Metastatic Lymphoepithelioma-like Hepatocellular Carcinoma: a Potential Diagnostic Pitfall and Demonstration of Pd-l1 Expression
Juan Putra
, Todd A. Anderson**, Sasan Roayaie***, Miho Maeda****, Swan N. Thung*
,
Corresponding author
* The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
** Department of Pathology, Lenox Hill Hospital, New York, NY, United States
*** Department of Surgery, Lenox Hill Hospital, New York, NY, United States
**** Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Read
1497
Timeswas read the article
407
Total PDF
1090
Total HTML
Share statistics
array:24 [ "pii" => "S1665268119303734" "issn" => "16652681" "doi" => "10.5604/16652681.1226936" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "70195" "copyright" => "Fundación Clínica Médica Sur, A.C." "copyrightAnyo" => "2017" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "mis" "cita" => "Ann Hepatol. 2017;16:157-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 94 "formatos" => array:3 [ "EPUB" => 12 "HTML" => 43 "PDF" => 39 ] ] "itemSiguiente" => array:19 [ "pii" => "S1665268119303746" "issn" => "16652681" "doi" => "10.5604/16652681.1226952" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "70196" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Ann Hepatol. 2017;16:160-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 180 "formatos" => array:3 [ "EPUB" => 16 "HTML" => 122 "PDF" => 42 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Acute Hepatitis E Mimicking a Flare of Disease in a Patient with Chronic Autoimmune Hepatitis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "160" "paginaFinal" => "163" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1105 "Ancho" => 1404 "Tamanyo" => 138732 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Time course of biochemical, serological and molecular laboratory during the episode of transaminitis due to autoimmune flare (November 2014) and during the episode of acute hepatitis E (February-March 2015).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Giorgio Calisti, Dianne N Irish, Samreen Ijaz, Richard S Tedder, Kevin Moore" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Giorgio" "apellidos" => "Calisti" ] 1 => array:2 [ "nombre" => "Dianne N" "apellidos" => "Irish" ] 2 => array:2 [ "nombre" => "Samreen" "apellidos" => "Ijaz" ] 3 => array:2 [ "nombre" => "Richard S" "apellidos" => "Tedder" ] 4 => array:2 [ "nombre" => "Kevin" "apellidos" => "Moore" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119303746?idApp=UINPBA00004N" "url" => "/16652681/0000001600000001/v1_201905311015/S1665268119303746/v1_201905311015/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119303722" "issn" => "16652681" "doi" => "10.5604/16652681.1226934" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "70194" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2017;16:149-56" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 100 "formatos" => array:3 [ "EPUB" => 8 "HTML" => 56 "PDF" => 36 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Complications of Liver Resection in Geriatric Patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "149" "paginaFinal" => "156" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0040" "etiqueta" => "Figure 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 780 "Ancho" => 1605 "Tamanyo" => 118616 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">12-month survival of patients older than 65 years according to histological findings.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ivana Dedinská, Ludovít Laca, Juraj Miklušica, Blažej Palkoci, Petra Skálová, Slavomíra Lauková, Denisa Osinová, Simona Strmeňová, Ján Janík, Marián Mokáň" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Ivana" "apellidos" => "Dedinská" ] 1 => array:2 [ "nombre" => "Ludovít" "apellidos" => "Laca" ] 2 => array:2 [ "nombre" => "Juraj" "apellidos" => "Miklušica" ] 3 => array:2 [ "nombre" => "Blažej" "apellidos" => "Palkoci" ] 4 => array:2 [ "nombre" => "Petra" "apellidos" => "Skálová" ] 5 => array:2 [ "nombre" => "Slavomíra" "apellidos" => "Lauková" ] 6 => array:2 [ "nombre" => "Denisa" "apellidos" => "Osinová" ] 7 => array:2 [ "nombre" => "Simona" "apellidos" => "Strmeňová" ] 8 => array:2 [ "nombre" => "Ján" "apellidos" => "Janík" ] 9 => array:2 [ "nombre" => "Marián" "apellidos" => "Mokáň" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119303722?idApp=UINPBA00004N" "url" => "/16652681/0000001600000001/v1_201905311015/S1665268119303722/v1_201905311015/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "titulo" => "Metastatic Lymphoepithelioma-like Hepatocellular Carcinoma: a Potential Diagnostic Pitfall and Demonstration of Pd-l1 Expression" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "157" "paginaFinal" => "159" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Juan