Clinical and histopathological features of choroidal melanoma-related enucleated eyes in a Spanish tertiary hospital | Archivos de la Sociedad Española de Oftalmología (English Edition)

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(b) Autofluorescence: without alterations one month after diagnostic and with areas of patched hyper- and hypofluorescence 3 years after diagnostic in the peripapillary zone outside of the arches. (c) Fluorescein angiography: slight hyperfluorescence in the zones comprised within the ring. (d) OCT with loss of outer layers, respecting the macular area and mfERG with persistence of electroretinographic alterations. (e) VF: generalized sensitivity loss respecting the macula." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. García-Torre, R. Castro-Flórez" "autores" => array:2 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "García-Torre" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Castro-Flórez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S036566911830306X" "doi" => "10.1016/j.oftal.2018.10.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S036566911830306X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579419300222?idApp=UINPBA00004N" "url" => "/21735794/0000009400000005/v1_201904290704/S2173579419300222/v1_201904290704/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S217357941930057X" "issn" => "21735794" "doi" => "10.1016/j.oftale.2019.01.010" "estado" => "S300" "fechaPublicacion" => "2019-05-01" "aid" => "1473" "copyright" => "Sociedad Española de Oftalmología" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Soc Esp Oftalmol. 2019;94:218-24" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "A retrospective review of conjunctival melanoma: Presentation, treatment and evolution" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "218" "paginaFinal" => "224" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Revisión retrospectiva del melanoma conjuntival: presentación, tratamiento y evolución" ] ] "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" => "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." ] ] ] "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." "apellidos" => "Alonso" ] 7 => array:2 [ "nombre" => "M.A." "apellidos" => "Saornil" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0365669119300401" "doi" => "10.1016/j.oftal.2019.01.008" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669119300401?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217357941930057X?idApp=UINPBA00004N" "url" => "/21735794/0000009400000005/v1_201904290704/S217357941930057X/v1_201904290704/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Clinical and histopathological features of choroidal melanoma-related enucleated eyes in a Spanish tertiary hospital" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "225" "paginaFinal" => "231" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. García Tirado, M. Asencio Durán, J. Peralta Calvo, A. Berjón, E. Ruiz Bravo-Burguillos" "autores" => array:5 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "García Tirado" "email" => array:1 [ 0 => "a.gartir@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Asencio Durán" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Peralta Calvo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "A." "apellidos" => "Berjón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "E." "apellidos" => "Ruiz Bravo-Burguillos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Ophthalmology, La Paz University Hospital, IdiPaz, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Pathological Anatomy, La Paz University Hospital, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Características clínicas e histopatológicas de ojos enucleados por melanoma uveal en un hospital terciario en España" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 494 "Ancho" => 1250 "Tamanyo" => 96689 ] ] "descripcion" => array:1 [ "en" => "Uveal malignant melanoma (MM). (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)." ] ] ] "textoCompleto" => "IntroductionThe present work analyzes the presence of several clinical and pathologic features that are assumed to be risk and poor-prognosis factors, in a series of MM cases that ended up requiring enucleation at a tertiary hospital in Madrid (Spain). Moreover, as part of the extension study performed in our sample, MRI's diagnostic reliability was also assessed.Uveal MM is the most frequent primary intraocular malignancy in adults. Its incidence rate is 5–6 new cases/million inhabitants<a class="elsevierStyleCrossRef" href="#bib0190">1</a> and it primarily affects individuals in their 50s or 60s.<a class="elsevierStyleCrossRef" href="#bib0195">2</a> This condition's predisposing factors haven’t been clearly determined yet, but the following are considered risk factors: fair-skin phenotype<a class="elsevierStyleCrossRef" href="#bib0200">3</a> and a personal history of melanocytic alterations of the eye.<a class="elsevierStyleCrossRef" href="#bib0205">4</a> MM's treatment approach has been and still is a subject of controversy. At present, the most frequently used methods are radiotherapy and enucleation. Thanks to the outcomes of the Collaborative Ocular Melanoma Study (COMS),<a class="elsevierStyleCrossRefs" href="#bib0210">5–8</a> at present the main treatment goal is to achieve the best systemic prognosis while trying always to preserve vision to the greatest extent possible.Regarding uveal MM diagnosis, a combination of indirect ophthalmoscopy and ultrasound turns out to be an effective assessment method in 98% of the cases.<a class="elsevierStyleCrossRefs" href="#bib0230">9,10</a> There are also other tests that have proven to be useful, such as fluorescein angiography, Doppler color imaging (DCI), MRI and even cytology and biopsy in particularly atypical lesions. MRI is also a key tool for the extension study required prior to treatment initiation.<a class="elsevierStyleCrossRef" href="#bib0240">11</a> An increasing number of researchers consider MRI to be the imaging technique of choice for the diagnosis and management of eye tumors.<a class="elsevierStyleCrossRef" href="#bib0245">12</a>Uveal MM prognosis involves outcomes related to ocular morbidity from tumor treatment and to systemic mortality from metastatic disease, which is a frequent event in MM.<a class="elsevierStyleCrossRef" href="#bib0250">13</a> To date, the clinical risk factor that has been most associated with metastatic-disease development is tumor size, whereas the molecular risk factor is the loss of one of the two copies of chromosome 3 (monosomy 3).<a class="elsevierStyleCrossRef" href="#bib0255">14</a>Materials and methodsData were collected from medical and pathology reports belonging to uveal MM patients who were enucleated—by means of the classical enucleation technique—at La Paz University Hospital's Ophthalmology Department between 2007 and 2003. Some of these patients underwent a de novo enucleation (group A), whereas others had previously received radiotherapy (group B). For all patients we followed the treatment protocol for choroidal MM that was in place at La Paz Hospital up until July 2013 (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Informed consent was obtained from all individual participants included in the study.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Clinical data<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-Epidemiological data: Age, gender, affected eye, personal history of dermatological conditions.</li><li class="elsevierStyleListItem" id="lsti0010">-Signs and symptoms: best corrected visual acuity at diagnosis and right before enucleation, tumor location (posterior choroid, anterior choroid or both), clinical appearance (fungiform/Bruch's membrane rupture, dome-shaped or diffuse) and the presence (or absence) of melanoma-related ocular complications (retinal detachment, subretinal hemorrhage, vitreous hemorrhage and/or Bruch's membrane rupture/fungiform appearance).</li><li class="elsevierStyleListItem" id="lsti0015">-Complementary tests:</li><li class="elsevierStyleListItem" id="lsti0020">•Ultrasound: Largest basal diameter (LBS) and tumor thickness, size—according to the COMS classification<a class="elsevierStyleCrossRef" href="#bib0210">5</a> and the 7th edititon TNM staging system's T by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC)<a class="elsevierStyleCrossRef" href="#bib0260">15</a>—, tumor appearance, tumor growth during the study.</li><li class="elsevierStyleListItem" id="lsti0025">•Color Doppler imaging (CDI): Radiologist-reported intratumoral vascularization level. Null, low (less than half of the tumor) or high (more than half of the tumor).</li><li class="elsevierStyleListItem" id="lsti0030">•MRI (1.5T): presence (or absence) of scleral infiltration and extra-scleral extension.Evolutionary: Main cause making enucleation necessary, time from diagnosis to enucleation, metastasis development during follow-up (Whole-Body PET/CT).