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En un trabajo basado en datos de la <span class="elsevierStyleItalic">National Cancer Institute&#39;s Surveillance&#44; Epidemiology and End Results</span> &#40;SEER&#41;&#44; se estim&#243; una incidencia de 0&#44;2 por cada 100&#46;000 habitantes-a&#241;o&#44; con un incremento de un 4&#44;6&#37; anual<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">5</span></a>&#46; Este incremento se atribuy&#243; a la relaci&#243;n del MD con la fotoexposici&#243;n&#44; al envejecimiento de la poblaci&#243;n y a la mejora en su diagn&#243;stico&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">El MD es m&#225;s frecuente en varones&#44; con una ratio hombre&#58;mujer de aproximadamente 1&#44;7-2&#58;1<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">5&#44;8&#44;9</span></a>&#46; La edad media al diagn&#243;stico se sit&#250;a entre 66-69 a&#241;os&#44; edad sensiblemente superior a la considerada para los melanomas no desmopl&#225;sicos &#40;MND&#41; que se sit&#250;a alrededor de los 60 a&#241;os<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">5&#44;8&#8211;10</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">De forma similar al lentigo maligno &#40;LM&#41; y al lentigo maligno melanoma &#40;LMM&#41;&#44; el MD tiende a aparecer en &#225;reas de exposici&#243;n solar cr&#243;nica&#44; siendo las localizaciones m&#225;s frecuentes la cabeza y el cuello &#40;50&#37; de los casos&#41;&#44; seguido del tronco &#40;20-25&#37;&#41; y las extremidades &#40;20-25&#37;&#41;&#46; No obstante&#44; han sido comunicados casos de MD tanto en las mucosas<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">11</span></a> como en localizaci&#243;n acral<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">12</span></a>&#44; donde la fotoexposicion cr&#243;nica no influir&#237;a como factor desencadenante&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Histopatolog&#237;a</span><p id="par0030" class="elsevierStylePara elsevierViewall">El MD es un tipo de melanoma infiltrante constituido predominantemente por melanocitos fusiformes amelan&#243;ticos inmersos en un estroma muy colagenizado<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">1&#44;8</span></a>&#46; Su aspecto morfol&#243;gico caracter&#237;stico es el de una neoplasia d&#233;rmica de silueta irregular&#44; contorno mal definido y paucicelular&#44; en la que la densidad melanocitaria es escasa o moderada y predomina el estroma de col&#225;geno &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>A&#41;&#46; T&#237;picamente&#44; las c&#233;lulas tumorales se disponen entre los haces de col&#225;geno de forma aislada y desorganizada<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">13</span></a>&#46; Los melanocitos suelen ser fusiformes y no pigmentados&#44; parecidos a los fibroblastos&#44; con citoplasmas y membranas citoplasm&#225;ticas mal definidas&#46; La atipia citol&#243;gica puede variar de m&#237;nima a moderada y las mitosis son infrecuentes &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>B&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">En casi la mitad de los casos&#44; la epidermis suprayacente no muestra alteraciones o estas son m&#237;nimas<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">14</span></a>&#44; y la apariencia es la de una neoplasia fibrosa o mesenquimal&#46; En el 50&#37; restante&#44; se identifica una proliferaci&#243;n melanoc&#237;tica at&#237;pica en la uni&#243;n dermoepid&#233;rmica o un melanoma <span class="elsevierStyleItalic">in situ</span>&#44; habitualmente tipo LM<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">15</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>C&#41;&#46; En estos casos&#44; el aspecto puede ser el de un melanoma <span class="elsevierStyleItalic">in situ</span> o el de una lesi&#243;n melanoc&#237;tica juncional con una cicatriz prominente subyacente<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">16&#44;17</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">El diagn&#243;stico histol&#243;gico del MD es dif&#237;cil<span class="elsevierStyleBold">&#46;</span> La apariencia inocente y enga&#241;osa del tumor y la superficialidad de algunas biopsias hacen que este pueda pasar desapercibido o que sea confundido con otros procesos&#46; El MD debe distinguirse de procesos o neoplasias benignas como una cicatriz&#44; un dermatofibroma&#44; un neurofibroma o un nevus desmopl&#225;sico&#44; pero tambi&#233;n de neoplasias malignas como un carcinoma sarcomatoide desmopl&#225;sico&#44; un fibroxantoma at&#237;pico&#44; un dermatofibrosarcoma protuberans&#44; un fibrosarcoma&#44; un leiomiosarcoma o un tumor maligno de la vaina del nervio perif&#233;rico&#44; entre otros&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Las t&#233;cnicas de inmunohistoqu&#237;mica pueden ser muy &#250;tiles en el diagn&#243;stico diferencial&#44; pero en algunos casos no nos ayudan&#46; En esta &#250;ltima situaci&#243;n es importante fijarse en las caracter&#237;sticas morfol&#243;gicas que son frecuentes en los MD&#44; aunque no espec&#237;ficas&#44; para poder llegar al diagn&#243;stico&#44; y son las siguientes&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8211;</span><p id="par0050" class="elsevierStylePara elsevierViewall">El MD suele extenderse en profundidad&#44; en muchos casos infiltra toda la dermis y alcanza el tejido subcut&#225;neo<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">18</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8211;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Es frecuente la presencia de estroma fibromixoide<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">19</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8211;</span><p id="par0060" class="elsevierStylePara elsevierViewall">En un 80&#37; de los casos se observa elastosis act&#237;nica en la dermis superficial<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">20</span></a>&#44; reflejo del da&#241;o solar en zonas fotoexpuestas&#46; Una buena clave diagn&#243;stica es identificar agregados de material elast&#243;tico atrapado en el seno del tumor&#44; incluso en su porci&#243;n profunda&#44; lo que no ocurre en las lesiones con las que nos podemos plantear el diagn&#243;stico diferencial &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>A&#41;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">16</span></a>&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8211;</span><p id="par0065" class="elsevierStylePara elsevierViewall">La presencia de peque&#241;os agregados de linfocitos en el tumor&#44; en el borde de infiltraci&#243;n y alrededor de los nervios&#44; puede ser muy &#250;til para sospechar un MD en los casos m&#225;s paucicelulares y con atipia m&#237;nima &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>B&#41;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">21</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8211;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Es frecuente el neurotropismo &#40;invasi&#243;n perineural o intraneural&#41;&#44; presente en un 30&#37; de los MD &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>C&#41;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">22</span></a>&#46; En ocasiones&#44; tambi&#233;n pueden mostrar transformaci&#243;n neural&#44; considerada en la actualidad como una forma de neurotropismo<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">23</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8211;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Siempre se podr&#225;n identificar&#44; aunque sea de forma muy focal&#44; algunos melanocitos con n&#250;cleos grandes e hipercrom&#225;ticos&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8211;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Se trata de un tumor predominantemente amelan&#243;tico y es muy inusual la pigmentaci&#243;n difusa&#46;</p></li></ul></p><p id="par0085" class="elsevierStylePara elsevierViewall">En 2004 Busam et al&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">13</span></a> propusieron clasificar el melanoma desmopl&#225;sico en MD puro o mixto&#44; bas&#225;ndose en la proporci&#243;n de melanoma desmopl&#225;sico frente a la del melanoma no desmopl&#225;sico en el tumor infiltrante&#46; En el MD puro se requer&#237;a que&#44; por lo menos&#44; el 90&#37; del componente infiltrante fuera desmopl&#225;sico &#40;asociado a un estroma fibroso&#41;&#46; Sin embargo&#44; en el MD mixto&#44; el componente desmopl&#225;sico representaba menos del 90&#37; del tumor infiltrante&#44; y se acompa&#241;aba de un componente de melanoma no desmopl&#225;sico&#44; constituido por grupos cohesivos de melanocitos epitelioides y&#47;o fusocelulares sin estroma fibroso intercelular &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>D&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Los subtipos histol&#243;gicos del MD muestran&#44; adem&#225;s&#44; otras diferencias microsc&#243;picas&#46; Los MD mixtos suelen ser m&#225;s celulares&#44; revelan m&#225;s atipia citol&#243;gica y presentan mayor &#237;ndice mit&#243;tico y proliferativo &#40;KI67&#41; que los MD puros&#46; Por el contrario&#44; es m&#225;s frecuente observar neurotropismo y diferenciaci&#243;n neural en los MD puros que en los MD mixtos<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">13&#44;24</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Adem&#225;s&#44; los autores demostraron que la clasificaci&#243;n histol&#243;gica del MD en puro y mixto podr&#237;a tener implicaciones pron&#243;sticas&#44; de lo que se derivaban manejos diferentes&#44; lo que pone de relieve la importancia de clasificarlos correctamente&#46; En algunos casos&#44; especialmente en MD m&#225;s celulares&#44; identificar el componente desmopl&#225;sico con la tinci&#243;n de hematoxilina-eosina puede ser dif&#237;cil y conducir a errores en su tipificaci&#243;n&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">El perfil inmunohistoqu&#237;mico m&#225;s habitual del MD es que los melanocitos muestren positividad para S100&#44; SOX10 y Nerve Growth Factor Receptor &#40;NGFR&#41; &#40;75&#37;&#41;&#44; y negatividad para los marcadores de diferenciaci&#243;n melanoc&#237;tica HMB45&#44; tirosinasa&#44; MiTF y melan-A &#40;MART1&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">25</span></a>&#46; Es importante correlacionar la positividad observada con la morfolog&#237;a&#44; especialmente en piezas de re-ex&#233;resis&#44; dado que la positividad para S100<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">26</span></a> y SOX-10<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">27</span></a> tambi&#233;n puede observarse en c&#233;lulas estromales e inflamatorias&#44; y NGFR tambi&#233;n se expresa en las c&#233;lulas mioepiteliales&#44; fibroblastos&#44; miofibroblastos reactivos y fibras nerviosas<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">28</span></a>&#46; Debe tenerse en cuenta que&#44; en algunos casos&#44; la positividad para SOX10 y&#47;o S100 logra ser m&#237;nima o estar ausente&#44; y no por ello debe descartarse la posibilidad de un MD<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">29</span></a>&#46; A diferencia del MD&#44; los melanocitos del melanoma <span class="elsevierStyleItalic">in situ</span> o del componente no desmopl&#225;sico de un MD mixto muestran positividad para HMB-45&#44; tirosinasa&#44; MITF y melan-A &#40;Mart1&#41;&#44; y no muestran expresi&#243;n de NGFR&#46; A diferencia de otros subtipos de melanoma donde su expresi&#243;n es m&#225;s frecuente&#44; solo el 35&#37; de los MD expresa <span class="elsevierStyleItalic">PReferentially expressed Antigen in MElanoma</span> &#40;PRAME&#41;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">30</span></a>&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">La mayor&#237;a de los MD localizados en zonas