EBV-associated plasmacytic variant of Castleman disease: more than a decade-long diagnostic odyssey –⁠ a case report

Overview

Background: Castleman disease is a rare and heterogeneous lymphoproliferative disorder with variable clinical presentation. The plasma cell variant, particularly when associated with Epstein–Barr virus (EBV), is uncommon and diagnostically challenging. We present a complex and long-lasting case of EBV-associated plasma cell variant Castleman disease with fluctuating systemic symptoms, multiorgan involvement, and delayed definitive diagnosis.

Case presentation: A 35year old man (born 1974) first presented in 2009 with high-grade fever, diarrhea, elevated inflammatory markers, hepatomegaly and biochemical signs of liver injury. Initial findings were attributed to rotavirus infection. Over the following years, he developed recurrent episodes of fever, night sweats, fatigue, arthralgias, hepatosplenomegaly, lymphadenopathy, and progressive laboratory abnormalities including persistent elevation of CRP, leukocytosis, hyperfibrinogenemia and polyclonal hypergammaglobulinemia. Extensive diagnostic workup repeatedly ruled out infectious, rheumatologic and malignant causes. Imaging eventually demonstrated retroperitoneal lymphadenopathy, hepatosplenomegaly, spinal lesions (Th5 –⁠ Th8), narrowing and occlusion of the inferior vena cava, and multiorgan inflammatory changes. Multiple biopsies (lymph nodes, spleen, liver, pancreas, bone lesions) initially showed only nonspecific reactive changes. Repeated PET/CT scans revealed multifocal FDG-avid lesions of low to moderate metabolic activity. In 2023, after multidisciplinary reassessment, lymph node tissue demonstrated EBV positivity in the absence of peripheral viremia, leading to a diagnosis of EBV-associated plasma cell variant Castleman disease. The patient was initiated on targeted therapy. During the third-line treatment, a sustained clinical and laboratory remission was achieved.

Conclusion: This case illustrates the diagnostic complexity of EBV-associated plasma cell variant Castleman disease, especially when presenting with longstanding systemic inflammation, nonspecific multiorgan involvement, and repeatedly inconclusive histopathology. Early consideration of Castleman disease in chronic inflammatory syndromes with lymphadenopathy may reduce diagnostic delay and improve outcome.

Keywords:

lymphadenopathy – Castleman disease – case report – chronic inflammation – plasma cell variant – EBV-associated lymphoproliferative disorder