Putra, Todd A. Anderson, Sasan Roayaie, Miho Maeda, Swan N. Thung" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Juan" "apellidos" => "Putra" "email" => array:1 [ 0 => "Juan_putra@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "Todd A." "apellidos" => "Anderson" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">**</span>" "identificador" => "aff2" ] ] ] 2 => array:3 [ "nombre" => "Sasan" "apellidos" => "Roayaie" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">***</span>" "identificador" => "aff3" ] ] ] 3 => array:3 [ "nombre" => "Miho" "apellidos" => "Maeda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">****</span>" "identificador" => "aff4" ] ] ] 4 => array:3 [ "nombre" => "Swan N." "apellidos" => "Thung" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "aff1" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, United States" "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Department of Pathology, Lenox Hill Hospital, New York, NY, United States" "etiqueta" => "**" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Department of Surgery, Lenox Hill Hospital, New York, NY, United States" "etiqueta" => "***" "identificador" => "aff3" ] 3 => array:3 [ "entidad" => "Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States" "etiqueta" => "****" "identificador" => "aff4" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 518 "Ancho" => 2075 "Tamanyo" => 220882 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span>. The periportal nodule was predominantly comprised of small atypical lymphocytes (hematoxylin-eosin, 100x). Inset shows scattered large atypical cells (hematoxylin-eosin, 400x). <span class="elsevierStyleBold">B</span>. Scattered malignant epithelial cells were seen in single-cell infiltrative pattern (cytokeratin AE13, 100x). <span class="elsevierStyleBold">C</span>. Focus of perineural invasion was also noted (asterix highlights the nerve) (hematoxylin-eosin, 400x).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Case Report</span><p id="p0005" class="elsevierStylePara elsevierViewall">A 73-year-old Asian female with chronic hepatitis B presented with periportal lymphadenopathy, 5 years after she underwent partial hepatectomy for hepatocellular carcinoma (HCC). Segment 7 liver resection specimen at the initial presentation revealed a cirrhotic liver with a 1.2 cm poorly-differentiated HCC accompanied by dense lym-phocytic inflammatory infiltrate (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>A) and micro-vascular invasion (stage pT2 based on American Joint Committee on Cancer, 7th edition). The tumor-infiltrating lymphocytes predominantly comprised of T-lymphocytes (Figures <a class="elsevierStyleCrossRef" href="#f0005">1B</a>-<a class="elsevierStyleCrossRef" href="#f0005">1C</a>) and the resection margin of the hepatecto-my specimen was negative for tumor involvement. During the most recent follow-up, computed tomography scan revealed a 3.4 cm mildly arterial enhancing nodule in porta hepatic with washout on venous phase, concerning for a recurrent HCC in the caudate lobe. Enlarged peripancreatic lymph node (1.6 cm) and precaval lymph node (1.1 cm) were also identified. Her serum alpha-fetoprotein level at the time was within normal limits, 2.4 ng/mL (reference range: 0.0-9.0 ng/mL). The patient subsequently underwent surgical resection for diagnostic and therapeutic purposes. At the time of surgery, no caudate lobe lesion was identified and the porta hepatic nodule was found to be an enlarged porta hepatic lymph node.</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0010" class="elsevierStylePara elsevierViewall">Histologic examination of the enlarged porta hepatic lymph node revealed neoplastic cells arranged in nests and sheets with a lymphoid-rich background (<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>A). Im-munohistochemical marker confirmed the epithelial origin of these lesional cells (<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>B). Histologic slides of the initial hepatic tumor were reviewed, and the metastat-ic neoplastic cells demonstrated similar morphology to the primary HCC. Meanwhile, microscopic examination of the periportal nodules revealed sheets of mildly atypical small-sized lymphocytes with scattered highly atypical large cells (<a class="elsevierStyleCrossRef" href="#f0015">Figure 3</a>A), concerning for a lymphoprolifera-tive disorder. However, immunohistochemical study demonstrated that the atypical large cells to be of epithelial origin (<a class="elsevierStyleCrossRef" href="#f0015">Figure 3</a>B) without evidence of monoclonal lym-phoid cell populations. In addition, perineural invasion was identified in one of the periportal lesions (<a class="elsevierStyleCrossRef" href="#f0015">Figure 3</a>C).