Systemic bone destruction as a presentation of idiopathic multicentric Castleman disease

A 78-year-old male was admitted to the Department of Dermatology with a 30-year history of progressively enlarging asymptomatic violaceous-grey plaques and nodules on the face, neck and trunk (upper left), accompanied by a 2-year history of bone pain in the pelvis and lower limbs. Physical examination showed generalised lymphadenopathy. Laboratory investigations revealed anaemia (haemoglobin 94 g/L), hypoalbuminaemia (albumin 22 g/L), hypergammaglobulinaemia (Immunoglobulin G (IgG) 58.28 g/L, normal: 8.6–17.4 g/L), elevated erythrocyte sedimentation rate (ESR) (117 mm/h) and interleukin-6 (IL-6) level (43.6 pg/mL, normal <5.4 pg/mL). Skin biopsy demonstrated dermal plasmacytosis (bottom left, Hematoxylin and Eosin stain (H&E), objective 20×). Lymph node biopsy revealed regressed germinal centres with interfollicular plasmacytosis (bottom middle, H&E, objective 20×). Immunohistochemistry of lymph node plasma cells showed CD79a+, CD19+, CD38+, CD138+, CD56− and no light chain restriction. Human Herpesvirus 8 (HHV-8) staining was negative. Immunohistochemistry of skin plasma cells yielded similar results. Polyclonality was confirmed by immunoglobulin gene rearrangement assay in skin and lymph node biopsies. The patient was diagnosed with plasma cell type idiopathic multicentric Castleman disease (CD). However, a Positron Emission Tomography - Computed Tomography (PET-CT) scan to evaluate systemic involvement revealed not only multiple hypermetabolic cutaneous nodules and lymphadenopathy but also widespread osteolytic lesions without increased Fluorodeoxyglucose (FDG) uptake (upper right, red arrows). We conducted the multiple myeloma workup, and M protein tests were negative. Bone marrow examination demonstrated 6.5% plasma cells, with no light chain restriction. We also performed a biopsy on the iliac osteolytic lesion, which revealed scattered infiltration of small lymphocytes and plasma cells (bottom right, H&E, objective 40×). Immunohistochemistry results were compatible with those of skin and lymph node. The patient was treated with the anti-IL-6 receptor monoclonal antibody tocilizumab. The regression of the skin lesions and bone pain was observed within 3 months, along with rapid decrease in ESR and amelioration of anaemia and hypoalbuminaemia. No previous case has reported osteolytic lesions in CD, suggesting that bone destruction in this entity is likely under-recognised. The dramatic response to tocilizumab validates the central pathogenic role of IL-6 in driving systemic involvement and disease progression.1, 2 This case underscores the necessity of a comprehensive evaluation of the skeletal system when related symptoms are present in patients with CD. This study was supported by the National Natural Science Foundation of China (82173407, 82430100), the Shanghai Natural Science Foundation (21ZR1440500) and the Innovative Research Team of High-Level Local Universities in Shanghai (SHSMU-ZDCX20211002). No ethics approval was necessary for this report. We have obtained the patient's consent to use clinical information and images for educational purpose. The authors declare no use of third-party material in this study for which formal permission is required.