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Carcinoma hepatoide del páncreas, presentación de caso

 

Hepatoid carcinoma of the pancreas, case presentation

 

 


1

Yohan Amador García                                          http://orcid.org/0000-0002-5938-1931

Hospital Universitario Comandan= te Faustino Pérez Hernández, Matanzas, Cuba yohanamador@gmail.com  

 

2

Evelyn Rangel Lorenzo                                        = http://orcid.org/0000-= 0003-4904-8323

Hospital Universitario Comandan= te Faustino Pérez Hernández, Matanzas, Cuba evelinr.mtz@infomed.sld.cu      

3

Luís Enrique Curbelo Gutiérrez<= span style=3D'mso-spacerun:yes'>                           http://orcid= .org/0000-0002-7761-9595

Hospital Universitario Comandan= te Faustino Pérez Hernández, Matanzas, Cuba

luis.curbelo@icloud.com

 

 

 

 

 

 

Artículo de Investigación Científica y Tecnológica

Enviado: 09/11/2021=

Revisado: 24/11/2021

Aceptado: 05/12/2021

Publicado:05/01/2022

DOI: https://doi.o= rg/10.33262/anatomiadigital.v5i1.1969    

 

 =

 

 

Cítese:

 

 

Amador García, Y., Rangel Lore= nzo, E., & Curbelo Gutiérrez, L. E. (2022). Carcinoma hepatoide del páncre= as, presentación de caso. Anatomía Digital, 5(1), 49-60. https://doi.org/10.33262/anatomiadigital.v= 5i1.1969

 

 

 

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Palabras claves: car= cinoma hepatoide, páncreas, extrahepática.

 

Resumen

Introducción: El carcinoma hep= atoide del páncreas (CHP) es extremadamente raro. Es una neoplasia extrahepática primaria que se asemeja al carcinoma hepatocelular en términos de morfolo= gía e inmunohistoquímica. En el páncreas, el carcinoma h= epatoide podría ser de forma pura o mezclarse con otros componentes histológicos c= omo el tumor neuroendocrino o el adenocarcinoma ductal pancreático. Objeti= vo: describir las características clínico- epidemiológicas del carcinoma hepatoide del páncreas. Metodología: hicimos una revisión de la bibliogra= fía sobre el tema y presentamos los resultados. Resultados: La inducc= ión de hepatocitos en el páncreas se ha realizado en varios modelos animales.= Se presenta un caso atendido en nuestra institución est= adiado T3 N0 M1, Etapa clínica IV, que recibió tratamiento = oncoespecífico con quimioterapia, esquema GEMOX (12 ciclos), con buena respuesta tumoral, que a los 6 meses se revalúa con TAC que evidencia ascitis de moderada cuantía, se decide tratamiento de segunda línea con esquema Gramont (6 ciclos) según respuesta.  Conc= lusiones: se trata de una entidad rara cuyo manejo se basa fundamentalmente en quimioterapia.

 

 

Keywords: hep= atoid carcinoma, pancreas, extrahepatic.<= /o:p>

 

Abstract

Introduction: Hepatoid carcinoma of the pancreas (CHP) is extremely rare. It is a primary extrahepatic neoplasm that resembles hepatocellular carcinoma in terms of morphology and immunohistochemistry.= In the pancreas, hepatoid carcinoma could be pure or mixed with other histological components such as neuroendocrine tumor or pancreatic ductal adenocarcinoma. Objective: to describe the clinical- epidemiologic= al characteristics of hepatoid carcinoma of the pancreas. Methodology: we made a review of the bibliography on the subject and presented the result= s. Results: Induction of hepatocytes in the pancreas has been performed in several animal models. A case is presented at our stately institution T3 N0 M1, Clinical Stage IV, which received oncospecific treatment with chemotherapy, GEMOX scheme (12 cycles), with good tumor response, which at 6 months is revalued   with CT that shows moderate ascites, second-line treatment with Gramont scheme (6 cycles) is decided according to response. Conclusions: it is a rare entity whose management is bas= ed on chemotherapy.

