Impacto diagnóstico de la PET/TC con <span class="elsevierStyleSup">18</span>F-FDG en el tratamiento de carcinomas de mama raros: carcinomas apocrinos y neuroendocrinos | Revista Española de Medicina Nuclear e Imagen Molecular

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">El carcinoma apocrino de mama &#40;apocrine breast carcinoma &#91;ABC&#93;&#41; y el carcinoma neuroendocrino primario de mama &#40;primary breast neuroendocrine carcinoma &#91;PBNEC&#93;&#41; son tumores infrecuentes de la mama&#46; Representan aproximadamente un 1-2&#37; de todas las neoplasias malignas de la mama<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">1&#44;2</span></a>&#46; Las c&#233;lulas apocrinas se caracterizan por un citoplasma eosinof&#237;lico y granular&#44; n&#250;cleos grandes en localizaci&#243;n central&#44; y c&#233;lulas marginales espec&#237;ficas&#44; positivas para el receptor androg&#233;nico &#40;adrogen receptor &#91;AR&#93;&#41;&#44; y generalmente con un perfil esteroideo negativo para receptores estrog&#233;nicos &#40;estrogen receptor &#91;ER&#93;&#41; y de progesterona &#40;progesterone receptor &#91;PR&#93;&#41;&#46; Con frecuencia&#44; se documenta una sobreexpresi&#243;n del receptor 2 del factor de crecimiento epid&#233;rmico humano &#40;human epidermal growth factor receptor &#91;HER 2&#93;&#41; y del receptor del factor de crecimiento epid&#233;rmico &#40;epidermal growth factor receptor &#91;EGFR&#93;&#41;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a>&#46; En los PBNEC&#44; la diferenciaci&#243;n morfol&#243;gica es m&#225;s dificultosa&#46; Los PBNEC presentan con mayor frecuencia un perfil ER&#47;PR&#43;&#44; HER2&#8722;&#46; El diagn&#243;stico de PBNEC se basa fundamentalmente en la expresi&#243;n de marcadores neuroendocrinos&#44; incluyendo la sinaptofisina y la cromogranina<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">3&#44;4</span></a>&#46; Seg&#250;n la clasificaci&#243;n de la Organizaci&#243;n Mundial de la Salud del 2012&#44; los PBNEC se dividen en 3 grupos&#58; carcinomas de mama con diferenciaci&#243;n neuroendocrina bien diferenciados&#44; mal diferenciados e infiltrantes<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">3</span></a>&#46; Existen datos publicados limitados sobre el conocimiento en su diagn&#243;stico y tratamiento de estos tumores agresivos<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">3&#44;5</span></a>&#46; Est&#225; ampliamente aceptado que el examen histopatol&#243;gico constituya el patr&#243;n de referencia para los ABC y PBNEC&#44; debido a su dificultad diagn&#243;stica mediante las pruebas de imagen convencionales<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">1&#44;3</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">En los &#250;ltimos a&#241;os&#44; la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG ha sido ampliamente documentada y utilizada como t&#233;cnica de imagen &#250;til para detectar el hipermetabolismo gluc&#237;dico&#44; especialmente en la estadificaci&#243;n preterap&#233;utica y en la detecci&#243;n de met&#225;stasis de los carcinomas de mama<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a>&#46; Los niveles del valor de captaci&#243;n m&#225;ximo estandarizado &#40;SUVm&#225;x&#41; se han asociado significativamente con el di&#225;metro tumoral&#44; el tipo histol&#243;gico&#44; un grado histol&#243;gico tumoral m&#225;s elevado&#44; el &#237;ndice Ki-67&#44; el estatus de los receptores hormonales&#44; la recidiva y el pron&#243;stico de la enfermedad<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">7&#8211;9</span></a>&#46; En el c&#225;ncer de mama se ha demostrado una relaci&#243;n entre la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG y el tipo histopatol&#243;gico&#46; Los valores de captaci&#243;n m&#225;s elevados se han observado en los carcinomas ductales invasivos y los apocrinos&#44; mientras que la captaci&#243;n m&#225;s baja se obtiene en el c&#225;ncer de mama de tipo lobulillar&#46; Adem&#225;s&#44; se ha descrito la asociaci&#243;n entre la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG y la negatividad de los receptores ER y PR&#44; la positividad del receptor HER2 y la elevada expresi&#243;n del Ki-67<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">10</span></a>&#46; En este estudio&#44; nuestro objetivo fue analizar los patrones de captaci&#243;n del <span class="elsevierStyleSup">18</span>F-FDG en pacientes con ABC y PBNEC&#44; as&#237; como compararlos con el carcinoma ductal invasivo &#40;CDI&#41;&#46; Adem&#225;s&#44; evaluamos el papel de la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG en la estadificaci&#243;n del ABC y el PBNEC&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Pacientes</span><p id="par0015" class="elsevierStylePara elsevierViewall">En el estudio se incluyeron un total de 570 pacientes &#40;585 lesiones&#41; que fueron intervenidos quir&#250;rgicamente o hab&#237;an sido sometidos a biopsia por aspiraci&#243;n con aguja fina o biopsia con aguja gruesa en nuestro centro entre marzo de 2009 y mayo de 2018&#46; Hubo 566 mujeres &#40;99&#44;3&#37;&#41; y 4 hombres &#40;0&#44;7&#37;&#41;&#44; con una edad media de 54&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#44;3 &#40;rango<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23-88&#41; a&#241;os&#46; En quince pacientes se diagnostic&#243; un tumor bilateral&#46; En las 585 lesiones se realiz&#243; su an&#225;lisis histopatol&#243;gico y una PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG preoperatoriamente&#46; Nuestro estudio retrospectivo fue aprobado por el comit&#233; &#233;tico local &#40;2015&#47;598&#41;&#44; y en todos los pacientes se solicit&#243; su consentimiento verbal o por escrito para la utilizaci&#243;n de sus hallazgos cl&#237;nicos individuales por motivos de investigaci&#243;n&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">An&#225;lisis histol&#243;gico</span><p id="par0020" class="elsevierStylePara elsevierViewall">El diagn&#243;stico del c&#225;ncer de mama primario y su an&#225;lisis histopatol&#243;gico se bas&#243; en muestras tisulares obtenidas mediante biopsia con aguja gruesa o por aspiraci&#243;n con aguja fina antes de la realizaci&#243;n de la PET&#47;TC&#44; o bien mediante biopsia por extirpaci&#243;n&#44; cirug&#237;a mamaria conservadora o mastectom&#237;a radical tras la PET&#47;TC&#46; Para la estadificaci&#243;n histol&#243;gica se utiliz&#243; la clasificaci&#243;n de Scarff Bloom Richardson&#46; Se acept&#243; una positividad igual