Scientific letter
Laryngeal Lymphomatoid Granulomatosis in a HIV Patient
Granulomatosis linfomatoide laríngea en paciente VIH positivo
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"autores" => array:4 [ 0 => array:4 [ "nombre" => "Emilio" "apellidos" => "Domínguez-Durán" "email" => array:1 [ 0 => "emiliodominguezorl@gmail.com" ] "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" => "Rafael" "apellidos" => "Luque-Márquez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "María" "apellidos" => "Fontillón-Alberdi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Antonio" "apellidos" => "Abrante-Jiménez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Departamento de Otorrinolaringología, Hospital Universitario Virgen del Rocío, Sevilla, España" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Enfermedades Infecciosas, Hospital Universitario Virgen del Rocío, Sevilla, España" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Anatomía Patológica, Hospital Universitario Virgen del Rocío, Sevilla, España" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Autor para correspondencia." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Granulomatosis linfomatoide laríngea en paciente VIH positivo" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 974 "Ancho" => 1300 "Tamanyo" => 494800 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Atypical lymphoid infiltrate containing large lymphoid cells surrounding vascular structures, hematoxylin-eosyn, 10×. Positivity of EBV with histosonda EBER, immunoperoxidase stain, 40×.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Lymphomatoid granulomatosis (LG) is a rare entity which was first reported in 1972 by Liebow et al.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is defined as a lymphoproliferative disorder caused by an Epstein-Barr virus-induced transformation of B-cells in a T-cell rich environment.</p><p id="par0010" class="elsevierStylePara elsevierViewall">LG can first appear with a huge variety of non-specific symptoms. Pulmonary lesions are found in almost all patients with LG. Extrapulmonary disease without lung involvement is uncommon and a laryngeal primary kind is exceptional.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The case of a 34-year-old man, heavy smoker of 30 cigarettes a day and suffering from HIV-1 infection is reported. Five years before his admission to our hospital, he was diagnosed with HIV-1 infection, probably sexually transmitted, in context of pulmonary tuberculosis and was subsequently treated with a nine-month chemotherapy course for tuberculosis and Tenofovir-Lamivudine-Efavirenz. The tuberculosis was successfully cured with this treatment. Later, the HAART was changed to Zidovudine-Lamivudine-Nevirapine with poor disease control (30 CD4 cell count/μl and 20 copies HIV-1/ml).</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the previous two years, he was treated with Abacavir-Lamivudine-Lopinavir/ritonavir with discordant response (last test before admission: 138 CD4 cell count/μl and 20 copies HIV-1/ml). Throughout his illness, he has suffered from two episodes of community acquired pneumonia.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The patient was admitted to our centre because of a fever syndrome of unknown origin which he had suffered for several months, as well as a recent dysphonia. The endoscopic examination of the larynx found bilateral Reinke's edema. We did not find any cause to explain the fever.