con severo da&#241;o act&#237;nico tienen cargas mutacionales muy elevadas con una fuerte firma de radiaci&#243;n UV&#46; En el MD suelen estar ausentes las mutaciones activadoras en la v&#237;a de se&#241;alizaci&#243;n de las MAPK m&#225;s frecuentes en otros tipos de melanomas &#40;como la mutaci&#243;n de BRAF V600E&#41;&#46; En cambio&#44; son frecuentes las mutaciones en los genes NF1 &#40;55&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">31</span></a>&#44; TP53 &#40;48&#37;&#41; y CDKN2A &#40;47&#37;&#41;&#44; y pueden observarse mutaciones activadoras en la v&#237;a de las MAPK menos frecuentes&#44; como la amplificaci&#243;n del gen del receptor de la tirosina quinasa &#40;EGFR&#44; MET y ERBB2&#41; y la inactivaci&#243;n de CBL<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">32</span></a>&#46; Algunas de estas alteraciones podr&#237;an ser potenciales dianas terap&#233;uticas&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Presentaci&#243;n cl&#237;nica</span><p id="par0110" class="elsevierStylePara elsevierViewall">El MD suele presentarse como una p&#225;pula o placa no pigmentada&#44; indurada y de bordes mal definidos&#44; localizada en piel con da&#241;o act&#237;nico &#40;<a class="elsevierStyleCrossRef" href="#fig0020">fig&#46; 4</a>&#41;&#46; Solo en menos de un tercio &#40;27&#37;&#41; de los casos el diagn&#243;stico de sospecha inicial es el de melanoma maligno<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">20</span></a>&#46; Cl&#237;nicamente se confunde con frecuencia con lesiones cut&#225;neas benignas como tejido cicatrizal&#44; dermatofibroma&#44; neurofibroma&#44; nevus melanoc&#237;tico intrad&#233;rmico o tumores cut&#225;neos malignos no melanoc&#237;ticos como el carcinoma basocelular o el carcinoma escamoso &#40;<a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">La diferenciaci&#243;n del MD en los subtipos mixto y puro tambi&#233;n conlleva diferencias en su presentaci&#243;n cl&#237;nica<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">13</span></a>&#46; As&#237;&#44; la presencia de un componente epid&#233;rmico en forma de LM&#44; LMM o melanoma de extensi&#243;n superficial parece estar presente en el 80-100&#37; de los casos de subtipo combinado&#46; Por este motivo&#44; con el fin de descartar la presencia de un n&#243;dulo subcut&#225;neo indurado sugestivo de DM&#44; se recomienda la palpaci&#243;n de lesiones sospechosas de LMM &#40;<a class="elsevierStyleCrossRef" href="#fig0030">fig&#46; 6</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">15</span></a>&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">La lesi&#243;n epid&#233;rmica asociada es menos frecuente en el MD puro &#40;63-80&#37; de los casos&#41; que suele presentarse en forma de n&#243;dulo o placa subcut&#225;nea indurada sin cambios en superficie lo que explica que el diagn&#243;stico del MD puro se retrase&#44; en general&#44; y a la vez tenga un grosor mayor que el MD mixto<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">20&#44;33</span></a>&#46; Tanto el MD puro como el combinado se caracterizan por un mayor espesor al diagn&#243;stico que el del melanoma convencional&#44; con un &#237;ndice de Breslow medio entre 2&#44;5-6&#44;5 mm y un nivel de Clark IV y V en la mayor&#237;a de los casos<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">5&#44;10&#44;20&#44;34</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">La utilizaci&#243;n de la dermatoscopia puede ser de utilidad en el diagn&#243;stico de MD&#46; La ausencia de un ret&#237;culo pigmentado junto con la presencia de estructuras de regresi&#243;n con &#225;reas blanquecinas cicatrizales y gr&#225;nulos &#40;peppering&#41;&#44; as&#237; como patrones vasculares at&#237;picos deber&#237;an alertar sobre un posible MD<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">35</span></a>&#46; Jaimes et al&#46; describieron en un estudio de 37 casos que la presencia de color rosado vascular&#44; los vasos polimorfos&#44; la presencia de gr&#225;nulos y la hiperpigmentaci&#243;n asim&#233;trica perifolicular eran las caracter&#237;sticas dermatosc&#243;picas m&#225;s frecuentes del MD<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">33</span></a>&#46; Solo el 43&#37; de las lesiones presentaban estructuras espec&#237;ficas de lesi&#243;n melanoc&#237;tica como gl&#243;bulos &#40;44&#37;&#41;&#44; ret&#237;culo pigmentado &#40;38&#37;&#41;&#44; pseudoret&#237;culo &#40;25&#37;&#41; o un ret&#237;culo invertido &#40;6&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0035">fig&#46; 7</a>&#41;&#46; No obstante&#44; en otras series&#44; todos los casos analizados presentaban al menos una caracter&#237;stica espec&#237;fica de melanoma<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">15&#44;33&#44;36</span></a>&#46; L&#243;gicamente en el subtipo de MD mixto&#44; asociado con mayor frecuencia a un componente epid&#233;rmico&#44; se evidenci&#243; un mayor n&#250;mero y variedad de caracter&#237;sticas especificas de melanoma y hallazgos dermatosc&#243;picos asociados a LM como el patr&#243;n anular&#8211;granular y las l&#237;neas poligonales<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">33</span></a>&#46;</p><elsevierMultimedia ident="fig0035"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">A&#250;n hay pocos datos que apoyen la utilidad de la microscopia confocal de reflectancia &#40;MCR&#41; en el diagn&#243;stico del MD&#46; En un estudio de 14 casos de MD con exploraci&#243;n mediante MCR y posterior an&#225;lisis histopatol&#243;gico&#44; Maher et al&#46; observaron la presencia de caracter&#237;sticas especificas de melanoma en la MCR &#40;c&#233;lulas pagetoides&#44; c&#233;lulas con atipia y c&#233;lulas nucleadas en dermis&#41; con una frecuencia similar a la que encontrar&#237;amos en otros subtipos de melanoma<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">36</span></a>&#46; Por el contrario&#44; la detecci&#243;n de abundantes c&#233;lulas fusiformes entremezcladas con fibras de col&#225;geno en la dermis superficial parece relacionarse con en el diagn&#243;stico espec&#237;fico del MD<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">36</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Pron&#243;stico</span><p id="par0135" class="elsevierStylePara elsevierViewall">La evidencia actual sugerir&#237;a que el comportamiento del MD es distinto al del melanoma convencional<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">3&#44;37</span></a>&#46; El MD presentar&#237;a un mayor riesgo de recurrencia local a la vez que una menor tasa de met&#225;stasis ganglionar<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">3&#44;34&#44;38</span></a>&#46; As&#237; el riesgo de afectaci&#243;n ganglionar ser&#237;a menor al de MND de similar grosor<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">3&#44;37</span></a>&#44; con un riesgo de afectaci&#243;n del ganglio centinela que var&#237;a en funci&#243;n de la serie entre 0 y 18&#44;2&#37;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">3</span></a>&#46; Es dif&#237;cil establecer el pron&#243;stico real del MD&#44; existen conclusiones contradictorias entre los distintos estudios y muchos de ellos no distinguen entre los subtipos de MD&#46; No obstante&#44; la mayor&#237;a de los trabajos recientes no encuentran diferencias significativas en la supervivencia respecto a los MND del mismo grosor<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">3&#44;6&#44;20&#44;37&#44;39&#44;40</span></a>&#46; La impresi&#243;n de que el MD puro tendr&#237;a una menor tendencia a las met&#225;stasis a distancia que el MD mixto&#44; y por tanto una mejor supervivencia&#44; no ha sido demostrada de forma constante&#46; Si bien Maurichi et al&#46; encontraron diferencias significativas entre la supervivencia global en funci&#243;n del subtipo de MD &#40;61&#44;3&#37; para el MD mixto vs&#46; 79&#44;5&#37; para el MD puro&#41;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">39</span></a>&#44; trabajos posteriores no han corroborado estos hallazgos<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">7&#44;41</span></a>&#46; Cuando ocurren&#44; las met&#225;stasis a distancia se han relacionado con recurrencias previas y lesiones profundas&#44; siendo el pulm&#243;n la localizaci&#243;n m&#225;s frecuente para las mismas<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">34</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">La mayor&#237;a de los trabajos coinciden que los MD tienen un riesgo elevado de recurrencia local&#44; de entre un 10-14&#37; aproximadamente<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">37&#44;39&#44;42&#44;43</span></a>&#44; y esta diferencia es mayor en los MD puros que en los MD mixtos <a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">39</span></a>&#46; Algunos autores atribuyen esta mayor agresividad local de los MD puros al retraso en el diagn&#243;stico dada la rareza y la presentaci&#243;n at&#237;pica de estos tumores y otros factores como su frecuente invasi&#243;n perineural y la extirpaci&#243;n con m&#225;rgenes quir&#250;rgicos insuficientes en muchos de los casos<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">20&#44;37</span></a>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Existen algunos factores que podr&#237;an condicionar un comportamiento m&#225;s agresivo del MD&#46; Shi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">38</span></a>&#44; en un estudio retrospectivo de 3&#46;657 casos de MD&#44; encontraron que una edad superior a 68 a&#241;os y el sexo masculino son factores pron&#243;stico independientes relacionados con una peor supervivencia tanto global como libre de enfermedad&#46; Aunque algunos trabajos respaldan estos hallazgos<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">31&#44;36&#44;40</span></a>&#44; otras series no encuentran diferencias para la supervivencia libre de enfermedad<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">37&#44;44&#44;45</span></a>&#46; Otro factor de mal pron&#243;stico descrito en los MD es la invasi&#243;n perineural<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">6&#44;46</span></a>&#44; encontrando una correlaci&#243;n significativa con un mayor espesor de Breslow en los casos que presentan invasi&#243;n perineural<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">20</span></a>&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Estrategias terap&#233;uticas en el melanoma desmopl&#225;sico</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Cirug&#237;a</span><p id="par0150" class="elsevierStylePara elsevierViewall">M&#250;ltiples estudios han demostrado que en el melanoma cut&#225;neo primario la ex&#233;resis amplia &#40;2 o m&#225;s cm&#41; en melanomas &#8804; 2 mm de grosor no aumenta la supervivencia<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">39&#44;47</span></a>&#46; Sin embargo&#44; los MD suelen tener en el momento del diagn&#243;stico un grosor mayor que los melanomas convencionales&#44; por lo que requieren m&#225;rgenes amplios de 2 cm con mayor frecuencia&#46; Este hecho tiene una especial importancia teniendo en cuenta la mayor tasa de recurrencia local descrita en los MD<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">6&#44;34&#44;42</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Una serie australiana<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">6</span></a> mostr&#243; una tasa menor de recurrencia en lesiones extirpadas con &#8805; 2 cm frente a lesiones extirpadas con &#60; 1 cm&#46; En la misma l&#237;nea Maurichi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">39</span></a> evaluaron el pron&#243;stico bas&#225;ndose en los diferentes subtipos de MD y los diversos m&#225;rgenes quir&#250;rgicos utilizados&#46; Los pacientes con MD puro con Breslow &#8804; 2 mm extirpados con 1 cm de margen tuvieron un peor pron&#243;stico&#44; con tasas de recurrencia