 

Introducción.

El carcinoma hepatoide del páncreas (CHP) es extremadamente raro. = (1) Es una neoplasia extrahepática primaria que se asemeja al carcinoma hepatocelular en términos de morfología e inmunohistoquímica y a menudo pro= duce alfafetoproteína (AFP). (2) La terminología ''hepatoide'' se refiere a un tumor ectópico ''similar al hígado'' que tiene característi= cas morfológicas similares a las del carcinoma hepatocelular (HCC). (3) El primer caso notificado fue por Ishikura et al. = en 1985 y descrito en el estómago, (4) mientras que Hruban et al. informaron del primer caso en páncreas en 1987. (5) Posteriormente, la documentación de esta característica histopatológica úni= ca se ha hecho en otros sitios extrahepáticos incluyendo el esófago, papila de= Vater, colon, pulmón, vesícula biliar, glándula suprarrenal, rińón, vejiga urinaria, ovario, útero, vagina, testículo e inc= luso con estroma linfoide. (6) La ubicación más común fue el estómago, seguido de ovario. (7) Sin embargo, el carcinoma hepatoide del páncreas es claramente poco frecuente, y todavía se desconoce la verdad= era incidencia. (8)

En el páncreas, el carcinoma hepatoide podría ser de forma pura o mezclarse con otros componentes histológicos como el tumor neuroendocrino o= el adenocarcinoma ductal pancreático. En cuanto a las características hepatocelulares puras, se han designado de manera diversa como carcinoma hepatoide, adenocarcinoma hepato= ide, carcinoma hepatocelular ectópico, variante hepatoide del cáncer de páncreas, carcinoma hepatocelular primario del páncreas, o tu= mor pancreático con diferenciación hepatoide. Microscópicamente se compone de láminas poligonales de células con abundante citoplasma y núcleos ubicados en el centro. Ocasionalmente, se visualizan l= os canalículos biliares y la formación de bilis real. Las células tumorales se organizan en patrones glandulares, medulares o trabeculares. (9)

Existe controversia s= obre la etiología y la patogénesis del CHP. La "transd= iferenciación" de páncreas a hígado se ha evaluado en modelos animales desde 1991, y muchos autores se han centrado en el mecanismo de diferenciación de hepatocitos en= el páncreas tras la reposición luego del agotamiento del cobre. Otro mecanismo patógeno se basa en el origen común del tejido pancreático y hepático de las células endodérmicas posteriores. Las células multipotentes pancreáticas normalmente suprimen los genes de diferenciación hepat= ocítica, que podrían activarse durante la génesis tumoral en condiciones ambientales particulares. En este sentido, el CHP pueden ser visto como una posibilidad= en el amplio espectro de la diferenciación plurifenotípic= a pancreática. (10)

La inducción de hepatocitos en el páncreas se ha realizado en varios modelos animales. Rao = et al. indujeron hepatocitos del páncreas en ratas manteniendo una dieta deficiente de cobre con su reposición posterior. Por lo tanto, puede existir una célula progenitora común en el páncreas de la que podrían devenir hepatocitos y células pancreáticas. (11) Sc= arpelli et al.  sugirió que los hepatocitos= en el páncreas de hámster se derivaban de células acinares, ya que la transformac= ión había sido aparentemente desencadenada por la nitrosamina (oxopropyl) administrada en el pico de la regeneración pancreática cuando la mayoría de= las células acinares estaban en fase S. (12) Pa= ner et al.  revisó 5 casos de carcinoma= hepatoide del páncreas. Tres mostraron carcinoma de c= élulas ductales, 1 mostró carcinoma de células acinar y 1 glucagonoma maligno. Por= lo tanto, la diferenciación hepática podría surgir de cualquiera de las 3 célu= las pancreáticas principales (acinar, ductal y células de los islotes). (<= span style=3D'mso-no-proof:yes'>13,14)

Dado su rareza y experiencia limitada en informes de casos esporádicos en la literatura, las características clínicas y los comportamientos del carcinoma hepatoide del páncreas no se han aclarado hasta ahora= . Los propósitos de este artículo son presentar nuestra experiencia clínica sobre carcinoma hepatoide del páncreas a partir de un= caso tratado en nuestra institución. Por lo tanto, se intenta aclarar las características, presentaciones clínicas, manejos y resultados de supervive= ncia de este tumor raro.