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Blood tests showed normochromic normocytic anemia and ESR 109<span class="elsevierStyleHsp" style=""></span>mm/h. CD4 count cell was 124 cells/μl and viral load 32 copies/ml. Chest radiograph was normal. No evidence of renal disease was found. Blood and urine cultures, mycobacterium and parasites tests, cytomegalovirus PCR assay and latex-cryptococcus antigen detection were negative. Tumor markers levels were not raised. A liver biopsy revealed unspecific hepatic granulomas which were cultured, but no mycobacteria grew in Löwenstein-Jensen medium. Bone marrow aspiration found non-specific alterations in all blood cells, related to an unknown illness.</p><p id="par0035" class="elsevierStylePara elsevierViewall">A cervical CT discovered a thickening of both vocal folds, compatible with Reinke's edema, but it extended into the subglottis and the normal sized laterocervical lymph nodes. Only laryngeal and cervical lymph nodes had values over their maximum standard in a PET/CT (SUV maximum 10.7).</p><p id="par0040" class="elsevierStylePara elsevierViewall">The tissue biopsy was reported as polymorph lymphoid proliferation related to post-transplant lymphoproliferative disorder. Neither T-cell nor B-cell clonality was found in the histochemical study and flow cytometry. Flow cytometry characteristics were CD1a negative, CD-3 negative, CD-5 negative, CD-10 negative, CD-20 negative, CD-30 positive in large cells, CD-68 positive in macrophages and cells surrounding vascular structures, CD-79a negative, CD-99 negative and CD-117-c-Kit negative. The EBER “in situ” hybridization was positive, pointing out the presence of EBV. Ziehl-Neelsen, P.A.S. and Congo red stains were negative.</p><p id="par0045" class="elsevierStylePara elsevierViewall">No treatment was given after the first biopsy and the subglottic mass grew fast and aggressively: over three months, it infiltrated the para-laryngeal space and destroyed cricoid cartilage. This local progress caused recurrent episodes of massive bleeding. We started him on steroids 1<span class="elsevierStyleHsp" style=""></span>mg/kg/day IV and cyclophosphamide 2<span class="elsevierStyleHsp" style=""></span>mg/kg/day IV treatment and an urgent total laryngectomy was performed due to the imminent risk of fatal haemorrhage. Two weeks after surgery, a large pharyngeal fistula was developed, showing necrotic tissues. Our patient died six months after being hospitalized, due to a severe local bleeding.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The histopathological examination of larynx showed an atypical lymphoid infiltration containing large lymphoid cells surrounding vascular structures accompanied by extensive areas of necrosis, and was finally reported as lymphomatoid granulomatosis grade III according to the proportion of EBV positive B cells.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The immunohistochemical analysis showed positivity for EBV-LMP-1 and negativity for CD20. The Ki67 labelling index was high. The PCR analysis showed polyclonal expansion of T-cells with the TCR and IgH gene, and positivity for of EBV with histosonda EBER (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">A literature search with no date limits in PubMed using the keywords “lymphomatoid granulomatosis” and “larynx” found only two reported cases where LG affects the larynx, but in both of them, laryngeal disease was associated with pulmonary involvement.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> The larynx has its own lymphatic structure called larynx-associated lymphoid tissue (LALT). In the subglottis, LALT is replaced throughout life by a diffuse infiltration of strong intensity consisting predominantly of CD3-positive T lymphocytes with scattered CD20-positive B cells,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> therefore LG could be originated in subglottic tissues.