fue de 59&#44;2 &#40;16-88&#41; a&#241;os&#59; 41&#37; hombres y 59&#37; mujeres&#44; con un seguimiento medio de 6&#44;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;8 a&#241;os&#46; Seg&#250;n el origen del melanoma conjuntival&#44; 16 casos &#40;59&#37;&#41; surgieron a partir de melanosis adquirida primaria&#44; el 26&#37; de nevus y el 15&#37; <span class="elsevierStyleItalic">de novo</span>&#46; Se realiz&#243; biopsia incisional o escisional en todos los pacientes&#44; quimioterapia local adyuvante en 15<span class="elsevierStyleHsp" style=""></span>casos &#40;56&#37;&#41; y braquiterapia en 5<span class="elsevierStyleHsp" style=""></span>pacientes &#40;18&#37;&#41;&#46; La supervivencia media fue de 18<span class="elsevierStyleHsp" style=""></span>a&#241;os &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#41; y la probabilidad de supervivencia a los 5 y 10<span class="elsevierStyleHsp" style=""></span>a&#241;os fue del 89 y del 69&#37;&#44; respectivamente&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El melanoma conjuntival es una enfermedad rara que se suele infravalorar en estadios iniciales&#44; lo que lleva a un tratamiento insuficiente y tard&#237;o&#46; El diagn&#243;stico y el tratamiento precoces son esenciales para prevenir las recurrencias y la extensi&#243;n sist&#233;mica y para preservar la visi&#243;n y la vida del paciente&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Pacheco GE&#44; Garcia-Onrubia L&#44; Garcia-Alvarez C&#44; Mu&#241;oz MF&#44; Garcia-Lagarto E&#44; Perez DM&#44; et al&#46; Revisi&#243;n retrospectiva del melanoma conjuntival&#58; presentaci&#243;n&#44; tratamiento y evoluci&#243;n&#46; Arch Soc Esp Oftalmol&#46; 2019&#59;94&#58;218&#8211;224&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Circumscribed conjunctival melanoma &#40;black arrow&#41; in upper nasal area invading the corner limbus&#44; treated with excisional biopsy with safety margin&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Nodular conjunctival melanoma &#40;&#42;&#41; in patient with primary acquired melanosis with multicenter pigmentation &#40;&#42;&#42;&#41;&#46; &#40;b&#41; Ultrasound biomicroscopy showing lesion invading superficial scleral layers&#44; having a base measuring 5&#46;34<span class="elsevierStyleHsp" style=""></span>mm &#40;red line&#41; and a height of 2&#46;27<span class="elsevierStyleHsp" style=""></span>mm &#40;green line&#41;&#46; &#40;c&#41; After adjuvant treatment with mitomycin C eyedrops&#44; scleral invasion was treated with episcleral brachytherapy with iodine-125 plate &#40;&#42;&#41;&#46; &#40;d&#41; No signs of recurrence were observed 5 years after treatment&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1488
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            "Tamanyo" => 97822
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Kaplan&#8211;Meier analysis&#46; Overall survival curve for patients with conjunctival melanoma diagnostic&#46; Survival probability at 5 and 10 years is 89 and 69&#46;4&#37;&#44; respectively&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 1509
            "Ancho" => 1514
            "Tamanyo" => 129172
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        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Kaplan&#8211;Meier analysis and generalized Wilcoxon comparison test&#46; In patients without recurrences&#44; the survival probability at 5 and 10 years is of 93&#46;1&#37;&#44; in contrast with those who had recurrences&#44; with a survival probability of 88&#46;9 and 61&#37;&#44; respectively&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Sex</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Male</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Female</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Laterality</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">RE</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">LE</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Initial consultation reason</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Routine checkup</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Inflammation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Growth</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Previous treatments</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Location</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Epibulbar</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Bulbar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Limbar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Corneal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Not epibulbar</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Fornix&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Tarsal conjuntiva&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Caruncle&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Form</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Circunscribed</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Multicenter</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Extension in quadrants</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Q1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Q2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Q3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Q4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Local extension</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Intraocular</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Orbital</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Clinic diagnostic</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Nevus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">PAM</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Melanoma</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Origin of melanoma</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">PAM</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Nevus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Treatment</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Biopsy</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Excisional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">1R</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">2R</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">3R</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Extension</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Systemic</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Specific mortality due to melanoma</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
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