o superior al 10&#37; de los receptores ER y PR en la tinci&#243;n inmunohistoqu&#237;mica del tejido tumoral&#46; La clasificaci&#243;n del HER2 se obtuvo como se especifica a continuaci&#243;n&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0025" class="elsevierStylePara elsevierViewall">Grado 0 &#40;negativa&#41;&#58; lesiones con inmunotinci&#243;n negativa&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0030" class="elsevierStylePara elsevierViewall">Grado 1&#58; tinci&#243;n d&#233;bil o inferior al 30&#37; de las c&#233;lulas tumorales&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0035" class="elsevierStylePara elsevierViewall">Grado 2&#58; tinci&#243;n completa de la membrana &#40;m&#237;nimo del 10&#37;&#41; incluso con tinci&#243;n uniforme o d&#233;bil&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall">Grado 3&#58; un m&#237;nimo del 30&#37; de tinci&#243;n de membrana uniforme y significativa en las c&#233;lulas tumorales&#46;</p></li></ul></p><p id="par0045" class="elsevierStylePara elsevierViewall">Durante el procedimiento rutinario&#44; se estableci&#243; un valor de corte del 15&#37; en el Ki-67 para diferenciar entre los tipos luminal A y B mediante m&#233;todos de perfilaci&#243;n inmunohistoqu&#237;mica y gen&#233;tica&#59; se aceptaron como negativos valores &#60; 15&#37; y positivos &#8805; 15&#37;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">8</span></a>&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Los tumores se clasificaron en 4 subgrupos moleculares en base al estatus de los receptores hormonales&#44; seg&#250;n los resultados del estudio histopatol&#243;gico&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">1&#46;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Luminal A&#58; ER&#40;&#43;&#41; y&#47;o PR&#40;&#43;&#41;&#44; HER2&#40;&#8722;&#41; y Ki-67 bajo &#40;&#60; 15&#37;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">2&#46;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Luminal B&#58; ER&#40;&#43;&#41; y&#47;o PR&#40;&#43;&#41;&#44; HER2&#40;&#43;&#41; o HER2&#40;&#8722;&#41; y Ki-67 alto &#40;&#8805; 15&#37;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">3&#46;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Triple negativo y de tipo basal &#40;TN&#41;&#58; ER&#40;&#8722;&#41;&#44; PR&#40;&#8722;&#41; y HER2&#40;&#8722;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">4&#46;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Tipo HER2&#58; ER&#40;&#8722;&#41;&#44; PR&#40;&#8722;&#41; y HER2&#40;&#43;&#41;&#46;</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG</span><p id="par0075" class="elsevierStylePara elsevierViewall">En nuestro estudio&#44; la tumoraci&#243;n mamaria primaria se caracteriz&#243; en t&#233;rminos de sus dimensiones&#44; localizaci&#243;n y cantidad &#40;multicentricidad&#44; multifocalidad&#41;&#59; SUVm&#225;x&#59; y met&#225;stasis linf&#225;tica y org&#225;nica a distancia en base a los hallazgos de la PET&#47;TC&#46; Se admitieron pacientes con niveles de glucemia inferior a 150 mg&#47;dl despu&#233;s de un m&#237;nimo de 6 h de ayunas&#46; A todos los pacientes se administr&#243; por v&#237;a intravenosa una dosis est&#225;ndar de 3&#44;7-5&#44;2<span class="elsevierStyleHsp" style=""></span>MBq&#47;kg de <span class="elsevierStyleSup">18</span>F-FDG&#46; Sesenta min despu&#233;s de la inyecci&#243;n IV del radiotrazador&#44; se obtuvieron im&#225;genes PET&#47;TC de cuerpo completo incluyendo desde el v&#233;rtice craneal hasta el tercio proximal de f&#233;mures con el paciente en posici&#243;n supina &#40;las primeras 108 exploraciones se realizaron con un tom&#243;grafo Siemens Biograph 6 HD LSO&#44; y las 462 subsiguientes se realizaron con un equipo Siemens mCT 20 ultra HD LSO PET&#47;CT &#91;Siemens Molecular Imaging&#59; Hoffman Estates&#44; IL&#44; EE&#46; UU&#46;&#93;&#41;&#46; Para el c&#225;lculo del SUVm&#225;x&#44; se dibujaron &#225;reas de inter&#233;s &#40;ROI&#41; en los cortes de la PET&#44; que incluyeron la captaci&#243;n m&#225;xima&#46; El SUVm&#225;x se calcul&#243; de acuerdo con la siguiente f&#243;rmula&#58; actividad m&#225;xima dentro de la ROI &#40;MBq&#47;g&#41;&#47;dosis inyectada de <span class="elsevierStyleSup">18</span>F-FDG&#47;peso corporal &#40;MBq&#47;kg&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">An&#225;lisis estad&#237;stico</span><p id="par0080" class="elsevierStylePara elsevierViewall">Todos los resultados se analizaron utilizando el programa inform&#225;tico SPSS &#40;Statistical Package for the Social Sciences&#41; para Windows &#40;v21&#46;0&#59; IBM&#44; Armonk&#44; NY&#44; EE&#46; UU&#46;&#41;&#46; Los datos individuales y globales se presentaron utilizando variables estad&#237;sticas descriptivas&#44; incluyendo media&#44; desviaciones est&#225;ndar&#44; medianas &#40;m&#237;n-m&#225;x&#41;&#44; distribuci&#243;n de frecuencias y porcentajes&#46; Se verific&#243; la normalidad en la distribuci&#243;n de los datos mediante la prueba de Kolmogorov-Smirnov&#46; Se realiz&#243; la comparaci&#243;n de las variables con la distribuci&#243;n normal mediante la prueba t de Student&#46; La evaluaci&#243;n de las variables categ&#243;ricas se realiz&#243; mediante la prueba de chi al cuadrado&#46; Para evaluar el grado de concordancia se calcul&#243; el valor estad&#237;stico kappa&#46; Se consider&#243; la significaci&#243;n estad&#237;stica con valores de la <span class="elsevierStyleItalic">p</span> &#60; 0&#44;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Resultados</span><p id="par0085" class="elsevierStylePara elsevierViewall">En nuestro grupo de estudio&#44; el carcinoma ductal invasivo fue el tipo de c&#225;ncer de mama m&#225;s frecuente&#44; con una incidencia del 77&#44;7&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>446&#41; &#40;media<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DE&#59; 54&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#44;1 a&#241;os&#41;&#46; En el 4&#44;1&#37; de los pacientes &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#41; se diagnostic&#243; un c&#225;ncer de mama de tipo apocrino&#44; y en el 2&#44;4&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; un PBNEC&#46; Las 101 lesiones restantes mostraron otros tipos histopatol&#243;gicos de c&#225;ncer de mama &#40;lobulillar invasivo&#44; mucinoso&#44; mixto&#44; etc&#46;&#41;&#46; La edad media de los pacientes con ABC fue de 55&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44;2 &#40;rango<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>38-81&#41;&#44; y