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Vitreoretinal lymphoma: a diagnostic challenge
Linfoma vitreoretiniano: un reto diagnóstico
E. Sáenz Deckera,
Corresponding author
elensdeck@gmail.com

Corresponding author.
, M. García Fernándeza, R. Gómez De la Torreb, R. Coto Hernándezb, L.I. Santana Garcíaa
a Servicio de Oftalmologia, Hospital Universitario Central de Asturias, Oviedo, Spain
b Servicio de Medicina Interna, Hospital Universitario Central de Asturias, Oviedo, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Vitreoretinal lymphoma presents as a high-grade extranodal non-Hodgkin lymphoma&#44; mainly of activated B-cell origin&#46; Despite its low incidence&#44; it has seen an increase in recent years as a consequence of increased life expectancy&#44; increased use of immunosuppressants and more accurate diagnostic techniques&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">It typically presents with <span class="elsevierStyleItalic">aurora borealis</span> or sheet vitritis accompanied by subepithelial or deep retinal pigmentary infiltrates&#44; and should be suspected in cases of torpid uveitis or uveitis refractory to corticosteroid treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical case</span><p id="par0015" class="elsevierStylePara elsevierViewall">We present the case of a 66-year-old male patient&#44; with no medical history of interest and a farmer&#44; who was referred to our hospital for evaluation of posterior uveitis in the right eye &#40;RE&#41; in relation to possible Lyme disease&#44; given the history of a recent tick bite and compatible complementary tests&#44; such as a positive immunoblot for <span class="elsevierStyleItalic">Borrelia burgdorferi</span>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient had been treated at his referral hospital with ceftriaxone and oral and intravenous corticosteroids&#44; as well as with oral doxycycline&#44; having presented numerous recurrences after lowering the dose of oral corticosteroid&#44; for which he was referred to our hospital for further evaluation&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The initial examination revealed a visual acuity &#40;VA&#41; of 0&#46;1 in the RE and 1&#46;0 in the left eye &#40;LE&#41;&#44; and funduscopy revealed mild vitritis in the RE&#44; optic disc hyperemia and peripheral pigment mobilisation&#44; with the appearance of the LE being normal &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Optical coherence tomography &#40;OCT&#41; showed cystic macular edema &#40;CME&#41; with disruption of the outer layers and choroidal thickening&#44; the OCT of the LE being null&#46; There was also significant thickening of the nerve fibre layer &#40;NLC&#41; in the RE&#44; which was normal in the LE&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A blood count&#44; uremia&#44; creatinine&#44; liver profile&#44; C-reactive protein and angiotensin-converting enzyme&#44; treponemal tests&#44; IgM and IgG serology for toxoplasmosis&#44; human immunodeficiency virus &#40;HIV&#41; serology and Mantoux&#44; as well as complementary tests&#44; including chest X-ray&#44; brain computed axial tomography &#40;CAT&#41; with and without contrast and lumbar puncture&#44; which were also found to be unremarkable&#46; Despite the unilateral nature of the picture and in order to rule out paraneoplastic syndrome&#44; a CT scan of the chest and abdomen&#44; anti-retinal antibodies &#40;anti-recoverin and anti-enolase&#41; and neurophysiological tests &#40;ERG&#44; EOG&#41; were requested&#46; In the absence of results&#44; it was decided to perform an anterior chamber puncture under topical anesthesia to determine the IL-10&#47;IL-6 ratio&#44; which was &#60;1 and therefore not suggestive of lymphoma&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In the presence of recurrences and in order to control the condition&#44; treatment was started with a descending course of oral corticosteroids at a dose of mg&#47;kg&#47;day&#44; with partial remission of the CMD&#44; so it was decided to perform an intravitreal injection of dexamethasone 700 micrograms &#40;Ozurdex&#174;&#41;&#44; with a complete response&#44; but with recurrence after 4 months&#44; requiring two additional injections of this drug in the RE&#46; Given the dependency on corticoids and macular involvement&#44; and after the relevant assessment by the internal medicine and preventive medicine services&#44; it was decided to start biological treatment as a corticosteroid-sparing treatment with adalimumab&#44; starting with a load of 80&#8239;mg subcutaneously and then 40&#8239;mg every 14 days&#46; The patient showed no improvement and was unable to avoid dependence on intravitreal corticosteroids&#44; despite the biologic treatment&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Four months later&#44; the patient presented with myodesopsia in the LE&#44; showing a VA of 0&#46;6 on examination&#44; with funduscopy showing sheet vitritis&#44; yellowish-white subretinal infiltrates in the inferior and nasal retina&#44; some with pigmentary mottling on the surface and the