Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies

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dc.contributor.authorWada, David A.
dc.contributor.authorLaw, Mark E.
dc.contributor.authorHsi, Eric D.
dc.contributor.authorDiCaudo, David J.
dc.contributor.authorMa, Linglei
dc.contributor.authorLim, Megan S.
dc.contributor.authorde Souza, Aieska
dc.contributor.authorComfere, Nneka I.
dc.contributor.authorWeenig, Roger H.
dc.contributor.authorMacon, William R.
dc.contributor.authorErickson, Lori A.
dc.contributor.authorOzsan, Nazan
dc.contributor.authorAnsell, Stephen M.
dc.contributor.authorDogan, Ahmet
dc.contributor.authorFeldman, Andrew L.
dc.date.accessioned2019-10-27T21:24:36Z
dc.date.available2019-10-27T21:24:36Z
dc.date.issued2011
dc.departmentEge Üniversitesien_US
dc.description.abstractCurrent pathologic criteria cannot reliably distinguish cutaneous anaplastic large cell lymphoma from other CD30-positive T-cell lymphoproliferative disorders (lymphomatoid papulosis, systemic anaplastic large cell lymphoma with skin involvement, and transformed mycosis fungoides). We previously reported IRF4 (interferon regulatory factor-4) translocations in cutaneous anaplastic large cell lymphomas. Here, we investigated the clinical utility of detecting IRF4 translocations in skin biopsies. We performed fluorescence in situ hybridization (FISH) for IRF4 in 204 biopsies involved by T-cell lymphoproliferative disorders from 182 patients at three institutions. In all, 9 of 45 (20%) cutaneous anaplastic large cell lymphomas and 1 of 32 (3%) cases of lymphomatoid papulosis with informative results demonstrated an IRF4 translocation. Remaining informative cases were negative for a translocation (7 systemic anaplastic large cell lymphomas; 44 cases of mycosis fungoides/Sezary syndrome (13 transformed); 24 peripheral T-cell lymphomas, not otherwise specified; 12 CD4-positive small/medium-sized pleomorphic T-cell lymphomas; 5 extranodal NK/T-cell lymphomas, nasal type; 4 gamma-delta T-cell lymphomas; and 5 other uncommon T-cell lymphoproliferative disorders). Among all cutaneous T-cell lymphoproliferative disorders, FISH for IRF4 had a specificity and positive predictive value for cutaneous anaplastic large cell lymphoma of 99 and 90%, respectively (P = 0.00002, Fisher's exact test). Among anaplastic large cell lymphomas, lymphomatoid papulosis, and transformed mycosis fungoides, specificity and positive predictive value were 98 and 90%, respectively (P = 0.005). FISH abnormalities other than translocations and IRF4 protein expression were seen in 13 and 65% of cases, respectively, but were nonspecific with regard to T-cell lymphoproliferative disorder subtype. Our findings support the clinical utility of FISH for IRF4 in the differential diagnosis of T-cell lymphoproliferative disorders in skin biopsies, with detection of a translocation favoring cutaneous anaplastic large cell lymphoma. Like all FISH studies, IRF4 testing must be interpreted in the context of morphology, phenotype, and clinical features. Modern Pathology (2011) 24, 596-605; doi: 10.1038/modpathol.2010.225; published online 17 December 2010en_US
dc.description.sponsorshipUniversity of Iowa [P50 CA097274]; National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI)en_US
dc.description.sponsorshipWe would like to acknowledge Dr Joshua Weaver at the Cleveland Clinic and Dr Thomas F Anderson at the University of Michigan for their contributions regarding clinical staging of cases at their respective institutions, and Matthew J Maurer at Mayo Clinic for help with the statistical analysis. ALF is a Damon Runyon Clinical Investigator supported by the Damon Runyon Cancer Research Foundation (CI-48-09). This work was supported in part by a Career Development Award to ALF under Public Health Service Grant number P50 CA097274 from the University of Iowa /Mayo Clinic Lymphoma Specialized Program of Research Excellence (UI/MC Lymphoma SPORE) and the National Cancer Institute. Portions of this study were presented at the 98th Annual Meeting of the United States and Canadian Academy of Pathology, 7-13 March 2009, Boston, MA, USA.en_US
dc.identifier.doi10.1038/modpathol.2010.225en_US
dc.identifier.endpage605en_US
dc.identifier.issn0893-3952
dc.identifier.issn1530-0285
dc.identifier.issue4en_US
dc.identifier.pmid21169992en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage596en_US
dc.identifier.urihttps://doi.org/10.1038/modpathol.2010.225
dc.identifier.urihttps://hdl.handle.net/11454/44595
dc.identifier.volume24en_US
dc.identifier.wosWOS:000289072100014en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofModern Pathologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectanaplastic large cell lymphomaen_US
dc.subjectfluorescence in situ hybridizationen_US
dc.subjectIRF4en_US
dc.subjectlymphomatoid papulosisen_US
dc.subjectMUM1en_US
dc.subjectmycosis fungoidesen_US
dc.subjectT-cell lymphomaen_US
dc.titleSpecificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsiesen_US
dc.typeArticleen_US

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