<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0001-6002</journal-id>
<journal-title><![CDATA[Acta Médica Costarricense]]></journal-title>
<abbrev-journal-title><![CDATA[Acta méd. costarric]]></abbrev-journal-title>
<issn>0001-6002</issn>
<publisher>
<publisher-name><![CDATA[Colegio de Médicos y Cirujanos de Costa Rica]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0001-60022003000300005</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Tumor neuroendocrino primario del hígado: histopatología e inmunohistoquímica de tres casos confirmados por autopsia]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Mita-Albán]]></surname>
<given-names><![CDATA[Luis Carlos]]></given-names>
</name>
<xref ref-type="aff" rid="A01"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Casco-Jarquín]]></surname>
<given-names><![CDATA[Ana María]]></given-names>
</name>
<xref ref-type="aff" rid="A02"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Álvarez-Ramírez]]></surname>
<given-names><![CDATA[Rodrigo]]></given-names>
</name>
<xref ref-type="aff" rid="A03"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ramírez-Corrales]]></surname>
<given-names><![CDATA[José Alberto]]></given-names>
</name>
</contrib>
</contrib-group>
<aff id="A01">
<institution><![CDATA[,CCSS Hospital Calderón Guardia Servicio de Patología]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<aff id="A02">
<institution><![CDATA[,Hospital William Allen  ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<aff id="A03">
<institution><![CDATA[,CCSS Hospital Calderón Guardia Servicio de Patología]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>09</month>
<year>2003</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>09</month>
<year>2003</year>
</pub-date>
<volume>45</volume>
<numero>3</numero>
<fpage>113</fpage>
<lpage>116</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.sa.cr/scielo.php?script=sci_arttext&amp;pid=S0001-60022003000300005&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.sa.cr/scielo.php?script=sci_abstract&amp;pid=S0001-60022003000300005&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.sa.cr/scielo.php?script=sci_pdf&amp;pid=S0001-60022003000300005&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[El tumor carcinoide primario hepático (TCPH) es poco común. Existen pocos carcinoides del hígado descritos como primarios y menos aún, confirmados con una autopsia completa. De marzo de 2000 a abril de 2001, encontramos 3 casos de TCPH en fase terminal, con un patrón histológico atípico. Cada caso fue positivo, para una variedad amplia de marcadores inmunohistoquímicos. Todos ellos fueron confirmados por una autopsia. Estas neoplasias pueden ser detectadas por métodos diagnósticos confiables, como la excreción urinaria de ácido 5 OH-indolacético.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[A primary hepatic carcinoid tumor (PHCT) is an uncommon finding. There are few reports of primary hepatic carcinoid tumors, and less confirmed with a complete autopsy. From March 2000 to April 2001 we found 3 cases of PHCT in terminal phase with an atypical histologic pattern . Each case was positive to a wide variety of inmuno histochemical markers . All of them were confirmed by an autopsy. These neoplasies can be detected by reliable diagnostic tools such as the urinary excretion of 5 OH indolacetic acids.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[Hígado]]></kwd>
<kwd lng="es"><![CDATA[carcinoide]]></kwd>
<kwd lng="es"><![CDATA[neuroendocrino]]></kwd>
<kwd lng="es"><![CDATA[inmunohistoquímica]]></kwd>
</kwd-group>
</article-meta>
