{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:08:16Z","timestamp":1792519696068,"version":"4.5.0"},"reference-count":250,"publisher":"Wiley","issue":"S270","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:label\/><jats:p>Ocular adnexal lymphoma is a relatively rare disease but is one of the most common malignancies in the ocular adnexa, and its incidence is steadily increasing. Ocular adnexal lymphoma consists mainly of four histopathological subtypes of non\u2010Hodgkin B\u2010cell lymphoma: extranodal marginal zone lymphoma (EMZL), follicular lymphoma (FL), mantle cell lymphoma (MCL) and large B\u2010cell lymphoma (LBCL). The clinical characteristics associated with each of the subtypes are not well known due to the sparsity of cases. Furthermore, a number of molecular and phenotypic features have been identified as recurrent and prognosticating in LBCL but are not yet well documented for the ocular adnexal region: concurrent<jats:italic>MYC<\/jats:italic>and<jats:italic>BCL2<\/jats:italic>and\/or<jats:italic>BCL6<\/jats:italic>rearrangements, MYC\/BCL2 double\u2010expressor phenotype (in diffuse large B\u2010cell lymphomas), and<jats:italic>MYD88<\/jats:italic>and<jats:italic>CD79B<\/jats:italic>mutations. Therefore, the present PhD study aimed to investigate the clinical features of (1) conjunctival lymphoma by subtype and (2) ocular adnexal MCL in an international multicentre cohort of 307 patients and (3) the clinical and genetic features of ocular adnexal LBCL in 34 Danish patients. This was performed by collecting clinical data on the patients and tissue samples of the LBCLs. The tissue samples were analysed immunohistochemically for phenotype, by allele\u2010specific PCR and Sanger sequencing for the presence of the mutations, and by fluorescence in situ hybridisation for the rearrangements. Statistical analyses were performed to detect correlations with clinical features and survival.<\/jats:p><jats:p>The analyses revealed that conjunctival EMZL and FL typically presented in individuals in their 60s as localised unilateral tumour masses and had favourable prognoses (5\u2010year disease\u2010specific survival: 82%\u201397%). LBCL and MCL were found in all the ocular adnexal structures, with the orbit being the most common location (82% and 58%, respectively). These lymphomas typically presented in patients in their 70s, with MCL having a male predominance. MCLs commonly presented with bilateral lesions and systemic involvement, while LBCLs were unilateral localised tumours. Both subtypes had poor prognoses, with 49%\u201362% of patients having succumbed to the disease within 5\u2009years.<\/jats:p><jats:p>Ocular adnexal LBCLs had presence of concurrent<jats:italic>MYC<\/jats:italic>and<jats:italic>BCL2<\/jats:italic>and\/or<jats:italic>BCL6<\/jats:italic>rearrangements in 16% of cases, MYC\/BCL2 double\u2010expressor phenotype in 44% of diffuse large B\u2010cell lymphomas, and<jats:italic>MYD88<\/jats:italic>\u00a0\u00b1\u00a0<jats:italic>CD79B<\/jats:italic>mutations in 29% of cases. MYC\/BCL2 double\u2010expressor phenotype and<jats:italic>MYD88<\/jats:italic>mutations were associated with adverse prognoses.<\/jats:p><jats:p>All in all, the results indicate that the histopathological subtype of ocular adnexal lymphoma is a major outcome predictor. Furthermore, the results underline the importance of analysing the expression of MYC and BCL2 by immunohistochemistry in diffuse large B\u2010cell lymphoma patients and advocate for incorporating the analysis of<jats:italic>MYD88<\/jats:italic>mutations in the routine diagnostic workup of ocular adnexal LBCL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Summary in Danish<\/jats:title><jats:p>Lymfomer i \u00f8jenregionen (orbita, conjunctiva, \u00f8jenl\u00e5g, t\u00e5rekirtel og t\u00e5res\u00e6k) er relativt sj\u00e6ldne tumorer, men er blandt de hyppigste cancerformer i denne region og forekomsten er hastigt stigende. Lymfomer i \u00f8jenregionen best\u00e5r hovedsageligt af 4 undertyper af non\u2010Hodgkin