Castleman's disease

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Castleman's diseases
Other namesGiant lymph node hyperplasia, lymphoid hamartoma, angiofollicular lymph node hyperplasia
Castleman disease - high mag.jpg
Micrograph of Castleman's disease showing hyaline vascular features including atrophic germinal center, expanded mantle zone, and a radially penetrating sclerotic blood vessel ("lollipop" sign). H&E stain.
Specialty Immunology, angiology   OOjs UI icon edit-ltr-progressive.svg

Castlemandisease 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.

Lymphadenopathy disorder of lymph nodes

Lymphadenopathy or adenopathy is disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type is lymphadenitis, producing swollen or enlarged lymph nodes. In clinical practice, the distinction between lymphadenopathy and lymphadenitis is rarely made and the words are usually treated as synonymous. Inflammation of the lymphatic vessels is known as lymphangitis. Infectious lymphadenitis affecting lymph nodes in the neck is often called scrofula.

Contents

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.

Unicentric Castleman disease Localized Castleman disease (LCD) is the most common form of Castleman disease (CD; see this term) and it is usually asymptomatic or it may present with enlarged lymph nodes. LCD may be cured by surgical resection.

Unicentric Castleman disease is a subtype of Castleman disease, a group of 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

Human herpesvirus 8 associated multicentric Castleman disease is a subtype of Castleman disease, a group of rare 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.

Idiopathic multicentric Castleman disease Castleman disease characterized by systemic inflammatory symptoms, polyclonal lymphoproliferation, cytopenias, and multiple organ system dysfunction caused by a cytokine storm often including interleukin-6

Idiopathic multicentric Castleman disease (iMCD) is a subtype of Castleman disease, a group of 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 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.

Benjamin Castleman American pathologist

Benjamin Castleman was an American physician and pathologist best known for describing Castleman's disease, which is named after him. He was also one of the authors of the first case series on pulmonary alveolar proteinosis in a 1958 article in the New England Journal of Medicine. Castleman undertook clinicopathologic investigations of parathyroid disease and wrote several important papers on diseases of the thymus and mediastinum. He wrote, or collaborated in writing, over 100 scholarly papers on a variety of disorders.

Classification

The subtypes of Castleman disease reflect the number of lymph node regions with enlarged lymph nodes and known causes of the disease. [1] 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. [1] There are three established subtypes of Castleman disease.

Kaposis sarcoma-associated herpesvirus species of virus

Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is Human gammaherpesvirus 8, or HHV-8 in short. Like other herpesviruses, its informal names are used interchangeably with its formal ICTV name. This virus causes Kaposi's sarcoma, a cancer commonly occurring in AIDS patients, as well as primary effusion lymphoma, HHV-8-associated multicentric Castleman's disease and KSHV inflammatory cytokine syndrome. It is one of seven currently known human cancer viruses, or oncoviruses.

Unicentric 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. [2] [3]

Lymph node organ of the lymphatic system

A lymph node or lymph gland is an ovoid or kidney-shaped organ of the lymphatic system and the adaptive immune system. Lymph nodes are widely present throughout the body and are linked by the lymphatic vessels as a part of the circulatory system. They are major sites of B and T lymphocytes and other white blood cells. Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles and cancer cells, but they do not have a detoxification function.

Idiopathic multicentric Castleman disease

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. [2]

Human herpesvirus 8 associated multicentric Castleman disease

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. [2]

Pathology

Castleman disease is defined by a range of characteristic features seen on microscopic analysis (histology) of tissue from enlarged lymph nodes. [4] 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. [3] 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. [4] The clinical utility of subtyping Castleman disease by histologic features is uncertain, as histologic subtypes do not consistently predict disease severity or treatment response. [4]

Staining with latency-associated nuclear antigen (LANA-1), a marker for HHV-8 infection, is positive only in HHV-8-associated MCD. [6]

Diseases other than Castleman disease can present with similar histologic findings in lymph node tissue, including: [4]

History

Unicentric Castleman disease was first described in a case series by Dr. Benjamin Castleman in 1956. [7] 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. [8] In 1995, the association between HHV-8 and Castleman disease was described in patients with HIV. [9] In 2017, international consensus diagnostic criteria for idiopathic multicentric Castleman disease (iMCD) were established for the first time. [4] In 2018, the first treatment guidelines for iMCD were established. [10]

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's disease, which was published in July 1956, [7] and the diagnostic criteria for idiopathic multicentric Castleman's disease, which were published in the journal Blood on March 23, 2017. [4]

Culture

The Castleman Disease Collaborative Network was founded in 2012 and is the largest organization to be focused on Castleman's disease. It is a global collaborative network involved in research, awareness, and patient support. [11]

Related Research Articles

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Non-Hodgkin lymphoma (NHL) is a group of blood cancers that includes all types of lymphoma except Hodgkin's lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss and tiredness. Other symptoms may include bone pain, chest pain or itchiness. Some forms are slow-growing, while others are fast-growing.

Roseola Human disease caused by human herpesviruses

Roseola is an infectious disease caused by certain types of virus. Most infections occur before the age of three. Symptoms vary from absent to the classic presentation of a fever of rapid onset followed by a rash. The fever generally lasts for three to five days. The rash is generally pink and lasts for less than three days. Complications may include febrile seizures, with serious complications being rare.