</p><p id="par0065" class="elsevierStylePara elsevierViewall">LG pathogenesis is unclear, but it has been linked to EBV and immunodeficiency. As regards the close to 100% EBV association with LG and the presumed wide expression of EBV latent encoded proteins, it has been strongly inferred that EBV is not just an innocent bystander in the pathogenesis of LG.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> When dealing with immunodeficiency, it has been proven that most patients with LG have defects in cytotoxic T cell function. That would explain how LG is less rare in many immunodeficiency states.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In our case, CD4 count cell was 124 cell/μl due to a good treatment compliance with discordant response.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Many studies have analyzed the connection between LG and AIDS. HIV infection is associated with an increased risk of lymphomas by 60-165 fold even in the combined antiretroviral therapy era. Excellent outcomes with infusion therapy and concurrent rituximab have been reported in the treatment of some of them.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">We report that laryngeal LG can mimic Reinke's edema in its early stages. In our own experience, Reinke's edema should not be treated as a casual finding in patients with fever of unknown origin or immunodeficiency.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Our current case was classified as grade III of LG, which is histologically considered as diffuse large B-cell malignant lymphoma,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> but the first biopsy was reported as polymorph lymphoid proliferation related to a post-transplant lymphoproliferative disorder (PTLD), which can simulate a lower grade of LG. LG and PTLD are associated with immunodeficiency and are driven by EBV. Histopathologically, they present a morphological spectrum spanning polymorphic through monomorphic lymphoid proliferations.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The distinctness of LG and PTLD has been emphasized by the difference in the immune response. While LG has a large population of background T-cells, PTLD is recognized by a poor T-cell enviroment.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">A better awareness of LG in recent years is at present allowing new therapeutic tools for this disease to be developed. Rituximab, a new monoclonal antibody anti-CD20 has shown promising results in some cases of LG with pulmonary involvement.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 974 "Ancho" => 1300 "Tamanyo" => 494800 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Atypical lymphoid infiltrate containing large lymphoid cells surrounding vascular structures, hematoxylin-eosyn, 10×. Positivity of EBV with histosonda EBER, immunoperoxidase stain, 40×.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lymphomatoid granulomatosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.A. Liebow" 1 => "C.R. Carrington" 2 => "P.J. Friedman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hum Pathol." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 0 | 3 |
| 2024 October | 15 | 12 | 27 |
| 2024 September | 30 | 24 | 54 |
| 2024 August | 16 | 6 | 22 |
| 2024 July | 14 | 7 | 21 |
| 2024 June | 22 | 1 | 23 |
| 2024 May | 7 | 8 | 15 |
| 2024 April | 17 | 9 | 26 |
| 2024 March | 15 | 12 | 27 |
| 2024 February | 21 | 7 | 28 |
| 2024 January | 18 | 3 | 21 |
| 2023 December | 28 | 5 | 33 |
| 2023 November | 22 | 5 | 27 |
| 2023 October | 23 | 12 | 35 |
| 2023 September | 11 | 2 | 13 |
| 2023 August | 11 | 4 | 15 |
| 2023 July | 13 | 25 | 38 |
| 2023 June | 7 | 25 | 32 |
| 2023 May | 24 | 10 | 34 |
| 2023 April | 21 | 2 | 23 |
| 2023 March | 12 | 4 | 16 |
| 2023 February | 24 | 4 | 28 |
| 2023 January | 14 | 5 | 19 |
| 2022 December | 30 | 6 | 36 |
