Diagnosis at first sight
Disseminated lymphadenopathy during chemotherapy for squamous cell lung carcinoma
Linfadenopatía generalizada durante tratamiento quimioterápico por carcinoma escamoso de pulmón
Sara Villara, Miguel Sogbeb,c, María José García-Vellosod, José Luis del Pozob,
Corresponding author
a Departamento de Hematología, Clínica Universidad de Navarra, Pamplona, Navarra, Spain
b Servicio de Enfermedades Infecciosas y Microbiología, Clínica Universidad de Navarra, Pamplona, Navarra, Spain
c Departamento de Medicina Interna, Clínica Universidad de Navarra. Pamplona, Navarra, Spain
d Departamento de Medicina Nuclear, Clínica Universidad de Navarra, Pamplona, Navarra, Spain
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Pamplona, Navarra, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Departamento de Medicina Nuclear, Clínica Universidad de Navarra, Pamplona, Navarra, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Linfadenopatía generalizada durante tratamiento quimioterápico por carcinoma escamoso de pulmón" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1425 "Ancho" => 2508 "Tamanyo" => 179802 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">PET at the end of the second cycle of chemotherapy showing progression of lymphadenopathy with uptake at the mediastinum, axilla and supraclavicular and cervical areas. Uptake in the colon had decreased when the metformin treatment was replaced with insulin.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case report</span><p id="par0005" class="elsevierStylePara elsevierViewall">We report the case of a 66-year-old male with diabetes on treatment with metformin, diagnosed with a 13-mm squamous cell carcinoma of the lung in the right upper lobe, with extension to a single subcarinal lymph node (T1N2M0) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). After administering the first cycle of chemotherapy with gemcitabine and cisplatin, the patient developed a fever of up to 39°C with no focal point, with associated mild pancytopenia. Empirical therapy was started with levofloxacin. One week later, episodes of intermittent fever persisted despite haematological recovery. At the end of the second cycle of chemotherapy, a PET scan showed progression of generalised lymphadenopathy (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Progress</span><p id="par0010" class="elsevierStylePara elsevierViewall">An excisional biopsy was performed of an enlarged left axillary lymph node that was lit up on the PET scan. The pathology diagnosis was consistent with sinus histiocytosis. Serologies against rubella, brucellosis, CMV, EBV, HIV, HHV-6, and syphilis were requested, all of which were negative for recent infection. The QuantiFERON<span class="elsevierStyleItalic">®</span> test (Qiagen, Hilden, Germany) for tuberculosis was negative. <span class="elsevierStyleItalic">Toxoplasma</span> IgG was positive (4642 IU/mL), as was IgM. PCR was performed on the lymph node tissue, resulting positive for <span class="elsevierStyleItalic">Toxoplasma</span> spp.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The diagnosis was made of toxoplasmosis reactivation. The patient began treatment with trimethoprim-sulfamethoxazole (800/160<span class="elsevierStyleHsp" style=""></span>mg every 8<span class="elsevierStyleHsp" style=""></span>h), showing a clear clinical improvement. The PET was repeated three weeks after treatment, showing a general decrease in the intensity of uptake in the different lymph node territories (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Serology performed one month after diagnosis showed an increase in IgG (11,034 IU/mL), which decreased in later tests, reflecting the natural history of reactivation. The patient subsequently started radiotherapy and completed concomitant chemotherapy with a good response, entering the periodic review programme and with no signs of reactivation of the infection to date (six months later).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Closing remarks</span><p id="par0020" class="elsevierStylePara elsevierViewall">Infection by <span class="elsevierStyleItalic">Toxoplasma gondii (T. gondii)</span> is usually asymptomatic in immunocompetent patients. After the initial infection (even when asymptomatic), the latent infection will persist for the lifetime of the host. In patients with some type of immune deficiency (chemotherapy with alkylating agents, antimetabolites, HIV infection, haematopoietic stem cell or solid organ transplant), it can give rise to disseminated symptoms with pulmonary, cardiac and, in particular, central nervous system involvement, as these are potential risk factors for the reactivation of <span class="elsevierStyleItalic">T. gondii</span>.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> In these cases, given the high prevalence of previous infection, reactivation is more common than primary infection.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The documented cases of toxoplasmosis reactivation have been linked to blood cancers.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> To our knowledge, the association with solid tumours found in our case has not been reported previously.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The diagnosis of toxoplasmosis can be a challenge in patients such as the one described here, in whom the manifestation of new-onset lymphadenopathy suggests a progression of the cancer. In toxoplasmosis, lymph node histology is usually nonspecific, with sinus histiocytosis being common.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3</span></a> A definitive diagnosis can be made by serology.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Primary infection is characterised by the appearance of IgM antibodies, accompanied by seroconversion with low-avidity IgG. IgM can remain in serum for a long period of time, and the concentration often rises in reactivations. The typical pattern of reactivation is characterised by an increase in high-avidity IgG concentrations, regardless of the presence of IgM.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Molecular diagnostic techniques, such as PCR for <span class="elsevierStyleItalic">T. gondii</span> in serum, cerebrospinal fluid or tissue biopsies, can be useful.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> These techniques can be helpful when serology is inconclusive, which is common in immunosuppressed patients.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Diagnostic imaging can be helpful in some cases<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>, such as cerebral toxoplasmosis, where a compatible image justifies beginning empirical therapy against toxoplasma. Other conditions that needed to be included in the differential diagnosis of this case, apart from cancer progression, were Rosai-Dorfman disease, lymphoproliferative syndromes, HIV, EBV, CMV and HHV-6 infection and mycobacteriosis.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion, the reactivation of toxoplasmosis should be part of the differential diagnosis when widespread lymphadenopathy is found in cancer patients, with serology and response to treatment being the main diagnostic tools. In view of the potential severity of the disseminated forms of the disease, early treatment is important and in many cases will lead to complete resolution of the condition.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Funding</span><p id="par0045" class="elsevierStylePara elsevierViewall">None.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">José Luis del Pozo has participated in training or consulting activities funded by Pfizer, MSD, Gilead and Novartis.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The other authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Case report" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Progress" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Closing remarks" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Funding" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 5 => array:2 [ "identificador" => "xack701126" "titulo" => "Acknowledgements" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1416 "Ancho" => 2508 "Tamanyo" => 158554 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Baseline PET showing a hyper-uptake image in the segmental bronchus of the right lower lobe (primary tumour) and subcarinal lymphadenopathy with less uptake. Uptake by the colon is common in patients on treatment with metformin.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1425 "Ancho" => 2508 "Tamanyo" => 179802 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">PET at the end of the second cycle of chemotherapy showing progression of lymphadenopathy with uptake at the mediastinum, axilla and supraclavicular and cervical areas. Uptake in the colon had decreased when the metformin treatment was replaced with insulin.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1388 "Ancho" => 2508 "Tamanyo" => 170654 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">PET showing a general decrease in uptake at the axilla and mediastinum after antibiotic therapy.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:4 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleItalic">Toxoplasma gondii</span> infection in immunocompromised patients: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Z.D. 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