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Double/triple hit lymphoma in the gastrointestinal tract: clinicopathological features, PD-L1 expression and screening strategy. 2022

Jianchun Guo, and Yuxiang Cai, and Zhe Wang, and Jian Xu, and Honglei Chen, and Jijun Zhang, and Xiuli Xu, and Huilan Rao, and Sufang Tian
Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China.

We aimed to detect the clinicopathological features and immune microenvironment of double-hit/triple-hit lymphoma in the gastrointestinal tract (GI-DHL/THL) and identify the best diagnostic strategies. A total of 114 cases, including 15 GI-DHL/THL, 42 non-GI-DHL/THL and 57 control diffuse large B-cell lymphoma (DLBCL) cases, were comparatively analyzed for their clinicopathological characteristics, the expression of the immune-regulatory checkpoint PD-L1 and immune microenvironment. We applied univariate and multivariate analyses to determine predictors of DHL/THL. GI-DHL/THL patients showed a higher prevalence of previous infection with hepatitis B virus (HBV) than those with GI-DLBCL. Morphologically, 87% of cases exhibited features of DLBCL. Regarding immunohistochemistry results, the MYC protein expression and the Ki-67 proliferation index were significantly higher in the GI-DHL/THL group than in the GI-DLBCL group. The main source of PD-L1 expression in DHL was tumor-associated macrophages, whereas some tumor cells were positive for PD-L1 in GI-DLBCL cases, as determined through multiplex immunofluorescence staining. The multivariable logistic analysis suggested that 5 variables, namely, age, Mum1, CD10, MYC, and HBV infection status, reflect the risk of DHL/THL. The GI-DHL/THL group show different clinicopathological features and immune microenvironments from DLBCL, which might suggest that different signaling pathways are involved. More work is needed to elucidate the pathogenic mechanism of GI-DHL/THL.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016271 Proto-Oncogene Proteins c-myc Basic helix-loop-helix transcription factors encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis. L-myc Proteins,N-myc Proteins,c-myc Proteins,myc Proto-Oncogene Proteins,p62(c-myc),Proto-Oncogene Products c-myc,Proto-Oncogene Proteins myc,myc Proto-Oncogene Product p62,p62 c-myc,L myc Proteins,N myc Proteins,Proteins myc, Proto-Oncogene,Proto Oncogene Products c myc,Proto Oncogene Proteins c myc,Proto Oncogene Proteins myc,Proto-Oncogene Proteins, myc,c myc Proteins,myc Proto Oncogene Product p62,myc Proto Oncogene Proteins,myc, Proto-Oncogene Proteins,p62 c myc
D016403 Lymphoma, Large B-Cell, Diffuse Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation. Diffuse Large B-Cell Lymphoma,Diffuse, Large B-Cell, Lymphoma,Histiocytic Lymphoma, Diffuse,Lymphoma, Histiocytic, Diffuse,Diffuse Large-Cell Lymphoma,Histiocytic Lymphoma,Large Lymphoid Lymphoma, Diffuse,Large-Cell Lymphoma, Diffuse,Lymphoma, Diffuse Large-Cell,Lymphoma, Histiocytic,Lymphoma, Large Cell, Diffuse,Lymphoma, Large Lymphoid, Diffuse,Lymphoma, Large-Cell, Diffuse,Diffuse Histiocytic Lymphoma,Diffuse Histiocytic Lymphomas,Diffuse Large B Cell Lymphoma,Diffuse Large Cell Lymphoma,Diffuse Large-Cell Lymphomas,Histiocytic Lymphomas,Large Cell Lymphoma, Diffuse,Lymphoma, Diffuse Histiocytic,Lymphoma, Diffuse Large Cell
D041981 Gastrointestinal Tract Generally refers to the digestive structures stretching from the MOUTH to ANUS, but does not include the accessory glandular organs (LIVER; BILIARY TRACT; PANCREAS). Digestive Tract,GI Tract,Digestive Tracts,GI Tracts,Gastrointestinal Tracts
D051560 Proto-Oncogene Proteins c-bcl-6 A DNA-binding protein that contains an N-terminal BTB (POZ) DOMAIN and C-terminal CYS2-HIS2 ZINC FINGERS. It represses GENETIC TRANSCRIPTION of target genes by recruiting HISTONE DEACETYLASES. Aberrant Blc-6 expression is associated with certain types of human B-CELL LYMPHOMA. bcl-6 Proto-Oncogene Proteins,c-bcl-6 Protein,c-bcl-6 Proto-Oncogene Proteins,B-Cell Lymphoma 6 Protein,Proto-Oncogene Protein bcl-6,Proto-Oncogene Protein c-bcl-6,Zinc Finger Protein 51,B Cell Lymphoma 6 Protein,Proto Oncogene Protein bcl 6,Proto Oncogene Protein c bcl 6,Proto Oncogene Proteins c bcl 6,Proto-Oncogene Proteins, bcl-6,Proto-Oncogene Proteins, c-bcl-6,bcl 6 Proto Oncogene Proteins,bcl-6, Proto-Oncogene Protein,c bcl 6 Protein,c bcl 6 Proto Oncogene Proteins,c-bcl-6, Proto-Oncogene Proteins
D059016 Tumor Microenvironment The milieu surrounding neoplasms consisting of cells, vessels, soluble factors, and molecules, that can influence and be influenced by, the neoplasm's growth. Cancer Microenvironment,Cancer Microenvironments,Microenvironment, Cancer,Microenvironment, Tumor,Microenvironments, Cancer,Microenvironments, Tumor,Tumor Microenvironments
D060890 B7-H1 Antigen An inhibitory B7 antigen that contains V-type and C2 type immunoglobulin domains. It has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN and provides negative signals that control and inhibit T-cell responses. It is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION. Antigens, CD274,PD-L1 Protein,Programmed Cell Death 1 Ligand 1 Protein,Programmed Death Ligand 1,B7-H1 Immune Costimulatory Protein,B7H1 Immune Costimulatory Protein,CD274 Antigen,PD-L1 Costimulatory Protein,Programmed Cell Death 1 Ligand 1,Antigen, B7-H1,Antigen, CD274,B7 H1 Antigen,B7 H1 Immune Costimulatory Protein,CD274 Antigens,Costimulatory Protein, PD-L1,PD L1 Costimulatory Protein,PD L1 Protein
D019253 Proto-Oncogene Proteins c-bcl-2 Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma. bcl-2 Proto-Oncogene Proteins,c-bcl-2 Proteins,B-Cell Leukemia 2 Family Proteins,BCL2 Family Proteins,BCL2 Proteins,B Cell Leukemia 2 Family Proteins,Family Proteins, BCL2,Proteins, BCL2,Proteins, BCL2 Family,Proto Oncogene Proteins c bcl 2,Proto-Oncogene Proteins, bcl-2,bcl 2 Proto Oncogene Proteins,c bcl 2 Proteins,c-bcl-2, Proto-Oncogene Proteins
D019394 Ki-67 Antigen A CELL CYCLE and tumor growth marker which can be readily detected using IMMUNOCYTOCHEMISTRY methods. Ki-67 is a nuclear antigen present only in the nuclei of cycling cells. Antigen Ki-67,MIB-1 Antigen,Antigen Ki67,Antigen Ki 67,Antigen, Ki-67,Antigen, MIB-1,Ki 67 Antigen,Ki-67, Antigen,Ki67, Antigen,MIB 1 Antigen

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