</li></ul>Pathological dataWith the help of the Pathology Department staff, a systematic re-reading of the enucleated samples was carried out, while the patient's treatment history and the tumor's clinical staging remained unknown to the technician.<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035">-Tumor's cellular type: epithelioid-cell, spindle-cell, mixed-cell tumor, following Callender's classification later modified by Seddon et al.<a class="elsevierStyleCrossRefs" href="#bib0265">16,17</a></li><li class="elsevierStyleListItem" id="lsti0040">-Tumor dimensions: LBS and thickness in millimeters (mm)</li><li class="elsevierStyleListItem" id="lsti0045">-Distance from the tumor to the optic nerve (mm).</li><li class="elsevierStyleListItem" id="lsti0050">-Whether or not optic nerve infiltration had occurred.</li><li class="elsevierStyleListItem" id="lsti0055">-The presence (or absence) of scleral and/or extrascleral invasion.</li><li class="elsevierStyleListItem" id="lsti0060">-Number of mitoses in 10 fields at 400 folds magnification (5 HPF). The proliferation level could not be measured by means of the Ki-67 or PCNA cell-proliferation markers<a class="elsevierStyleCrossRef" href="#bib0275">18</a> since this required the samples being sent to a different facility.</li><li class="elsevierStyleListItem" id="lsti0065">-The presence/absence of infiltration by macrophages, necrosis and tumor fibrosis (5 HPF).</li></ul>Moreover, and bearing in mind that group B was likely to show specific pathological features, the presence of balloon cells, and the retinal degeneration type (if any; cystic and/or atrophic type) was also assessed.Statistical analysisThe statistical software package SPSS v.15.0 for Windows (SPSS Inc., Chicago, Illinois, USA) was used to perform a descriptive analysis of the collected data.ResultsA total of 30 enucleated eyes from 30 patients were included in the study. Among them 20 eyes (group A) were enucleated right after the first visit, while the remaining 10 (group B) underwent radiotherapy (85-Gy dose at the apex) prior to enucleation. In 7 out of these 10 cases iodine 125 plaques were used, in 1 it was ruthenium 106+Transpupillary Thermotherapy (TTT) and 1 relied on a proton beam at Lausanne (Switzerland).Demographic featuresOur sample consisted of 57% of male and 43% of female patients. Mean age at diagnosis was 57±16.15 years (23–84 years). Only 15% of the patients showed predisposing dermatological alterations: fair skin phototype and light-colored eyes, other dermatological tumors and/or melanosis oculi.Clinical featuresIn 80% of the cases MM presented with reduced visual acuity, while in the remaining 20% the malignancy was found by chance.Visual acuity at the time of diagnosis was equal to or greater than 0.5 in 40% of the patients. However, right before enucleation, it had dropped to below 0.1 in 65% of the cases. Mean time from tumor detection to enucleation was 10±13.4 (0.5–41) months.Regarding tumor location, in 80% of the cases it was located in the posterior choroid, in 7% of them in the anterior choroid (ciliary body and iris) and in the remaining cases the tumor covered both areas. As for the tumor's appearance, in 45% of the cases it was mushroom-shaped, in another 45% it was dome-shaped and the remaining 10% of tumors had a diffuse shape. At the time of diagnosis, retinal detachment was observed in 80% of the cases, subretinal hemorrhages in 50% of them and vitreous hemorrhage in 75% of them.According to ultrasound measurements, 50% of the tumors were classified as large and the remaining 50% were considered to be medium-sized (COMS classification). In 75% of the cases the tumor was staged as T3 or above (AJCC/UICC 7th edition classification). The CDI revealed the presence of intratumoral vascularization at the time of diagnosis in 85% of the cases. All patients had a MRI done, and this test unveiled the presence of scleral invasion in 40% of the cases and extrascleral extension in one of them (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The reasons for enucleation were the tumor's initial size (50% of the cases), tumor growth despite treatment (25% of the cases, all from group B) and in the remaining 25% of the cases it was due to secondary-to-treatment complications (all from group B) or to the patient's total lack of vision in the affected eye.Metastatic disease developed in two cases; lung metastasis in one case and liver metastasis in the other one. The incidence of metastatic disease upon study completion was 6%, whereas the overall survival rate was 100% for a mean follow-up period of 3±1.5 (1.2–6) years.Histopathological featuresThe prevailing cell type was spindle-cell (60% of the cases) followed by the epithelioid cell type (25% of the cases).The tumor was less than 2mm away from the optic nerve in 55% of the cases; in 10% of them the tumor had infiltrated the optic nerve. Moreover, in 73% of the cases there had been scleral infiltration and in one case extrascleral invasion was observed.Regarding the number of mitoses in 10 HPF: in 55% of the patients none were found, in 45% only 1 or 2 were observed, while in 2 cases (both belonging to group A) up to 8 mitoses were found. In 25% of the tumors there was macrophage infiltration.Finally, the following histological findings were observed: fibrosis (15% of the cases), necrosis (20%), the presence of balloon-like cells (7% of the samples) and cystoid degeneration of the retina (70%) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>MRI reliabilityIn our population, MRI's sensitivity to detect scleral infiltration amounted to 27% and this test's specificity was 75%. As for extrascleral-involvement detection, MRI's sensitivity was 100% and its specificity was as high as 97%.DiscussionThe epidemiological variables that were assessed in our population—typical tumor location, initial clinical presentation<a class="elsevierStyleCrossRef" href="#bib0280">19</a> and age at the time of diagnosis2—are in good agreement with the values described in the literature. However, we observed that, in our sample, fair-skin phenotype and concomitant dermatological alterations were not so present. This finding differs from other authors’ claims<a class="elsevierStyleCrossRefs" href="#bib0200">3,20</a> but it supports the hypothesis that within the Spanish population having a fair-skin phototype is not so determinant because this phototype is not the typical one in our latitudes (Muiños et al., personal communication, ISSO Congress Cambridge, 2009).Focusing on the clinical variables, all enucleated tumors shared the following adverse-prognosis features, which lead to a particularly aggressive behavior and, consequently, would highlight the need for enucleation as definite treatment approach.A significant size.<a class="elsevierStyleCrossRefs" href="#bib0255">14,21</a> All tumors assessed in this study were either large (50%) or medium-sized (50%)—according to the COMS classification—and 75% of them were classified as stage T3 or above—according to the AJCC/UICC staging system—; these are sizes for which enucleation is indicated as initial curative treatment.<a class="elsevierStyleCrossRef" href="#bib0215">6</a>Most cases initially presented with retinal detachment (80%), subretinal bleeding (50%) and/or vitreous hemorrhage (75%), which aside from suggesting that Bruch's membrane rupture has occurred due to the MM (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>)—which, in itself, is an additional poor-prognosis risk factor<a class="elsevierStyleCrossRefs" href="#bib0295">22,23</a>—, they result in poorer visual acuity, which is one of the parameters to be born in mind when considering treatment options and opting for enucleation.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Other adverse-prognosis clinical factors described in the literature have been: tumor growth despite an active treatment being applied<a class="elsevierStyleCrossRef" href="#bib0305">24</a>—which happened in only 23% of our cases (group B) and anterior tumor location<a class="elsevierStyleCrossRef" href="#bib0310">25</a>; in our sample 6% of the tumors were in the ciliary body and 17% had mixed location. Therefore, we can conclude that for our sample these clinical factors did not turn out to be so determinant of poor prognosis.Regarding intratumoral vascularization, it is worth highlighting that extravascular matrix patterns that reflect the arrangement of tumor microcirculation<a class="elsevierStyleCrossRef" href="#bib0315">26</a> and high microvascular density<a class="elsevierStyleCrossRef" href="#bib0320">27</a> seen in histological samples are independently associated with shorter time to metastatic death in uveal MM. In this study, a histopathological analysis of the enucleated samples’ vascular formations could not be carried out. Therefore, we analyzed, at the time of diagnosis, the intratumoral vascularization level using Doppler ultrasound.<a class="elsevierStyleCrossRef" href="#bib0325">28</a> This criterion has not been internationally-accepted as a poor prognosis indicator. Besides, it is well known that there is no correlation between MM size and its internal vascularization level described by means of CDI.