Castleman disease

Castleman disease is a group of uncommon lymphoproliferative disorders characterized by lymph node enlargement, characteristic features on microscopic analysis of enlarged lymph node tissue, and a range of symptoms and clinical findings. Castleman disease is a group of uncommon lymphoproliferative disorders characterized by lymph node enlargement, characteristic features on microscopic analysis of enlarged lymph node tissue, and a range of symptoms and clinical findings. Castleman disease includes at least 3 distinct subtypes; unicentric Castleman disease (UCD), human herpesvirus 8 associated multicentric Castleman disease (HHV-8-associated MCD), and idiopathic multicentric Castleman disease (iMCD). These are differentiated by the number and location of affected lymph nodes and the presence of human herpesvirus 8, a known causative agent. Correctly classifying the Castleman disease subtype is important, as the three subtypes vary significantly in symptoms, clinical findings, disease mechanism, treatment approach, and prognosis. Castleman disease is named after Dr. Benjamin Castleman, who first described the disease in 1956. The Castleman Disease Collaborative Network is the largest organization focused on the disease and is involved in research, awareness, and patient support. The subtypes of Castleman disease reflect the number of lymph node regions with enlarged lymph nodes and known causes of the disease. In unicentric disease, one or more enlarged lymph nodes are present in a single region of lymph nodes. In multicentric disease, enlarged lymph nodes are present in multiple regions of lymph nodes. The only known cause of Castleman disease is uncontrolled infection with human herpesvirus 8, which has only been reported in cases of multicentric disease. There are three established subtypes of Castleman disease. In unicentric Castleman disease (UCD) one or more enlarged lymph nodes are present in a single region of lymph nodes. It is the most common subtype of Castleman disease and compared to HHV-8-associated MCD and iMCD, symptoms are typically milder, organ dysfunction is uncommon, and surgical removal of enlarged lymph nodes is the treatment of choice. In idiopathic multicentric Castleman disease (iMCD), enlarged lymph nodes are present in multiple lymph node regions and no known cause for the disease is identified. It is less common than unicentric Castleman disease (UCD) and compared to UCD, symptoms are typically more severe, laboratory abnormalities must be present for diagnosis, and medications are used for treatment as surgery is ineffective. In human herpesvirus 8 associated multicentric Castelman disease (HHV-8-associated MCD), enlarged lymph nodes are present in multiple lymph node regions and infection with human herpesvirus 8 is present. It is less common than unicentric Castleman disease and diagnosed most frequently in patients infected with human immunodeficiency virus (HIV). Compared to UCD and iMCD, HHV-8-associated MCD presents with similar symptoms and clinical findings to iMCD. While UCD is readily treatable with surgery, HHV-8-associated MCD, like iMCD, is treated with medications as surgery is ineffective. Castleman disease is defined by a range of characteristic features seen on microscopic analysis (histology) of tissue from enlarged lymph nodes. Histologic features consistent with Castleman disease are categorized into common patterns: UCD most commonly demonstrates hyaline vascular features, but plasmacytic features or a mix of features may also be seen. iMCD more commonly demonstrates plasmacytic features, but hypervascular features or a mix of features are also seen. All cases of HHV-8-associated MCD are thought to demonstrate plasmablastic features--similar to plasmacytic features, but with plasmablasts present. The clinical utility of subtyping Castleman disease by histologic features is uncertain, as histologic subtypes do not consistently predict disease severity or treatment response.