| 2022 November | 51 | 7 | 58 |
| 2022 October | 32 | 4 | 36 |
| 2022 September | 25 | 11 | 36 |
| 2022 August | 23 | 19 | 42 |
| 2022 July | 21 | 10 | 31 |
| 2022 June | 15 | 9 | 24 |
| 2022 May | 14 | 8 | 22 |
| 2022 April | 21 | 11 | 32 |
| 2022 March | 17 | 8 | 25 |
| 2022 February | 12 | 7 | 19 |
| 2022 January | 14 | 7 | 21 |
| 2021 December | 14 | 13 | 27 |
| 2021 November | 14 | 8 | 22 |
| 2021 October | 25 | 10 | 35 |
| 2021 September | 14 | 5 | 19 |
| 2021 August | 13 | 6 | 19 |
| 2021 July | 34 | 13 | 47 |
| 2021 June | 20 | 10 | 30 |
| 2021 May | 28 | 6 | 34 |
| 2021 April | 46 | 10 | 56 |
| 2021 March | 43 | 6 | 49 |
| 2021 February | 26 | 5 | 31 |
| 2021 January | 26 | 16 | 42 |
| 2020 December | 19 | 11 | 30 |
| 2020 November | 10 | 7 | 17 |
| 2020 October | 11 | 9 | 20 |
| 2020 September | 32 | 5 | 37 |
| 2020 August | 22 | 10 | 32 |
| 2020 July | 20 | 2 | 22 |
| 2020 June | 11 | 4 | 15 |
| 2020 May | 13 | 8 | 21 |
| 2020 April | 6 | 3 | 9 |
| 2020 March | 8 | 6 | 14 |
| 2020 February | 11 | 5 | 16 |
| 2020 January | 18 | 10 | 28 |
| 2019 December | 24 | 17 | 41 |
| 2019 November | 17 | 9 | 26 |
| 2019 October | 19 | 4 | 23 |
| 2019 September | 13 | 8 | 21 |
| 2019 August | 6 | 3 | 9 |
| 2019 July | 15 | 35 | 50 |
| 2019 June | 38 | 18 | 56 |
| 2019 May | 90 | 45 | 135 |
| 2019 April | 34 | 38 | 72 |
| 2019 March | 6 | 4 | 10 |
| 2019 February | 15 | 16 | 31 |
| 2019 January | 12 | 6 | 18 |
| 2018 December | 15 | 9 | 24 |
| 2018 November | 18 | 17 | 35 |
| 2018 October | 19 | 7 | 26 |
| 2018 September | 12 | 3 | 15 |
| 2018 August | 7 | 5 | 12 |
| 2018 July | 18 | 2 | 20 |
| 2018 June | 6 | 1 | 7 |
| 2018 May | 12 | 7 | 19 |
| 2018 April | 30 | 1 | 31 |
| 2018 March | 10 | 2 | 12 |
| 2018 February | 8 | 1 | 9 |
| 2018 January | 6 | 2 | 8 |
| 2017 December | 15 | 1 | 16 |
| 2017 November | 6 | 4 | 10 |
| 2017 October | 9 | 0 | 9 |
| 2017 September | 7 | 17 | 24 |
| 2017 August | 13 | 1 | 14 |
| 2017 July | 18 | 4 | 22 |
| 2017 June | 15 | 16 | 31 |
| 2017 May | 25 | 5 | 30 |
| 2017 April | 27 | 5 | 32 |
| 2017 March | 35 | 2 | 37 |
| 2017 February | 23 | 1 | 24 |
| 2017 January | 24 | 2 | 26 |
| 2016 December | 25 | 8 | 33 |
| 2016 November | 29 | 5 | 34 |
| 2016 October | 62 | 5 | 67 |
| 2016 September | 64 | 3 | 67 |
| 2016 August | 37 | 1 | 38 |
| 2016 July | 22 | 1 | 23 |
| 2016 June | 40 | 10 | 50 |
| 2016 May | 33 | 1 | 34 |
| 2016 April | 13 | 2 | 15 |
| 2016 March | 19 | 4 | 23 |
| 2016 February | 23 | 5 | 28 |
| 2016 January | 28 | 10 | 38 |
| 2015 December | 27 | 8 | 35 |
| 2015 November | 24 | 2 | 26 |
| 2015 October | 37 | 6 | 43 |
| 2015 September | 39 | 6 | 45 |
| 2015 August | 15 | 4 | 19 |
| 2015 July | 20 | 5 | 25 |
| 2015 June | 12 | 1 | 13 |
| 2015 May | 23 | 2 | 25 |
| 2015 April | 32 | 5 | 37 |
| 2015 March | 37 | 3 | 40 |
| 2015 February | 19 | 2 | 21 |
| 2015 January | 30 | 1 | 31 |
| 2014 December | 34 | 4 | 38 |
| 2014 November | 27 | 2 | 29 |
| 2014 October | 21 | 3 | 24 |
| 2014 September | 36 | 5 | 41 |
| 2014 August | 19 | 1 | 20 |
| 2014 July | 30 | 3 | 33 |
| 2014 June | 23 | 2 | 25 |
| 2014 May | 20 | 4 | 24 |
| 2014 April | 32 | 1 | 33 |
| 2014 March | 46 | 9 | 55 |
| 2014 February | 43 | 9 | 52 |
| 2014 January | 32 | 7 | 39 |
| 2013 December | 54 | 8 | 62 |
| 2013 November | 41 | 19 | 60 |
| 2013 October | 61 | 18 | 79 |
| 2013 September | 47 | 13 | 60 |
| 2013 August | 70 | 6 | 76 |
| 2013 July | 54 | 10 | 64 |
| 2013 June | 23 | 6 | 29 |
| 2013 May | 23 | 5 | 28 |
| 2013 April | 32 | 12 | 44 |
| 2013 March | 12 | 11 | 23 |
| 2013 February | 5 | 3 | 8 |
| 2013 January | 9 | 2 | 11 |
| 2012 December | 7 | 5 | 12 |
| 2012 November | 0 | 2 | 2 |
| 2012 October | 2 | 2 | 4 |
| 2011 July | 612 | 0 | 612 |
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