<a class="elsevierStyleCrossRef" href="#bib0330">29</a> Anyhow, in our sample, comprising well-known poor-prognosis tumors, half of them had at diagnosis a high vascularization level by the CDI. At present, there are already some studies describing the characteristic microvascular patterns for uveal MM by optical-coherence tomography angiography (OCT-A) and comparing them with the samples’ histological analysis.<a class="elsevierStyleCrossRef" href="#bib0335">30</a> Perhaps, in the near future OCT-A may end up replacing the pathology study when estimating the prognosis for this type of tumors.Focusing on those pathological variables that are known to be linked to an adverse prognosis, in the present study the most relevant ones turned out to be: distance to the optic nerve—since in most of our cases (55% of them) this value was ≤2mm<a class="elsevierStyleCrossRefs" href="#bib0340">31,32</a>—and scleral infiltration,<a class="elsevierStyleCrossRef" href="#bib0350">33</a> which occurred in 73% of our sample's tumors. This latter fact, which suggests that enucleation was indeed an appropriate treatment, might explain why our survival rate was high, since enucleation eradicates the disease if it hasn’t spread yet.<a class="elsevierStyleCrossRef" href="#bib0215">6</a> As for brachytherapy, it also becomes an eradicating treatment approach for medium-sized tumors even in those cases with scleral infiltration but if it is limited.<a class="elsevierStyleCrossRef" href="#bib0220">7</a> In our sample most tumors had a size greater than or equal to T3 (AJCC/UICC staging system, which is equivalent to the COMS classification's medium-to-large-sized tumors) and in most cases the sclera had been infiltrated.Other well-known histopathological adverse factors that, for our sample, didn’t turn out to be as relevant were: epithelioid cell type,<a class="elsevierStyleCrossRef" href="#bib0250">13</a> which was detected in only 25% of the cases; Infiltration by macrophages,<a class="elsevierStyleCrossRef" href="#bib0355">34</a> which occurred in 25% of the histopathological sections; optic-nerve infiltration,<a class="elsevierStyleCrossRef" href="#bib0360">35</a> found in only 3 cases; and the number of mitoses,<a class="elsevierStyleCrossRef" href="#bib0275">18</a> which wasn’t high in most of the cases. Nonetheless, 2 patients from group A, that is, tumors of large size, which is the clinical risk factor that is most associated with the development of metastasis,<a class="elsevierStyleCrossRef" href="#bib0255">14</a> ended up developing metastatic disease.Additional findings emerging from the histological analysis that are worth highlighting are necrosis (detected in 20% of the cases) and fibrosis (15%), both occurring mainly in group B eyes. These side effects can be attributed to brachytherapy and they tell us that the treatment was indeed working, at least in part of the tumor.<a class="elsevierStyleCrossRef" href="#bib0340">31</a> The presence of balloon-like cells and the occurrence of cystoid degeneration of the retina, also side effects of radiation therapy, were detected exclusively in group-B tumors.<a class="elsevierStyleCrossRef" href="#bib0360">35</a>In terms of survival, according to the outcome data published by the COMS, the 5-year mortality rate for post-treatment uveal melanoma equals 40% for large-size tumors<a class="elsevierStyleCrossRef" href="#bib0215">6</a> and 20% for medium-sized ones.<a class="elsevierStyleCrossRef" href="#bib0220">7</a> In our sample, which comprised large and medium-sized tumors, whose genetic characteristics are unknown – because they were not evaluated in this study – survival was as high as 100%. We must also admit that the follow-up period was shorter; namely, 3±1.5 (1.2–6) years.Contrary to other published studies, for our case series of 30 cases, MRI (1.5T) didn’t turn out to be a good screening test to detect scleral infiltration—more specifically, sensitivity was as low as 27%—but the technique did prove to be rather specific (75% specificity). However, it turned out to be a good technique to detect extrascleral extension, since it had 100% sensitivity and 97% specificity, which is in good agreement with previous studies.<a class="elsevierStyleCrossRefs" href="#bib0365">36,37</a>ConclusionThe analyses of clinical and pathologic data collected in the framework of this study justify enucleation as the treatment of choice for our patients. MRI (1.5T) didn’t turn out to be an optimum screening method to detect scleral infiltration.The present work aims to be a local approximation to other published studies. Its outcomes cannot be generalized since sample size was small. We intend to extend the case series in the near future by adding a genetic assessment.Conflict of interestThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1184805" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 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" => "xpalclavsec1104915" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1184804" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1104914" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Clinical data" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Pathological data" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Demographic features" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Clinical features" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Histopathological features" ] 3 => array:2 [ "identificador" => "sec0050" "titulo" => "MRI reliability" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-10-15" "fechaAceptado" => "2018-12-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1104915" "palabras" => array:3 [ 0 => "Uveal melanoma prognosis features" 1 => "Uveal melanoma histopathology" 2 => "Uveal melanoma MRI" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1104914" "palabras" => array:3 [ 0 => "Factores pronóstico en melanoma uveal" 1 => "Histopatología en melanoma uveal" 2 => "RMN en melanoma uveal" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectivesTo study clinical and pathological variables leading to a poor prognosis in a sample of uveal malignant melanoma patients who required eyeball enucleation as final treatment approach. All patients were seen and treated in the same public tertiary hospital in Madrid (Spain) within a 6-year time-period. MethodsLongitudinal observational retrospective study. The presence of clinical and pathologic factors known to be linked to poor prognosis – as well as other features – was assessed in 30 malignant melanoma: 20 de novo-enucleated malignant melanoma eyes (group A), and 10 in eyes that received radiotherapy prior to enucleation (group B). The diagnostic reliability of magnetic resonance imaging was assessed by comparing it with the histology results – “gold standard” – as a means to detect scleral and extra-scleral extension. ResultsTumor size, Bruch's membrane rupture, scleral infiltration, and distance to the optic nerve were the most decisive factors for a poor prognosis in the study sample. In 93% of cases the condition was under control, with a 6% incidence rate of metastatic spread and a 100% rate of overall survival for a mean follow-up period of 3±1.5 (range 1.2–6) years. In the study population, the sensitivity of the magnetic resonance imaging to detect scleral infiltration was 27%, which increased to 100% for identifying extra-scleral involvement. ConclusionsThe analyses of the clinical and pathological data collected within the framework of this study justify enucleation as the treatment of choice for the patients of this study. Magnetic resonance imaging was not found to be an optimum screening method to detect scleral infiltration in this study sample." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 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" => "ObjetivoEstudiar las variables clínicas y anatomopatológicas de mal pronóstico en una muestra de pacientes con melanoma maligno de úvea que requirieron enucleación como tratamiento definitivo en un hospital terciario en Madrid (España) durante un período de tiempo de 6 años. Material y métodosEstudio retrospectivo, observacional, longitudinal. Se analiza la presencia de factores clínicos y anatomopatológicos conocidos de mal pronóstico y otros en 30 melanomas malignos: 20 enucleados de novo (grupo A) y 10 tras recibir tratamiento con radioterapia (grupo B). Se estudia el grado de fiabilidad diagnóstica de la resonancia magnética nuclear, comparándola con la histología (gold standard) para predecir la presencia de invasión escleral y extraescleral. ResultadosEl tamaño tumoral, la rotura de la membrana de Bruch, la invasión escleral y la proximidad al nervio óptico fueron los factores de mal pronóstico más determinantes. Se logró controlar la enfermedad en el 93% de los casos, con una incidencia de diseminación metastásica del 6% y una supervivencia del 100% a una media de seguimiento de 3±1,5 (rango 1,2-6) años. La sensibilidad de la resonancia magnética nuclear, en nuestra población, para detectar infiltración escleral fue del 27%, y extraescleral, del 100%. ConclusionesEl análisis de los datos clínicos e histopatológicos recogidos justifican la enucleación como tratamiento final en los pacientes estudiados. La resonancia magnética nuclear no resultó un buen método de cribado para detectar la extensión escleral." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y 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: García Tirado A, Asencio Durán M, Peralta Calvo J, Berjón A, Ruiz Bravo-Burguillos E. Características clínicas e histopatológicas de ojos enucleados por melanoma uveal en un hospital terciario en España. Arch Soc Esp Oftalmol. 2019;94:225–231." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 494 "Ancho" => 1250 "Tamanyo" => 96689 ] ] "descripcion" => array:1 [ "en" => "Uveal malignant melanoma (MM). (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)." ] ] 1 => 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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anamnesis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-Medical history -Ultrasound and CDI -Local extension study -Systemic extension study: Laboratory tests Imaging studies: -Chest X-ray and liver ultrasound. -If necessary whole body positron emission tomography/computed tomography (whole-body PET/CT) \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">Treatment (based mainly on the COMS classification) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-Large tumors: Enucleation -Medium tumors: Brachytherapy+/−TTT •>8mm thick/T3 (AJCC/UICC 7th ed): enucleation is considered as initial treatment -Small tumors: Observation or treatment according to number of risk factors. •If there are: poor prognosis factors, complications due to the tumor or its treatment, null eye vision and/or express desire of the patient the enucleation is always valued as initial treatment. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2019730.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Treatment protocol for choroidal MM that was in place at La Paz Hospital up until July 2013." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "BCVA: Best-Corrected Visual Acuity." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \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">Results \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="2" align="left" valign="top">BCVA (logMAR)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">At diagnosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥0.5 (40%) \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">Pre-enucleation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≤0.5 (100%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≤0.1 (65%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Tumor location</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anterior choroid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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">Posterior choroid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80% \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">Both \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Tumor shape</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fungiform/Bruch's membrane rupture \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45% \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">Dome-shaped \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45% \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">Diffuse \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Melanoma-related ocular complications</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Retinal detachment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80% \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">Subretinal hemorrhage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50% \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">Vitreous hemorrhage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">75% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Ultrasound</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">COMS classification</td><td class="td" title="table-entry " align="left" valign="top">50% large \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">50% medium \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">AJCC/UICC classification</td><td class="td" title="table-entry " align="left" valign="top">T1 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">T2 20% \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">T3 50% \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">T4 25% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">CDI</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Intratumoral vascularization</td><td class="td" title="table-entry " align="left" valign="top">Null 15% \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">Low 20% \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">High 65% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">MRI</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Scleral infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40% \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">Extra-scleral infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2019731.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical features of the sample." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "5 HPF: 5 fields at high-power field (400 fold magnification). 10 HPF: 10 fields at high-power field (400 fold magnification)." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \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">Results \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="2" align="left" valign="top">Tumor's cellular type</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Epithelioid-cell \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60% \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">Spindle-cell \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25% \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">Mixed-cell \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Distance to the optic nerve</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥2mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45% \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">≤2mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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">Optic nerve infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10% \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">Scleral invasion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">73% \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">Extra-scleral invasion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Number of mitoses (10 HPF)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45% \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">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">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">Infiltration by macrophages(5HPF) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Necrosis (5HPF)</td><td class="td" title="table-entry " align="left" valign="top">20% \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">10% Group A \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">40% Group B \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">Fibrosis (5HPF) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15% Group B/0% Group A \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">Balloon cells(5HPF) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7% Group B/0% Group A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Retinal degeneration type(5HPF)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cystic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70% Group B/0% Group A \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">Atrophic type \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25% Group B/0% Group A \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">Mixed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5% Group B/0% Group A \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2019729.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Histopathological features of the sample." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:37 [ 0 => array:3 [ "identificador" => "bib0190" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Uveal melanoma: trends in incidence, treatment, and survival" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.D. 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Clinical and histopathological features of choroidal melanoma-related enucleated eyes in a Spanish tertiary hospital

Características clínicas e histopatológicas de ojos enucleados por melanoma uveal en un hospital terciario en España

A. García Tiradoa,

Corresponding author

a.gartir@gmail.com

Corresponding author.