de 67&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#44;1 &#40;rango<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>47-85&#41; a&#241;os para los pacientes con PBNEC&#46; La edad media del grupo con ABC fue similar al del CDI&#44; y no hubo diferencias significativas entre ambos grupos &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;29&#41;&#46; Sin embargo&#44; la edad media del grupo con PBNEC fue significativamente mayor en comparaci&#243;n con el grupo con CDI &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">La <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> muestra los hallazgos histopatol&#243;gicos y de la PET&#47;TC de los pacientes con ABC&#46; La media <span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DE del SUVm&#225;x del tumor primario del grupo con ABC fue similar a la del grupo con CDI&#44; y no se observaron diferencias estad&#237;sticamente significativas entre ambos grupos &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;46&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; La <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a> compara los hallazgos histopatol&#243;gicos y de la PET&#47;TC de los pacientes con CDI y ABC&#46; La incidencia de receptores ER y PR positivos fue estad&#237;sticamente mayor en el grupo con CDI respecto al grupo con ABC &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;012 y <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;016&#44; respectivamente&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46; En el 84&#44;3&#37; de los pacientes con CDI se observ&#243; una expresi&#243;n elevada &#40;&#8805;15&#37;&#41; del Ki-67 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>376&#41;&#44; pero esta fue elevada en todo el grupo con ABC&#46; Hubo diferencias significativas entre ambos grupos &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;035&#41;&#46; La incidencia de HER2 positivo fue estad&#237;sticamente mayor en el grupo con ABC respecto al de CDI &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;021&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">En el 68&#44;2&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>304&#41; de los pacientes con CDI y en el 91&#44;7&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>22&#41; de los pacientes con ABC se observ&#243; afectaci&#243;n ganglionar axilar en la PET&#47;TC&#46; La incidencia de afectaci&#243;n axilar en pacientes con ABC fue estad&#237;sticamente superior &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;015&#41; que con el CDI&#46; Teniendo en cuenta los resultados del an&#225;lisis histopatol&#243;gico&#44; en el grupo con ABC la sensibilidad y especificidad de la PET&#47;TC para la afectaci&#243;n ganglionar axilar fue del 100&#37; y del 80&#37;&#44; respectivamente&#46; No hubo diferencias estad&#237;sticamente significativas entre los grupos ABC y CDI respecto a la afectaci&#243;n ganglionar a distancia ni en las met&#225;stasis org&#225;nicas &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">La <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> muestra la media <span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DE del SUVm&#225;x del tumor primario en los subtipos histopatol&#243;gicos de los pacientes con ABC&#46; El subtipo HER2 mostr&#243; el valor medio<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DE de SUVm&#225;x m&#225;s elevado de la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG en el tumor primario&#44; y el &#237;ndice de captaci&#243;n de este subtipo fue significativamente superior al del subtipo luminal B en pacientes con ABC &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;038&#41;&#46; Adem&#225;s&#44; seg&#250;n la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG en los pacientes con ABC&#44; hubo una diferencia estad&#237;sticamente significativa entre los subtipos TN y luminal B &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;019&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46; El n&#250;mero de pacientes con subtipo TN en el grupo con CDI fue de 48 &#40;10&#44;8&#37;&#41;&#46; En este grupo&#44; el valor medio <span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DE del SUVm&#225;x del tumor primario fue de 19&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#44;7&#46; En 6 pacientes &#40;25&#37;&#41; con ABC TN el valor medio <span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DE del SUVm&#225;x del tumor primario fue de 16&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;0&#46; No hubo diferencias significativas entre estos dos grupos &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;272&#41;&#44; y tampoco hubo diferencias significativas entre el subtipo HER2 de los grupos con CDI y ABC &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;29&#41; en relaci&#243;n con la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG del tumor primario&#46; Sin embargo&#44; en nuestro estudio el valor medio de SUVm&#225;x en pacientes con CDI y subtipo TN fue significativamente superior respecto a los subtipos luminal A &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>237&#41; y luminal B &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>130&#41; de pacientes con CDI &#40;10&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;1 y 12&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;7&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001 y <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001 respectivamente&#41;&#46; El valor medio de SUVm&#225;x en el subtipo HER2 fue de 15&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#44;8 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>31&#41; en los pacientes con CDI&#44; y hubo diferencias significativas entre los subtipos HER2 y luminal A &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figs&#46; 1-3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">El valor medio <span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DE m&#237;nimo del SUVm&#225;x se obtuvo en el grupo con PBNEC&#44; pero no hubo diferencias significativas entre los grupos PBNEC&#44; CDI y ABC &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; La <a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a> muestra los hallazgos histopatol&#243;gicos y de la PET&#47;TC de los pacientes con PBNEC&#46; La <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a> muestra la comparaci&#243;n entre los hallazgos histopatol&#243;gicos y de la PET&#47;TC de pacientes con PBNEC y CDI&#46; Se observ&#243; que la incidencia