title: Intrafollicular Epstein-Barr virus-positive large B cell lymphoma. A variant of "germinotropic" lymphoproliferative disorder.
abstract: Germinotropic lymphoproliferative disorders were previously described as localized disorders associated with coinfection by human herpes virus 8 and Epstein-Barr virus and characterized by good clinical outcome. We report the clinical, morphological, phenotypical, and molecular features of three cases of a hitherto unreported variant of Epstein-Barr virus (EBV)-positive, human herpes virus 8 (HHV8)-negative large B cell lymphoma with exclusive intrafollicular localization. All cases occurred in elderly individuals (63, 77, and 65 years old; one male, two females) without obvious immunedeficiency, who presented with high stage disease. Lymph nodes showed an effaced nodular architecture with abnormal B follicles colonized by EBV+ large, pleomorphic atypical cells, including Reed-Sternberg-like cells, showing an activated B cell phenotype (CD10-FOXP1-Bcl6-IRF4+ or CD10-FOXP1+Bcl6+IRF4+) and intense expression of CD30. No monoclonal light-chain restriction was detected by immunohistochemistry or in situ hybridization, and IGH rearrangement was polyclonal; notably, EBV clonality was detectable in one case. Lymphoma cells in all cases showed diffuse expression of the c-Myc protein, while Bcl2 was dim or negative; moreover, the strong expression of phosphorylated-STAT3 in tumor cell nuclei suggested activation of the JAK-STAT pathway. FISH analysis was performed in two cases and showed no translocations of BCL2, BCL6, MYC, and PAX5 genes. Response to treatment was poor in 2/3 patients: one died after 18 months, one is alive with disease after 12 months. The intrafollicular EBV-positive large B cell lymphoma expands the spectrum of EBV-associated lymphoproliferative disorders in immunocompetent individuals.
authors.affiliation: Department of Molecular and Translational Medicine; Section of Pathology, University of Brescia, Spedali Civili, 25123, Brescia, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Lorenzi
authors.affiliation: Department of Molecular and Translational Medicine; Section of Pathology, University of Brescia, Spedali Civili, 25123, Brescia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lonardi
authors.affiliation: Department of Molecular and Translational Medicine; Section of Pathology, University of Brescia, Spedali Civili, 25123, Brescia, Italy.
authors.forename: Murad H M
authors.initials: MH
authors.lastname: Essatari
authors.affiliation: Department of Molecular and Translational Medicine; Section of Pathology, University of Brescia, Spedali Civili, 25123, Brescia, Italy.
authors.forename: Vilma
authors.initials: V
authors.lastname: Pellegrini
authors.affiliation: Department of Molecular and Translational Medicine; Section of Pathology, University of Brescia, Spedali Civili, 25123, Brescia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Fisogni
authors.affiliation: Department of Experimental Hematopathology and Hematology Sections, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Gazzola
authors.affiliation: Department of Experimental Hematopathology and Hematology Sections, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Agostinelli
authors.affiliation: Department of Molecular and Translational Medicine; Section of Pathology, University of Brescia, Spedali Civili, 25123, Brescia, Italy.
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.affiliation: Department of Hematology, Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Departments of Clinical and Experimental Medicine, Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: Giovannino
authors.initials: G
authors.lastname: Massarelli
authors.affiliation: European Institute of Oncology, Milano, Italy.|School of Medicine, Bologna University, Bologna, Italy.
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.affiliation: Department of Molecular and Translational Medicine; Section of Pathology, University of Brescia, Spedali Civili, 25123, Brescia, Italy. fabio.facchetti@unibs.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
mesh_terms: D000368:Aged; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D018858:Germinal Center / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction
keywords: B cell lymphoma; Epstein-Barr virus; Germinotropic