</p><elsevierMultimedia ident="f0010"></elsevierMultimedia><elsevierMultimedia ident="f0015"></elsevierMultimedia><p id="p0015" class="elsevierStylePara elsevierViewall">The patient was doing well after the surgery and she subsequently received adjuvant external-beam radiotherapy due to lymphovascular and perineural invasions identified in the porta hepatic nodule.</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Discussion</span><p id="p0020" class="elsevierStylePara elsevierViewall">Lymphoepithelioma was initially described as a distinctive type of nasopharyngeal undifferentiated carcinoma with brisk lymphocytic infiltrates and a strong association with Epstein-Barr virus (EBV);<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> while tumors with similar morphology that arise outside of the nasopharynx are designated as lymphoepithelioma-like carcinomas. Primary lymphoepithelioma-like carcinomas in the liver, which include cases of lymphopeithelioma-like cholangiocarcinoma (LEL-CC) and lymphopeithelioma-like hepatocellular carcinoma (LEL-HCC), are particularly rare. LEL-CC is characterized by female predominance, favorable overall survival, and an association with EBV.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> LEL-HCC, which is less common than LEL-CC, is also characterized by female predominance and better overall and progression-free survivals compared to HCC without significant tumor infiltrating lymphocytes. However, there is no established association between LEL-HCC and EBV based on the case series reported by Chan, <span class="elsevierStyleItalic">et al.</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and Patel, <span class="elsevierStyleItalic">et al.</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="p0025" class="elsevierStylePara elsevierViewall">The histologic diagnosis of metastatic LEL-HCC can be challenging, particularly in cases without known primary tumor. Differential diagnoses include LEL carcinoma from other organs, medullary carcinoma, metastatic melanoma, and lymphoma. LEL-HCC is notably difficult to distinguish from the latter in lesions with single-cell infiltrative pattern. The highly atypical neoplastic cells interspersed between small lymphocytes may resemble Reed-Sternberg cells seen in Hodgkin's lymphoma.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Immunohistochemistry is helpful to characterize the origin of these neoplastic cells. The presence of aberrant im-munophenotype in the lymphoid component would also support the diagnosis of lymphoma. In addition, flow cytometry might be helpful to make or exclude the diagnosis in cases with suspected lymphoma.</p><p id="p0030" class="elsevierStylePara elsevierViewall">Recently, Calderaro, <span class="elsevierStyleItalic">et al</span>.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> reported high expression of programmed death ligand 1 (PD-L1) immune checkpoint in the inflammatory cells of LEL-HCC. PD-L1 expression by the neoplastic cells was associated with markers of tumor aggressiveness (high serum alpha-protein level, macro- and microvascular invasion, and satellite nodules) and with the progenitor subtype of HCC.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In our patient, the metastatic tumor cells and tumor infiltrating lymphocytes in the periportal lesion showed positive membranous staining for PD-L1 (<a class="elsevierStyleCrossRef" href="#f0020">Figure 4</a>) (Anti-PD-L1 205921, Abcam, Cambridge, MA, United States). This information will be pertinent for patients with particular HCC subtypes as targeted therapy becomes available in the future.</p><elsevierMultimedia ident="f0020"></elsevierMultimedia><p id="p0035" class="elsevierStylePara elsevierViewall">In conclusion, we reported a case of a patient with chronic hepatitis B who presented with a small, solitary LEL-HCC and developed metastatic disease 5 years later. The metastatic lesions demonstrated different morphologic features. The hilar lymph node showed a straightforward diagnosis of metastatic carcinoma with sheets of malignant epithelial cells. Meanwhile, the morphologic findings of the periportal nodules were more subtle, as the predominant component of these lesions was the (tumor-infiltrating) lymphocytes. Immunohistochemistry is an important diagnostic tool in making the diagnosis. Finally, LEL-HCC has also been associated with frequent PD-L1 expression which might have prognostic and therapeutic implications.