de positividad a los receptores ER y PR fue mayor en el grupo con PBNEC que en el CDI&#44; pero solamente hubo diferencias significativas en la tasa de receptores PR &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;036&#41;&#46; Sin embargo&#44; la positividad de los receptores HER2 fue similar en el grupo con PBNEC respecto al de CDI &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;373&#41;&#46; En el 71&#44;4&#37; de los pacientes con PBNEC la expresi&#243;n de Ki-67 fue inferior al 15&#37;&#44; y fue significativamente mayor que en el grupo con CDI &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Seg&#250;n la PET&#47;TC&#44; la incidencia de afectaci&#243;n ganglionar axilar y de met&#225;stasis org&#225;nicas a distancia fue similar en los pacientes con CDI y PBNEC &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;796 y <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;993&#44; respectivamente&#41;&#46; En nuestro estudio&#44; la sensibilidad y especificidad de la PET&#47;TC para la afectaci&#243;n axilar fue del 90&#37; y el 75&#37;&#44; respectivamente&#46; Sin embargo&#44; hubo diferencias estad&#237;sticamente significativas entre los grupos PBNEC y CDI en relaci&#243;n con las met&#225;stasis ganglionares a distancia &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Cuando se evalu&#243; la relaci&#243;n existente entre la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG y el subtipo molecular de los pacientes con PBNEC&#44; el valor medio de SUVm&#225;x del subtipo luminal A fue inferior respecto al subtipo luminal B&#44; aunque no se apreciaron diferencias estad&#237;sticamente significativas entre ambos subtipos &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;1&#41;&#46; Adem&#225;s&#44; tampoco hubo diferencias significativas entre los grupos con CDI y PBNEC en relaci&#243;n con los subtipos luminal A y B &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;259 y <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;488&#44; respectivamente&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discusi&#243;n</span><p id="par0125" class="elsevierStylePara elsevierViewall">Los tumores de mama de tipo apocrino y los PBNEC son neoplasias infrecuentes y en la literatura se ha publicado un n&#250;mero limitado de art&#237;culos&#44; siendo la mayor&#237;a de ellos casos cl&#237;nicos o series cortas<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">3&#44;11</span></a>&#46; Kitajima et al&#46; describieron una incidencia de ABC del 0&#44;64&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; en 306 pacientes<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">12</span></a>&#46; Dicha incidencia ha sido similar en un estudio realizado con 89 casos por Miyake et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">13</span></a>&#46; Por otra parte&#44; la Universidad de Helsinki describi&#243; una incidencia del 0&#44;1&#37; de PBNEC en 1367 casos<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">2</span></a>&#46; Sin embargo&#44; en comparaci&#243;n con los art&#237;culos publicados&#44; en nuestro estudio la incidencia de pacientes con ABC y PBNEC es significativamente superior&#46; La incidencia fue de 4&#44;1&#37; para ABC y del 2&#44;4&#37; para PBNEC&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">El c&#225;ncer de mama de tipo apocrino debe diferenciarse del tipo CDI porque puede ser resistente a los tratamientos hormonales cl&#225;sicos debido a su diferente perfil de los receptores hormonales y a su comportamiento cl&#237;nico agresivo<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a>&#46; Sin embargo&#44; las similitudes existentes en las caracter&#237;sticas cl&#237;nicas y pron&#243;sticas del ABC y el CDI pueden ofrecer problemas diagn&#243;sticos<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">15</span></a>&#46; En nuestro estudio&#44; la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG en el tumor primario de pacientes con ABC o CDI fue similar&#46; Es bien conocido que la expresi&#243;n de ER y PR en el carcinoma de mama se asocia a un buen pron&#243;stico&#44; mientras que expresiones negativas de ER y PR y positivas de HER2 se asocian a un mal pron&#243;stico<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a>&#46; El perfil hormonal caracter&#237;stico del subtipo ABC &#40;ER&#8722;&#44; PR&#8722;&#44; y AR&#43;&#41; juega un papel principal en su diferenciaci&#243;n del CDI<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">2</span></a>&#46; En la literatura&#44; en el ABC se ha descrito una positividad ER del 3&#44;8-60&#37;&#44; del 4&#44;8-40&#37; para el PR&#44; y del 50&#37; para el HER2<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">17</span></a>&#46; Zhang et al&#46; compararon las caracter&#237;sticas cl&#237;nico-patol&#243;gicas de 260&#46;596 casos formados por 840 pacientes con ABC &#40;0&#44;32&#37;&#41; y 259&#46;756 con CDI &#40;99&#44;68&#37;&#41;&#46; Los investigadores proporcionaron los datos de estos pacientes procedentes de la base de datos Surveillance Epidemiology and End Result &#40;SEER&#44; Vigilancia Epidemiol&#243;gica y Resultados Definitivos&#41; del 2017&#46; Se describi&#243; que el 29&#44;9&#37; de las lesiones ABC y el 77&#44;2&#37; de los CDI se identificaban como ER positivos&#59; el 23&#44;2&#37; de las lesiones ABC y el 67&#44;1&#37; de los CDI se identificaban como PR positivos&#46; En base a la expresi&#243;n de ER y PR&#44; hubo diferencias estad&#237;sticamente significativas entre los grupos ABC y CDI &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">18</span></a>&#46; En consonancia con estos resultados&#44; los &#237;ndices de positividad de receptores ER y PR observados en nuestro estudio fueron estad&#237;sticamente inferiores en el grupo con ABC respecto al de CDI&#46; Sin embargo&#44; en nuestros resultados el estatus del receptor HER2 fue significativamente mayor en el grupo con ABC en comparaci&#243;n con el de CDI&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">El PBNEC aparece con mayor frecuencia en mujeres mayores&#46; Yang et al&#46; describieron una edad media de 59&#44;2 a&#241;os en las pacientes con PBNEC<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">3</span></a>&#46; De forma parecida&#44; en nuestro estudio la edad media de los pacientes con PBNEC fue de 67&#44;9 a&#241;os&#44; que fue superior a la edad media de los pacientes con ABC y CDI &#40;55&#44;5 y 54&#44;0 a&#241;os&#44; respectivamente&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">En algunos estudios