m&#225;s altas y peor supervivencia global a los cinco a&#241;os&#44; comparado con los que fueron tratados con 2 cm de margen quir&#250;rgico&#46; Sin embargo&#44; el pron&#243;stico fue similar entre pacientes con MD puro y Breslow &#8804; 2 mm y MD puro con Breslow &#62; 2 mm que fueron tratados con 2 cm de margen quir&#250;rgico&#46; Para los MD mixtos&#44; no hubo diferencias significativas en el pron&#243;stico en funci&#243;n del margen quir&#250;rgico otorgado&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Por todo ello&#44; en MD puros se debe considerar un margen quir&#250;rgico de 2 cm incluso en lesiones &#60; 2 mm de grosor &#40;m&#225;s controvertido parecer&#237;a en lesiones de grosor &#60; 1 mm para los que no hay estudios que eval&#250;en la posibilidad de establecer un margen de 1 cm<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">3</span></a>&#41;&#46; Es decir&#44; el margen quir&#250;rgico amplio deber&#237;a priorizarse siempre que sea posible en MD puros para evitar recurrencias locales&#44; pero se debe tener en cuenta que en muchos casos esto puede verse condicionado porque las lesiones frecuentemente se localizan en cabeza y cuello&#44; en &#225;reas anat&#243;micas complejas<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">15</span></a>&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Biopsia selectiva del ganglio centinela</span><p id="par0165" class="elsevierStylePara elsevierViewall">La indicaci&#243;n de la biopsia selectiva del ganglio centinela &#40;BSGC&#41; en el MD es controvertida&#46; Actualmente la utilidad de la BSGC en melanoma es identificar aquellos pacientes con un peor pron&#243;stico y a los que se podr&#237;a ofrecer un tratamiento adyuvante&#46; La evidencia de su utilidad en el MD se obtiene de series de casos retrospectivas&#46; En varias de ellas se evidencian claras diferencias en la supervivencia espec&#237;fica del melanoma en funci&#243;n del estado del ganglio centinela &#40;GC&#41;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">5&#44;37&#44;40&#44;44</span></a>&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Una probabilidad del 5&#37; de afectaci&#243;n del GC es el umbral a partir del cual suele considerar la indicaci&#243;n de la BSGC<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">48</span></a>&#46; En las series m&#225;s recientes sobre melanoma desmopl&#225;sico el porcentaje de afectaci&#243;n del GC varia entre 0&#8211;18&#44;2&#37;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">7&#44;37&#44;39&#8211;43&#44;49&#8211;58</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; Debe destacarse que los cinco trabajos que reportan un 0&#37; de afectaci&#243;n del GC son series de menos de 25 pacientes<a class="elsevierStyleCrossRefs" href="#bib0580"><span class="elsevierStyleSup">42&#44;43&#44;49&#44;50&#44;55</span></a>&#46; En la revisi&#243;n sistem&#225;tica realizada por Dunne et al&#46; publicada en 2017 y que recog&#237;a los estudios publicados hasta la fecha la tasa de afectaci&#243;n del GC fue del 6&#44;5&#37;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">59</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">La distinci&#243;n entre las variantes histol&#243;gicas de melanoma desmopl&#225;sico parece &#250;til para establecer el riesgo de afectaci&#243;n del GC y la propia indicaci&#243;n de la BSGC&#46; As&#237;&#44; el riesgo de afectaci&#243;n del GC es mayor en la variante mixta &#40;8&#44;5-25&#37;&#41; que en el melanoma desmopl&#225;sico puro &#40;0-18&#44;2&#37;&#41;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">7&#44;39&#44;41&#44;52&#44;54&#8211;56&#44;58&#44;60</span></a>&#46; En la revisi&#243;n de Dunne et al&#46; se evidenci&#243; una afectaci&#243;n del GC en el 13&#46;8&#37; de los MD mixtos y del 5&#44;4&#37; de los puros<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">59</span></a>&#46; Solo un estudio ha se&#241;alado un riesgo mayor de afectaci&#243;n del GC en la variante pura que en la variante mixta<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">41</span></a>&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">En definitiva&#44; la indicaci&#243;n de la BSGC en el MD es m&#225;s clara en la variante mixta y controvertida en los MD puros&#46; Sin embargo&#44; deben valorarse otros factores como la edad del paciente&#44; sus comorbilidades y la localizaci&#243;n del tumor primario&#46; En este sentido&#44; tanto la localizaci&#243;n del tumor primario en cabeza y cuello como la edad avanzada que suelen presentar los pacientes con MD&#44; son dos factores que cl&#225;sicamente se asocian a una menor afectaci&#243;n del GC<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">61</span></a>&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Pocos estudios se&#241;alan la tasa de afectaci&#243;n de los ganglios no centinela &#40;GNC&#41; en una disecci&#243;n ganglionar completa tras una BSGC positiva en el MD&#46; Dos estudios con m&#225;s de 200 pacientes cada uno han obtenido afectaci&#243;n de los GNC en MD en porcentajes del 16&#44;7&#37; y 23&#44;5&#37;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">37&#44;58</span></a>&#44; datos similares a los que se obtienen en MND<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">62</span></a>&#46; En este sentido&#44; con las limitaciones de la evidencia actual&#44; parece sensato aplicar el mismo algoritmo de manejo del paciente con GC positivo que se utiliza en el melanoma convencional<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">63</span></a>&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Radioterapia</span><p id="par0190" class="elsevierStylePara elsevierViewall">Teniendo en cuenta las altas tasas de recurrencia local descritas en los MD<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">37&#44;64</span></a>&#44; la adyuvancia con radioterapia &#40;RDT&#41; se ha planteado como una opci&#243;n terap&#233;utica interesante&#46; A diferencia del melanoma convencional&#44; que es relativamente resistente a la radioterapia&#44; en el MD hay varios estudios que demuestran que su uso como tratamiento adyuvante puede ser eficaz en el control local de la enfermedad<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">3&#44;34&#44;65</span></a>&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Hay varios trabajos que exponen el potencial beneficio de la RDT adyuvante cuando el MD presenta factores de riesgo asociados &#40;invasi&#243;n perineural&#44; desmoplasia extensa&#44; m&#225;rgenes positivos o enfermedad recurrente&#41;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">38&#44;66&#44;67</span></a>&#46; Dos estudios m&#225;s recientes afianzan esta asociaci&#243;n entre la RDT adyuvante y la mejor&#237;a del control local en los MD&#46; Por un lado&#44; Guadagnolo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">68</span></a> evaluaron 130 pacientes con MD que hab&#237;an sido tratados exclusivamente con cirug&#237;a o con cirug&#237;a m&#225;s radioterapia adyuvante&#46; Los autores encontraron que el 24&#37; de los pacientes que se sometieron &#250;nicamente a tratamiento quir&#250;rgico y s&#243;lo el 7&#37; de los pacientes que se sometieron a cirug&#237;a m&#225;s RDT adyuvante desarrollaron una recurrencia local&#44; demostrando una correlaci&#243;n significativa con un mejor control local en el an&#225;lisis multivariable&#46; Por otro lado&#44; Strom et al&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">69</span></a> tambi&#233;n encontraron que el uso de la RDT adyuvante mejoraba significativamente el control local en el an&#225;lisis multivariable&#46; Los pacientes con m&#225;rgenes de resecci&#243;n positivos tuvieron particularmente una mayor reducci&#243;n de la tasa de recurrencia local&#44; 54&#37; sin el uso de RDT adyuvante frente al 14&#37; con cirug&#237;a m&#225;s RDT adyuvante&#46; Adem&#225;s&#44; estos autores describen factores pron&#243;sticos para seleccionar los MD con m&#225;rgenes negativos que se beneficiar&#237;an de la RDT adyuvante&#58; tumores localizados en cabeza y cuello&#44; Breslow &#62; 4 mm&#44; y nivel V de Clark&#46; Tambi&#233;n Oliver et al&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">70</span></a>&#44; en un estudio retrospectivo m&#225;s reciente&#44; evaluaron a 100 pacientes con MD tratados &#250;nicamente con cirug&#237;a&#44; cirug&#237;a m&#225;s RDT adyuvante o RDT radical en recurrencias post-cirug&#237;a&#46; En este estudio eval&#250;an el valor de la RDT como tratamiento radical en recurrencias&#44; as&#237; como el de la adyuvancia post-intervenci&#243;n&#44; encontrando un control local del 100&#37; de los casos tanto en los 10 pacientes tratados con RDT adyuvante como en los siete pacientes tratados con RDT radical&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Sin embargo&#44; la evidencia actual se basa en estudios retrospectivos y se precisan estudios prospectivos randomizados para afianzar estas conclusiones&#46; Actualmente hay en marcha un ensayo cl&#237;nico &#40;NCT00975520&#41;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">71</span></a> que compara el tratamiento exclusivamente quir&#250;rgico frente a cirug&#237;a m&#225;s radioterapia adyuvante en pacientes con MD extirpados con m&#225;rgenes amplios negativos&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Tratamiento sist&#233;mico</span><p id="par0205" class="elsevierStylePara elsevierViewall">La inmunoterapia mediante f&#225;rmacos anti-PD1 ha demostrado su eficacia en el tratamiento del MD metast&#225;sico&#46; En un reciente estudio multic&#233;ntrico retrospectivo donde se analizaron 60 casos de MD metast&#225;sico tratados con f&#225;rmacos anti-PD1 se evidenci&#243; una respuesta objetiva en el 70&#37; de ellos&#44; con un 32&#37; de respuestas completas con un seguimiento medio de 22 meses<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">72</span></a>&#46; Esta respuesta&#44; incluso superior a la observada en el MND&#44; podr&#237;a explicarse por la alta carga de mutaciones inducidas por la radiaci&#243;n ultravioleta que presenta el MD&#46; Se estima que la inmunoterapia podr&#237;a ser m&#225;s eficaz en neoplasias como el MD que presentan una alta carga mutacional<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">73</span></a>&#46; Estos prometedores resultados deben ser confirmados en ensayos cl&#237;nicos prospectivos&#46; En la actualidad existe un ensayo en fase II &#40;NCT02775851&#41;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">74</span></a> en periodo de reclutamiento sobre la eficacia de pembrolizumab en el MD&#46; La ausencia de mutaciones de BRAF en la mayor&#237;a de los melanomas desmopl&#225;sicos hace que los inhibidores de BRAF no sean un tratamiento &#250;til en estos pacientes&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusiones</span><p id="par0210" class="elsevierStylePara elsevierViewall">El MD es una variante poco frecuente de melanoma con una conducta biol&#243;gica distinta que requiere estrategias diagn&#243;sticas y terap&#233;uticas diferentes al del melanoma convencional&#46; Su diagn&#243;stico representa un reto tanto para el cl&#237;nico como para el pat&#243;logo&#46; La clasificaci&#243;n histol&#243;gica del MD en los subtipos puro y mixto parece ofrecer informaci&#243;n importante sobre el comportamiento del tumor&#44; que debe tenerse en cuenta para su tratamiento&#46; El MD puro es aquel donde por lo menos el 90&#37; del componente infiltrante es desmopl&#225;sico mientras que en el MD mixto&#44; el componente desmopl&#225;sico representa menos del 90&#37; del tumor infiltrante&#44; y se acompa&#241;aba de un componente de melanoma no desmopl&#225;sico&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">La cirug&#237;a con m&#225;rgenes amplios es esencial para prevenir futuras reca&#237;das que condicionan una peor supervivencia&#46; El estado del ganglio centinela parece tener valor pron&#243;stico