B\u2010celle lymfom: ekstranodalt marginal zone lymfom, follikul\u00e6rt lymfom, storcellet B\u2010celle lymfom og mantle celle lymfom. Grundet sygdommens sj\u00e6ldenhed er kliniske karakteristika ved de forskellige lymfomundertyper kun sparsomt unders\u00f8gt. Endvidere er der blevet identificeret en r\u00e6kke prognostisk vigtige molekyl\u00e6re og f\u00e6notypiske kendetegn ved storcellede B\u2010celle lymfomer, som endnu ikke er velunders\u00f8gt i \u00f8jenregionen. Det drejer sig om samtidig rearrangement i<jats:italic>MYC<\/jats:italic>og<jats:italic>BCL2<\/jats:italic>og\/eller<jats:italic>BCL6<\/jats:italic>, samtidig overekspression af MYC og BCL2 samt<jats:italic>MYD88<\/jats:italic>og<jats:italic>CD79B<\/jats:italic>mutationer. Dette ph.d.\u2010studie havde derfor til form\u00e5l at unders\u00f8ge de kliniske kendetegn ved (1) mantle celle lymfomer i \u00f8jenregionen og (2) de forskellige undertyper af conjunktivale lymfomer i en international kohorte med 307 patienter samt (4) de kliniske, molekyl\u00e6re og f\u00e6notypiske kendetegn ved storcellet B\u2010celle lymfom i 34 danske patienter.<\/jats:p><jats:p>V\u00e6vsmaterialet med storcellede B\u2010celle lymfomer blev unders\u00f8gt ved hj\u00e6lp af immunhistokemi for f\u00e6notypen, ved hj\u00e6lp af allel\u2010specifik PCR og Sanger sekventering for mutationerne og ved hj\u00e6lp af fluorescens in situ\u2010hybridisering for rearrangementerne. Der blev udf\u00f8rt statistiske analyser med henblik p\u00e5 at finde eventuelle sammenh\u00e6nge med kliniske karakteristika og overlevelse.<\/jats:p><jats:p>Analyserne viste, at conjunctivalt ekstranodalt marginal zone lymfom og follikul\u00e6rt lymfom typisk forekom blandt patienter i 60erne som ensidige tumorer uden spredning og var forbundet med en god prognose (5\u2010\u00e5rs sygdomsspecifik overlevelse p\u00e5 82\u201397%). Storcellet B\u2010celle lymfom og mantle celle lymfom blev fundet i samtlige strukturer i \u00f8jenregionen med orbita som den hyppigste lokalisation (hhv. 82% og 58%). Disse lymfomundertyper forekom prim\u00e6rt hos patienter i 70erne med overv\u00e6gt af m\u00e6nd blandt mantle celle lymfomerne. Mantle celle lymfomerne pr\u00e6senterede sig typisk som dobbeltsidige l\u00e6sioner i \u00f8jenregionen med systemisk involvering, mens storcellede B\u2010celle lymfomer var ensidige tumorer uden spredning. Begge undertyper havde en d\u00e5rlig prognose, hvor cirka halvdelen af patienterne d\u00f8de af sygdommen indenfor 5 \u00e5r.<\/jats:p><jats:p>Genetisk var storcellede B\u2010celle lymfomer i \u00f8jenregionen karakteriseret ved betydelig pr\u00e6valens af<jats:italic>MYD88<\/jats:italic>mutationer (29%), som var forbundet med en d\u00e5rlig prognose. Rearrangementer i<jats:italic>MYC<\/jats:italic>og<jats:italic>BCL2<\/jats:italic>og\/eller<jats:italic>BCL6<\/jats:italic>forekom i 16% af tilf\u00e6ldene. Derudover havde 44% af diffuse storcellede B\u2010celle lymfomer samtidig overekspression af MYC og BCL2, som var associeret med en d\u00e5rlig prognose for patienterne.<\/jats:p><jats:p>Alt i alt viser resultaterne, at den histologiske undertype er en vigtig prognostisk faktor for lymfomer i \u00f8jenregionen. Derudover fremh\u00e6ver resultaterne vigtigheden af unders\u00f8gelsen af MYC\/BCL2 f\u00e6notypen og implementeringen af<jats:italic>MYD88<\/jats:italic>mutationsunders\u00f8gelsen i rutinediagnostikken af storcellede B\u2010celle lymfomer i \u00f8jenregionen.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.15248","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T09:21:36Z","timestamp":1664961696000},"page":"3-37","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Ocular adnexal lymphoma: Subtype\u2010specific clinical and genetic features"],"prefix":"10.1111","volume":"100","author":[{"given":"Marina Knudsen","family":"Kirkegaard","sequence":"first","affiliation":[{"name":"Department of Pathology, Eye Section, Copenhagen University Hospital Rigshospitalet Copenhagen 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