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:3 [ "identificador" => "xres1198042" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0010" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1116686" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "Case Report" ] 3 => array:2 [ "identificador" => "s0010" "titulo" => "Discussion" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-10-05" "fechaAceptado" => "2016-10-24" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1116686" "palabras" => array:4 [ 0 => "Lymphoepithelioma-like hepatocellular carcinoma" 1 => "Chronic hepatitis B" 2 => "Metastatic hepatocellular carcinoma" 3 => "Programmed death ligand-1" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a rare primary hepatic neoplasm with female predominance and relatively good prognosis. We report a 73-year-old female with chronic hepatitis B who developed metastatic lesions 5 years after underwent resection for LEL-HCC. The metastatic lesions showed a spectrum of morphologic findings, which could be mistaken for other entities such as lymphoma, particularly in lesions with single-cell infiltrative pattern and abundant tumor-infiltrating lymphocytes. Im-munohistochemical study to confirm the origin of the neoplastic cells is important to make the diagnosis. We also highlighted the clin-icopathologic correlation and potential therapeutic implication of programmed death ligand-1 expression in LEL-HCC.</p></span>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 523 "Ancho" => 2075 "Tamanyo" => 311352 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span>. The primary hepatic tumor shows a poorly differentiated carcinoma with abundant tumor-infiltrating lymphocytes (hematoxylin-eosin, 100x). <span class="elsevierStyleBold">B</span>. These tumor-infiltrating lymphocytes were predominantly T-lymphocytes, highlighted by CD3 immunostain (100x). <span class="elsevierStyleBold">C</span>. Less B-lymphocytes were identified, highlighted by CD20 immunostain (100x). The findings are consistent with lymphoepithelioma-like hepatocellular carcinoma.</p>" ] ] 1 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 554 "Ancho" => 1470 "Tamanyo" => 271992 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span>. The hilar lymph node showed metastatic carcinoma with sheets of malignant neoplastic cells with a lymphoid background (hematoxylin-eosin, 100x). <span class="elsevierStyleBold">B</span>. These neoplastic cells were confirmed to be of epithelial origin (CAM 5.2, 100x).</p>" ] ] 2 => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 518 "Ancho" => 2075 "Tamanyo" => 220882 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span>. The periportal nodule was predominantly comprised of small atypical lymphocytes (hematoxylin-eosin, 100x). Inset shows scattered large atypical cells (hematoxylin-eosin, 400x). <span class="elsevierStyleBold">B</span>. Scattered malignant epithelial cells were seen in single-cell infiltrative pattern (cytokeratin AE13, 100x). <span class="elsevierStyleBold">C</span>. Focus of perineural invasion was also noted (asterix highlights the nerve) (hematoxylin-eosin, 400x).</p>" ] ] 3 => array:7 [ "identificador" => "f0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 749 "Ancho" => 1000 "Tamanyo" => 187840 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Programmed death ligand-1 membranous positivity in the neo-plastic cells and tumor-infiltrating lymphocytes of the periportal lesion (PD-L1, 400x).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0010" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lymphoepithelioma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Ewing J." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Pathol" "fecha" => "1929" "volumen" => "5" "paginaInicial" => "99" "paginaFinal" => "108" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19969843" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of lymphoepi-thelioma and lymphoepithelioma-like carcinomas for Epstein-Barr viral genomes by in situ hybridization" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Weiss L.M." 1 => "Movahed L.A." 2 => "Butler A.E." 3 => "Swanson S.A." 4 => "Frierson H.F. Jr" 5 => "Cooper P.H." 6 => "Colby T.V." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Am J Surg Pathol" "fecha" => "1989" "volumen" => "13" "paginaInicial" => "625" "paginaFinal" => "631" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2546458" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673612621278" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epstein-Barr virus-associated lymphoepithelioma-like cholangiocarcinoma: a rare variant of intrahepatic cholangiocarcinoma with favorable outcome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Chan A.W." 1 => "Tong J.H." 2 => "Sung M.Y." 3 => "Lai P.B." 4 => "To K.F." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/his.12455" "Revista" => array:6 [ "tituloSerie" => "Histopathology" "fecha" => "2014" "volumen" => "65" "paginaInicial" => "674" "paginaFinal" => "683" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24804938" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lymphoepithelioma-like hepatocellular carcinoma: an uncommon variant of hepatocellular carcinoma with favorable outcome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Chan A.W." 1 => "Tong J.H." 2 => "Pan Y." 3 => "Chan S.L." 4 => "Wong G.L." 5 => "Wong V.W." 6 => "Lai P.B." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/PAS.0000000000000376" "Revista" => array:6 [ "tituloSerie" => "Am J Surg Pathol" "fecha" => "2015" "volumen" => "39" "paginaInicial" => "304" "paginaFinal" => "312" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25675010" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characterization of inflammatory (lymphoepithelioma-like) hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Patel K.R." 1 => "Liu T." 2 => "Vaccharajani N." 3 => "Chapman W.C." 4 => "Brunt E.M." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5858/arpa.2013-0371-OA" "Revista" => array:6 [ "tituloSerie" => "Arch Pathol Lab Med" "fecha" => "2014" "volumen" => "138" "paginaInicial" => "1193" "paginaFinal" => "1202" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25171701" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lym-phoepithelioma-like carcinoma of the breast mimicking nodular sclerosing Hodgkin’s lymphoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Saleh R." 1 => "DaCamara P." 2 => "Radhi J." 3 => "Boutross-Tadross O." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1075-122X.2005.21577.x" "Revista" => array:6 [ "tituloSerie" => "Breast J" "fecha" => "2005" "volumen" => "11" "paginaInicial" => "353" "paginaFinal" => "354" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16174158" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Programmed death ligand 1 expression in hepatocellular carcinoma: relationship with clinical and pathological features" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Calderaro J." 1 => "Rousseau B." 2 => "Amaddeo G." 3 => "Mercey M." 4 => "Charpy C." 5 => "Constentin C." 6 => "Luciani A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.28710" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2016" "volumen" => "64" "paginaInicial" => "2038" "paginaFinal" => "2046" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27359084" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/0000001600000001/v1_201905311015/S1665268119303734/v1_201905311015/en/main.assets" "Apartado" => array:4 [ "identificador" => "77922" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Images in Hepatology" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/16652681/0000001600000001/v1_201905311015/S1665268119303734/v1_201905311015/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119303734?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 0 | 4 |
| 2024 October | 9 | 3 | 12 |
| 2024 September | 10 | 9 | 19 |
| 2024 August | 11 | 6 | 17 |
| 2024 July | 15 | 2 | 17 |
| 2024 June | 11 | 3 | 14 |
| 2024 May | 22 | 4 | 26 |
| 2024 April | 14 | 2 | 16 |
| 2024 March | 19 | 4 | 23 |
| 2024 February | 8 | 6 | 14 |
| 2024 January | 8 | 5 | 13 |
| 2023 December | 16 | 2 | 18 |
| 2023 November | 17 | 5 | 22 |
| 2023 October | 25 | 9 | 34 |
| 2023 September | 9 | 3 | 12 |
| 2023 August | 25 | 3 | 28 |
| 2023 July | 4 | 4 | 8 |
| 2023 June | 15 | 9 | 24 |
| 2023 May | 45 | 6 | 51 |
| 2023 April | 36 | 2 | 38 |
| 2023 March | 26 | 3 | 29 |
| 2023 February | 13 | 3 | 16 |
| 2023 January | 14 | 4 | 18 |
| 2022 December | 24 | 5 | 29 |
| 2022 November | 54 | 5 | 59 |
| 2022 October | 36 | 7 | 43 |
| 2022 September | 54 | 14 | 68 |
| 2022 August | 24 | 11 | 35 |
| 2022 July | 13 | 6 | 19 |
| 2022 June | 15 | 8 | 23 |
| 2022 May | 10 | 8 | 18 |
| 2022 April | 8 | 11 | 19 |
| 2022 March | 11 | 12 | 23 |
| 2022 February | 10 | 6 | 16 |
| 2022 January | 17 | 5 | 22 |
| 2021 December | 19 | 12 | 31 |
| 2021 November | 32 | 6 | 38 |
| 2021 October | 67 | 8 | 75 |
| 2021 September | 40 | 9 | 49 |
| 2021 August | 22 | 6 | 28 |
| 2021 July | 19 | 9 | 28 |
| 2021 June | 17 | 9 | 26 |
| 2021 May | 23 | 10 | 33 |
| 2021 April | 33 | 13 | 46 |
| 2021 March | 18 | 8 | 26 |
| 2021 February | 5 | 5 | 10 |
| 2021 January | 7 | 9 | 16 |
| 2020 December | 12 | 8 | 20 |
| 2020 November | 8 | 10 | 18 |
| 2020 October | 4 | 9 | 13 |
| 2020 September | 13 | 10 | 23 |
| 2020 August | 13 | 5 | 18 |
| 2020 July | 8 | 8 | 16 |
| 2020 June | 13 | 10 | 23 |
| 2020 May | 10 | 2 | 12 |
| 2020 April | 3 | 3 | 6 |
| 2020 March | 5 | 3 | 8 |
| 2020 February | 7 | 3 | 10 |
| 2020 January | 5 | 4 | 9 |
| 2019 December | 7 | 7 | 14 |
| 2019 November | 2 | 2 | 4 |
| 2019 October | 4 | 4 | 8 |
| 2019 September | 3 | 1 | 4 |
| 2019 August | 1 | 2 | 3 |
| 2019 July | 11 | 6 | 17 |
| 2019 June | 5 | 7 | 12 |
| 2019 May | 2 | 4 | 6 |
Show all