appearance of adjacent flat retinal detachment&#46; OCT again showed CME in the RE&#44; being normal in the LE &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; In view of the evidence of vitritis in the oleopharyngeal eye and despite the negative results of the complementary tests performed&#44; vitrectomy and biopsy of the chorioretinal lesion in the LE was decided&#44; after suspending systemic corticosteroid treatment for 7 days&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Vitrectomy 23&#8239;G via pars plana was performed under air and at low cutting speed and a sample of undiluted vitreous humour was collected&#46; Subsequently&#44; endolaser was applied to the largest nasal subretinal yellowish focus&#44; and retinotomy was performed on the centre of the focus&#44; aspirating the subretinal content&#46; Flow cytometry was positive for lymphomatous infiltration of type B lymphoma&#44; phenotypically compatible with CD10 large cell lymphoma&#46; In view of the results obtained&#44; the patient was admitted for lumbar puncture&#44; which was negative&#44; including flow cytometry analysis&#44; which was phenotypically normal&#44; ruling out leptomeningeal involvement&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">After confirmation of the diagnosis&#44; the patient was referred to the hematology department and treatment was started with intravenous systemic chemotherapy with BRAM &#40;carmustine&#44; methotrexate&#44; ara-C and rituximab&#41;&#46; Two months later&#44; VA is 0&#46;3 in AO&#44; and the fundus shows a significant reduction in optic nerve infiltration&#44; with regressive appearance of the lesions&#44; appearance of pigmentary mottling throughout the posterior pole and resolution of the exudative retinal detachment &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">As a result of long-term ocular inflammation&#44; vitrectomy and prolonged treatment with corticosteroids&#44; the patient developed cataracts with a posterior subcapsular component bilaterally&#44; which were operated on&#44; finally achieving 0&#46;7 vision in AO&#46; The VA and the regressive appearance of the lesions were maintained during the 3 years of follow-up&#44; without developing CNS involvement or at any other level&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">Recurrent uveitis with partial response to steroid treatment should raise suspicion of vitreoretinal lymphoma&#44; even in the presence of retinal scar lesions as the only finding&#44; as in the present case&#44; especially when the uveitis could not be assessed in the acute phase or was initially treated with steroids&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In case of negative supplementary tests &#40;blood tests&#44; serology&#44; Mantoux&#44; chest X-ray&#44; thoracoabdominal CT and brain MRI&#41;&#44; diagnostic vitrectomy for biopsy and cytology of the vitreous sample should be considered&#46; In a high percentage of cases this test is inconclusive&#44; as most patients are on corticosteroid treatment&#44; which masks the diagnosis&#44; so it is essential to reduce or stop steroid treatment weeks before the surgical procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In order to increase the diagnostic yield&#44; an adequate undiluted vitreous sample should also be collected and analysed early&#44; and good communication with the pathologist is essential&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Diagnosis of <span class="elsevierStyleItalic">Borrelia burgdorferi</span> infection is commonly made by serological tests including the indirect fluorescent antibody test &#40;IFAT&#41;&#44; whole cell ELISA&#44; Western blot &#40;WB&#41; and a bead-based multiple antigen ELISA assay&#46; Serological interpretation is problematic and focuses on the heterogeneity of assays&#44; the high seroprevalence in endemic areas&#44; the lack of clinical validation of assays in Europe and the presence of diverse <span class="elsevierStyleItalic">Borrelia</span> strains in the US and Europe&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Regardless of methodology&#44; a positive serological test can be interpreted as current or past infection&#44; but has a low positive predictive value for clinical disease&#46; It has not been determined whether prolongation over time of a positive serology is due to persistence of infection&#44; reinfection&#44; exposure or an immune response to <span class="elsevierStyleItalic">Borrelia</span> with continued production of IgG against <span class="elsevierStyleItalic">Borrelia</span> antigens after elimination of the organism&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Positive <span class="elsevierStyleItalic">Borrelia</span> serology results should therefore be interpreted with caution and the possibility of other etiologies should always be kept in mind depending on the clinical appearance and evolution of the patient&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The relevance of the present case lies in its diagnostic challenge&#44; due to the initial absence of typical vitreoretinal lymphoma