, M. Asencio Durána, J. Peralta Calvoa, A. Berjónb, E. Ruiz Bravo-Burguillosb

a Department of Ophthalmology, La Paz University Hospital, IdiPaz, Madrid, Spain

b Department of Pathological Anatomy, La Paz University Hospital, Madrid, Spain

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but the following are considered risk factors&#58; fair-skin phenotype<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">3</span></a> and a personal history of melanocytic alterations of the eye&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">4</span></a> MM&#39;s treatment approach has been and still is a subject of controversy&#46; At present&#44; the most frequently used methods are radiotherapy and enucleation&#46; Thanks to the outcomes of the Collaborative Ocular Melanoma Study &#40;COMS&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">5&#8211;8</span></a> at present the main treatment goal is to achieve the best systemic prognosis while trying always to preserve vision to the greatest extent possible&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Regarding uveal MM diagnosis&#44; a combination of indirect ophthalmoscopy and ultrasound turns out to be an effective assessment method in 98&#37; of the cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">9&#44;10</span></a> There are also other tests that have proven to be useful&#44; such as fluorescein angiography&#44; Doppler color imaging &#40;DCI&#41;&#44; MRI and even cytology and biopsy in particularly atypical lesions&#46; MRI is also a key tool for the extension study required prior to treatment initiation&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">11</span></a> An increasing number of researchers consider MRI to be the imaging technique of choice for the diagnosis and management of eye tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Uveal MM prognosis involves outcomes related to ocular morbidity from tumor treatment and to systemic mortality from metastatic disease&#44; which is a frequent event in MM&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">13</span></a> To date&#44; 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Informed consent was obtained from all individual participants included in the study&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Clinical data</span><p id="par0030" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Epidemiological data</span>&#58; Age&#44; gender&#44; affected eye&#44; personal history of dermatological conditions&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Signs and symptoms</span>&#58; best corrected visual acuity at diagnosis and right before enucleation&#44; tumor location &#40;posterior choroid&#44; anterior choroid or both&#41;&#44; clinical appearance &#40;fungiform&#47;Bruch&#39;s membrane rupture&#44; dome-shaped or diffuse&#41; and the presence &#40;or absence&#41; of melanoma-related ocular complications &#40;retinal detachment&#44; subretinal hemorrhage&#44; vitreous hemorrhage and&#47;or Bruch&#39;s membrane rupture&#47;fungiform appearance&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0045" class="elsevierStylePara elsevierViewall">Complementary tests&#58;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Ultrasound</span>&#58; Largest basal diameter &#40;LBS&#41; and tumor thickness&#44; size&#8212;according to the COMS classification<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">5</span></a> and the 7th edititon TNM staging system&#39;s T by the American Joint Committee on Cancer &#40;AJCC&#41; and the International Union Against Cancer &#40;UICC&#41;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">15</span></a>&#8212;&#44; tumor appearance&#44; tumor growth during the study&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Color Doppler imaging &#40;CDI&#41;</span>&#58; Radiologist-reported intratumoral vascularization level&#46; Null&#44; low &#40;less than half of the tumor&#41; or high &#40;more than half of the tumor&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0060" class="elsevierStylePara elsevierViewall">MRI &#40;1&#46;5<span class="elsevierStyleHsp" style=""></span>T&#41;&#58; presence &#40;or absence&#41; of scleral infiltration and extra-scleral extension&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Evolutionary&#58; Main cause making enucleation necessary&#44; time from diagnosis to enucleation&#44; metastasis development during follow-up &#40;Whole-Body PET&#47;CT&#41;&#46;</p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Pathological data</span><p id="par0070" class="elsevierStylePara elsevierViewall">With the help of the Pathology Department staff&#44; a systematic re-reading of the enucleated samples was carried out&#44; while the patient&#39;s treatment history and the tumor&#39;s clinical staging remained unknown to the technician&#46;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Tumor&#39;s cellular type</span>&#58; epithelioid-cell&#44; spindle-cell&#44; mixed-cell tumor&#44; following Callender&#39;s classification later modified by Seddon et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">16&#44;17</span></a></p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Tumor dimensions</span>&#58; LBS and thickness in millimeters &#40;mm&#41;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0085" class="elsevierStylePara elsevierViewall">Distance from the tumor to the optic nerve &#40;mm&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0090" class="elsevierStylePara elsevierViewall">Whether or not <span class="elsevierStyleItalic">optic nerve infiltration</span> had occurred&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0095" class="elsevierStylePara elsevierViewall">The presence &#40;or absence&#41; of scleral and&#47;or extrascleral invasion&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Number of mitoses</span> in 10 fields at 400 folds magnification &#40;5 HPF&#41;&#46; The proliferation level could not be measured by means of the Ki-67 or PCNA cell-proliferation markers<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">18</span></a> since this required the samples being sent to a different facility&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">The presence&#47;absence of <span class="elsevierStyleItalic">infiltration by macrophages</span>&#44; <span class="elsevierStyleItalic">necrosis</span> and tumor <span class="elsevierStyleItalic">fibrosis</span> &#40;5 HPF&#41;&#46;</p></li></ul></p><p id="par0110" class="elsevierStylePara elsevierViewall">Moreover&#44; and bearing in mind that group B was likely to show specific pathological features&#44; the <span class="elsevierStyleItalic">presence of balloon cells</span>&#44; and the <span class="elsevierStyleItalic">retinal degeneration type</span> &#40;if any&#59; cystic and&#47;or atrophic type&#41; was also assessed&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0115" class="elsevierStylePara elsevierViewall">The statistical software package SPSS v&#46;15&#46;0 for Windows &#40;SPSS Inc&#46;&#44; Chicago&#44; Illinois&#44; USA&#41; was used to perform a descriptive analysis of the collected data&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0120" class="elsevierStylePara elsevierViewall">A total of 30 enucleated eyes from 30 patients were included in the study&#46; Among them 20 eyes &#40;group A&#41; were enucleated right after the first visit&#44; while the remaining 10 &#40;group B&#41; underwent radiotherapy &#40;85-Gy dose at the apex&#41; prior to enucleation&#46; In 7 out of these 10 cases iodine 125 plaques were used&#44; in 1 it was ruthenium 106<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Transpupillary Thermotherapy &#40;TTT&#41; and 1 relied on a proton beam at Lausanne &#40;Switzerland&#41;&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Demographic features</span><p id="par0125" class="elsevierStylePara elsevierViewall">Our sample consisted of 57&#37; of male and 43&#37; of female patients&#46; Mean age at diagnosis was 57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;15 years &#40;23&#8211;84 years&#41;&#46; Only 15&#37; of the patients showed predisposing dermatological alterations&#58; fair skin phototype and light-colored eyes&#44; other dermatological tumors and&#47;or melanosis oculi&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Clinical features</span><p id="par0130" class="elsevierStylePara elsevierViewall">In 80&#37; of the cases MM presented with reduced visual acuity&#44; while in the remaining 20&#37; the malignancy was found by chance&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Visual acuity at the time of diagnosis was equal to or greater than 0&#46;5 in 40&#37; of the patients&#46; However&#44; right before enucleation&#44; it had dropped to below 0&#46;1 in 65&#37; of the cases&#46; Mean time from tumor detection to enucleation was 10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;4 &#40;0&#46;5&#8211;41&#41; months&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Regarding tumor location&#44; in 80&#37; of the cases it was located in the posterior choroid&#44; in 7&#37; of them in the anterior choroid &#40;ciliary body and iris&#41; and in the remaining cases the