Next Generation Sequencing Analysis of Fibrin-associated Large B-cell Lymphoma Reveals Pathogenic Single Nucleotide Variants.

Abstract

Fibrin-associated large B-cell lymphoma (FA-LBCL) is a newly identified subtype of Epstein-Barr virus (EBV)-associated lymphoma. Arising within fibrinous material in confined spaces, FA-LBCL is associated with chronic inflammation. We herein report histopathologic features and molecular alterations of three cases of FA-LBCL to refine this new disease entity. We performed immunohistochemical staining for CD3, CD20, CD10, Bcl-2, Bcl-6, MUM-1, CD10, and c-Myc and in situ hybridization for EBV-encoded RNA. Additionally, targeted DNA sequencing was conducted using commercially available gene panels. Three cases of FA-LBCL developed underlying lesions of retroperitoneal cyst, cardiac myxoma, and pancreatic cyst. Histopathologic features of these lesions were characterized by aggregates of atypical large cells in a background of fibrinous cellular debris. Atypical lymphoid cells were positive for CD20, Bcl-2, MUM-1, and EBV-in situ hybridization, negative for CD10, and variably positive for Bcl-6 and c-Myc. NGS analysis revealed the presence of pathogenic mutations in BRIP1, SOCS1, and KRAS. This is the first report of NGS analysis in FA-LBCL cases. It provides precise clinicopathological and molecular traits and allows its recognition as a new entity.