A novel FAS mutation with variable expressivity in a family with unicentric and idiopathic multicentric Castleman disease

Castleman disease (CD) is a group of rare lymphoproliferative disorders that share characteristic lymph node histopathological features. CD is classified based on the number of regions of enlarged lymph nodes and includes a localized form (unicentric Castleman disease [UCD]) and a systemic form (multicentric Castleman disease [MCD]). Patients with UCD are generally asymptomatic or only mildly symptomatic. The cause of UCD is unknown. MCD involves multiple regions of enlarged lymph nodes, constitutional symptoms, cytopenias, and, in severe cases, multiple organ dysfunction and death. MCD is divided into 2 subtypes depending on the presence or absence of human herpesvirus 8 infection.1 The etiology of human herpesvirus 8–negative MCD, also known as idiopathic MCD (iMCD), is unknown. Treatment options for iMCD are limited, and 35% of patients diagnosed with iMCD die within 5 years.2-4 Thus, elucidating the etiology and pathogenesis of iMCD remains a critical area of study for patients suffering from this condition. There are no known reports of UCD transitioning into iMCD, leading to speculation that these 2 clinical entities do not share etiologies. In this report, we investigated a unique case in which UCD and iMCD were diagnosed within the same family.