tumor covered both areas&#46; As for the tumor&#39;s appearance&#44; in 45&#37; of the cases it was mushroom-shaped&#44; in another 45&#37; it was dome-shaped and the remaining 10&#37; of tumors had a diffuse shape&#46; At the time of diagnosis&#44; retinal detachment was observed in 80&#37; of the cases&#44; subretinal hemorrhages in 50&#37; of them and vitreous hemorrhage in 75&#37; of them&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">According to ultrasound measurements&#44; 50&#37; of the tumors were classified as large and the remaining 50&#37; were considered to be medium-sized &#40;COMS classification&#41;&#46; In 75&#37; of the cases the tumor was staged as T3 or above &#40;AJCC&#47;UICC 7th edition classification&#41;&#46; The CDI revealed the presence of intratumoral vascularization at the time of diagnosis in 85&#37; of the cases&#46; All patients had a MRI done&#44; and this test unveiled the presence of scleral invasion in 40&#37; of the cases and extrascleral extension in one of them &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">The reasons for enucleation were the tumor&#39;s initial size &#40;50&#37; of the cases&#41;&#44; tumor growth despite treatment &#40;25&#37; of the cases&#44; all from group B&#41; and in the remaining 25&#37; of the cases it was due to secondary-to-treatment complications &#40;all from group B&#41; or to the patient&#39;s total lack of vision in the affected eye&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Metastatic disease developed in two cases&#59; lung metastasis in one case and liver metastasis in the other one&#46; The incidence of metastatic disease upon study completion was 6&#37;&#44; whereas the overall survival rate was 100&#37; for a mean follow-up period of 3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5 &#40;1&#46;2&#8211;6&#41; years&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Histopathological features</span><p id="par0160" class="elsevierStylePara elsevierViewall">The prevailing cell type was spindle-cell &#40;60&#37; of the cases&#41; followed by the epithelioid cell type &#40;25&#37; of the cases&#41;&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The tumor was less than 2<span class="elsevierStyleHsp" style=""></span>mm away from the optic nerve in 55&#37; of the cases&#59; in 10&#37; of them the tumor had infiltrated the optic nerve&#46; Moreover&#44; in 73&#37; of the cases there had been scleral infiltration and in one case extrascleral invasion was observed&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Regarding the number of mitoses in 10 HPF&#58; in 55&#37; of the patients none were found&#44; in 45&#37; only 1 or 2 were observed&#44; while in 2 cases &#40;both belonging to group A&#41; up to 8 mitoses were found&#46; In 25&#37; of the tumors there was macrophage infiltration&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Finally&#44; the following histological findings were observed&#58; fibrosis &#40;15&#37; of the cases&#41;&#44; necrosis &#40;20&#37;&#41;&#44; the presence of balloon-like cells &#40;7&#37; of the samples&#41; and cystoid degeneration of the retina &#40;70&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">MRI reliability</span><p id="par0180" class="elsevierStylePara elsevierViewall">In our population&#44; MRI&#39;s sensitivity to detect scleral infiltration amounted to 27&#37; and this test&#39;s specificity was 75&#37;&#46; As for extrascleral-involvement detection&#44; MRI&#39;s sensitivity was 100&#37; and its specificity was as high as 97&#37;&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0185" class="elsevierStylePara elsevierViewall">The epidemiological variables that were assessed in our population&#8212;typical tumor location&#44; initial clinical presentation<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">19</span></a> and age at the time of diagnosis<span class="elsevierStyleSup">2</span>&#8212;are in good agreement with the values described in the literature&#46; However&#44; we observed that&#44; in our sample&#44; fair-skin phenotype and concomitant dermatological alterations were not so present&#46; This finding differs from other authors&#8217; claims<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">3&#44;20</span></a> but it supports the hypothesis that within the Spanish population having a fair-skin phototype is not so determinant because this phototype is not the typical one in our latitudes &#40;Mui&#241;os et al&#46;&#44; personal communication&#44; ISSO Congress Cambridge&#44; 2009&#41;&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Focusing on the clinical variables&#44; all enucleated tumors shared the following adverse-prognosis features&#44; which lead to a particularly aggressive behavior and&#44; consequently&#44; would highlight the need for enucleation as definite treatment approach&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">A significant size</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">14&#44;21</span></a> All tumors assessed in this study were either large &#40;50&#37;&#41; or medium-sized &#40;50&#37;&#41;&#8212;according to the COMS classification&#8212;and 75&#37; of them were classified as stage T3 or above&#8212;according to the AJCC&#47;UICC staging system&#8212;&#59; these are sizes for which enucleation is indicated as initial curative treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">6</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Most cases initially presented with retinal detachment &#40;80&#37;&#41;&#44; subretinal bleeding &#40;50&#37;&#41; and&#47;or vitreous hemorrhage &#40;75&#37;&#41;&#44; which aside from suggesting that <span class="elsevierStyleItalic">Bruch&#39;s membrane rupture</span> has occurred due to the MM &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#8212;which&#44; in itself&#44; is an additional poor-prognosis risk factor<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">22&#44;23</span></a>&#8212;&#44; they result in poorer visual acuity&#44; which is one of the parameters to be born in mind when considering treatment options and opting for enucleation&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0205" class="elsevierStylePara elsevierViewall">Other adverse-prognosis clinical factors described in the literature have been&#58; tumor growth despite an active treatment being applied<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">24</span></a>&#8212;which happened in only 23&#37; of our cases &#40;group B&#41; and anterior tumor location<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">25</span></a>&#59; in our sample 6&#37; of the tumors were in the ciliary body and 17&#37; had mixed location&#46; Therefore&#44; we can conclude that for our sample these clinical factors did not turn out to be so determinant of poor prognosis&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Regarding intratumoral vascularization&#44; it is worth highlighting that extravascular matrix patterns that reflect the arrangement of tumor microcirculation<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">26</span></a> and high microvascular density<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">27</span></a> seen in histological samples are independently associated with shorter time to metastatic death in uveal MM&#46; In this study&#44; a histopathological analysis of the enucleated samples&#8217; vascular formations could not be carried out&#46; Therefore&#44; we analyzed&#44; at the time of diagnosis&#44; the intratumoral vascularization level using Doppler ultrasound&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">28</span></a> This criterion has not been internationally-accepted as a poor prognosis indicator&#46; Besides&#44; it is well known that there is no correlation between MM size and its internal vascularization level described by means of CDI&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">29</span></a> Anyhow&#44; in our sample&#44; comprising well-known poor-prognosis tumors&#44; half of them had at diagnosis a high vascularization level by the CDI&#46; At present&#44; there are already some studies describing the characteristic microvascular patterns for uveal MM by optical-coherence tomography angiography &#40;OCT-A&#41; and comparing them with the samples&#8217; histological analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">30</span></a> Perhaps&#44; in the near future OCT-A may end up replacing the pathology study when estimating the prognosis for this type of tumors&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Focusing on those pathological variables that are known to be linked to an adverse prognosis&#44; in the present study the most relevant ones turned out to be&#58; <span class="elsevierStyleItalic">distance to the optic nerve</span>&#8212;since in most of our cases &#40;55&#37; of them&#41; this value was &#8804;2<span class="elsevierStyleHsp" style=""></span>mm<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">31&#44;32</span></a>&#8212;and <span class="elsevierStyleItalic">scleral infiltration</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">33</span></a> which occurred in 73&#37; of our sample&#39;s tumors&#46; This latter