</front><body><![CDATA[ <center><b><font face="Arial">Tumor neuroendocrino primario del h&iacute;gado.</font></b></center>        <center><b><font face="Arial">Histopatolog&iacute;a e inmunohistoqu&iacute;mica  de tres casos confirmados por autopsia</font></b></center>  &nbsp;     <br> &nbsp;      <center><font size="-1"><font face="Arial">&nbsp;Luis Carlos Mita-Alb&aacute;n&nbsp;<a name="R1"></a>  </font><sup><font face="Arial,Helvetica"><a href="#A1">1</a>  </font></sup><font face="Arial">, Ana Mar&iacute;a Casco-Jarqu&iacute;n </font><sup><font face="Arial,Helvetica"><a href="#A1">2</a>  </font></sup><font face="Arial">, Rodrigo &Aacute;lvarez-Ram&iacute;rez </font><sup><font face="Arial,Helvetica"><a href="#A1"> 3</a>  </font></sup><font face="Arial">, Jos&eacute; Alberto Ram&iacute;rez-Corrales </font><sup><font face="Arial,Helvetica"><a href="#A1">4</a>  </font></sup><font face="Arial">.</font></font></center>  &nbsp;       <p><b><font face="Arial"><font size="-1">Resumen    <br> &nbsp; &nbsp;    <br> </font></font></b></p>     <div align="Justify"><font face="Arial"><font size="-1">El tumor carcinoide primario hep&aacute;tico (TCPH) es poco com&uacute;n. Existen pocos carcinoides del h&iacute;gado descritos como primarios y menos a&uacute;n, confirmados con una autopsia completa. De marzo de 2000 a abril de 2001, encontramos 3 casos de TCPH en fase terminal, con un patr&oacute;n histol&oacute;gico at&iacute;pico. Cada caso fue positivo, para una variedad amplia de marcadores inmunohistoqu&iacute;micos. Todos ellos fueron confirmados por una autopsia. Estas neoplasias pueden ser detectadas por m&eacute;todos diagn&oacute;sticos confiables, como la excreci&oacute;n urinaria de &aacute;cido 5 OH-indolac&eacute;tico.</font></font>    <br> <font face="Arial"><font size="-1"><b>&nbsp; &nbsp;</b></font></font>    <br> <font face="Arial"><font size="-1"><b>Descriptores: </b>H&iacute;gado, carcinoide, neuroendocrino, inmunohistoqu&iacute;mica.</font></font>  </div>     ]]></body>
<body><![CDATA[<div align="Justify">     <p><font face="Arial"><font size="-1">Recibido: 22 de enero, 2003</font></font>      <br> <font face="Arial"><font size="-1">Aceptado: 01 dejulio, 2003</font></font>      <br> <font face="Arial"><font size="-1">&nbsp;</font></font>     <br> <font face="Arial"><font size="-1"><b>Abreviaturas: </b>TCPH, tumor carcinoide  primario hep&aacute;tico; CAP, campos de alto poder.</font></font><font face="Arial"><font size="-1"> Los tumores carcinoides son la segunda neoplasia m&aacute;s com&uacute;n del tracto gastrointestinal, despu&eacute;s del adenocarcinoma <sup><a href="#1"> 1</a>  </sup>. De modo general, se caracterizan por tasas de crecimiento relativamente  bajas, as&iacute; como por pocas diseminaciones locales y generales comparadas  con otras neoplasias malignas <sup><a href="#2">2</a>  </sup>. Se dispone de poca informaci&oacute;n en cuanto a palogenia, exceptuando los g&aacute;stricos, para los cuales ha sido sugerido el rol de la hipergastrinemia <sup><a href="#3">3</a>  </sup>. En la mayor&iacute;a de los casos, los s&iacute;ntomas se asocian  con enfermedad metast&aacute;sica, no obstante, esto no es la regla, Cooper  y Smith reportaron 4 pacientes con s&iacute;ndrome carcinoide sin enfermedad  metast&aacute;sica <sup><a href="#4">4</a>  </sup>. Todos ellos ten&iacute;an masas retroperitoneales o intraabdominales drenando a la circulaci&oacute;n sist&eacute;mica. El TCPH es una neoplasia poco com&uacute;n, Sano y Makuuchi en su revisi&oacute;n mundial de bibliograf&iacute;a, informaron solamente 30 casos conocidos hasta 1999 <sup><a href="#5">5</a>  </sup>. Existen pocos reportes confirmados por autopsia completa, ya que a&uacute;n en casos de fallecimiento las autopsias pueden ser denegadas por los familiares <sup><a href="#6">6</a>  </sup>.