se han destacado los inconvenientes que suponen los PBNEC mal diferenciados para la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">19</span></a>&#46; La sensibilidad de esta t&#233;cnica de imagen depende del tama&#241;o tumoral&#44; de su actividad metab&#243;lica&#44; del tejido circundante y de los niveles de glucemia del paciente&#46; Pueden aparecer resultados falsos negativos en las lesiones de peque&#241;o tama&#241;o&#44; o en aquellas con escasa actividad metab&#243;lica<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">20</span></a>&#46; Kamaleshwaran et al&#46; detectaron en la PET&#47;TC de cuerpo entero una captaci&#243;n intensa de <span class="elsevierStyleSup">18</span>F-FDG en el cuadrante interno de la mama izquierda y mostraron una met&#225;stasis en D4 en una paciente de 45 a&#241;os&#44; y los investigadores remarcaron que la PET&#47;TC con<span class="elsevierStyleSup">18</span>F-FDG resultaba beneficiosa para detectar tanto el NEC primario como las met&#225;stasis &#243;seas<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">21</span></a>&#46; En nuestro estudio&#44; aunque la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG en los pacientes con PBNEC fue menor en comparaci&#243;n con los pacientes con ABC y CDI&#44; no hubo diferencias significativas entre los diferentes grupos&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">En numerosos estudios se ha documentado que la afectaci&#243;n ganglionar axilar en el c&#225;ncer de mama es el factor pron&#243;stico m&#225;s importante que condiciona su supervivencia<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">22</span></a>&#46; Aunque en el ABC se ha descrito una prevalencia de invasi&#243;n axilar de entre 1&#37; y 4&#37;&#44; Dreyer et al&#46; describieron afectaci&#243;n ganglionar axilar en 6 de 14 pacientes con ABC triple negativo<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">17&#44;23</span></a>&#46; En otro estudio Olewniczak et al&#46; detectaron invasi&#243;n axilar en 128 &#40;50&#44;9&#37;&#41; de 251 pacientes con CDI<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">24</span></a>&#46; En nuestro estudio&#44; en el 91&#44;7&#37; de los pacientes con ABC se observ&#243; invasi&#243;n ganglionar axilar&#44; y esta prevalencia fue significativamente superior que en los pacientes con CDI y PBNEC seg&#250;n la PET&#47;TC &#40;68&#44;2&#37; y 71&#44;4&#37;&#44; respectivamente&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">En un metaan&#225;lisis realizado sobre 58 art&#237;culos y 108 pacientes diagnosticados con PBNEC&#44; el di&#225;metro tumoral medio fue de 3&#44;7 cm&#46; La incidencia de afectaci&#243;n ganglionar axilar fue del 51&#37;&#44; y de met&#225;stasis a distancia fue del 9&#37;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">25</span></a>&#46; Adem&#225;s&#44; Roininen et al&#46;&#44; describieron en su estudio un tama&#241;o medio del tumor primario de 2&#44;2 cm&#44; invasi&#243;n axilar en el 39&#44;6&#37; y met&#225;stasis a distancia en el 9&#44;3&#37;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">2</span></a>&#46; En nuestro estudio&#44; el di&#225;metro medio del tumor primario fue de 3 cm&#44; hubo invasi&#243;n ganglionar axilar y met&#225;stasis a distancia en el 28&#44;6&#37; y 21&#44;4&#37; de los casos&#44; respectivamente&#46; A diferencia de lo expuesto en la literatura&#44; en nuestro grupo con PBNEC se observ&#243; una elevada incidencia de met&#225;stasis a distancia&#44; aunque se detect&#243; una menor incidencia de afectaci&#243;n axilar&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">En los datos publicados&#44; se destaca el elevado &#237;ndice de captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG en pacientes con c&#225;ncer de mama de subtipo TN<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">22</span></a>&#46; En un estudio realizado por Keam et al&#46;&#44; con 78 casos&#44; se document&#243; un SUVm&#225;x significativamente aumentado en el grupo con TN &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;008&#41;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">26</span></a>&#46; El subtipo TN es un grupo heterog&#233;neo desde el punto de vista morfol&#243;gico y de respuesta terap&#233;utica&#46; Los investigadores han subrayado el comportamiento cl&#237;nico agresivo y el mal pron&#243;stico del subtipo TN del CDI&#44; pero la rareza en la prevalencia de ABC con subtipo TN limita considerablemente el conocimiento disponible en la literatura<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a>&#46; Choi et al&#46;&#44; detectaron que el 9&#44;8&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41; de los122 pacientes con el subtipo TN ten&#237;an el subtipo ABC<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">27</span></a>&#46; Tsutsumi ha detectado el subtipo TN en el 48&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#47;44&#41; de ABC de un total de 429 casos&#46; En este mismo estudio&#44; se describi&#243; un 7&#44;07&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#47;325&#41; del subtipo TN dentro del subtipo CDI<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">28</span></a>&#46; Sin embargo&#44; Guo et al&#46; detectaron un 48&#44;9&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&#47;90&#41; de casos HER2 negativos en ABC con subtipos ER y PR negativos<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a>&#46; En nuestro estudio&#44; los &#237;ndices del subtipo TN y HER2 en el grupo con ABC fueron del 25&#37; y el 16&#44;7&#37;&#44; y en el grupo con CDI estos &#237;ndices fueron del 10&#44;8&#37; y el 6&#44;9&#37;&#44; respectivamente&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">En conclusi&#243;n</span>&#44; no existen estudios que hayan evaluado las caracter&#237;sticas cl&#237;nicas de los subtipos de ABC mediante la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG&#44; y en nuestro estudio se ha comparado por primera vez el SUVm&#225;x del subtipo ABC TN con el de los pacientes ABC no TN y con CDI TN&#46; La m&#225;xima captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG se detect&#243; en los casos con CDI subtipo TN&#44; y en los ABC con subtipo HER2&#46; Un an&#225;lisis m&#225;s profundo de la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG en los subtipos TN y HER2 de pacientes con ABC y CDI puede contribuir a un mayor conocimiento sobre el comportamiento de estos tumores y al tratamiento de los pacientes con ABC&#44; especialmente del subtipo TN&#46; Por otra parte&#44; este estudio ha analizado con detalle por primera vez las caracter&#237;sticas metab&#243;licas de los PBNEC mediante la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG&#46; Aunque la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG fue superior en el PBNEC con subtipo luminal B respecto al luminal A&#44; esta diferencia no fue estad&#237;sticamente significativa&#46; Aunque la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG fuera menor en el grupo PBNEC en relaci&#243;n con el resto de grupos&#44; en nuestro estudio se observ&#243; que la PET&#47;TC fue suficiente para el prop&#243;sito de la estadificaci&#243;n inicial&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicto de intereses</span><p id="par0165" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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        8 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Conflicto de intereses"