en el MD y debe valorarse su indicaci&#243;n en el subtipo mixto&#46; M&#225;s discutible parece ser su indicaci&#243;n en MD puro&#46; La RDT adyuvante sobre el lecho tumoral puede ser &#250;til en algunos casos con factores de riesgo asociados&#46; En caso de desarrollo de met&#225;stasis la evidencia actual sugiere unas buenas tasas de respuesta con los inhibidores de puntos de control inmunol&#243;gico&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Financiaci&#243;n</span><p id="par0220" class="elsevierStylePara elsevierViewall">Este trabajo no ha recibido ning&#250;n tipo de financiaci&#243;n&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflicto de intereses</span><p id="par0225" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El melanoma desmopl&#225;sico &#40;MD&#41; representa entre el 0&#44;4-4&#37; de todos los melanomas&#46; Se presenta como un tumor constituido predominantemente por melanocitos fusiformes amelan&#243;ticos inmersos en un estroma col&#225;geno abundante&#46; Se clasifica en MD puro o mixto&#44; bas&#225;ndose en la proporci&#243;n de melanoma desmopl&#225;sico frente a la del melanoma no desmopl&#225;sico presente en el tumor infiltrante&#46; En el MD puro el componente desmopl&#225;sico representa m&#225;s del 90&#37; del melanoma infiltrante mientras que&#44; en el MD combinado o mixto&#44; el componente desmopl&#225;sico representa menos del 90&#37;&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">El MD es m&#225;s frecuente en varones &#40;ratio 1&#44;7-2&#58;1&#41;&#59; la edad media al diagn&#243;stico oscila entre 66-69 a&#241;os y suele localizarse en &#225;reas de fotoexposici&#243;n cr&#243;nica&#44; a menudo asociado a un lentigo maligno&#46; Su reconocimiento cl&#237;nico es dif&#237;cil ya que se presenta como una p&#225;pula o placa no pigmentada&#44; indurada y de bordes mal definidos&#44; que recuerda a una cicatriz&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El MD es un tumor con una alta tendencia a la recurrencia local y en el caso del MD puro&#44; una baja tendencia a la diseminaci&#243;n ganglionar&#46; Sin embargo&#44; en las series m&#225;s contempor&#225;neas&#44; su pron&#243;stico global parece ser similar al de melanomas no desmopl&#225;sicos &#40;MND&#41; del mismo grosor&#46; Su abordaje cl&#237;nico posee algunos matices diferenciales&#44; en comparaci&#243;n al resto de melanomas&#44; que se revisan en el presente trabajo&#46;</p></span>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Desmoplastic melanoma &#40;DM&#41; accounts for 0&#46;4&#37; to 4&#37; of all melanomas&#46; These skin tumors are mainly formed by amelanotic spindled melanocytes immersed in an abundant collagen stroma and are classified as pure when the desmoplastic component accounts for at least 90&#37; of the invasive tumor and as mixed or combined otherwise&#46; DMs are more common in men &#40;male to female ratio&#44; 1&#46;7 to 2&#58;1&#41;&#44; and the mean age at diagnosis is 66 to 69 years&#46; The tumors tend to occur in chronically sun-exposed areas&#44; often in association with lentigo maligna&#44; and are difficult to recognize because they can resemble a scar&#44; presenting as a firm&#44; unpigmented papule or plaque with poorly defined borders&#46; DMs also have a strong tendency to recur locally&#44; and pure variants rarely spread to the lymph nodes&#46; Nonetheless&#44; recently published series suggest that patients with DM have a similar prognosis to those with nondesmoplastic melanoma of the same thickness&#46; The clinical management of DM varies in certain aspects from that of other melanomas and is reviewed in this article&#46;</p></span>"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0245" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Anexo A"
            "titulo" => "Material adicional"
            "identificador" => "sec0085"
          ]
        ]
      ]
    ]
    "multimedia" => array:10 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 984
            "Ancho" => 1305
            "Tamanyo" => 481844
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A&#41; Melanoma desmopl&#225;sico &#40;MD&#41; infiltrando en profundidad&#44; alcanzando la dermis reticular profunda &#40;HEx20&#41;&#46; B&#41; MD con melanocitos fusiformes con algunos n&#250;cleos grandes e hipercrom&#225;ticos&#44; dispuestos de forma aislada y desorganizada en un estroma ligeramente fibromixoide &#40;HEx200&#41;&#46; C&#41; MD asociado a un melanoma <span class="elsevierStyleItalic">in situ</span> &#40;HEx200&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figura 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 984
            "Ancho" => 1305
            "Tamanyo" => 576168
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A&#41; MD con elastosis act&#237;nica y atrapamiento de material elast&#243;tico &#40;HEx100&#41;&#46; B&#41; MD con un agregado nodular de linfocitos &#40;HEx200&#41;&#46; C&#41; MD con invasi&#243;n perineural&#46; &#40;HEx200&#41;&#46; D&#41; MD combinado&#46; En el extremo superior derecho se identifica el componente de melanoma no desmopl&#225;sico formado por nidos compactos de melanocitos epitelioides&#46; En la regi&#243;n inferior&#44; se observa el componente desmopl&#225;sico que representa menos del 90&#37; del tumor infiltrante &#40;HEx100&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figura 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 984
            "Ancho" => 1305
            "Tamanyo" => 393807
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">MD asociado a un melanoma <span class="elsevierStyleItalic">in situ</span> de extensi&#243;n superficial&#46; A&#41; y B&#41;&#46; Tinciones inmunohistoqu&#237;micas de S100 &#40;x100&#41; y SOX10 &#40;x100&#41;&#58; en ambas tinciones se observa positividad en las c&#233;lulas del MD y del melanoma <span class="elsevierStyleItalic">in situ</span>&#46; C&#41; y D&#41; Tinciones inmunohistoqu&#237;micas de melanA &#40;x100&#41; y HMB-45 &#40;x100&#41;&#58; en ambas tinciones se identifica expresi&#243;n en el melanoma in situ y ausencia de expresi&#243;n en el MD&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figura 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 605
            "Ancho" => 805
            "Tamanyo" => 86681
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Imagen cl&#237;nica de un MD&#46; Var&#243;n de 62 a&#241;os que consult&#243; por lesi&#243;n de crecimiento progresivo en mejilla&#46; Se apreci&#243; una lesi&#243;n en forma de placa marr&#243;n clara&#44; indurada de aspecto cicatricial&#46; Se correspondi&#243; con un MD puro de 5 mm de espesor&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figura 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 680
            "Ancho" => 905
            "Tamanyo" => 108676
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Imagen cl&#237;nica de un MD&#46; Mujer de 53 a&#241;os con tumoraci&#243;n interescapular en forma de tumor rosado de tacto firme&#46; Hab&#237;a sido inicialmente orientada de queloide&#46; La biopsia revel&#243; un MD puro de 8&#44;5 mm de espesor&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "fig0030"
        "etiqueta" => "Figura 6"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr6.jpeg"
            "Alto" => 539
            "Ancho" => 805
            "Tamanyo" => 73958
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Imagen cl&#237;nica de un MD asociado a un lentigo maligno &#40;LM&#41;&#46; Mujer de 89 a&#241;os con una lesi&#243;n en la frente sugestiva de LM&#46; Su ex&#233;resis revel&#243; la existencia de un MD asociado que alcanzaba 2&#44;95 mm de grosor&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "fig0035"
        "etiqueta" => "Figura 7"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr7.jpeg"
            "Alto" => 605
            "Ancho" => 805
            "Tamanyo" => 59172
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Imagen dermatosc&#243;pica de la tumoraci&#243;n de la Figura 4&#46; Se trata de una tumoraci&#243;n con un componente palpable de coloraci&#243;n rosada&#46; En este caso la presencia de ret&#237;culo pigmentado en varias &#225;reas de la lesi&#243;n debe orientar el diagn&#243;stico hac&#237;a una lesi&#243;n melanoc&#237;tica&#46;</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabla 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Estudio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">A&#241;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dise&#241;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Origen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Periodo &#40;a&#241;os&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">numero pacientes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Edad media&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Relaci&#243;n H&#58;M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Breslow medio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Localizaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Casos BSGC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Positividad GC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Casos MD mixto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Positividad GC MD mixto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Casos MD puro&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Positividad GC MD puro&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Jaroszewski&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Thelmo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gyorki&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;8&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Su&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;1&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Livestro&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Casos-controles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pawlik&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;3&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posther&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">129&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cummins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maurichi&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Italia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">242&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;3&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">George&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Murali&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Australia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">252&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;9&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">252&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">129&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">123&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;9&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mohebati&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cabeza y cuello&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Broer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Egger&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;1&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Han&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">205&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">205&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#44;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Conic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de Casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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Revisión
Actualización en el diagnóstico y manejo del melanoma desmoplásico
Update on the Diagnosis and Management of Desmoplastic Melanoma
A. Boada Garciaa,b,c,
Corresponding author
aboada.germanstrias@gencat.cat

Autor para correspondencia.