Metodologia.<= /o:p>

Varias bases de datos= de PubMed y la Biblioteca Nacional de Medicina fueron buscadas para estudios en todo el mundo que fueron publicados en inglés y traducidos al espańol entre= los ańos 2015 y 2020. Después de examinar todos los resúmenes de las publicacio= nes identificadas por la búsqueda inicial, se incluyeron en el análisis estudio= s e informes de casos sobre pacientes con diagnóstico de carcinoma hepatoide del páncreas. La idoneidad de los estudios = se definió a los efectos de esta revisión como la notificación de las características clínicas o biológicas, el tratamiento o los resultados clín= icos de los pacientes con este diagnóstico.

Resultados.

Se trata de un pacien= te B/M de 69 ańos de edad con antecedentes de hipertensión arterial hace más m= enos 10 ańos con tratamiento estable y de gastritis crónica sin agudizaciones en seguimiento estable. Antecedentes Patológicos Familiares: Madre cardiopatía isquémica y neoplasia de colon. Padre fallecido de neoplasia de próstata.Historia de la en= fermedad actual: Hace aproximadamente 1ańo y medio comenzó a presentar dolor abdomin= al difuso, acompańado de palidez cutánea mucosa y pérdida de peso de más menos= 10 libras, asociado a decaimiento marcado y en una ocasión presentó heces feca= les oscuras con sangre, motivo por lo cual es ingresado en el servicio de cirug= ía del hospital Faustino Pérez para mejor estudio y tratamiento.

Examen Físico:

Mucosas: húmedas e hipocoloreadas.

Respiratorio: murmullo vesicular audible no estertores, frecuencia respiratoria 18.

Cardiovascular: ruidos cardíacos rítmicos de buen tono e intensidad, no soplos, pulsos periféricos presentes y sincrónicos frecuencia cardiaca 78, tensión arterial 120/80.

Abdomen: globuloso, suave, depresible, no doloroso, se palpa hepatomegalia de aproximadamente 2 centímetros por debajo del reborde costal derecho, ruidos hidroaéreos prese= ntes y normales.

Tejido celular subcut= áneo no infiltrado

Sistema nervioso cent= ral sin alteraciones

En dicho centro se le realizan estudios:

Analítica sanguínea:<= o:p>

Hematocrito: 0.32%        plaquetas:290 x109/L       Eritrosedimentación:40mmol/l<= /o:p>

Leucograma: 5.2 x109/= L

Segmentados: 56.4%  linfocitos: 31.2%   monocitos: 12.4%=

TGP: 56.6 mmol/L     TGO: 41.8 mmol/L    Glicemia: 6 mmol/L =

Ultrasonido: se reali= za ultrasonido de hígado en modo 2D con técnica doppler observándose múltiples imágenes nodulares hipoecogénic= as, algunas de ellas con patrón de circulación periférica e intralesional. (Figs. 1 y 2)

Endoscopia: gastritis eritematosa antral moderada, acalasia esofágica, lesión gástrica ulcerada en fundus.<= /span>

Colonoscopia: se visualiza la mucosa del fondo del ciego, la válvula ileocecal y el orificio apendicular donde se observa mucosa irregular eritematosa y congestiva; se = toma muestra para biopsia que es no concluyente.

