01/24/2022 In Castleman disease, the immune system becomes activated and releases inflammatory proteins called cytokines. These cytokines cause vital organs (liver, kidneys, bone marrow) to not work well and to shut down. We don’t know which immune cells or pathways are activated. This study looks for the activated immune cells and cellular pathways in the bone marrow. Researchers will examine Castleman Disease bone marrow using immunohistochemistry, a process that causes certain cellular markers to light up.
Idiopathic multicentric Castleman disease (iMCD) is a polyclonal lymphoprolifer- ative disorder characterized by constitutional symptoms, generalized lymphade- nopathy, cytopenias, and multi‐organ dysfunction due to excessive cytokines, notably Interleukin‐6. Idiopathic multicentric Castleman disease is often sub‐classified into iMCD‐TAFRO, which is associated with thrombocytopenia (T), anasarca (A), fever/elevated C‐reactive protein (F), renal dysfunction (R), and organomegaly (O), and iMCD not otherwise specified (iMCD‐NOS), which is typi- cally associated with thrombocytosis and hypergammaglobulinemia. The diagnosis of iMCD is challenging as consensus clinico‐pathological diagnostic criteria were only recently established and include several non‐specific lymph node histopatho- logical features. Identification of further clinico‐pathological features commonly found in iMCD could contribute to more accurate and timely diagnoses. We set out to characterize bone marrow (BM) histopathological features in iMCD, assess dif- ferences between iMCD‐TAFRO and iMCD‐NOS, and determine if these findings are specific to iMCD. Examination of BM specimens from 24 iMCD patients revealed a high proportion with hypercellularity, megakaryocytic atypia, reticulin fibrosis, and plasmacytosis across patients with both iMCD‐NOS and iMCD‐TAFRO with significantly more megakaryocytic hyperplasia (p = 0.001) in the iMCD‐TAFRO cases. These findings were also consistent with BM findings from 185 published cases of iMCD‐NOS and iMCD‐TAFRO. However, these findings are relatively nonspecific as they can be seen in various other infectious, malignant, and auto- immune diseases.