</font></font>    <br> <b><font face="Arial"><font size="-1">&nbsp;     <br> Descripci&oacute;n de casos</font></font></b><font face="Arial"><font size="-1">    <br> &nbsp; &nbsp;    <br> Caso 1 (A-00.147) Mujer de 43 a&ntilde;os. Present&oacute; astenia y dolores osteomusculares de 6 meses de evoluci&oacute;n. Ingres&oacute; por cuadro de sangrado digestivo alto. En el examen f&iacute;sico se document&oacute; hepatomegalia leve. El ultrasonido abdominal revel&oacute; m&uacute;ltiples lesiones hep&aacute;ticas bien definidas. Falleci&oacute; a los 20 d&iacute;as del ingreso, con diagn&oacute;stico cl&iacute;nico de "sepsis de origen pulmonar". En la autopsia se encontr&oacute; un proceso bronconeum&oacute;nico severo. El h&iacute;gado, no cirr&oacute;tico, pes&oacute; 1850 gm, ten&iacute;a masas m&uacute;ltiples, en el l&oacute;bulo derecho, la mayor de 10 cm. de di&aacute;metro y varias sat&eacute;lites de hasta 2 cm, de di&aacute;metro, blanquecinas, firmes, sin necrosis, con escasos focos de hemorragia.</font></font>   </p>     <p><font face="Arial"><font size="-1">Caso 2 (A.00.167) Mujer de 77 a&ntilde;os.  Present&oacute; dolor abdominal de 22 d&iacute;as de evoluci&oacute;n con  hiporexia y disnea. En el ex&aacute;men f&iacute;sico de ingreso se palp&oacute;  el h&iacute;gado a 3 cm bajo el reborde costal derecho. El ultrasonido abdominal revel&oacute; m&uacute;ltiples lesiones nodulares hep&aacute;ticas. La paciente present&oacute; una evoluci&oacute;n t&oacute;rpida y falleci&oacute; 18 d&iacute;as despu&eacute;s de su ingreso. Hallazgos: El h&iacute;gado pes&oacute; 4580 g y ten&iacute;a un patr&oacute;n nodular cirr&oacute;tico. En el l&oacute;bulo derecho hab&iacute;a un n&oacute;dulo firme amarillento, de 8 cm y m&uacute;ltiples sat&eacute;lites hasta de 1 cm de di&aacute;metro (el mayor de ellos). Todos presentaban zonas centrales necr&oacute;ticas. Hab&iacute;a infiltraci&oacute;n de la cabeza del p&aacute;ncreas y masas pulmonares peque&ntilde;as en l&oacute;bulo superior derecho, con bronconeumon&iacute;a concomitante.</font></font>  </p> </div>     ]]></body>
<body><![CDATA[<div align="Justify">     <p><font face="Arial"><font size="-1">Caso 3 (A 00.91). Hombre de 67 a&ntilde;os.  Etilista activo. Hipertenso y diab&eacute;tico tipo 11 en tratamiento. Ingres&oacute; al Servicio de Emergencias del H.C.G, por cuadro de hematemesis. Por endoscop&iacute;a se confirm&oacute; una v&aacute;rice subcardial sangrante. Se control&oacute; el cuadro inicial, pero resangr&oacute; a las 72 horas de la primera endoscop&iacute;a y falleci&oacute; a los 3 d&iacute;as del ingreso. Se encontr&oacute; un h&iacute;gado de 2030 gramos, cirr&oacute;tico, de color amarillento y consistencia aumentada; al corte se hallaron zonas reblandecidas y dos n&oacute;dulos de 9 cm de di&aacute;metro cada uno, en el l&oacute;bulo derecho, con infiltraci&oacute;n difusa del l&oacute;bulo izquierdo por m&uacute;ltiples sat&eacute;lites de hasta 4 cm de di&aacute;metro, con afecci&oacute;n de entre un 75 % y un 85 % del par&eacute;nquima hep&aacute;tico. Se document&oacute; sangrado digestivo por v&aacute;rice subcardial y neumon&iacute;a bibasal en hepatizaci&oacute;n roja. Histolog&iacute;a e inmuno histoqu&iacute;mica en <a href="#cuadro1"> Cuadro 1</a>  . En la <a href="#fig1">figura 1</a>  se muestran aspectos micro y maerosc&oacute;picos de las neoplasias.</font></font>      <br> &nbsp; </p>     <center><a name="cuadro1"></a> <img src="/img/fbpe/amc/v45n3/2197i01.JPG" height="433" width="508"> </center>        
<center>&nbsp;</center>        <center>&nbsp;<a name="fig1"></a> &nbsp;<img src="/img/fbpe/amc/v45n3/2197i2.JPG" height="519" width="553"> </center>        
