Developmental Therapeutics Implications of Next-Generation Sequencing in Human Herpesvirus 8–Negative Castleman Disease

Castleman disease (CD) comprises a heterogeneous group of lymphoproliferative disorders that share similar histopathological lymph node changes. They are separated into unicentric CD (UCD), which is characterized by lymph node enlargement localized to 1 nodal region and few to no systemic symptoms, or multicentric CD (MCD), which is characterized by generalized lymphadenopathy and often systemic symptoms. Multicentric CD can be further subdivided into human herpesvirus 8 (HHV-8)-positive and HHV-8–negative MCD (or idiopathic MCD). In this issue of JAMA Dermatology, Patel et al¹ documented a very elegant use of next-generation sequencing to explain the dramatic response to therapy in a very rare, cutaneous-only manifestation of CD and, by doing so, have provided important therapeutic and future study–design guidance for patients with CD.