T-cell/Histiocyte-rich Large B-cell Lymphoma : Molecular Genetics

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) with a low fraction of tumor B-cells in a background rich in T-cells and histiocytes. Patients are in 6th or 7th decade of life with a slight male predominance. It is primarily a nodal disease. Extranodal sites include bone marrow (60% of cases), spleen (25%) and liver. Patients present with fever, malaise, splenomegaly, and/or hepatomegaly. It is more aggressive than DLBCL and likely to present as stage III or IV disease. Nodal architecture is effaced by a polymorphic infiltrate of reactive T-cells and a small number of neoplastic large B-cells scattered singly without forming aggregates or sheets. Large B-cells should make up <10% of the cellular population. Histiocytes, eosinophils, and plasma cells are also present. THRLBCL shows clonally rearranged immunoglobulin genes. BCL2 is rearranged in 25% of cases. Gains of 2p16.1 and losses of 2p11.2 and 9p11.2 have been reported as have recurrent mutations in JUNB, DUSP2, SGK1, SOCS1, and CREBBP genes. Large neoplastic cells express pan B-cell markers (CD19, CD20, CD22, CD79a, PAX5) with variable light chain restriction. They also express BCL2 (40%), BCL6 (40-60%), and EMA (30%). Negative markers include CD15, CD30, CD5, and CD10. Background lymphocyctes are reactive T-cells of cytotoxic type expressing CD3, CD8, and TIA-1. CD68+ and CD163+ histiocytes are also present. References: Jaffe, E. S. et al (2017). Hematopathology - Second Edition. Philadelphia, PA. Elsevier. Swerdlow, S. H. et al (2017). WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, Revised 4th Edition; IARC, Lyon, France.