        ]
        9 => array:1 [
          "titulo" => "Bibliograf&#237;a"
        ]
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    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-09-03"
    "fechaAceptado" => "2018-11-23"
    "PalabrasClave" => array:2 [
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1272442"
          "palabras" => array:3 [
            0 => "Carcinoma apocrino de mama"
            1 => "Carcinoma neuroendocrino de mama primario"
            2 => "<span class="elsevierStyleSup">18</span>F-FDG PET&#47;TC"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1272443"
          "palabras" => array:3 [
            0 => "Apocrine breast carcinoma"
            1 => "Primary breast neuroendocrine carcinoma"
            2 => "<span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">El objetivo fue evaluar el impacto diagn&#243;stico y la estadificaci&#243;n mediante PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG en carcinomas apocrinos &#40;ABC&#41; y carcinomas neuroendocrinos &#40;PBNEC&#41; y detectar posibles alteraciones en la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG seg&#250;n el subtipo histol&#243;gico de estos tumores&#46; Adem&#225;s&#44; nuestro objetivo fue comparar los hallazgos de la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG entre ABC&#44; PBNEC y el carcinoma ductal invasivo de mama&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron restrospectivamente un total de 570 pacientes y 585 lesiones mamarias&#46; Despu&#233;s de clasificar a los pacientes en subtipos moleculares de acuerdo con el an&#225;lisis histopatol&#243;gico&#44; se realizaron im&#225;genes de PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG y se compararon los hallazgos del an&#225;lisis visual y SUVm&#225;x de los tumores primarios entre los distintos grupos&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">El carcinoma ductal invasivo fue el carcinoma de mayor prevalencia&#44; con una tasa de detecci&#243;n del 77&#44;7&#37; &#40;n &#61; 446&#41; en nuestro estudio&#46; Sin embargo&#44; se diagnosticaron 4&#44;1&#37; &#40;n &#61; 24&#41; ABC y 2&#44;4&#37; &#40;n &#61; 14&#41; PBNEC&#46; El SUVm&#225;x medio m&#225;s alto se registr&#243; en el subtipo HER2 del ABC y se encontr&#243; una diferencia estad&#237;sticamente significativa entre la ratio de captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG de los subtipos HER2 y TN comparados con el tipo luminal B del ABC &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;038&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#44;019&#44; respectivamente&#41;&#46; Aunque la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG en el subtipo luminal B de PBNEC fue mayor que el subtipo luminal A&#44; la diferencia no fue estad&#237;sticamente significativa&#46; Adem&#225;s&#44; la tasa de met&#225;stasis axilar fue significativamente mayor en el grupo ABC que en los otros grupos &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;015&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Los subtipos histopatol&#243;gicos del grupo ABC mostraron diferentes grados de captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG con respecto a los subtipos del grupo carcinoma ductal invasivo&#44; a pesar de que en general la captaci&#243;n de <span class="elsevierStyleSup">18</span>F-FDG fue menor en el grupo de PBNEC&#46; La PET&#47;TC demostr&#243; ser adecuada en la detecci&#243;n de tumores primarios y met&#225;stasis en nuestro estudio&#46; Los resultados de la exploraci&#243;n PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG pueden contribuir a la estadificaci&#243;n inicial y al manejo de pacientes con ABC y PBNEC&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objetivo"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "M&#233;todos"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusiones"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">We aimed to evaluate the diagnostic impact of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in staging apocrine breast carcinoma &#40;ABC&#41; and primary breast neuroendocrine carcinoma &#40;PBNEC&#41; and to demonstrate possible alterations of the <span class="elsevierStyleSup">18</span>F-FDG uptake in these histopathologic subtypes&#46; In addition&#44; we aimed to compare <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT findings between ABC&#44; PBNEC and invasive ductal carcinoma&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A total of 570 patients and 585 breast lesions were retrospectively included in this study&#46; After patients were classified into molecular subtypes according to the histopathological analysis&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT imaging was performed&#46; The SUVmax findings of primary tumors obtained from <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT were compared between the groups&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Invasive ductal carcinoma was the most prevalent breast carcinoma &#40;77&#46;7&#37;&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>446&#41;&#44; with a low proportion of ABC &#40;4&#46;1&#37;&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#41; and PBNEC &#40;2&#46;4&#37;&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; diagnosed&#46; The highest mean SUVmax was calculated in HER2 subtype of ABC and <span class="elsevierStyleSup">18</span>F-FDG uptake ratio in HER2 and TN subtypes were found statistically higher than Luminal B type of ABC &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;038 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;019&#44; respectively&#41;&#46; Although <span class="elsevierStyleSup">18</span>F-FDG uptake in Luminal B subtype of PBNEC was higher than Luminal A subtype&#44; difference was not statistically significant&#46; Additionally&#44; the axillary metastasis rate was significantly higher in the ABC group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;015&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The histopathological ABC subtype group showed different <span class="elsevierStyleSup">18</span>F-FDG uptake than the invasive ductal carcinoma group&#46; Even if <span class="elsevierStyleSup">18</span>F-FDG uptake was lower in the PBNEC group than in the other groups&#44; PET&#47;CT showed and adequate performance in detecting primary tumors and metastases&#46; The <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT scan results may contribute to the initial staging and management of ABC and PBNEC patients&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0025"
