Castleman disease

The subtypes of Castleman disease reflect the number of lymph node regions with enlarged lymph nodes and known causes of the disease.[3] 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.[3] There are three established subtypes of Castleman disease.[4]

Castleman disease is defined by a range of characteristic features seen on microscopic analysis (histology) of tissue from enlarged lymph nodes.[10] Histologic features consistent with Castleman disease are categorized into common patterns:

• Hyaline vascular: regressed germinal centers, follicular dendritic cell prominence or displasia, hypervascularity in interfollicular regions, sclerotic vessels, prominent mantle zones with an “onion-skin” appearance.[11]
• Plasmacytic: increased number of follicles with large hyperplastic germinal centers and sheetlike plasmacytosis (increased number plasma cells).[10][11]
• 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.[11]
• Mixed: presence of a combination of hyaline vascular, plasmacytic, and/or hypervascular features

UCD most commonly demonstrates hyaline vascular features, but plasmacytic features or a mix of features may also be seen.[7] 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.[10] The clinical utility of subtyping Castleman disease by histologic features is uncertain, as histologic subtypes do not consistently predict disease severity or treatment response.[10]

Staining with latency-associated nuclear antigen (LANA-1), a marker for HHV-8 infection, is positive only in HHV-8-associated MCD.[12]

Diseases other than Castleman disease can present with similar histologic findings in lymph node tissue, including:[10]

• Infectious causes: Epstein-Barr virus, human immunodeficiency virus, tuberculosis
• Autoimmune diseases: Systemic lupus erythematosus, rheumatoid arthritis
• Lymphoproliferative disorders: lymphoma, autoimmune lymphoproliferative syndrome

Unicentric Castleman disease was first described in a case series by Benjamin Castleman in 1956.[13] 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 Kaposi's sarcoma.[14] In 1995, the association between HHV-8 and Castleman disease was described in patients with HIV.[15] Formal diagnostic criteria and definition of the disease was established in 2016, which will allow for better understanding and the ability to appropriately track and research CD. In 2017, international consensus diagnostic criteria for idiopathic multicentric Castleman disease (iMCD) were established for the first time.[10] In 2018, the first treatment guidelines for iMCD were established.[16]

World Castleman Disease Day was established in 2018 and is held every year on July 23. This date was chosen for Benjamin Castleman's initial case series describing Castleman disease, which was published in July 1956,[13] and the diagnostic criteria for idiopathic multicentric Castleman disease, which were published in the journal Blood on March 23, 2017.[10]

The Castleman Disease Collaborative Network was founded in 2012 and is the largest organization to be focused on Castleman disease.[17] It is a global collaborative network involved in research, awareness, and patient support.[18]

• Fajgenbaum, David (2019). Chasing My Cure: A Doctor's Race to Turn Hope into Action; a Memoir. New York: Ballantine Books. ISBN 9781524799618. OCLC 1144129598. Book by the founder of the Castleman Disease Collaborative Network.