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Splenic and lung metastases of hepatocellular carcinoma detected at 13N-ammonia PET/CT
Metástasis esplénica y pulmonar de carcinoma hepatocelular detectado en 13N-NH3 PET/TC
Valentina Scolozzia,
, Romina Grazia Giancipolia, Frediano Inzanib, Francesca Romana Ponzianic,d, Silvia Tarallia
Corresponding author
a UOC di Medicina Nucleare, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
b Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
c Internal Medicine and Gastroenterology — Hepatology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
d Università cattolica del sacro Cuore, Roma, Italy
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Gemelli IRCCS, Roma, Italy" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Internal Medicine and Gastroenterology — Hepatology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Università cattolica del sacro Cuore, Roma, Italy" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Metástasis esplénica y pulmonar de carcinoma hepatocelular detectado en <span class="elsevierStyleSup">13</span>N-NH3 PET/TC" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1179 "Ancho" => 3341 "Tamanyo" => 1046760 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0055" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">At EUS-needle biopsy of the splenic nodule, histological examination revealed a solid-trabecular proliferation of atypical epithelial cells with prominent nucleoli (H&E, <span class="elsevierStyleBold">A</span>) with diffuse expression of HepPar1 at immunohistochemistry (immunoperoxidase, <span class="elsevierStyleBold">B</span>), consistent with HCC localization.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We report the case of a 62-year-old man with history of surgically treated advanced hepatocellular carcinoma (HCC). A restaging CT scan performed for markedly increase of serum alpha-fetoprotein level described a nodule in the upper splenic pole (axial diameter: 35<span class="elsevierStyleHsp" style=""></span>mm) and two other nodules in the right lung (axial diameter: 14<span class="elsevierStyleHsp" style=""></span>mm and 10<span class="elsevierStyleHsp" style=""></span>mm), all findings suggestive for HCC metastases. As candidate to systemic therapy with an anti-angiogenic tyrosine kinase inhibitor, the patient was enrolled in a prospective clinical trial that included a dynamic PET/CT with the perfusion tracer <span class="elsevierStyleSup">13</span>N-ammonia, to evaluate both lesions’ perfusion and disease extent. A dynamic PET/CT acquisition, lasting 20<span class="elsevierStyleHsp" style=""></span>min and centred on the upper abdomen, was performed simultaneously with the intravenous injection of 370<span class="elsevierStyleHsp" style=""></span>MBq of <span class="elsevierStyleSup">13</span>N-ammonia, followed by a whole-body acquisition. PET images showed focal increased <span class="elsevierStyleSup">13</span>N-ammonia uptake in both pulmonary lesions and in the splenic nodule, consistent with HCC localizations (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). No other foci of abnormal tracer uptake were observed. At subsequent endoscopic ultrasound (EUS)-needle biopsy of the splenic nodule, histological examination proved HCC metastasis (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The planned systemic treatment was started.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">While lung involvement from HCC is not so infrequent, splenic metastases are sporadic findings seen in approximately 0.8% of cases, usually spreading by hematogenous route or direct seeding. To our knowledge, our case is the first in literature reporting on the detection of HCC splenic metastasis at PET/CT with <span class="elsevierStyleSup">13</span>N-ammonia, a perfusion tracer historically used in clinical practice to measure myocardial perfusion. The diagnostic performance of <span class="elsevierStyleSup">13</span>N-ammonia was also evaluated in the oncology field, with several neoplasms (including HCC) showing increased tracer uptake, depending on tumour capillary blood flow and tracer extraction efficiency.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In particular, the <span class="elsevierStyleSup">13</span>N-ammonia uptake degree in neoplastic cells also depends on up- or down-regulation of specific enzymes responsible for the amino acid synthesis, such as glutamine synthetase. The application of <span class="elsevierStyleSup">13</span>N-ammonia PET in HCC was firstly investigated by Hayashi et al. and Shibata et al., demonstrating a relationship between tumour vascularization and tracer uptake.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Indeed, given the rich blood supply of HCC from the hepatic artery, <span class="elsevierStyleSup">13</span>N-ammonia mainly flows into HCC primary lesions in the early phase of the dynamic acquisition, displaying high tumour uptake and an optimal visual contrast to normal liver parenchyma, that shows more gradual radiotracer accumulation over time (blood supply mostly derived from the portal vein). In our case, the high <span class="elsevierStyleSup">13</span>N-ammonia uptake observed in distant metastases suggests that HCC localizations may share a similar PET pattern with primary tumour, reflecting similar perfusion behaviour.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0015" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1403 "Ancho" => 3341 "Tamanyo" => 270181 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0050" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Maximum intensity projection (<span class="elsevierStyleBold">A</span>), axial PET and fused PET/CT images showed high <span class="elsevierStyleSup">13</span>N-ammonia uptake in two pulmonary nodules located in the anterior basal segment of the right lower lobe (<span class="elsevierStyleBold">B</span>, <span class="elsevierStyleBold">C</span>, arrowed) and in the middle lobe (<span class="elsevierStyleBold">D</span>, <span class="elsevierStyleBold">E</span>, arrowed), respectively, and in a hypodense nodule in the upper splenic pole (<span class="elsevierStyleBold">F</span>, <span class="elsevierStyleBold">G</span>, arrowed).</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1179 "Ancho" => 3341 "Tamanyo" => 1046760 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0055" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">At EUS-needle biopsy of the splenic nodule, histological examination revealed a solid-trabecular proliferation of atypical epithelial cells with prominent nucleoli (H&E, <span class="elsevierStyleBold">A</span>) with diffuse expression of HepPar1 at immunohistochemistry (immunoperoxidase, <span class="elsevierStyleBold">B</span>), consistent with HCC localization.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:3 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "(13)N-NH3 PET/CT in oncological disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D. Albano" 1 => "R. Giubbini" 2 => "F. Bertagna" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Jpn J Radiol" "fecha" => "2019" "volumen" => "37" "paginaInicial" => "799" "paginaFinal" => "807" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imaging of the hepatocellular carcinoma using dynamic positron emission tomography with nitrogen-13 ammonia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Hayashi" 1 => "N. Tamaki" 2 => "Y. Yonekura" 3 => "M. Senda" 4 => "H. Saji" 5 => "K. Yamamoto" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Nucl Med" "fecha" => "1985" "volumen" => "26" "paginaInicial" => "254" "paginaFinal" => "257" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dynamic positron emission tomography with 13N-ammonia in liver tumors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Shibata" 1 => "K. Yamamoto" 2 => "N. Hayashi" 3 => "Y. Yonekura" 4 => "T. Nagara" 5 => "H. Saji" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/BF00251784" "Revista" => array:6 [ "tituloSerie" => "Eur J Nucl Med" "fecha" => "1988" "volumen" => "14" "paginaInicial" => "607" "paginaFinal" => "611" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2854065" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/22538089/0000004200000006/v1_202311030524/S2253808923000617/v1_202311030524/en/main.assets" "Apartado" => array:4 [ "identificador" => "7927" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Interesting images" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/22538089/0000004200000006/v1_202311030524/S2253808923000617/v1_202311030524/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253808923000617?idApp=UINPBA00004N" ]