Figura 1: Ultrasonido de Hígado                         <= b>Figura 2: Ultrasonido de Hígado Doppler

 

 

 

Fuente: Historia Clínica                                             Fuente: Historia Clínica

TAC de tórax y abdome= n: a cortes de 5mm observándose en abdomen hígado aumentado de tamańo ocupado en= su totalidad por lesiones nodulares múltiples de aspecto metastásico, con atro= fia de la cabeza pancreática, y cola aumentada de tamańo aproximadamente 4,5 cm= , de aspecto tumoral con comportamiento isodensoy pe= queńas adenopatías peripancreáticas. (Fig. 3)

Figura 3: TAC de abdomen

 

 

 

 

Fuente: Historia Clínica

Biopsia: tru-cut hepático: metástasis hepática de carcinoma hepatoide bien diferenciado de origen pancreático.

Se valoró posteriorme= nte en consulta central de vías digestivas en el Hospital Faustino Pérez y se diagnosticó carcinoma hepatoide de páncreas con metástasis hepática, en estadío T3 N0 M1, Etapa clínica IV, se decidió tratamiento oncoespecífico con quimioterapia, esquema GEMOX (12 ciclos), al cabo de dos meses de tratamien= to se evaluó respuesta tumoral con TAC que informó desaparición de la lesión pancreática y disminución del tamańo de las lesiones hepáticas. Continuó en seguimiento y a los 6 meses se revaluó con TAC que informó las mismas características descritas anteriormente, pero en esta ocasión con presencia= de ascitis de moderada cuantía, se decidió tratamiento de segunda línea con esquema Gramont (6 ciclos) según respuesta completando 3 ciclos de este esquema, luego de lo cual abandonó el tratamiento por trastornos psiquiátri= cos y 3 meses después falleció.

Discusión<= o:p>

En un estudio realiza= do por Kuo PC, et all.= se analizaron 23 casos de carcinoma hepatoide del páncreas. Este tumor se produjo con mayor frecuencia en hombres que en muje= res (69,6 frente a 30,4 %. (15) Los tamańos de los tumores oscilan e= ntre 0,5 y 11,0 cm con una mediana de 6,0 cm. El síntoma más común fue dolor epigástrico (36,4 %). Cuando el tumor se encuentra en la cabeza pancreática, náuseas/vómitos (62,5 %) son más frecuentes, seguidos de ictericia y dolor epigástrico (50,0 %). Para los que se encuentran en la cola pancreática, el 42,9 % de los pacientes no presentaron ningún síntoma. La alfafetoproteína (AFP) fue anormalmente elevada en el 60 % de los casos. Su histología podría ser pura o mixta con otros neoplasias malignas (= 40,9 %), más frecuentemente combinado con patrón neuroendocrino (22,7 %). La metástasis se produjo en el 36,4 % de los casos en el diagnóstico de este tumor, incluida la metástasis hepática en el 31,8 % y la metástasis a gangl= ios linfáticos en el 21,1 %. La tasa global de supervivencia a 1 ańo fue del 71= ,1 % y del 50,4 % a 5 ańos, con una mediana de 13,0 meses. Las metástasis hepáti= cas y de los ganglios linfáticos se asocian con un impacto negativo en el resul= tado de supervivencia.

En la literatura, se notificaron 10 casos de CHP "puro" y 11 de CHP asociados a otro componente. El componente mixto fue el siguiente: 4 casos con carcinoma neuroendocrino, 1 caso asociado con glucagonoma maligno, 1 con insulinoma maligno, 1 caso con acinar y 4 con adenocarcinoma ductal. Cuilliere et al. documentaron el único caso reportado de una neoplasia hepatocelular benigna que surgió en el páncreas, que era un adenoma sólido encapsulado en= el páncreas que mostraba exclusivamente diferenciación hepatocelular. El tumor= se consideró benigno debido a la ausencia de mitosis, atipia nuclear e invasión vascular. (16)