fact&#44; which suggests that enucleation was indeed an appropriate treatment&#44; might explain why our survival rate was high&#44; since enucleation eradicates the disease if it hasn&#8217;t spread yet&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">6</span></a> As for brachytherapy&#44; it also becomes an eradicating treatment approach for medium-sized tumors even in those cases with scleral infiltration but if it is limited&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">7</span></a> In our sample most tumors had a size greater than or equal to T3 &#40;AJCC&#47;UICC staging system&#44; which is equivalent to the COMS classification&#39;s medium-to-large-sized tumors&#41; and in most cases the sclera had been infiltrated&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Other well-known histopathological adverse factors that&#44; for our sample&#44; didn&#8217;t turn out to be as relevant were&#58; epithelioid cell type&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">13</span></a> which was detected in only 25&#37; of the cases&#59; Infiltration by macrophages&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">34</span></a> which occurred in 25&#37; of the histopathological sections&#59; optic-nerve infiltration&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">35</span></a> found in only 3 cases&#59; and the number of mitoses&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">18</span></a> which wasn&#8217;t high in most of the cases&#46; Nonetheless&#44; 2 patients from group A&#44; that is&#44; tumors of large size&#44; which is the clinical risk factor that is most associated with the development of metastasis&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">14</span></a> ended up developing metastatic disease&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Additional findings emerging from the histological analysis that are worth highlighting are necrosis &#40;detected in 20&#37; of the cases&#41; and fibrosis &#40;15&#37;&#41;&#44; both occurring mainly in group B eyes&#46; These side effects can be attributed to brachytherapy and they tell us that the treatment was indeed working&#44; at least in part of the tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">31</span></a> The presence of balloon-like cells and the occurrence of cystoid degeneration of the retina&#44; also side effects of radiation therapy&#44; were detected exclusively in group-B tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">35</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">In terms of survival&#44; according to the outcome data published by the COMS&#44; the 5-year mortality rate for post-treatment uveal melanoma equals 40&#37; for large-size tumors<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">6</span></a> and 20&#37; for medium-sized ones&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">7</span></a> In our sample&#44; which comprised large and medium-sized tumors&#44; whose genetic characteristics are unknown &#8211; because they were not evaluated in this study &#8211; survival was as high as 100&#37;&#46; We must also admit that the follow-up period was shorter&#59; namely&#44; 3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5 &#40;1&#46;2&#8211;6&#41; years&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Contrary to other published studies&#44; for our case series of 30 cases&#44; MRI &#40;1&#46;5<span class="elsevierStyleHsp" style=""></span>T&#41; didn&#8217;t turn out to be a good screening test to detect scleral infiltration&#8212;more specifically&#44; sensitivity was as low as 27&#37;&#8212;but the technique did prove to be rather specific &#40;75&#37; specificity&#41;&#46; However&#44; it turned out to be a good technique to detect extrascleral extension&#44; since it had 100&#37; sensitivity and 97&#37; specificity&#44; which is in good agreement with previous studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">36&#44;37</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusion</span><p id="par0240" class="elsevierStylePara elsevierViewall">The analyses of clinical and pathologic data collected in the framework of this study justify enucleation as the treatment of choice for our patients&#46; MRI &#40;1&#46;5<span class="elsevierStyleHsp" style=""></span>T&#41; didn&#8217;t turn out to be an optimum screening method to detect scleral infiltration&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">The present work aims to be a local approximation to other published studies&#46; Its outcomes cannot be generalized since sample size was small&#46; We intend to extend the case series in the near future by adding a genetic assessment&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interest</span><p id="par0250" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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          "titulo" => "Conclusion"
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          "identificador" => "sec0065"
          "titulo" => "Conflict of interest"
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          "titulo" => "References"
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    "fechaRecibido" => "2018-10-15"
    "fechaAceptado" => "2018-12-03"
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        0 => array:4 [
          "clase" => "keyword"
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          "identificador" => "xpalclavsec1104915"
          "palabras" => array:3 [
            0 => "Uveal melanoma prognosis features"
            1 => "Uveal melanoma histopathology"
            2 => "Uveal melanoma MRI"
          ]
        ]
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1104914"
          "palabras" => array:3 [
            0 => "Factores pron&#243;stico en melanoma uveal"
            1 => "Histopatolog&#237;a en melanoma uveal"
            2 => "RMN en melanoma uveal"
          ]
        ]
      ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To study clinical and pathological variables leading to a poor prognosis in a sample of uveal malignant melanoma patients who required eyeball enucleation as final treatment approach&#46; All patients were seen and treated in the same public tertiary hospital in Madrid &#40;Spain&#41; within a 6-year time-period&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Longitudinal observational retrospective study&#46; The presence of clinical and pathologic factors known to be linked to poor prognosis &#8211; as well as other features &#8211; was assessed in 30 malignant melanoma&#58; 20 <span class="elsevierStyleItalic">de novo</span>-enucleated malignant melanoma eyes &#40;group A&#41;&#44; and 10 in eyes that received radiotherapy prior to enucleation &#40;group B&#41;&#46; The diagnostic reliability of magnetic resonance imaging was assessed by comparing it with the histology results &#8211; &#8220;gold standard&#8221; &#8211; as a means to detect scleral and extra-scleral extension&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Tumor size&#44; Bruch&#39;s membrane rupture&#44; scleral infiltration&#44; and distance to the optic nerve were the most decisive factors for a poor prognosis in the study sample&#46; In 93&#37; of cases the condition was under control&#44; with a 6&#37; incidence rate of metastatic spread and a 100&#37; rate of overall survival for a mean follow-up period of 3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5 &#40;range 1&#46;2&#8211;6&#41; years&#46; In the study population&#44; the sensitivity of the magnetic resonance imaging to detect scleral infiltration was 27&#37;&#44; which increased to 100&#37; for identifying extra-scleral involvement&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The analyses of the clinical and pathological data collected within the framework of this study justify enucleation as the treatment of choice for the patients of this study&#46; Magnetic resonance imaging was not found to be an optimum screening method to detect scleral infiltration in this study sample&#46;</p></span>"
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            "titulo" => "Methods"
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            "identificador" => "abst0015"