Kikuchi disease rare disease

Kikuchi disease was described in 1972 in Japan. It is also known as histiocytic necrotizing lymphadenitis, Kikuchi necrotizing lymphadenitis, phagocytic necrotizing lymphadenitis, subacute necrotizing lymphadenitis, and necrotizing lymphadenitis.Kikuchi disease occur sporadically in people with no family history of the condition.

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Anaplastic large-cell lymphoma non-Hodgkin lymphoma involving aberrant T-cells

Anaplastic large-cell lymphoma (ALCL) is a type of non-Hodgkin lymphoma involving aberrant T cells or null lymphocytes. It is described in detail in the "Classification of Tumours of the Haematopoietic and Lymphoid Tissues" edited by experts of the World Health Organisation (WHO). The term anaplastic large-cell lymphoma (ALCL) encompasses at least four different clinical entities, all sharing the same name, which histologically share the presence of large pleomorphic cells that express CD30 and T-cell markers. Two types of ALCL present as systemic disease and are considered as aggressive lymphomas, while two types present as localized disease and may progress locally. Anaplastic large cell lymphoma is associated with various types of medical implants.

POEMS syndrome is a rare paraneoplastic syndrome caused by a clone of aberrant plasma cells. The name POEMS is an acronym for some of the disease's major signs and symptoms, as is PEP.

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Siltuximab is a chimeric monoclonal antibody. It binds to interleukin-6. Siltuximab has been investigated for the treatment of neoplastic diseases: metastatic renal cell cancer, prostate cancer, and Castleman's disease, among other types of cancer.

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Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease is a type of large B-cell lymphoma, recognized in the WHO 2008 classification. It is sometimes called the plasmablastic form of multicentric Castleman disease. It has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. It has variable CD20 expression and unmutated immunoglobulin variable region genes.

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References

  1. 1 2 Fajgenbaum DC, Shilling D (February 2018). "Castleman Disease Pathogenesis". Hematology/Oncology Clinics of North America. 32 (1): 11–21. doi:10.1016/j.hoc.2017.09.002. PMID   29157613.
  2. 1 2 3 Oksenhendler E, Boutboul D, Fajgenbaum D, Mirouse A, Fieschi C, Malphettes M, Vercellino L, Meignin V, Gérard L, Galicier L (January 2018). "The full spectrum of Castleman disease: 273 patients studied over 20 years". British Journal of Haematology. 180 (2): 206–216. doi:10.1111/bjh.15019. PMID   29143319.
  3. 1 2 Talat N, Belgaumkar AP, Schulte KM (April 2012). "Surgery in Castleman's disease: a systematic review of 404 published cases". Annals of Surgery. 255 (4): 677–84. doi:10.1097/SLA.0b013e318249dcdc. PMID   22367441.
  4. 1 2 3 4 5 6 7 Fajgenbaum DC, Uldrick TS, Bagg A, Frank D, Wu D, Srkalovic G, et al. (March 2017). "International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease". Blood. 129 (12): 1646–1657. doi:10.1182/blood-2016-10-746933. PMC   5364342 . PMID   28087540.
  5. 1 2 3 Keller AR, Hochholzer L, Castleman B (March 1972). "Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations". Cancer. 29 (3): 670–83. doi:10.1002/1097-0142(197203)29:3<670::aid-cncr2820290321>3.0.co;2-#. PMID   4551306.
  6. ↑ Liu AY, Nabel CS, Finkelman BS, Ruth JR, Kurzrock R, van Rhee F, Krymskaya VP, Kelleher D, Rubenstein AH, Fajgenbaum DC (April 2016). "Idiopathic multicentric Castleman's disease: a systematic literature review". The Lancet. Haematology. 3 (4): e163–75. doi:10.1016/S2352-3026(16)00006-5. PMID   27063975.
  7. 1 2 Castleman, B.; Iverson, L.; Menendez, V. P. (July 1956). "Localized mediastinal lymphnode hyperplasia resembling thymoma". Cancer. 9 (4): 822–830. doi:10.1002/1097-0142(195607/08)9:4<822::aid-cncr2820090430>3.0.co;2-4. ISSN   0008-543X. PMID   13356266.
  8. ↑ Chen KT (April 1984). "Multicentric Castleman's disease and Kaposi's sarcoma". The American Journal of Surgical Pathology. 8 (4): 287–93. doi:10.1097/00000478-198404000-00006. PMID   6711739.
  9. ↑ Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem D, Babinet P, et al. (August 1995). "Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease". Blood. 86 (4): 1276–80. PMID   7632932.
  10. ↑ van Rhee, Frits; Voorhees, Peter; Dispenzieri, Angela; Fosså, Alexander; Srkalovic, Gordan; Ide, Makoto; Munshi, Nikhil; Schey, Stephen; Streetly, Matthew (2018-09-04). "International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease". Blood. 132 (20): blood-2018–07-862334. doi:10.1182/blood-2018-07-862334. ISSN   1528-0020. PMC   6238190 . PMID   30181172.
  11. ↑ Fajgenbaum, David C.; Ruth, Jason R.; Kelleher, Dermot; Rubenstein, Arthur H. (April 2016). "The collaborative network approach: a new framework to accelerate Castleman's disease and other rare disease research". The Lancet. Haematology. 3 (4): e150–152. doi:10.1016/S2352-3026(16)00007-7. ISSN   2352-3026. PMID   27063967.
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