Castleman disease represents a rare, heterogeneous group of lymphoproliferative disorders, often categorized as unicentric or multicentric, with plasma-cell (PC), hyaline-vascular, or mixed histology. Idiopathic multicentric Castleman disease (iMCD) remains a diagnostic and therapeutic challenge, particularly in patients presenting with systemic inflammation and polyclonal plasmacytosis without overt clonal plasma cell disorder. We present the case of a patient with plasma-cell–predominant iMCD, successfully treated with IL-6 blockade, emphasizing the diagnostic pitfalls and the importance of early therapeutic intervention.

A male patient was admitted to the Department of Hematology, Çukurova University, with a 1-year history of progressive fatigue, weight loss, abdominal fullness, and generalized lymphadenopathy. Physical examination revealed widespread lymphadenopathy and splenomegaly. Laboratory tests demonstrated normocytic anemia, elevated CRP and ferritin, mildly increased IgG, and elevated β2-microglobulin. Excisional lymph node biopsy and splenectomy specimens were evaluated by histopathology and immunohistochemistry. Imaging studies included CT and PET-CT for staging., Türkiye

Histopathology revealed follicular hyperplasia with regressed germinal centers and interfollicular plasmacytosis. Immunohistochemistry confirmed CD38+ and CD138+ plasma-cell infiltration, HHV-8 negativity, and a non-clonal kappa/lambda pattern. IgG4/IgG ratio was 22%. PET-CT demonstrated widespread FDG-avid lymphadenopathy (SUVmax 4–6) and splenomegaly, without extranodal organ involvement. Bone marrow evaluation was negative for clonal plasma cell infiltration. The case was classified as idiopathic multicentric Castleman disease, plasma-cell variant (iMCD-PC).

The patient was initiated on tocilizumab (anti-IL-6R) in combination with corticosteroids. Within 6 weeks, systemic symptoms and inflammatory markers improved significantly, with partial regression of lymphadenopathy on imaging. In the event of refractoriness, lenalidomide or sirolimus were considered as second-line options. Close follow-up with PET-CT and serum paraproteins was arranged to monitor potential clonal evolution into plasma cell neoplasia.

This case illustrates the diagnostic complexity of iMCD-PC, which may mimic lymphoid malignancies and overlap with monoclonal gammopathies. The absence of monoclonality and CRAB criteria excluded multiple myeloma, while systemic inflammatory features and IL-6 axis dysregulation supported iMCD. Tocilizumab provided meaningful clinical and biochemical improvement. The case is valuable as an example of iMCD with strong plasmacytic component, highlighting the necessity of long-term surveillance due to the risk of clonal transformation.

Plasma-cell–predominant iMCD is a rare and diagnostically challenging entity requiring integration of histopathology, immunohistochemistry, imaging, and laboratory findings. Anti–IL-6–directed therapy represents an effective treatment option, but close monitoring remains mandatory. This case underlines the importance of early recognition and targeted therapy in preventing disease-related morbidity.