Track

Clinical Studies

Abstract

Cutaneous Castleman disease (CD) represents a rare presentation with distinctive clinicopathologic features that parallel, but are not identical to, nodal disease, and systematic characterization will clarify its diagnostic spectrum and pathogenetic underpinnings. A retrospective review of a single institution dermatopathology database (2000–2024) identified cases of histologically confirmed cutaneous CD. Clinical records, histopathology, immunophenotyping, and in situ hybridization were analyzed. Histologic subtyping followed established criteria for hyaline vascular/hypervascular (HV), plasma cell (PC), and mixed variants. Nine patients (5 females, 4 males; mean age 42.8, range 5–82 years) were identified, including eight unicentric (UCD) and one multicentric (MCD) case. All lesions localized to the dermis/subcutis. HV features: atrophic, centrocyte/centroblast-depleted germinal centers with concentric mantle lymphocytes, interfollicular hypervascularity, and CD21⁺ dendritic cell proliferation were present in all cases. Five UCDs exhibited a mixed HV+PC pattern; two were HV-dominant. Distinctive findings included hyalinizing fibrosis with psammomatous calcification, angiolymphoid hyperplasia–like vascular proliferations, and benign λ-restricted plasma cell populations. The single MCD case presented with multifocal plaques, systemic lymphadenopathy, polyclonal hypergammaglobulinemia, and mixed histology. IL-6 localization studies (1 case) showed expression in CD8⁺ T cells and macrophages at germinal center peripheries. Cutaneous CD is exceedingly rare, predominantly UCD with mixed HV+PC morphology, and generally asymptomatic except for mass effect. MCD with cutaneous involvement reflects systemic disease. Histopathologic overlap between UCD and MCD underscores shared IL-6–driven pathogenesis, linking hypervascularity, fibrosis, calcification, and plasma cell proliferation. Recognition of these patterns is critical for accurate diagnosis, prognostication, and therapeutic targeting of IL-6–mediated pathways.