            "titulo" => "Results"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Estudiar las variables cl&#237;nicas y anatomopatol&#243;gicas de mal pron&#243;stico en una muestra de pacientes con melanoma maligno de &#250;vea que requirieron enucleaci&#243;n como tratamiento definitivo en un hospital terciario en Madrid &#40;Espa&#241;a&#41; durante un per&#237;odo de tiempo de 6 a&#241;os&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo&#44; observacional&#44; longitudinal&#46; Se analiza la presencia de factores cl&#237;nicos y anatomopatol&#243;gicos conocidos de mal pron&#243;stico y otros en 30 melanomas malignos&#58; 20 enucleados <span class="elsevierStyleItalic">de novo</span> &#40;grupo A&#41; y 10 tras recibir tratamiento con radioterapia &#40;grupo B&#41;&#46; Se estudia el grado de fiabilidad diagn&#243;stica de la resonancia magn&#233;tica nuclear&#44; compar&#225;ndola con la histolog&#237;a <span class="elsevierStyleItalic">&#40;gold standard&#41;</span> para predecir la presencia de invasi&#243;n escleral y extraescleral&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El tama&#241;o tumoral&#44; la rotura de la membrana de Bruch&#44; la invasi&#243;n escleral y la proximidad al nervio &#243;ptico fueron los factores de mal pron&#243;stico m&#225;s determinantes&#46; Se logr&#243; controlar la enfermedad en el 93&#37; de los casos&#44; con una incidencia de diseminaci&#243;n metast&#225;sica del 6&#37; y una supervivencia del 100&#37; a una media de seguimiento de 3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;5 &#40;rango 1&#44;2-6&#41; a&#241;os&#46; La sensibilidad de la resonancia magn&#233;tica nuclear&#44; en nuestra poblaci&#243;n&#44; para detectar infiltraci&#243;n escleral fue del 27&#37;&#44; y extraescleral&#44; del 100&#37;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El an&#225;lisis de los datos cl&#237;nicos e histopatol&#243;gicos recogidos justifican la enucleaci&#243;n como tratamiento final en los pacientes estudiados&#46; La resonancia magn&#233;tica nuclear no result&#243; un buen m&#233;todo de cribado para detectar la extensi&#243;n escleral&#46;</p></span>"
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            "identificador" => "abst0035"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Garc&#237;a Tirado A&#44; Asencio Dur&#225;n M&#44; Peralta Calvo J&#44; Berj&#243;n A&#44; Ruiz Bravo-Burguillos E&#46; Caracter&#237;sticas cl&#237;nicas e histopatol&#243;gicas de ojos enucleados por melanoma uveal en un hospital terciario en Espa&#241;a&#46; Arch Soc Esp Oftalmol&#46; 2019&#59;94&#58;225&#8211;231&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Uveal malignant melanoma &#40;MM&#41;&#46; &#40;a&#41; Retinography&#58; clinical appearance of mushroom-shaped melanoma &#40;red arrow&#41;&#46; &#40;b&#41; Ultrasound of mushroom-shaped melanoma&#58; Bruch&#39;s membrane rupture and fungiform appearance of MM &#40;red arrow&#41;&#44; retinal detachment &#40;blue arrow&#41;&#46; &#40;c&#41; T2 MRI coronal plane&#58; mushroom-shaped melanoma &#40;red arrow&#41;&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anamnesis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Medical history<br>-Ultrasound and CDI<br>-Local extension study<br>-Systemic extension study&#58;<br><span class="elsevierStyleHsp" style=""></span>Laboratory tests<br><span class="elsevierStyleHsp" style=""></span>Imaging studies&#58;<br><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>-Chest X-ray and liver ultrasound&#46;<br><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>-If necessary whole body positron emission tomography&#47;computed tomography &#40;whole-body PET&#47;CT&#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">Treatment &#40;based mainly on the COMS classification&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Large tumors&#58;<br><span class="elsevierStyleHsp" style=""></span>Enucleation<br>-Medium tumors&#58;<br><span class="elsevierStyleHsp" style=""></span>Brachytherapy<span class="elsevierStyleHsp" style=""></span>&#43;&#47;&#8722;<span class="elsevierStyleHsp" style=""></span>TTT<br><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#8226;&#62;<span class="elsevierStyleHsp" style=""></span>8<span class="elsevierStyleHsp" style=""></span>mm thick&#47;T3 &#40;AJCC&#47;UICC 7th ed&#41;&#58; enucleation is considered as initial treatment<br>-Small tumors&#58;<br><span class="elsevierStyleHsp" style=""></span>Observation or treatment according to number of risk factors&#46;<br><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#8226;If there are&#58; poor prognosis factors&#44; complications due to the tumor or its treatment&#44; null eye vision and&#47;or express desire of the patient the enucleation is always valued as initial treatment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">BCVA&#58; Best-Corrected Visual Acuity&#46;</p>"
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                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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables&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">Results&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="2" align="left" valign="top"><span class="elsevierStyleItalic">BCVA &#40;log</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">MAR&#41;</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>At diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;0&#46;5 &#40;40&#37;&#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>Pre-enucleation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8804;0&#46;5 &#40;100&#37;&#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  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8804;0&#46;1 &#40;65&#37;&#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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Tumor location</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>Anterior choroid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#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>Posterior choroid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&#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>Both&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Tumor shape</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>Fungiform&#47;Bruch&#39;s membrane rupture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45&#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>Dome-shaped&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45&#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>Diffuse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Melanoma-related ocular complications</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>Retinal detachment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&#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>Subretinal hemorrhage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&#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>Vitreous hemorrhage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">75&#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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Ultrasound</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>COMS classification</td><td class="td" title="table-entry  " align="left" valign="top">50&#37; large&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">50&#37; medium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="4" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>AJCC&#47;UICC classification</td><td class="td" title="table-entry  " align="left" valign="top">T1 5&#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">T2 20&#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">T3 50&#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">T4 25&#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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">CDI</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Intratumoral vascularization</td><td class="td" title="table-entry  " align="left" valign="top">Null 15&#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">Low 20&#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">High 65&#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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">MRI</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>Scleral infiltration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&#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>Extra-scleral infiltration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">5 HPF&#58; 5 fields at high-power field &#40;400 fold magnification&#41;&#46; 10 HPF&#58; 10 fields at high-power field &#40;400 fold magnification&#41;&#46;</p>"
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                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Results&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="2" align="left" valign="top"><span class="elsevierStyleItalic">Tumor&#39;s cellular type</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>Epithelioid-cell&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60&#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>Spindle-cell&nbsp;\t\t\t\t\t\t\n
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                  \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>Mixed-cell&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Distance to the optic nerve</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>&#8805;2<span class="elsevierStyleHsp" style=""></span>mm&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Number of mitoses &#40;10 HPF&#41;</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>0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70&#37; Group B&#47;0&#37; Group A&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>Atrophic type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#37; Group B&#47;0&#37; Group A&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>Mixed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#37; Group B&#47;0&#37; Group A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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