The Evolution and Recent Advances in Diagnostic Criteria for Idiopathic Multicentric Castleman Disease

Abstract

Idiopathic multicentric Castleman disease (iMCD) is a rare cytokine-driven disorder characterized by systemic inflammation, organ dysfunction, and altered lymph node microscopic architecture. Over the past decade, diagnostic criteria have evolved significantly, integrating clinical, histopathological, and molecular biomarker advancements. Key drivers of iMCD pathogenesis, such as interleukin-6 dysregulation and other dysfunctional cytokine signaling, have been identified and led to the development of targeted therapies like siltuximab and tocilizumab. Histopathologic refinements have highlighted distinct subtypes, such as hypervascular, plasmacytic, and mixed histologic patterns, while molecular discoveries have unveiled potential paraneoplastic and clonal processes. Emerging technologies, including single-cell sequencing, spatial transcriptomics, and digital pathology, offer promise in refining diagnostic precision and advancing personalized medicine. This review synthesizes historical frameworks, recent breakthroughs, and future directions in iMCD diagnostics, emphasizing the importance of multidisciplinary approaches for improved patient outcomes.