lesions&#44; manifesting as cicatricial lesions on arrival at our centre as a consequence of previous treatment with corticosteroids&#46; This&#44; added to the positive serological findings for <span class="elsevierStyleItalic">Borrelia burgdorferi</span>&#44; led to an erroneous diagnosis&#44; even leading to the use of biological treatment as a corticosteroid sparing treatment&#44; which masked the process&#44; delaying the appearance of lesions characteristic of vitreoretinal lymphoma and&#44; therefore&#44; the proper diagnosis until after one year&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">In this case&#44; the success of the diagnostic vitrectomy is related to the suspension of corticosteroid treatment prior to the intervention&#44; the collection of two samples &#40;one of undiluted vitreous and one of diluted vitreous&#41; and the subsequent retinotomy of the lesion with aspiration of the subretinal material&#44; given that the vitritis was not extensive and the vitreous sample could be insufficient&#46; In addition&#44; an early analysis of the sample was performed after prior communication with the anatomical pathology department&#44; which facilitated the diagnosis&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Vitrectomy is considered the <span class="elsevierStyleItalic">gold standard for</span> the diagnosis of ocular lymphomas&#44; with cytometry having a high positive predictive value&#44; so a positive result will confirm the diagnosis&#59; furthermore&#44; in a high percentage of cases&#44; surgery manages to considerably reduce ocular symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="par0095" class="elsevierStylePara elsevierViewall">In cases such as the present one&#44; where there is no evidence of symptoms or signs at the extraocular level&#44; it is essential to make an early diagnosis&#44; allowing early systemic treatment to be initiated in order to avoid potential CNS involvement and thus reduce the morbidity and mortality of the disease&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Funding</span><p id="par0100" class="elsevierStylePara elsevierViewall">This research has not received specific support from public sector agencies&#44; the commercial sector or non-profit organisations&#46;</p></span><span id="sec1025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect3045">Conflict of interests</span><p id="par5100" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A 66-year-old man with posterior uveitis and recurrent cystic macular edema related to possible previously treated Lyme disease is presented&#46; Due to the recurrence of macular edema despite systemic and local corticosteroid treatment with intravitreal dexamethasone&#44; biological treatment with Adalimumab was established&#46; During follow-up&#44; the patient developed bilateral subretinal lesions compatible with Vitreoretinal Lymphoma &#40;VRL&#41;&#44; so vitrectomy was performed&#44; confirming the diagnosis of large B-cell lymphoma&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Treatment with systemic chemotherapy with BRAM-Carmustine&#44; Metrotexate&#44; Ara C&#44; and Rituximab was started with a good answer&#46; Two years later&#44; the patient remains without ocular or systemic recurrences&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Vitreoretinal Lymphoma is a rare type of primary central nervous system lymphoma&#46; The diagnosis is frequently delayed due to the nonspecific symptoms&#44; which mimic chronic posterior uveitis&#44; hence the importance with a diagnostic suspicion&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se presenta el caso de un var&#243;n de 66 a&#241;os remitido por uve&#237;tis posterior con edema macular qu&#237;stico recurrente en relaci&#243;n con posible enfermedad de Lyme previamente tratada&#46; Debido a la recurrencia del edema macular pese al tratamiento corticoideo sist&#233;mico y local con dexametasona intrav&#237;trea&#44; se instaura tratamiento biol&#243;gico con Adalimumab&#46; Durante el seguimiento el paciente desarrolla lesiones subretinianas bilaterales compatibles con Linfoma Vitreorretiniano &#40;LVR&#41;&#44; por lo que se realiza vitrectom&#237;a confirmando el diagn&#243;stico de linfoma de c&#233;lula B grande&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se inicia tratamiento con quimioterapia sist&#233;mica con BRAM- Carmustina&#44; Metrotexate&#44; Ara C y Rituximab&#44; con buena respuesta&#46; Dos a&#241;os despu&#233;s&#44; el paciente permanece sin recurrencias a nivel ocular ni sist&#233;mico&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">El Linfoma Vitreoretiniano es un tipo poco frecuente de linfoma primario del sistema nervioso central&#46; El diagn&#243;stico se ve frecuentemente retrasado debido a la inespecificidad de su sintomatolog&#237;a&#44; que simula una uve&#237;tis posterior cr&#243;nica&#44; de ah&#237; la importancia de la sospecha diagn&#243;stica&#46;</p></span>"
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Article information
ISSN: 21735794
Original language: English
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