Though all forms of MCD involve excessive production of cytokines and a cytokine storm, iMCD has important differences in symptoms, disease course, and treatment from POEMS-associated MCD and HHV-8-associated MCD. First line treatment for iMCD is anti-IL-6 therapy with siltuximab (or tocilizumab, if siltuximab is not available). Siltuximab is the only FDA-approved treatment for iMCD and patients who respond to siltuximab tend to have long-term responses. In critically ill patients, chemotherapy and corticosteroids are recommended if the patient is demonstrating disease progression while on siltuximab. Approximately half of iMCD patients do not improve with anti-IL-6 therapy. In patients where siltuximab is not effective, other treatments such as rituximab and sirolimus can be used.iMCD can be further sub-classified into three clinical subgroups:
iMCD with TAFRO Syndrome (iMCD-TAFRO): characterized by acute episodes of Thrombocytopenia, Anasarca, Fever, Renal dysfunction or mylefibrosis, and Organomegaly.iMCD with idiopathic plasmacytic lymphadenopathy (iMCD-IPL): characterized by thrombocytosis, hypergammaglobulinemia, and a more chronic disease course.iMCD, not otherwise specified (iMCD-NOS): is diagnosed in iMCD patients who do not have iMCD-TAFRO or iMCD-IPL. Pathology
Castleman disease is defined by a range of characteristic features seen on microscopic analysis (histology) of tissue from enlarged lymph nodes. Variations in the lymph node tissues of patients with CD have led to 4 histological classifications:

Plasmacytic: increased number of follicles with large hyperplastic germinal centers and sheetlike plasmacytosis (increased number plasma cells). Germinal centers may also show regressed features
Hyaline vascular: regressed germinal centers, follicular dendritic cell prominence or dysplasia, hypervascularity in interfollicular regions, sclerotic vessels, prominent mantle zones with an "onion-skin" appearance.
Hypervascular: similar to hyaline vascular features, but seen in iMCD rather than UCD. Includes regressed germinal centers, follicular dendritic cell prominence, hypervascularity in interfollicular regions, and prominent mantle zones with an "onion-skin" appearance. Mixed: presence of a combination of hyaline vascular/hypervascular and plasmacytic features in the same lymph node.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. Guidelines recommend against using histologic subtype to guide treatment decisions. Staining with latency-associated nuclear antigen (LANA-1), a marker for HHV-8 infection, should be measured in all forms of Castleman disease but is positive only in HHV-8-associated MCD.Diseases other than Castleman disease can present with similar histologic findings in lymph node tissue, including:
Infectious causes: Epstein-Barr virus, human immunodeficiency virus, tuberculosis
Autoimmune diseases: Systemic lupus erythematosus, rheumatoid arthritis
Lymphoproliferative disorders: lymphoma, autoimmune lymphoproliferative syndrome

History
Unicentric Castleman disease was first described in a case series by Benjamin Castleman in 1956. By 1984, a number of case reports had been published describing a multicentric variant of the disease and with some reports describing an association with Kaposis sarcoma. In 1995, the association between HHV-8 and Castleman disease was described in patients with HIV.