, A. Quer Pi-Sunyerd, N. Richarza,b,c, A. Jaka-Morenoa,b,c
a Servicio de Dermatología. Hospital Universitari Germans Trias i Pujol. Badalona, Barcelona, España
b Institut d’investigació Germans Trias. Badalona, Barcelona, España
c Universitat Autónoma de Barcelona, Barcelona, España
d Servicio de Anatomía Patológica. Hospital Universitari Germans Trias i Pujol. Badalona, Barcelona, España
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una b&#250;squeda en Pubmed&#44; EMBASE y Google Acad&#233;mico&#46; La estrategia utilizada fue &#171;<span class="elsevierStyleItalic">desmoplastic melanoma</span>&#187;&#44; a&#241;adiendo diferentes t&#233;rminos en funci&#243;n del subapartado estudiado&#46; Las referencias de los art&#237;culos elegidos fueron revisadas con el fin de identificar otros art&#237;culos relevantes&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Epidemiolog&#237;a</span><p id="par0015" class="elsevierStylePara elsevierViewall">El MD es una variante poco frecuente de melanoma representando menos del 4&#37; de todos los melanomas<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">5&#44;6</span></a>&#46; En un estudio retrospectivo reciente basado en los casos de MD diagnosticados en Holanda entre los a&#241;os 2000 a 2014 se determin&#243; que solo el 0&#44;4&#37; de todos los melanomas eran MD<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">7</span></a>&#46; En un trabajo basado en datos de la <span class="elsevierStyleItalic">National Cancer Institute&#39;s Surveillance&#44; Epidemiology and End Results</span> &#40;SEER&#41;&#44; se estim&#243; una incidencia de 0&#44;2 por cada 100&#46;000 habitantes-a&#241;o&#44; con un incremento de un 4&#44;6&#37; anual<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">5</span></a>&#46; Este incremento se atribuy&#243; a la relaci&#243;n del MD con la fotoexposici&#243;n&#44; al envejecimiento de la poblaci&#243;n y a la mejora en su diagn&#243;stico&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">El MD es m&#225;s frecuente en varones&#44; con una ratio hombre&#58;mujer de aproximadamente 1&#44;7-2&#58;1<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">5&#44;8&#44;9</span></a>&#46; La edad media al diagn&#243;stico se sit&#250;a entre 66-69 a&#241;os&#44; edad sensiblemente superior a la considerada para los melanomas no desmopl&#225;sicos &#40;MND&#41; que se sit&#250;a alrededor de los 60 a&#241;os<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">5&#44;8&#8211;10</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">De forma similar al lentigo maligno &#40;LM&#41; y al lentigo maligno melanoma &#40;LMM&#41;&#44; el MD tiende a aparecer en &#225;reas de exposici&#243;n solar cr&#243;nica&#44; siendo las localizaciones m&#225;s frecuentes la cabeza y el cuello &#40;50&#37; de los casos&#41;&#44; seguido del tronco &#40;20-25&#37;&#41; y las extremidades &#40;20-25&#37;&#41;&#46; No obstante&#44; han sido comunicados casos de MD tanto en las mucosas<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">11</span></a> como en localizaci&#243;n acral<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">12</span></a>&#44; donde la fotoexposicion cr&#243;nica no influir&#237;a como factor desencadenante&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Histopatolog&#237;a</span><p id="par0030" class="elsevierStylePara elsevierViewall">El MD es un tipo de melanoma infiltrante constituido predominantemente por melanocitos fusiformes amelan&#243;ticos inmersos en un estroma muy colagenizado<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">1&#44;8</span></a>&#46; Su aspecto morfol&#243;gico caracter&#237;stico es el de una neoplasia d&#233;rmica de silueta irregular&#44; contorno mal definido y paucicelular&#44; en la que la densidad melanocitaria es escasa o moderada y predomina el estroma de col&#225;geno &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>A&#41;&#46; T&#237;picamente&#44; las c&#233;lulas tumorales se disponen entre los haces de col&#225;geno de forma aislada y desorganizada<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">13</span></a>&#46; Los melanocitos suelen ser fusiformes y no pigmentados&#44; parecidos a los fibroblastos&#44; con citoplasmas y membranas citoplasm&#225;ticas mal definidas&#46; La atipia citol&#243;gica puede variar de m&#237;nima a moderada y las mitosis son infrecuentes &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>B&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">En casi la mitad de los casos&#44; la epidermis suprayacente no muestra alteraciones o estas son m&#237;nimas<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">14</span></a>&#44; y la apariencia es la de una neoplasia fibrosa o mesenquimal&#46; En el 50&#37; restante&#44; se identifica una proliferaci&#243;n melanoc&#237;tica at&#237;pica en la uni&#243;n dermoepid&#233;rmica o un melanoma <span class="elsevierStyleItalic">in situ</span>&#44; habitualmente tipo LM<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">15</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>C&#41;&#46; En estos casos&#44; el aspecto puede ser el de un melanoma <span class="elsevierStyleItalic">in situ</span> o el de una lesi&#243;n melanoc&#237;tica juncional con una cicatriz prominente subyacente<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">16&#44;17</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">El diagn&#243;stico histol&#243;gico del MD es dif&#237;cil<span class="elsevierStyleBold">&#46;</span> La apariencia inocente y enga&#241;osa del tumor y la superficialidad de algunas biopsias hacen que este pueda pasar desapercibido o que sea confundido con otros procesos&#46; El MD debe distinguirse de procesos o neoplasias benignas como una cicatriz&#44; un dermatofibroma&#44; un neurofibroma o un nevus desmopl&#225;sico&#44; pero tambi&#233;n de neoplasias malignas como un carcinoma sarcomatoide desmopl&#225;sico&#44; un fibroxantoma at&#237;pico&#44; un dermatofibrosarcoma protuberans&#44; un fibrosarcoma&#44; un leiomiosarcoma o un tumor maligno de la vaina del nervio perif&#233;rico&#44; entre otros&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Las t&#233;cnicas de inmunohistoqu&#237;mica pueden ser muy &#250;tiles en el diagn&#243;stico diferencial&#44; pero en algunos casos no nos ayudan&#46; En esta &#250;ltima situaci&#243;n es importante fijarse en las caracter&#237;sticas morfol&#243;gicas que son frecuentes en los MD&#44; aunque no espec&#237;ficas&#44; para poder llegar al diagn&#243;stico&#44; y son las siguientes&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8211;</span><p id="par0050" class="elsevierStylePara elsevierViewall">El MD suele extenderse en profundidad&#44; en muchos casos infiltra toda la dermis y alcanza el tejido subcut&#225;neo<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">18</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8211;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Es frecuente la presencia de estroma fibromixoide<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">19</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8211;</span><p id="par0060" class="elsevierStylePara elsevierViewall">En un 80&#37; de los casos se observa elastosis act&#237;nica en la dermis superficial<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">20</span></a>&#44; reflejo del da&#241;o solar en zonas fotoexpuestas&#46; Una buena clave diagn&#243;stica es identificar agregados de material elast&#243;tico atrapado en el seno del tumor&#44; incluso en su porci&#243;n profunda&#44; lo que no ocurre en las lesiones con las que nos podemos plantear el diagn&#243;stico diferencial &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>A&#41;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">16</span></a>&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8211;</span><p id="par0065" class="elsevierStylePara elsevierViewall">La presencia de peque&#241;os agregados de linfocitos en el tumor&#44; en el borde de infiltraci&#243;n y alrededor de los nervios&#44; puede ser muy &#250;til para sospechar un MD en los casos m&#225;s paucicelulares y con atipia m&#237;nima &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>B&#41;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">21</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8211;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Es frecuente el neurotropismo &#40;invasi&#243;n perineural o intraneural&#41;&#44; presente en un 30&#37; de los MD &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>C&#41;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">22</span></a>&#46; En ocasiones&#44; tambi&#233;n pueden mostrar transformaci&#243;n neural&#44; considerada en la actualidad como una forma de neurotropismo<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">23</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8211;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Siempre se podr&#225;n identificar&#44; aunque sea de forma muy focal&#44; algunos melanocitos con n&#250;cleos grandes e hipercrom&#225;ticos&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8211;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Se trata de un tumor predominantemente amelan&#243;tico y es muy inusual la pigmentaci&#243;n difusa&#46;</p></li></ul></p><p id="par0085" class="elsevierStylePara elsevierViewall">En 2004 Busam et al&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">13</span></a> propusieron clasificar el melanoma desmopl&#225;sico en MD puro o mixto&#44; bas&#225;ndose en la proporci&#243;n de melanoma desmopl&#225;sico frente a la del melanoma no desmopl&#225;sico en el tumor infiltrante&#46; En el MD puro se requer&#237;a que&#44; por lo menos&#44; el 90&#37; del componente infiltrante fuera desmopl&#225;sico &#40;asociado a un estroma fibroso&#41;&#46; Sin embargo&#44; en el MD mixto&#44; el componente desmopl&#225;sico representaba menos del 90&#37; del tumor infiltrante&#44; y se acompa&#241;aba de un componente de melanoma no desmopl&#225;sico&#44; constituido por grupos cohesivos de melanocitos epitelioides y&#47;o fusocelulares sin estroma fibroso intercelular &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>D&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Los subtipos histol&#243;gicos del MD muestran&#44; adem&#225;s&#44; otras diferencias microsc&#243;picas&#46; Los MD mixtos suelen ser m&#225;s celulares&#44; revelan m&#225;s atipia citol&#243;gica y presentan mayor &#237;ndice mit&#243;tico y proliferativo &#40;KI67&#41; que los MD puros&#46; Por el contrario&#44; es m&#225;s frecuente observar neurotropismo y diferenciaci&#243;n neural en los MD puros que en los MD mixtos<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">13&#44;24</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Adem&#225;s&#44; los autores demostraron que la clasificaci&#243;n histol&#243;gica del MD en puro y mixto podr&#237;a tener implicaciones pron&#243;sticas&#44; de lo que se derivaban manejos diferentes&#44; lo que pone de relieve la importancia de clasificarlos correctamente&#46; En algunos casos&#44; especialmente en MD m&#225;s celulares&#44; identificar el componente desmopl&#225;sico con la tinci&#243;n de hematoxilina-eosina puede ser dif&#237;cil y conducir a errores en su tipificaci&#243;n&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">El perfil inmunohistoqu&#237;mico m&#225;s habitual del MD es que los melanocitos muestren positividad para S100&#44; SOX10 y Nerve Growth Factor Receptor &#40;NGFR&#41; &#40;75&#37;&#41;&#44; y negatividad para los marcadores de diferenciaci&#243;n melanoc&#237;tica HMB45&#44; tirosinasa&#44; MiTF y melan-A &#40;MART1&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">25</span></a>&#46; Es importante correlacionar la positividad observada con la morfolog&#237;a&#44; especialmente en piezas de re-ex&#233;resis&#44; dado que la positividad para S100<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">26</span></a> y SOX-10<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">27</span></a> tambi&#233;n puede observarse en c&#233;lulas estromales e inflamatorias&#44; y NGFR tambi&#233;n se expresa en las c&#233;lulas mioepiteliales&#44; fibroblastos&#44; miofibroblastos reactivos y fibras nerviosas<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">28</span></a>&#46; Debe tenerse en cuenta que&#44; en algunos casos&#44; la positividad para SOX10 y&#47;o S100 logra