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Granulomatous reaction induced by Nivolumab. A case report
Reacción granulomatosa inducida por nivolumab. A propósito de un caso
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A case report" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "272" "paginaFinal" => "273" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "C. Sandoval-Moreno, J.A. Duarte-Luna, C. Escolano-Escobar, B. Manzarbeitia-Arroba, A. Herrero-Muñoz, M.Á. Balsa-Bretón" "autores" => array:6 [ 0 => array:4 [ "nombre" => "C." "apellidos" => "Sandoval-Moreno" "email" => array:2 [ 0 => "cristycsm@gmail.com" 1 => "cristina.sandoval@salud.madrid.org" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J.A." "apellidos" => "Duarte-Luna" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "C." 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"apellidos" => "Balsa-Bretón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Hospital Universitario de Getafe, Getafe, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario de Getafe, Getafe, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Universitario de Getafe, Getafe, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Reacción granulomatosa inducida por nivolumab. A propósito de un caso" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1328 "Ancho" => 2351 "Tamanyo" => 202258 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">18F-FDG-PET/CT studies after initiation of immunotherapy with Nivolumab. (a) Baseline study, with evidence of pathological FDG uptake in mediastinal lymphadenopathy, hilar and bone involvement. (b) Control two months after the start of treatment: response of the bone involvement with persistent adenopathic involvement. (c) Control five months after the start of treatment: adenopathic progression with supra and infradiaphragmatic involvement.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The development of immunotherapy-based treatments has led to a change in the management of different neoplasms, as well as in the interpretation of imaging tests during follow-up.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a patient diagnosed with stage IIIA Hodgkin’s Lymphoma (HL) who, after autotransplantation, has an early relapse with mediastinal adenopathic and bone involvement, with a positive biopsy for PD-1 and PDL-1. Treatment with Nivolumab prior to allogeneic transplantation was administrated.</p><p id="par0015" class="elsevierStylePara elsevierViewall">PET/CT studies (Siemens Biograph 6) were performed (including orbits to proximal thighs), after intravenous administration of 3.7 MBq/kg of 18F-FDG and fasting for 6 h, for follow up. Two months after the start of immunotherapy, response to treatment was evidenced on the bone metastasis with persistence of lymph node involvement. Three months later the PET/CT showed lymph node progression (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Given the clinical-radiological disassociation, a lymph node biopsy was performed with the result of non-necrotizing granulomatous lymphadenitis in both cases (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Immunotherapy is based on activating the immune system through various mechanisms, unblocking the inhibitory pathways (CTLA-4 or PD-1/PDL-1) and stimulating T lymphocytes<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>. Nivolumab is a monoclonal IgG4 antibody against the PD-1 receptor being indicated in the treatment of LH<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Pseudoprogression consists of an increase in size, metabolism and number of lesions due to an infiltration of inflammatory cells, necrosis and T lymphocytes. It is described in up to 10% of the treatments with anti-PD-1, sarcoidosis being one of the effects less frequent adverse events<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>.</p><p id="par0030" class="elsevierStylePara elsevierViewall">It has been reported that in active sarcoidosis, the PD-1 receptor is increased with overexpression of PDL-1<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>. On the other hand, it has been observed that T cells with PD-1 expression regain their proliferative capacity with anti-PD-1<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>. Although these theories could explain the development of inflammatory pathologies, it has not been established as a cause.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Several criteria to assess the response to immunotherapy treatments have been published (irREiCIST, PECRIT, PERCIMT …), without establishing any of them. What they seem to agree on is that the progression of the disease must be confirmed in separate studies at least four weeks before deciding to suspend treatment in those patients with clinical improvement<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>. For this reason, together with the negative biopsy for malignancy obtained two months after starting Nivolumab, it was decided to continue treatment given the clinical benefit that could be obtained.</p><p id="par0040" class="elsevierStylePara elsevierViewall">This case shows us the importance of knowing the possible side effects of immunotherapy and its diagnosis, differentiating them from a true progression of the disease in order to offer patients the best therapeutic option.</p></span>" "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" => 1328 "Ancho" => 2351 "Tamanyo" => 202258 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">18F-FDG-PET/CT studies after initiation of immunotherapy with Nivolumab. (a) Baseline study, with evidence of pathological FDG uptake in mediastinal lymphadenopathy, hilar and bone involvement. (b) Control two months after the start of treatment: response of the bone involvement with persistent adenopathic involvement. (c) Control five months after the start of treatment: adenopathic progression with supra and infradiaphragmatic involvement.</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" => 1274 "Ancho" => 2176 "Tamanyo" => 457323 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Biopsy for Aortopulmonary window adenopathy biopsy. A and B. Nodal tissue replaced by numerous aggregates of epithelioid histiocytes forming microgranulomas, without necrosis.</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" => "Immunotherapy, cancer and PET" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Simó-Perdigó" 1 => "J.L. Vercher-Conejero" 2 => "S. Viteri" 3 => "M.J. 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