<center><font face="Arial,Helvetica"><font size="-1">Figura 1. Aspectos macro  y microsc&oacute;pico (40 x) de las neoplasias hep&aacute;ticas. A: Masa dominante bien delimitada en l&oacute;bulo derecho. Nidos organoides y trab&eacute;culas, rodeadas de trama capilar tina, con c&eacute;lulas de citoplasma amplio y ocasionales figuras de mitosis B: Masas dominantes en l&oacute;bulo derecho y extensa infiltraci&oacute;n del par&eacute;nquima.&nbsp; C&eacute;lulas de citoplasma amplio con mayor pleomorfismo y alteraci&oacute;n de la relaci&oacute;n n&uacute;cleo citoplasma. C: Masas en l&oacute;bulo derecho e izquierdo con m&uacute;ltiples sat&eacute;lites. Las c&eacute;lulas tienen citoplasma escaso y n&uacute;cleos amplios.</font></font></center>        <center>&nbsp;</center>         <p><b><font face="Arial"><font size="-1">Discusi&oacute;n</font></font></b><font face="Arial"><font size="-1">    <br> &nbsp; &nbsp;    ]]></body>
<body><![CDATA[<br> Los casos aqu&iacute; reportados corresponden a neoplasias primarias del h&iacute;gado, confirmadas todas por autopsia completa. La sintomatolog&iacute;a presentada por estos pacientes es at&iacute;pica en cuanto al patr&oacute;n descrito para los tumores carcinoides, no obstante, esto es frecuente entre aquellos derivados del intestino anterior <sup><a href="#7">7</a>  </sup>.</font></font>  </p> </div>     <div align="Justify"><font face="Arial"><font size="-1">El aspecto macrosc&oacute;pico de estos tumores en el h&iacute;gado es variable, encontr&aacute;ndose casos descritos como primarios multinodales <sup><a href="#5">5</a>  ,<a href="#6">6</a>  ,<a href="#8">8</a>  ,<a href="#9">9</a>  </sup>,<b> </b>en tanto que otros autores describen casos de masa &uacute;nica <sup><a href="#10">10</a>  ,<a href="#11">11</a>  </sup>. El patr&oacute;n histol&oacute;gico encontrado en estos tumores corresponde al descrito por Moyana <sup><a href="#12">12</a>  </sup>para los carcinoides moderadamente diferenciados (casos 1 y 2) y pobremente diferenciados (caso 3). De acuerdo con Staren, nuestros dos primeros casos se clasificar&iacute;an como carcinomas neuroendocrinos, del tipo c&eacute;lula intermedia y de c&eacute;lula peque&ntilde;a, el &uacute;ltimo <sup><a href="#13"> 13</a>  </sup>. Las caracter&iacute;sticas histoqu&iacute;micas e inmunohistoqu&iacute;micas de estas neoplasias son tambi&eacute;n variables entre los informes de varios autores; el patr&oacute;n t&iacute;pico de positividad para Grimelius, Enolasa Neuroespec&iacute;fica, Cromogranina -A y de negatividad para Fontana Masson, en los derivados del intestino anterior, es reportado por la mayor&iacute;a de ellos <sup><a href="#5">5</a>  , <a href="#6">6</a>  , <a href="#8">8</a>  , <a href="#9">9</a>  , <a href="#10">10</a>  , <a href="#14">14</a>  </sup>. En nuestros casos, la tinci&oacute;n de Fontana Masson fue negativa en todos, lo cual es compatible con el patr&oacute;n de los derivados de intestino anterior; fueron positivos para Cromogranina -A y Enolasa (en menor grado en el caso 3). La tinci&oacute;n por gastrina revela una positividad m&aacute;s extensa en estos casos complicados con sangrado digestivo, uno de ellos con una &uacute;lcera antral, cuyo examen histol&oacute;gico en m&uacute;ltiples cortes no revel&oacute; malformaciones vasculares, como varios autores han reportado <sup><a href="#15">15</a>  </sup>. La autopsia descart&oacute; la posibilidad de met&aacute;stasis hacia el h&iacute;gado de un carcinoide g&aacute;strico, como se han reportado en algunos casos <sup><a href="#16">16</a>  </sup>. La escasa sobrevida intrahospitalaria de nuestros tres pacientes es atribuible