ser m&#237;nima o estar ausente&#44; y no por ello debe descartarse la posibilidad de un MD<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">29</span></a>&#46; A diferencia del MD&#44; los melanocitos del melanoma <span class="elsevierStyleItalic">in situ</span> o del componente no desmopl&#225;sico de un MD mixto muestran positividad para HMB-45&#44; tirosinasa&#44; MITF y melan-A &#40;Mart1&#41;&#44; y no muestran expresi&#243;n de NGFR&#46; A diferencia de otros subtipos de melanoma donde su expresi&#243;n es m&#225;s frecuente&#44; solo el 35&#37; de los MD expresa <span class="elsevierStyleItalic">PReferentially expressed Antigen in MElanoma</span> &#40;PRAME&#41;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">30</span></a>&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">La mayor&#237;a de los MD localizados en zonas con severo da&#241;o act&#237;nico tienen cargas mutacionales muy elevadas con una fuerte firma de radiaci&#243;n UV&#46; En el MD suelen estar ausentes las mutaciones activadoras en la v&#237;a de se&#241;alizaci&#243;n de las MAPK m&#225;s frecuentes en otros tipos de melanomas &#40;como la mutaci&#243;n de BRAF V600E&#41;&#46; En cambio&#44; son frecuentes las mutaciones en los genes NF1 &#40;55&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">31</span></a>&#44; TP53 &#40;48&#37;&#41; y CDKN2A &#40;47&#37;&#41;&#44; y pueden observarse mutaciones activadoras en la v&#237;a de las MAPK menos frecuentes&#44; como la amplificaci&#243;n del gen del receptor de la tirosina quinasa &#40;EGFR&#44; MET y ERBB2&#41; y la inactivaci&#243;n de CBL<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">32</span></a>&#46; Algunas de estas alteraciones podr&#237;an ser potenciales dianas terap&#233;uticas&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Presentaci&#243;n cl&#237;nica</span><p id="par0110" class="elsevierStylePara elsevierViewall">El MD suele presentarse como una p&#225;pula o placa no pigmentada&#44; indurada y de bordes mal definidos&#44; localizada en piel con da&#241;o act&#237;nico &#40;<a class="elsevierStyleCrossRef" href="#fig0020">fig&#46; 4</a>&#41;&#46; Solo en menos de un tercio &#40;27&#37;&#41; de los casos el diagn&#243;stico de sospecha inicial es el de melanoma maligno<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">20</span></a>&#46; Cl&#237;nicamente se confunde con frecuencia con lesiones cut&#225;neas benignas como tejido cicatrizal&#44; dermatofibroma&#44; neurofibroma&#44; nevus melanoc&#237;tico intrad&#233;rmico o tumores cut&#225;neos malignos no melanoc&#237;ticos como el carcinoma basocelular o el carcinoma escamoso &#40;<a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">La diferenciaci&#243;n del MD en los subtipos mixto y puro tambi&#233;n conlleva diferencias en su presentaci&#243;n cl&#237;nica<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">13</span></a>&#46; As&#237;&#44; la presencia de un componente epid&#233;rmico en forma de LM&#44; LMM o melanoma de extensi&#243;n superficial parece estar presente en el 80-100&#37; de los casos de subtipo combinado&#46; Por este motivo&#44; con el fin de descartar la presencia de un n&#243;dulo subcut&#225;neo indurado sugestivo de DM&#44; se recomienda la palpaci&#243;n de lesiones sospechosas de LMM &#40;<a class="elsevierStyleCrossRef" href="#fig0030">fig&#46; 6</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">15</span></a>&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">La lesi&#243;n epid&#233;rmica asociada es menos frecuente en el MD puro &#40;63-80&#37; de los casos&#41; que suele presentarse en forma de n&#243;dulo o placa subcut&#225;nea indurada sin cambios en superficie lo que explica que el diagn&#243;stico del MD puro se retrase&#44; en general&#44; y a la vez tenga un grosor mayor que el MD mixto<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">20&#44;33</span></a>&#46; Tanto el MD puro como el combinado se caracterizan por un mayor espesor al diagn&#243;stico que el del melanoma convencional&#44; con un &#237;ndice de Breslow medio entre 2&#44;5-6&#44;5 mm y un nivel de Clark IV y V en la mayor&#237;a de los casos<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">5&#44;10&#44;20&#44;34</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">La utilizaci&#243;n de la dermatoscopia puede ser de utilidad en el diagn&#243;stico de MD&#46; La ausencia de un ret&#237;culo pigmentado junto con la presencia de estructuras de regresi&#243;n con &#225;reas blanquecinas cicatrizales y gr&#225;nulos &#40;peppering&#41;&#44; as&#237; como patrones vasculares at&#237;picos deber&#237;an alertar sobre un posible MD<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">35</span></a>&#46; Jaimes et al&#46; describieron en un estudio de 37 casos que la presencia de color rosado vascular&#44; los vasos polimorfos&#44; la presencia de gr&#225;nulos y la hiperpigmentaci&#243;n asim&#233;trica perifolicular eran las caracter&#237;sticas dermatosc&#243;picas m&#225;s frecuentes del MD<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">33</span></a>&#46; Solo el 43&#37; de las lesiones presentaban estructuras espec&#237;ficas de lesi&#243;n melanoc&#237;tica como gl&#243;bulos &#40;44&#37;&#41;&#44; ret&#237;culo pigmentado &#40;38&#37;&#41;&#44; pseudoret&#237;culo &#40;25&#37;&#41; o un ret&#237;culo invertido &#40;6&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0035">fig&#46; 7</a>&#41;&#46; No obstante&#44; en otras series&#44; todos los casos analizados presentaban al menos una caracter&#237;stica espec&#237;fica de melanoma<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">15&#44;33&#44;36</span></a>&#46; L&#243;gicamente en el subtipo de MD mixto&#44; asociado con mayor frecuencia a un componente epid&#233;rmico&#44; se evidenci&#243; un mayor n&#250;mero y variedad de caracter&#237;sticas especificas de melanoma y hallazgos dermatosc&#243;picos asociados a LM como el patr&#243;n anular&#8211;granular y las l&#237;neas poligonales<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">33</span></a>&#46;</p><elsevierMultimedia ident="fig0035"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">A&#250;n hay pocos datos que apoyen la utilidad de la microscopia confocal de reflectancia &#40;MCR&#41; en el diagn&#243;stico del MD&#46; En un estudio de 14 casos de MD con exploraci&#243;n mediante MCR y posterior an&#225;lisis histopatol&#243;gico&#44; Maher et al&#46; observaron la presencia de caracter&#237;sticas especificas de melanoma en la MCR &#40;c&#233;lulas pagetoides&#44; c&#233;lulas con atipia y c&#233;lulas nucleadas en dermis&#41; con una frecuencia similar a la que encontrar&#237;amos en otros subtipos de melanoma<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">36</span></a>&#46; Por el contrario&#44; la detecci&#243;n de abundantes c&#233;lulas fusiformes entremezcladas con fibras de col&#225;geno en la dermis superficial parece relacionarse con en el diagn&#243;stico espec&#237;fico del MD<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">36</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Pron&#243;stico</span><p id="par0135" class="elsevierStylePara elsevierViewall">La evidencia actual sugerir&#237;a que el comportamiento del MD es distinto al del melanoma convencional<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">3&#44;37</span></a>&#46; El MD presentar&#237;a un mayor riesgo de recurrencia local a la vez que una menor tasa de met&#225;stasis ganglionar<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">3&#44;34&#44;38</span></a>&#46; As&#237; el riesgo de afectaci&#243;n ganglionar ser&#237;a menor al de MND de similar grosor<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">3&#44;37</span></a>&#44; con un riesgo de afectaci&#243;n del ganglio centinela que var&#237;a en funci&#243;n de la serie entre 0 y 18&#44;2&#37;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">3</span></a>&#46; Es dif&#237;cil establecer el pron&#243;stico real del MD&#44; existen conclusiones contradictorias entre los distintos estudios y muchos de ellos no distinguen entre los subtipos de MD&#46; No obstante&#44; la mayor&#237;a de los trabajos recientes no encuentran diferencias significativas en la supervivencia respecto a los MND del mismo grosor<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">3&#44;6&#44;20&#44;37&#44;39&#44;40</span></a>&#46; La impresi&#243;n de que el MD puro tendr&#237;a una menor tendencia a las met&#225;stasis a distancia que el MD mixto&#44; y por tanto una mejor supervivencia&#44; no ha sido demostrada de forma constante&#46; Si bien Maurichi et al&#46; encontraron diferencias significativas entre la supervivencia global en funci&#243;n del subtipo de MD &#40;61&#44;3&#37; para el MD mixto vs&#46; 79&#44;5&#37; para el MD puro&#41;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">39</span></a>&#44; trabajos posteriores no han corroborado estos hallazgos<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">7&#44;41</span></a>&#46; Cuando ocurren&#44; las met&#225;stasis a distancia se han relacionado con recurrencias previas y lesiones profundas&#44; siendo el pulm&#243;n la localizaci&#243;n m&#225;s frecuente para las mismas<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">34</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">La mayor&#237;a de los trabajos coinciden que los MD tienen un riesgo elevado de recurrencia local&#44; de entre un 10-14&#37; aproximadamente<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">37&#44;39&#44;42&#44;43</span></a>&#44; y esta diferencia es mayor en los MD puros que en los MD mixtos <a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">39</span></a>&#46; Algunos autores atribuyen esta mayor agresividad local de los MD puros al retraso en el diagn&#243;stico dada la rareza y la presentaci&#243;n at&#237;pica de estos tumores y otros factores como su frecuente invasi&#243;n perineural y la extirpaci&#243;n con m&#225;rgenes quir&#250;rgicos insuficientes en muchos de los casos<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">20&#44;37</span></a>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Existen algunos factores que podr&#237;an condicionar un comportamiento m&#225;s agresivo del MD&#46; Shi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">38</span></a>&#44; en un estudio retrospectivo de 3&#46;657 casos de MD&#44; encontraron que una edad superior a 68 a&#241;os y el sexo masculino son factores pron&#243;stico independientes relacionados con una peor supervivencia tanto global como libre de enfermedad&#46; Aunque algunos trabajos respaldan estos hallazgos<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">31&#44;36&#44;40</span></a>&#44; otras series no encuentran diferencias para la supervivencia libre de enfermedad<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">37&#44;44&#44;45</span></a>&#46; Otro factor de mal pron&#243;stico descrito en los MD es la invasi&#243;n perineural<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">6&#44;46</span></a>&#44; encontrando una correlaci&#243;n significativa con un mayor espesor de Breslow en los casos que presentan invasi&#243;n perineural<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">20</span></a>&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Estrategias terap&#233;uticas en el melanoma desmopl&#225;sico</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Cirug&#237;a</span><p id="par0150" class="elsevierStylePara elsevierViewall">M&#250;ltiples estudios han demostrado que en el melanoma cut&#225;neo primario la ex&#233;resis amplia &#40;2 o m&#225;s cm&#41; en melanomas &#8804; 2 mm de grosor no aumenta la supervivencia<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">39&#44;47</span></a>&#46; Sin embargo&#44; los MD suelen tener en el momento del diagn&#243;stico un grosor mayor que los melanomas convencionales&#44; por lo que requieren m&#225;rgenes amplios de 2 cm con mayor frecuencia&#46; Este hecho tiene una especial importancia teniendo en cuenta la mayor tasa de recurrencia local descrita en los MD<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">6&#44;34&#44;42</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Una serie australiana<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">6</span></a> mostr&#243; una tasa menor de recurrencia en lesiones extirpadas con &#8805; 2 cm frente a lesiones extirpadas con &#60; 1 cm&#46; En la misma l&#237;nea