Case Report: Primary Immunodeficiencies, Massive EBV+ T-Cell Lympoproliferation Leading to the Diagnosis of ICF2 Syndrome

Abstract

In immunocompromised patients, EBV may elicit B-cell transformation and proliferation. A 5-year-old microcephalic boy was admitted with fever and non-malignant polymorphic T-cell lymphoproliferative disease associated with EBV. A presumptive diagnosis of primary immunodeficiency with inability to control EBV was made and next-generation sequencing led to the identification of a novel ZBTB24 mutation (ICF2-syndrome). This case shows that susceptibility to EBV seems to be particular of ICF-2 as it has not been described in the other types of ICF. It is mandatory to raise the hypothesis of an underlying PID in case of severe EBV infection.

Lymphoproliferation in Inborn Errors of Immunity: The Eye Does Not See What the Mind Does Not Know

“…Among B-cell lymphomas, classical HL, diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL) are commonly described ( 1 ). Immunodeficiency with centromeric instability and facial anomalies type 2 (ICF2) is a DNA-methylation disorder with a high susceptibility to EBV infection manifesting as EBV+ IM, HLH, chronic active EBV infection (CAEBV), HL, large B-cell lymphoma, and polymorphic non-clonal T-cell LPD ( 16 ). Patients with Di-George syndrome may present with CD8+ granulomatous cutaneous T-cell lymphoma and granulomatous lymphocytic interstitial lung disease (GLILD) characterized by ill-defined non-necrotizing lymphohistiocytic granulomas, CD20+ B-cell-rich lymphoid nodules, CD4+ T-cell-rich interstitial pneumonia, and peribronchiolar follicular hyperplasia with reduced regulatory T-cells (Tregs) ( 17 ).…”