            "titulo" => "Objective"
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            "identificador" => "abst0030"
            "titulo" => "Material and methods"
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            "identificador" => "abst0035"
            "titulo" => "Results"
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            "identificador" => "abst0040"
            "titulo" => "Conclusions"
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Cortes de PET&#44; TC&#44; fusi&#243;n &#40;F&#41;&#44; e imagen de proyecci&#243;n de intensidad m&#225;xima &#40;MIP&#41; de una paciente mujer de 43 a&#241;os de edad con carcinoma apocrino de tipo luminal B en el cuadrante inferior externo de la mama derecha&#46; El tama&#241;o del tumor primario fue de 2&#44;5 cm&#44; SUVm&#225;x 10&#44;6 &#40;flechas negra y blanca&#41;&#46; El di&#225;metro del eje corto de la adenopat&#237;a metast&#225;sica fue de 0&#44;8 cm&#44; SUVm&#225;x 9&#44;2 &#40;flechas punteadas negra y blanca&#41;&#46;</p>"
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          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Cortes de PET&#44; TC&#44; fusi&#243;n &#40;F&#41;&#44; e imagen MIP de una paciente mujer de 81 a&#241;os con carcinoma apocrino multifocal triple negativo en el cuadrante superior externo de la mama izquierda&#46; El tama&#241;o del tumor primario mayor fue de 1&#44;8 cm&#44; SUVm&#225;x 18&#44;6 &#40;flechas negras y blancas&#41;&#46; El di&#225;metro del eje corto de la adenopat&#237;a metast&#225;sica fue de 2&#44;1 cm&#44; SUVm&#225;x 21&#44;0 &#40;flechas punteadas negras y blancas&#41;&#46; Los cortes de la PET&#47;TC tambi&#233;n muestran adenopat&#237;as metast&#225;sicas en la cadena mamaria interna izquierda &#40;punta de flecha&#41; y en la regi&#243;n axilar derecha &#40;flechas punteadas&#41;&#46;</p>"
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        "etiqueta" => "Figura 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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            "imagen" => "gr3.jpeg"
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          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Cortes de PET&#44; TC&#44; fusi&#243;n &#40;F&#41;&#44; e imagen MIP de una paciente mujer de 85 a&#241;os con tumor neuroendocrino primario en uni&#243;n de cuadrantes inferiores de la mama derecha&#46; El tama&#241;o del tumor primario mayor fue de 3 cm&#44; SUVm&#225;x 9&#44;7 &#40;flechas negras y blancas&#41;&#46; El di&#225;metro del eje corto de la adenopat&#237;a metast&#225;sica fue de 1&#44;1 cm&#44; SUVm&#225;x 12&#44;5 &#40;flechas negras y blancas punteadas&#41;&#46; La paciente presentaba una adenopat&#237;a metast&#225;sica en la regi&#243;n hiliar derecha &#40;flechas rojas delgadas&#41;&#44; as&#237; como una met&#225;stasis a distancia en el cuadrante superior externo de mama izquierda &#40;1 cm&#44; SUVm&#225;x 5&#44;1&#41; &#40;flechas rojas punteadas&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">HER2&#58; tipo HER2&#59; LB&#58; tipo luminal B&#59; SUVm&#225;x&#58; valor de captaci&#243;n m&#225;ximo estandarizado&#59; TN&#58; tipo triple negativo&#46;</p>"
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                  \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">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Edad&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Histopatolog&#237;a&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Met&#225;stasis linf&#225;tica a distancia &#40;PET&#47;TC&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">45&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">LB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \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">23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HER2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8722;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">HER2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">20&#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">15&#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">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#211;seo&nbsp;\t\t\t\t\t\t\n
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          "es" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Hallazgos histopatol&#243;gicos y de la PET&#47;TC en pacientes con carcinoma de mama de tipo apocrino</p>"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">AC&#58; carcinoma apocrino&#59; CDI&#58; carcinoma ductal invasivo&#59; n&#58; n&#250;mero de pacientes&#59; PBNEC&#58; carcinoma neuroendocrino primario de mama&#59; SUVm&#225;x&#58; valor de captaci&#243;n m&#225;ximo estandarizado&#46;</p>"
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            0 => array:2 [
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                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">SUVm&#225;x &#40;media<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DE&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Valor de la <span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Valor de la <span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CDI vs&#46; AC&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">CDI vs&#46; PBNEC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">CDI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#44;7 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>446&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \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