Petrelli, et all. informaron de 3 casos y llevaron a cabo la revis= ión de otros 31 casos en la literatura. Los 3 pacientes estudiados fueron varones = (83, 72 y 54 ańos, respectivamente). La AFP se elevó en 1 paciente (caso 3, 8338 ng/ml) y no se midió en los otros dos. El CHP en el paciente 1 (etapa patológica pT2N0M0) y el paciente 2 (pT3N0M0) mostró morfología pura del carcinoma hepatocelular (HCC), mientras que en el caso 3 era un CHP con ver= dadera diferenciación glandular (pT4N0M0). El diagnóstico se confirmó con tinción inmunohistoquímica. El paciente 1 no recibió tratamiento adicional después = de la resección y estaba vivo sin evidencia de enfermedad a los 107 meses. El paciente 2 murió de complicaciones postoperatorias, mientras que el pacient= e 3 recibió quimiorradiación posquirúrgica y murió = de enfermedad a los 29 meses. (17)

El diagnóstico diferencial histológico depende principalmente del grado de diferenciación = de los hepatoides y de la cantidad del componente = no hepatoide, si existe. Al diagnosticar el CHP primario= , es importante excluir el carcinoma hepatocelular metastásico y el carcinoma hepatocelular ectópico mediante un examen clínico y patológico. No se han establecido criterios estandarizados para el diagnóstico de CHP, pero se requiere similitud morfológica e inmunohistoquímica con el carcinoma hepatocelular. Las características morfológicas pueden sugerir diferenciaci= ón hepatocelular, y la producción de bilis es confirmatoria, pero por lo gener= al sólo se observa en tumores bien diferenciados.  La incidencia de carcinoma hepatocelular que se disemina al páncreas= es de sólo 2,7–5,6%, y la metástasis suele ser un hallazgo tardío; sin embargo= , se debe considerar. Se necesita un seguimiento a largo plazo para excluir la posibilidad de que el tumor pancreático represente una metástasis del hígado.  Carcinoma hepatoide del páncreas y carcinoma hepatocelular comparten numerosas características clínicas, como morfología, AFP sérica elevada y tinción positiva AFP en histología, CEA de patrón canalicular y α = 1 -antitripsina. Esto hace que el diagnóstico diferencia= l sea particularmente difícil con un tumor primario desconocido.  La diferenciación entre los dos se puede hacer esencialmente por inmunohistoquímica, con un perfil expresado de CK. = Si la producción de bilis no se puede identificar histológicamente, entonces el diagnóstico diferencial también incluiría otros tumores pancreáticos que ti= enen grandes células tumorales eosinofílicas, como neoplasias papilares intraductales, pancreatoblastoma y carcinoma de células acinares. (18)

El tratamiento asocia= do con la mejor supervivencia libre de enfermedad sigue siendo la resección quirúrgica radical. De los 22 casos notificados en la literatura, 10 (46%) tenía metástasis distantes al momento de presentación, 16 (87%) se sometier= on a cirugía y 9 (41%) murieron por la enfermedad.  La tasa media de supervivencia de los pacientes que murieron de enfermedad fue de 18 meses. (19)

El papel de la terapia adyuvante después de la resección de la cirugía aún no está claro y se basa= en pocas experiencias.  Aunque algunos autores han abogado por la quimioterapia adyuvante debido al potencial metastásico del tumor, otros no han indicado eventos discernibles. Se notif= icó un cierto grado de respuesta a la quimioterapia con supervivencia a largo p= lazo en enfermedades localmente no resecables, metastásicas o recurrentes.  Por lo tanto, el tratamiento agresivo p= arece justificado incluso en el caso de enfermedades localmente avanzadas, y la resección de metástasis también puede ser considerada. Debido a su rareza, = la historia natural y el pronóstico de la enfermedad no se pueden predecir con precisión.  El período más largo lo= grado sin ningún tratamiento adyuvante fue de 48 meses. El intervalo libre de enfermedad más largo después de la resección notificada en la literatura es= de 102 meses con quimioterapia adyuvante. Esto sugiere que la quimioterapia pu= ede tener un papel en la enfermedad recurrente, residual no resecable y metastá= sica, pero los datos son limitados. (20)