a lo avanzado de su enfermedad al momento del diagn&oacute;stico. En conclusi&oacute;n: entre marzo de 2000 y abril del 2001 encontramos tres casos de TCPH en estadios terminales con un patr&oacute;n histol&oacute;gico no t&iacute;pico, el cual incluy&oacute; conteo de mitosis elevada. La asociaci&oacute;n  entre patrones arquitecturales histol&oacute;gicos y citol&oacute;gicos at&iacute;picos y conteos de mitosis elevados (m&aacute;s de dos mitosis en 10 CAP), fue descrita por Travis en sus series de carcinomas neuroendocrinos pulmonares <sup><a href="#17">17</a>  ,<a href="#18">18</a>  </sup>. No obstante, dado que desconocemos la evoluci&oacute;n cronol&oacute;gica real de estos pacientes no nos es posible correlacionar, en nuestros casos, el conteo de mitosis con la agresividad cl&iacute;nica. La sintomatolog&iacute;a  de los casos fue, a todas luces, at&iacute;pica <sup><a href="#19">19</a>  </sup>. La probabilidad de tumor neuroendocrino no fue planteada cl&iacute;nicamente  en ninguno de los tres. Tal baja sospecha diagn&oacute;stica es atribuible  a la poca frecuencia de estas neoplasias <sup><a href="#5">5</a>  , <a href="#6">6</a>  , <a href="#8">8-10</a>  , <a href="#14">14</a>  , <a href="#19">19</a>  </sup>.<b> </b>Las neoplasias pueden ser detectadas por m&eacute;todos diagn&oacute;sticos  r&aacute;pidos y contables, como la excreci&oacute;n en orina de 24 horas  de &aacute;cido 50H- Indol ac&eacute;tico, con tal prueba se obtiene entre  un 65 % y un 75 % de sensibilidad y un 90% y un 100% de especificidad <sup><a href="#20"> 20</a>  </sup>. Por &uacute;ltimo, la realizaci&oacute;n de autopsia, y no otros  procedimientos diagn&oacute;sticos premortem, permiti&oacute; identificar  los primarios hep&aacute;ticos, lo cual recalca una vez m&aacute;s la importancia  de la autopsia como generadora de conocimiento.</font></font><b><font face="Arial"><font size="-1"> &nbsp;</font></font></b>     <br> </div>     <p><b><font face="Arial"><font size="-1">&nbsp;     <br> Abstract</font></font></b>     <br> </p>     <div align="Justify"><font face="Arial"><font size="-1">A primary hepatic carcinoid tumor (PHCT) is an uncommon finding. There are few reports of primary hepatic carcinoid tumors, and less confirmed with a complete autopsy. From March 2000 to April 2001 we found 3 cases of PHCT in terminal phase with an atypical histologic pattern . Each case was positive to a wide variety of inmuno histochemical markers . All of them were confirmed by an autopsy. These neoplasies can be detected by reliable diagnostic tools such as the urinary excretion of 5 OH indolacetic acids.</font></font></div>     <div align="Justify">     <br> &nbsp;<b><font face="Arial"><font size="-1"> &nbsp;</font></font></b>    <br> <b><font face="Arial"><font size="-1">Referencias</font></font></b>     ]]></body>
<body><![CDATA[<br> &nbsp;     <!-- ref --><br> <a name="1"></a> <font face="Arial"><font size="-1">1. Angeletti S, Annibale B , Marignani M , Corleto VD . Natural history of intestinal carcinoids. Ital J Gastroenterol Hepatol 1999; 31 Suppl 2: S108-10.</font></font>  </div>    &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;[&#160;<a href="javascript:void(0);" onclick="javascript: window.open('/scielo.php?script=sci_nlinks&ref=013870&pid=S0001-6002200300030000500001&lng=','','width=640,height=500,resizable=yes,scrollbars=1,menubar=yes,');">Links</a>&#160;]<!-- end-ref --><div align="Justify">     <!-- ref --><p><a name="2"></a> <font face="Arial"><font size="-1">2. Shebani KO, Souba WW, Finkelstein DM, Ott MJ. Prognosis andsurvival in patients with gastrointestinal tract carcinoiod tumors. 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