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                  \t\t\t\t">AC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;33&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \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
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">10&#44;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;4 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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          "es" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Comparaci&#243;n del SUVm&#225;x entre los grupos con CDI&#44; ABC y PBNEC</p>"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">ER&#58; receptor estrog&#233;nico&#59; HER2&#58; tipo HER2&#59; PR&#58; receptor progester&#243;nico&#59; SUVm&#225;x&#58; valor de captaci&#243;n m&#225;ximo estandarizado&#46;</p>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Variable cl&#237;nica&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">CDI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">AC&nbsp;\t\t\t\t\t\t\n
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                  \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">PBNEC&nbsp;\t\t\t\t\t\t\n
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                  \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">Valor de la <span class="elsevierStyleItalic">p</span>&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">Valor de la <span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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">CDI vs&#46; AC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CDI vs&#46; PBNEC&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" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8804; 50 a&#241;os&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">197 &#40;44&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;14&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;809&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;026</span><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62; 50 a&#241;os&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tama&#241;o tumoral</span></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"><span class="elsevierStyleHsp" style=""></span>&#60; 2<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">101 &#40;22&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#40;4&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;21&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;032</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;914&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"><span class="elsevierStyleHsp" style=""></span>&#8805; 2<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">345 &#40;77&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">23 &#40;95&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">11 &#40;88&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">ER</span></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"><span class="elsevierStyleHsp" style=""></span>Negativo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90 &#40;20&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;41&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;012</span><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\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&#44;06&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"><span class="elsevierStyleHsp" style=""></span>Positivo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">356 &#40;79&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">14 &#40;58&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">PR</span></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"><span class="elsevierStyleHsp" style=""></span>Negativo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">107 &#40;24&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\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 &#40;45&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\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 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;016</span><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;036</span><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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"><span class="elsevierStyleHsp" style=""></span>Positivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">339 &#40;76&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">13 &#40;54&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\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 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \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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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>Negativo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">336 &#40;75&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\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 &#40;54&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;85&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;021</span><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#44;373&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"><span class="elsevierStyleHsp" style=""></span>Positivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">110 &#40;24&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\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 &#40;45&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;14&#44;3&#41;&nbsp;\t\t\t\t\t\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
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Pulm&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab2380358.png"
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        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Hallazgos histopatol&#243;gicos y de la PET&#47;TC de pacientes con carcinoma neuroendocrino primario de mama</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Bibliograf&#237;a"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:28 [
            0 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Apocrine carcinoma of the breast&#58; a brief update on the molecular features and targetable biomarkers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46; Vranic"
                            1 => "R&#46; Feldman"
                            2 => "Z&#46; Gatalica"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.17305/bjbms.2016.1811"
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