Con respecto a los agentes quimioterapéuticos, el fluoro- uracilo se puede utilizar para proporcionar cierto control de los síntomas, y la gemc= itabina ha demostrado ser útil como agente paliativo en pacientes con estadíos avanzado.  Los regímenes basados en doxorrubicina tienen la mayor eficacia, pero poco impacto en la supervivencia global. Del mismo modo, como los agentes quimioterapéuticos tienen una eficacia limitada contra los tumores del pánc= reas o del hígado, no existe ninguna terapia estándar para el tratamiento de tum= ores hepatoides. (21)

Hasta ahora, los datos limitados sugieren que alrededor del 50% de los pacientes adultos morirán de esta enfermedad dentro de los 3 ańos posteriores al diagnóstico inicial.  Debido a su rareza, el enfoque de manej= o está lejos de ser estandarizado.  Se sug= iere por lo tanto que la resección quirúrgica sea el tratamiento de elección sie= mpre que sea posible, y la resección completa del tumor parece ser la mejor opci= ón; sin embargo, el seguimiento a largo plazo está justificado ya que la recurrencia parece común.

Conclusiones.

ˇ&nb= sp;        El carcinoma hepatoide del páncreas (CHP) es una e= ntidad rara, más frecuente en hombres.

ˇ&nb= sp;        Los síntomas más comunes son náuseas/vómitos, seguidos de ictericia y dolor epigástrico.

ˇ      =    El pronóstico no es bueno y empeora cuando se diagnostica en etapas avanzadas = y su manejo se basa en el uso de quimioterapia.

ˇ      =     

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Yang C, Sun L, Lai JZ, Zhou L, Liu Z, Xi Y, et al. Primary Hepatoid Carcinoma of the Pancreas: A Clinicopathological Study of 3 Cases With Review of Additional 31 Cases in the Literature. = Int J Surg Pathol [Internet]. 1 de febrero de 2019 [citado 14 de diciembre de 2020];27(1):28-42. Disponible = en: https://pubmed.ncbi.nlm.nih.gov/29961402/

Marchegiani G, Gareer H, Parisi A, Capelli P, Bassi C, Salvi= a R. Pancreatic hepatoid carcinoma: A review of the literature [Internet]. Vol. 30, Digestive Surgery. S. Karger AG; 20= 14 [citado 14 de diciembre de 2020]. p. 425-33. Disponib= le en: https://pubmed.ncbi.nlm.nih.gov/24281319/

Kai K, Nakamura J, Ide T, Masuda M, Kitaha-ra K, Miyoshi A, et al: Hepatoid carcinoma of the pancreas penetrating into the gastric cav-ity: a case report and literature r= eview. Pathol Int 2012; 62: 485–490.

Shih NN, Tsung JS, Yang AH, Tsou MH, Cheng TY: A unique pancreatic t= umor with exclusive hepatocytic differentiation. Ann Clin Lab Sci 2006; 36: 216–= 221.

Petrelli, F, Ghilardi M, Colombo S, Stringhi<= /span> E, Barbara C, Cabiddu, M, et al: A rare case of metastatic pancreatic hepatoid carcinoma treated with sorafenib. J Gastroint= est Cancer 2011; 43: 97–102.

 

 

 

 

 

 

 

 

 

 

El artíc= ulo que se publica es de exclusiva responsabilidad de los autores y no necesariamente reflejan el pensamiento de la Revista Anatomía Digital.

 


El artículo queda en propiedad de la revista y, por tanto, su publicación parcial y/o total en otro medio tiene que ser autoriz= ado por el director de la Revista Anatomía Digital.

 

 


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ISSN: 2697-3391

Vol. 5 No. 1,  pp. 49 – 60 , enero – marzo 202= 2

 

 

 

                                      Medicina Molecular               Página 37 | 12

 

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