Epstein-Barr Virus-Positive B-Cell Lymphoproliferative Disorder Complicated by Septic Shock in Activated PI3Kδ...

Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare inborn error of immunity caused by gain-of-function variants in PIK3CD and characterized by recurrent infections, lymphoproliferation, and impaired viral control. We report a 17-year-old male with a heterozygous PIK3CD c.3061G > A (p.E1021K) variant who presented with progressive edema, extensive hypermetabolic lymphadenopathy, splenomegaly, and Epstein-Barr virus (EBV) DNAemia. A core needle biopsy of the right inguinal lymph node demonstrated an immunodeficiency-associated EBV-positive B-cell lymphoproliferative disorder with extensive monotypic plasmacytoid differentiation. Because the biopsy contained limited mature B-cell tissue, the pathological findings favored a polymorphic B-LPD although EBV-positive diffuse large B-cell lymphoma with plasmacytic differentiation could not be excluded. The patient received anti-B-cell-directed therapy and supportive treatment. He was subsequently readmitted with septic shock and acute respiratory distress syndrome. Blood metagenomic next-generation sequencing detected Escherichia coli and Klebsiella pneumoniae, together with antimicrobial-resistance genes including blaNDM. Despite intensive antimicrobial and organ-supportive treatment, the patient remained critically ill and was discharged at his family's request for transfer to a local hospital; his subsequent outcome was unavailable. This case highlights the diagnostic difficulty of classifying EBV-positive B-cell proliferations using limited biopsy tissue in APDS and the competing risks of lymphoproliferative disease and severe infection. Adequate tissue sampling and pathological characterization, close microbiological surveillance, and individualized multidisciplinary management are essential in this setting.