Maurichi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">39</span></a> evaluaron el pron&#243;stico bas&#225;ndose en los diferentes subtipos de MD y los diversos m&#225;rgenes quir&#250;rgicos utilizados&#46; Los pacientes con MD puro con Breslow &#8804; 2 mm extirpados con 1 cm de margen tuvieron un peor pron&#243;stico&#44; con tasas de recurrencia m&#225;s altas y peor supervivencia global a los cinco a&#241;os&#44; comparado con los que fueron tratados con 2 cm de margen quir&#250;rgico&#46; Sin embargo&#44; el pron&#243;stico fue similar entre pacientes con MD puro y Breslow &#8804; 2 mm y MD puro con Breslow &#62; 2 mm que fueron tratados con 2 cm de margen quir&#250;rgico&#46; Para los MD mixtos&#44; no hubo diferencias significativas en el pron&#243;stico en funci&#243;n del margen quir&#250;rgico otorgado&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Por todo ello&#44; en MD puros se debe considerar un margen quir&#250;rgico de 2 cm incluso en lesiones &#60; 2 mm de grosor &#40;m&#225;s controvertido parecer&#237;a en lesiones de grosor &#60; 1 mm para los que no hay estudios que eval&#250;en la posibilidad de establecer un margen de 1 cm<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">3</span></a>&#41;&#46; Es decir&#44; el margen quir&#250;rgico amplio deber&#237;a priorizarse siempre que sea posible en MD puros para evitar recurrencias locales&#44; pero se debe tener en cuenta que en muchos casos esto puede verse condicionado porque las lesiones frecuentemente se localizan en cabeza y cuello&#44; en &#225;reas anat&#243;micas complejas<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">15</span></a>&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Biopsia selectiva del ganglio centinela</span><p id="par0165" class="elsevierStylePara elsevierViewall">La indicaci&#243;n de la biopsia selectiva del ganglio centinela &#40;BSGC&#41; en el MD es controvertida&#46; Actualmente la utilidad de la BSGC en melanoma es identificar aquellos pacientes con un peor pron&#243;stico y a los que se podr&#237;a ofrecer un tratamiento adyuvante&#46; La evidencia de su utilidad en el MD se obtiene de series de casos retrospectivas&#46; En varias de ellas se evidencian claras diferencias en la supervivencia espec&#237;fica del melanoma en funci&#243;n del estado del ganglio centinela &#40;GC&#41;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">5&#44;37&#44;40&#44;44</span></a>&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Una probabilidad del 5&#37; de afectaci&#243;n del GC es el umbral a partir del cual suele considerar la indicaci&#243;n de la BSGC<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">48</span></a>&#46; En las series m&#225;s recientes sobre melanoma desmopl&#225;sico el porcentaje de afectaci&#243;n del GC varia entre 0&#8211;18&#44;2&#37;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">7&#44;37&#44;39&#8211;43&#44;49&#8211;58</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; Debe destacarse que los cinco trabajos que reportan un 0&#37; de afectaci&#243;n del GC son series de menos de 25 pacientes<a class="elsevierStyleCrossRefs" href="#bib0580"><span class="elsevierStyleSup">42&#44;43&#44;49&#44;50&#44;55</span></a>&#46; En la revisi&#243;n sistem&#225;tica realizada por Dunne et al&#46; publicada en 2017 y que recog&#237;a los estudios publicados hasta la fecha la tasa de afectaci&#243;n del GC fue del 6&#44;5&#37;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">59</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">La distinci&#243;n entre las variantes histol&#243;gicas de melanoma desmopl&#225;sico parece &#250;til para establecer el riesgo de afectaci&#243;n del GC y la propia indicaci&#243;n de la BSGC&#46; As&#237;&#44; el riesgo de afectaci&#243;n del GC es mayor en la variante mixta &#40;8&#44;5-25&#37;&#41; que en el melanoma desmopl&#225;sico puro &#40;0-18&#44;2&#37;&#41;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">7&#44;39&#44;41&#44;52&#44;54&#8211;56&#44;58&#44;60</span></a>&#46; En la revisi&#243;n de Dunne et al&#46; se evidenci&#243; una afectaci&#243;n del GC en el 13&#46;8&#37; de los MD mixtos y del 5&#44;4&#37; de los puros<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">59</span></a>&#46; Solo un estudio ha se&#241;alado un riesgo mayor de afectaci&#243;n del GC en la variante pura que en la variante mixta<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">41</span></a>&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">En definitiva&#44; la indicaci&#243;n de la BSGC en el MD es m&#225;s clara en la variante mixta y controvertida en los MD puros&#46; Sin embargo&#44; deben valorarse otros factores como la edad del paciente&#44; sus comorbilidades y la localizaci&#243;n del tumor primario&#46; En este sentido&#44; tanto la localizaci&#243;n del tumor primario en cabeza y cuello como la edad avanzada que suelen presentar los pacientes con MD&#44; son dos factores que cl&#225;sicamente se asocian a una menor afectaci&#243;n del GC<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">61</span></a>&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Pocos estudios se&#241;alan la tasa de afectaci&#243;n de los ganglios no centinela &#40;GNC&#41; en una disecci&#243;n ganglionar completa tras una BSGC positiva en el MD&#46; Dos estudios con m&#225;s de 200 pacientes cada uno han obtenido afectaci&#243;n de los GNC en MD en porcentajes del 16&#44;7&#37; y 23&#44;5&#37;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">37&#44;58</span></a>&#44; datos similares a los que se obtienen en MND<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">62</span></a>&#46; En este sentido&#44; con las limitaciones de la evidencia actual&#44; parece sensato aplicar el mismo algoritmo de manejo del paciente con GC positivo que se utiliza en el melanoma convencional<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">63</span></a>&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Radioterapia</span><p id="par0190" class="elsevierStylePara elsevierViewall">Teniendo en cuenta las altas tasas de recurrencia local descritas en los MD<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">37&#44;64</span></a>&#44; la adyuvancia con radioterapia &#40;RDT&#41; se ha planteado como una opci&#243;n terap&#233;utica interesante&#46; A diferencia del melanoma convencional&#44; que es relativamente resistente a la radioterapia&#44; en el MD hay varios estudios que demuestran que su uso como tratamiento adyuvante puede ser eficaz en el control local de la enfermedad<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">3&#44;34&#44;65</span></a>&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Hay varios trabajos que exponen el potencial beneficio de la RDT adyuvante cuando el MD presenta factores de riesgo asociados &#40;invasi&#243;n perineural&#44; desmoplasia extensa&#44; m&#225;rgenes positivos o enfermedad recurrente&#41;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">38&#44;66&#44;67</span></a>&#46; Dos estudios m&#225;s recientes afianzan esta asociaci&#243;n entre la RDT adyuvante y la mejor&#237;a del control local en los MD&#46; Por un lado&#44; Guadagnolo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">68</span></a> evaluaron 130 pacientes con MD que hab&#237;an sido tratados exclusivamente con cirug&#237;a o con cirug&#237;a m&#225;s radioterapia adyuvante&#46; Los autores encontraron que el 24&#37; de los pacientes que se sometieron &#250;nicamente a tratamiento quir&#250;rgico y s&#243;lo el 7&#37; de los pacientes que se sometieron a cirug&#237;a m&#225;s RDT adyuvante desarrollaron una recurrencia local&#44; demostrando una correlaci&#243;n significativa con un mejor control local en el an&#225;lisis multivariable&#46; Por otro lado&#44; Strom et al&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">69</span></a> tambi&#233;n encontraron que el uso de la RDT adyuvante mejoraba significativamente el control local en el an&#225;lisis multivariable&#46; Los pacientes con m&#225;rgenes de resecci&#243;n positivos tuvieron particularmente una mayor reducci&#243;n de la tasa de recurrencia local&#44; 54&#37; sin el uso de RDT adyuvante frente al 14&#37; con cirug&#237;a m&#225;s RDT adyuvante&#46; Adem&#225;s&#44; estos autores describen factores pron&#243;sticos para seleccionar los MD con m&#225;rgenes negativos que se beneficiar&#237;an de la RDT adyuvante&#58; tumores localizados en cabeza y cuello&#44; Breslow &#62; 4 mm&#44; y nivel V de Clark&#46; Tambi&#233;n Oliver et al&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">70</span></a>&#44; en un estudio retrospectivo m&#225;s reciente&#44; evaluaron a 100 pacientes con MD tratados &#250;nicamente con cirug&#237;a&#44; cirug&#237;a m&#225;s RDT adyuvante o RDT radical en recurrencias post-cirug&#237;a&#46; En este estudio eval&#250;an el valor de la RDT como tratamiento radical en recurrencias&#44; as&#237; como el de la adyuvancia post-intervenci&#243;n&#44; encontrando un control local del 100&#37; de los casos tanto en los 10 pacientes tratados con RDT adyuvante como en los siete pacientes tratados con RDT radical&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Sin embargo&#44; la evidencia actual se basa en estudios retrospectivos y se precisan estudios prospectivos randomizados para afianzar estas conclusiones&#46; Actualmente hay en marcha un ensayo cl&#237;nico &#40;NCT00975520&#41;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">71</span></a> que compara el tratamiento exclusivamente quir&#250;rgico frente a cirug&#237;a m&#225;s radioterapia adyuvante en pacientes con MD extirpados con m&#225;rgenes amplios negativos&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Tratamiento sist&#233;mico</span><p id="par0205" class="elsevierStylePara elsevierViewall">La inmunoterapia mediante f&#225;rmacos anti-PD1 ha demostrado su eficacia en el tratamiento del MD metast&#225;sico&#46; En un reciente estudio multic&#233;ntrico retrospectivo donde se analizaron 60 casos de MD metast&#225;sico tratados con f&#225;rmacos anti-PD1 se evidenci&#243; una respuesta objetiva en el 70&#37; de ellos&#44; con un 32&#37; de respuestas completas con un seguimiento medio de 22 meses<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">72</span></a>&#46; Esta respuesta&#44; incluso superior a la observada en el MND&#44; podr&#237;a explicarse por la alta carga de mutaciones inducidas por la radiaci&#243;n ultravioleta que presenta el MD&#46; Se estima que la inmunoterapia podr&#237;a ser m&#225;s eficaz en neoplasias como el MD que presentan una alta carga mutacional<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">73</span></a>&#46; Estos prometedores resultados deben ser confirmados en ensayos cl&#237;nicos prospectivos&#46; En la actualidad existe un ensayo en fase II &#40;NCT02775851&#41;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">74</span></a> en periodo de reclutamiento sobre la eficacia de pembrolizumab en el MD&#46; La ausencia de mutaciones de BRAF en la mayor&#237;a de los melanomas desmopl&#225;sicos hace que los inhibidores de BRAF no sean un tratamiento &#250;til en estos pacientes&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusiones</span><p id="par0210" class="elsevierStylePara elsevierViewall">El MD es una variante poco frecuente de melanoma con una conducta biol&#243;gica distinta que requiere estrategias diagn&#243;sticas y terap&#233;uticas diferentes al del melanoma convencional&#46; Su diagn&#243;stico representa un reto tanto para el cl&#237;nico como para el pat&#243;logo&#46; La clasificaci&#243;n histol&#243;gica del MD en los subtipos puro y mixto parece ofrecer informaci&#243;n importante sobre el comportamiento del tumor&#44; que debe tenerse en cuenta para su tratamiento&#46; El MD puro es aquel donde por lo menos el 90&#37; del componente infiltrante es desmopl&#225;sico mientras que en el MD mixto&#44; el componente desmopl&#225;sico representa menos del 90&#37; del tumor infiltrante&#44; y se acompa&#241;aba de un componente de melanoma no desmopl&#225;sico&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">La cirug&#237;a con m&#225;rgenes amplios es esencial para prevenir futuras reca&#237;das que condicionan una peor supervivencia&#46; El estado del ganglio centinela parece tener valor pron&#243;stico en el MD y debe valorarse su indicaci&#243;n en el subtipo mixto&#46; M&#225;s discutible parece ser su indicaci&#243;n en MD puro&#46; La RDT adyuvante sobre el