Camboni, Alessandra

Candaele, Ann-Sophie

Deryck, Frédéric

Geenen, Sofie

Libbrecht, Louis

Van Bockstal, Mieke

Van Dorpe, Jo

Vandemaele, Lies

Verbeke, Sofie

Ghent University Academic Bibliography

Thyroid-specific transcription factor 1 (TTF-1) is a transcription factor encoded bythe NKX2-1 gene. TTF-1 expression is assumed to be restricted to pulmonary andthyroid epithelium.However, nuclear staining has been described in colorectal cancer, breast cancer,cholangiocarcinoma and adenocarcinoma of the cervix and endometrium, amongstothers. This aspecific immunohistochemical staining occurred in both primarytumours and metastases.Two commercially available monoclonal anti-TTF-1 antibodies are commonly used:SPT24 and 8G7G3/1. The SPT24 clone is suspected to be more sensitive but lessspecific than the 8G7G3/1 clone.TTF-1 expression in diffuse large B-cell lymphoma:a confusing game of clones.Ann-Sophie Candaele1, Mieke Van Bockstal1,2, Alessandra Camboni3, Sofie Geenen1, Lies Vandemaele1,  Frédéric De Ryck4, Louis Libbrecht3, Sofie Verbeke1,2, Jo Van Dorpe1,21 Department of pathology, Ghent University Hospital (Ghent, Belgium), 2 Cancer Research Institute Ghent (CRIG, Ghent, Belgium), 3 Department of pathology, Saint-Luc Hospital (Brussels, Belgium), 4 Department of thoracic and vascular surgery, Ghent University Hospital (Ghent, Belgium).BackgroundConclusionIndex caseContact :  alessandra.camboni@uclouvain.be  and mieke.vanbockstal@ugent.beMaterials & methodsArchived paraffin-embedded tissue blocks were retrieved from106 DLBCL cases, of which 32 were diagnosed at the St LucHospital (Brussels, Belgium) and 74 were diagnosed at GhentUniversity Hospital (Ghent, Belgium).Immunohistochemistry for TTF-1 was performed on 3,5 µmtissue sections using an automated immunostainer (BenchmarkXT, Ventana Medical Systems, Oro Valley, AZ, USA). Two anti-TTF-1 clones were used: the SPT24 clone (dilution 1/20,NovocastraTM liquid mouse monoclonal antibody, LeicaBiosystems Newcastle Ltd, UK) and the 8G7G3/1-clone (dilution1/50, mouse monoclonal, Dako Cytomation, Glostrup, Denmark).Information on germinal center B-cell-like (GCB) and non-GCBimmunohistochemical subgroups based on the Hans algorithm(immunohistochemistry for CD10, Bcl-6 and MUM1) wasretrieved from histopathological reports and was available for 93of 106 cases (88%).Aim of this studyTo our knowledge, TTF-1 expression has not yet been described in diffuse large B-cell lymphoma (DLBCL). We encountered an index case of DLBCL expressingTTF-1, which prompted us to investigate TTF-1 expression in a series of DLBCL.A man with a history of pulmonaryadenocarcinoma presented with asubcutaneous mass on the thoracic wall.Routine hematoxylin/eosin stainingshowed a poorly differentiated large cellneoplasm.Initial immunohistochemistry showed alesion which was broad spectrumcytokeratin negative, S100 negative, andCD45 positive. Although the positivity forCD45 indicated a lymphoma, this lesionpresented TTF-1/SPT24 expression aswell. Additional staining with the8G7G3/1 clone for TTF-1 was negative.Further immunohistochemical analysisshowed a diffuse large B-cell lymphoma,non-GCB type, with double expression ofc-Myc and Bcl-2 without rearrangementof MYC and BCL2 genes.CD45CD20CytokeratinTTF-1/SPT24Hematoxylin/eosinTTF-1/8G7G3/1TTF-1 expression in a cohort of 105 DLBCLTTF-1/SPT24 TTF-1/SPT24TTF-1/8G7G3/1  TTF-1/8G7G3/1A BC DImmunohistochemical analysis of 105additional DLBCL cases revealed nuclearstaining for TTF-1/SPT24 in 3 extra DLBCLcases (Figures C-D). No nuclear stainingfor TTF-1/G87G3/1 was observed (FiguresA-B). None of the cases presented withcytoplasmic positivity for either of the TTF-1 clones.In all, this cohort of 106 DLBCL contained4 cases (3,8%) with nuclear positivity forTTF-1/SPT4. According to the Hansalgorithm, two of these DLBCL casesbelonged to the germinal center B-cell-like(GCB) immunohistochemical subgroupand two were non-GCB type.Figures A and B show no immunohistochemicalstaining for TTF-1 with the 8G7G3/1 clone in 2 DLBCLcases, whereas figures C and D (same cases) clearlypresent nuclear staining with the TTF-1/SPT24 clone.Both the 8G7G3/1 andSPT24 clones for TTF-1 arewidely used, but our studyshows that the SPT24 clonemight result in false positiveTTF-1 expression in 3,8% ofDLBCL. Although this is arather rare phenomenon, itcould present an importantdiagnostic pitfall during theinvestigation of a poorlydifferentiated malignancy.To increase awareness, werecommend that thisphenomenon should beincluded in the datasheet ofthe NovocastraTM liquidmouse monoclonal SPT24antibody (Leica BiosystemsNewcastle, UK).

TTF-1 expression in diffuse large B-cell lymphoma : a confusing game of clones

https://biblio.ugent.be/publication/8536918/file/8536919

TTF-1 expression in diffuse large B-cell lymphoma : a confusing game of clones

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Ghent University Academic Bibliography