lecho tumoral puede ser &#250;til en algunos casos con factores de riesgo asociados&#46; En caso de desarrollo de met&#225;stasis la evidencia actual sugiere unas buenas tasas de respuesta con los inhibidores de puntos de control inmunol&#243;gico&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Financiaci&#243;n</span><p id="par0220" class="elsevierStylePara elsevierViewall">Este trabajo no ha recibido ning&#250;n tipo de financiaci&#243;n&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflicto de intereses</span><p id="par0225" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El melanoma desmopl&#225;sico &#40;MD&#41; representa entre el 0&#44;4-4&#37; de todos los melanomas&#46; Se presenta como un tumor constituido predominantemente por melanocitos fusiformes amelan&#243;ticos inmersos en un estroma col&#225;geno abundante&#46; Se clasifica en MD puro o mixto&#44; bas&#225;ndose en la proporci&#243;n de melanoma desmopl&#225;sico frente a la del melanoma no desmopl&#225;sico presente en el tumor infiltrante&#46; En el MD puro el componente desmopl&#225;sico representa m&#225;s del 90&#37; del melanoma infiltrante mientras que&#44; en el MD combinado o mixto&#44; el componente desmopl&#225;sico representa menos del 90&#37;&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">El MD es m&#225;s frecuente en varones &#40;ratio 1&#44;7-2&#58;1&#41;&#59; la edad media al diagn&#243;stico oscila entre 66-69 a&#241;os y suele localizarse en &#225;reas de fotoexposici&#243;n cr&#243;nica&#44; a menudo asociado a un lentigo maligno&#46; Su reconocimiento cl&#237;nico es dif&#237;cil ya que se presenta como una p&#225;pula o placa no pigmentada&#44; indurada y de bordes mal definidos&#44; que recuerda a una cicatriz&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El MD es un tumor con una alta tendencia a la recurrencia local y en el caso del MD puro&#44; una baja tendencia a la diseminaci&#243;n ganglionar&#46; Sin embargo&#44; en las series m&#225;s contempor&#225;neas&#44; su pron&#243;stico global parece ser similar al de melanomas no desmopl&#225;sicos &#40;MND&#41; del mismo grosor&#46; Su abordaje cl&#237;nico posee algunos matices diferenciales&#44; en comparaci&#243;n al resto de melanomas&#44; que se revisan en el presente trabajo&#46;</p></span>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Desmoplastic melanoma &#40;DM&#41; accounts for 0&#46;4&#37; to 4&#37; of all melanomas&#46; These skin tumors are mainly formed by amelanotic spindled melanocytes immersed in an abundant collagen stroma and are classified as pure when the desmoplastic component accounts for at least 90&#37; of the invasive tumor and as mixed or combined otherwise&#46; DMs are more common in men &#40;male to female ratio&#44; 1&#46;7 to 2&#58;1&#41;&#44; and the mean age at diagnosis is 66 to 69 years&#46; The tumors tend to occur in chronically sun-exposed areas&#44; often in association with lentigo maligna&#44; and are difficult to recognize because they can resemble a scar&#44; presenting as a firm&#44; unpigmented papule or plaque with poorly defined borders&#46; DMs also have a strong tendency to recur locally&#44; and pure variants rarely spread to the lymph nodes&#46; Nonetheless&#44; recently published series suggest that patients with DM have a similar prognosis to those with nondesmoplastic melanoma of the same thickness&#46; The clinical management of DM varies in certain aspects from that of other melanomas and is reviewed in this article&#46;</p></span>"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0245" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Anexo A"
            "titulo" => "Material adicional"
            "identificador" => "sec0085"
          ]
        ]
      ]
    ]
    "multimedia" => array:10 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 984
            "Ancho" => 1305
            "Tamanyo" => 481844
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A&#41; Melanoma desmopl&#225;sico &#40;MD&#41; infiltrando en profundidad&#44; alcanzando la dermis reticular profunda &#40;HEx20&#41;&#46; B&#41; MD con melanocitos fusiformes con algunos n&#250;cleos grandes e hipercrom&#225;ticos&#44; dispuestos de forma aislada y desorganizada en un estroma ligeramente fibromixoide &#40;HEx200&#41;&#46; C&#41; MD asociado a un melanoma <span class="elsevierStyleItalic">in situ</span> &#40;HEx200&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figura 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 984
            "Ancho" => 1305
            "Tamanyo" => 576168
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A&#41; MD con elastosis act&#237;nica y atrapamiento de material elast&#243;tico &#40;HEx100&#41;&#46; B&#41; MD con un agregado nodular de linfocitos &#40;HEx200&#41;&#46; C&#41; MD con invasi&#243;n perineural&#46; &#40;HEx200&#41;&#46; D&#41; MD combinado&#46; En el extremo superior derecho se identifica el componente de melanoma no desmopl&#225;sico formado por nidos compactos de melanocitos epitelioides&#46; En la regi&#243;n inferior&#44; se observa el componente desmopl&#225;sico que representa menos del 90&#37; del tumor infiltrante &#40;HEx100&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figura 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 984
            "Ancho" => 1305
            "Tamanyo" => 393807
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">MD asociado a un melanoma <span class="elsevierStyleItalic">in situ</span> de extensi&#243;n superficial&#46; A&#41; y B&#41;&#46; Tinciones inmunohistoqu&#237;micas de S100 &#40;x100&#41; y SOX10 &#40;x100&#41;&#58; en ambas tinciones se observa positividad en las c&#233;lulas del MD y del melanoma <span class="elsevierStyleItalic">in situ</span>&#46; C&#41; y D&#41; Tinciones inmunohistoqu&#237;micas de melanA &#40;x100&#41; y HMB-45 &#40;x100&#41;&#58; en ambas tinciones se identifica expresi&#243;n en el melanoma in situ y ausencia de expresi&#243;n en el MD&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figura 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 605
            "Ancho" => 805
            "Tamanyo" => 86681
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Imagen cl&#237;nica de un MD&#46; Var&#243;n de 62 a&#241;os que consult&#243; por lesi&#243;n de crecimiento progresivo en mejilla&#46; Se apreci&#243; una lesi&#243;n en forma de placa marr&#243;n clara&#44; indurada de aspecto cicatricial&#46; Se correspondi&#243; con un MD puro de 5 mm de espesor&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figura 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 680
            "Ancho" => 905
            "Tamanyo" => 108676
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Imagen cl&#237;nica de un MD&#46; Mujer de 53 a&#241;os con tumoraci&#243;n interescapular en forma de tumor rosado de tacto firme&#46; Hab&#237;a sido inicialmente orientada de queloide&#46; La biopsia revel&#243; un MD puro de 8&#44;5 mm de espesor&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "fig0030"
        "etiqueta" => "Figura 6"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr6.jpeg"
            "Alto" => 539
            "Ancho" => 805
            "Tamanyo" => 73958
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Imagen cl&#237;nica de un MD asociado a un lentigo maligno &#40;LM&#41;&#46; Mujer de 89 a&#241;os con una lesi&#243;n en la frente sugestiva de LM&#46; Su ex&#233;resis revel&#243; la existencia de un MD asociado que alcanzaba 2&#44;95 mm de grosor&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "fig0035"
        "etiqueta" => "Figura 7"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr7.jpeg"
            "Alto" => 605
            "Ancho" => 805
            "Tamanyo" => 59172
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Imagen dermatosc&#243;pica de la tumoraci&#243;n de la Figura 4&#46; Se trata de una tumoraci&#243;n con un componente palpable de coloraci&#243;n rosada&#46; En este caso la presencia de ret&#237;culo pigmentado en varias &#225;reas de la lesi&#243;n debe orientar el diagn&#243;stico hac&#237;a una lesi&#243;n melanoc&#237;tica&#46;</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabla 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Estudio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">A&#241;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dise&#241;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Origen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Periodo &#40;a&#241;os&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">numero pacientes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Edad media&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Relaci&#243;n H&#58;M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Breslow medio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Localizaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Casos BSGC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Positividad GC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Casos MD mixto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Positividad GC MD mixto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Casos MD puro&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Positividad GC MD puro&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Jaroszewski&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Thelmo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gyorki&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;8&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Su&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;1&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Livestro&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Casos-controles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pawlik&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;3&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posther&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">129&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cummins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maurichi&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Italia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">242&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;3&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">George&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Murali&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Australia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">252&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;9&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">252&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">129&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">123&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;9&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mohebati&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cabeza y cuello&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Broer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Egger&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;1&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Han&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">205&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Todas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">205&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#44;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Conic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serie de Casos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EE&#46; UU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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Article information
ISSN: 00017310
Original language: Spanish
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2023 June 456 68 524
2023 May 616 104 720
2023 April 434 78 512
2023 March 527 124 651
2023 February 324 87 411
2023 January 353 99 452
2022 December 359 134 493
2022 November 509 144 653
2022 October 782 146 928
2022 September 552 151 703
2022 August 521 128 649
2022 July 471 170 641
2022 June 461 136 597
2022 May 428 189 617
2022 April 241 135 376
2022 March 319 175 494
2022 February 316 160 476
2022 January 224 59 283
2021 December 197 45 242
2021 November 209 67 276
2021 October 210 100 310
2021 September 182 75 257
2021 August 109 57 166
2021 July 87 58 145
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¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?