User:CDK55/Unicentric Castleman disease

= Unicentric Castleman disease = Unicentric Castleman disease is a subtype of Castleman disease (also known as giant lymph node hyperplasia, lymphoid hamartoma, or angiofollicular lymph node hyperplasia), a group of rare lymphoproliferative disorders that share characteristic features on microscopic analysis of affected lymph node tissue.

Castleman disease includes at least 3 distinct disorders—unicentric Castleman disease (UCD), human herpesvirus 8 associated multicentric Castelman disease (HHV-8-associated MCD), and idiopathic multicentric Castleman disease (iMCD)—which 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 disease is important, as the three disorders vary significantly in symptoms, clinical findings, disease mechanism, treatment approach, and prognosis.

In unicentric Castleman disease (UCD) a single lymph node or region of lymph nodes is affected. 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 treatment is curative in the majority of patients.

Castleman disease is named after Dr. Benjamin Castleman. The Castleman Disease Collaborative Network (CDCN) is the largest organization related to the disease, focusing on advancing research efforts, raising awareness, and supporting patients.

Classification
Castleman disease is classified into unicentric and multicentric variants based on the number and location of affected lymph nodes. UCD involves a single lymph node or region of lymph nodes, whereas HHV-8-associated MCD and iMCD involve multiple lymph node regions.

Symptoms
UCD commonly presents without symptoms; however, patients may notice enlarged lymph nodes or report symptoms related to compression of neighboring structures by affected lymph nodes such as difficulty breathing and pain or pressure in the abdomen or chest. Systemic symptoms (fever, night sweats, weight loss, fatigue) and symptoms associated with extravascular fluid accumulation (extremity swelling, abdominal distention), both of which are commonly seen in HHV-8-associated MCD and iMCD, are uncommon in UCD.

Clinical Findings
In patients with UCD, physical exam may reveal a single enlarged lymph node, or multiple enlarged lymph nodes in a single region. Laboratory testing is typically normal, including blood counts, metabolic tests, and inflammatory markers. Radiologic imaging will show an enlarged lymph node or multiple enlarged lymph nodes in a single region, which are typically 18F-fluorodoxyglucose (FDG) avid on positron-emission tomography (PET).

In some patients diagnosed with UCD, clinical features typical of HHV-8-associated MCD and iMCD may be present. Physical exam may demonstrate signs of extravascular fluid accumulation (peripheral edema, ascites, pleural effusions) or enlargement of the liver and/or spleen. Laboratory testing may show low hemoglobin levels (anemia), abnormal platelet counts, low albumin levels, elevated inflammatory markers, kidney dysfunction, increased levels of immunoglobulins, and elevation of specific small molecules involved in cellular signaling (cytokines), such as interleukin 6 (IL-6).

Pathology
The microscopic appearance (histology) of biopsied tissue from lymph nodes affected by UCD will be consistent with Castleman disease. Histologic features characteristic of UCD fit into two distinct categories :


 * Hyaline vascular - regressed germinal centers, follicular dendritic cell prominence, hypervascularity in interfollicular regions, and prominent mantle zones with an “onion-skin” appearance.
 * Plasmacytic – increased number of follicles with large hyperplastic germinal centers and sheetlike plasmacytosis (increased number plasma cells).

UCD most commonly demonstrates hyaline vascular features; however, plasmacytic features or a mixture of both hyaline vascular and plasmacytic features may also be seen in UCD lymph nodes. The clinical utility of subtyping Castleman disease by histologic features is uncertain, as histologic subtypes do not consistently predict disease severity or treatment response.

Staining with latency-associated nuclear antigen (LANA-1), a marker for HHV-8 infection, will be negative.

Associated Diseases
UCD is associated with increased risk of paraneoplastic pemphigus.

Causes
UCD has no known causes or risk factors. Cases of Castleman disease running in families have been reported; however, no causative genetic variants have been identified.

Mechanism
The mechanism of UCD is poorly understood. Most published research supports a growth of abnormal immune system cells (neoplasm) as the most likely cause of UCD, but this has not been conclusively demonstrated or fully characterized. Other proposed mechanisms include viral infections and autoimmune processes. Because surgical removal of affected lymph nodes in UCD is typically curative and recurrence is rare, it is believed that the pathologic process is limited to affected lymph nodes. Unlike HHV-8-associated MCD, which is caused by the HHV-8 virus, UCD has not been associated with HHV-8 infection1.

When findings typically seen in MCD, such as systemic symptoms and laboratory abnormalities,  are present in UCD, they are likely related to increased levels of molecules that stimulate the immune system (cytokines), such as interleukin 6 (IL-6). Systemic symptoms and laboratory abnormalities may be associated with the presence of plasmacytic features on microscopic analysis of affected lymph node tissue.

There have been no reported cases of UCD transforming into iMCD.

Epidemiology
There are approximately 5000-6000 new cases of UCD diagnosed per year in the United States, making it the most common form of Castleman disease. UCD can occur at any age, but the median age at presentation is approximately 35 years old. There is a slightly increased incidence of UCD in women.

There have been no published epidemiologic studies of Castleman disease outside of the United States; however, there is no evidence of increased or decreased incidence of Castleman disease in specific regions or ethnicities.

Diagnosis
UCD is diagnosed based on patient history, physical exam, laboratory testing, radiologic imaging, and microscopic analysis (histology) of biopsied tissue from an affected lymph node. Diagnosis requires involvement of a single lymph node or region of lymph nodes, typically confirmed with radiologic imaging, and biopsy of an affected lymph node demonstrating characteristic features of Castleman disease.

Diagnosis of UCD requires ruling out other diseases with similar clinical and lymph node findings. Diseases that can present with isolated lymph node involvement and microscopic lymph node findings similar to Castleman disease include infectious causes, such as toxoplsasma lymphadenitis, and cancers, including Hodgkin lymphoma, follicular dendritic cell sarcoma, and plasmacytoma.

Treatment
Due to the rarity of the disease, data regarding treatment is limited to observational case series and case reports. No randomized trials have been conducted comparing treatment options for UCD.

Complete surgical removal of the involved lymph node or region of lymph nodes is considered the gold standard treatment for UCD and is typically curative, with resolution of symptoms and lab abnormalities attributable to the disease.

Occasionally, surgical removal of involved lymph nodes may be prohibitively high risk at the time of diagnosis due to large size or proximity to critical structures. This is more common with lymph nodes located deep in the chest, which may be close to major airways and blood vessels. In these cases, chemotherapy, immunosuppressive medications, catheter embolization of blood vessels supplying the lymph node, and/or radiation therapy may be used to shrink the involved lymph nodes, potentially reducing the risk of surgery to acceptable levels. If surgical risk remains too high after treatment to shrink the involved lymph node, treatments used to reduce the size of the lymph node may be continued to control symptoms related to the disease.

Follow-up
After initiation of treatment, patients are regularly evaluated for recurrence of disease and response to treatment with laboratory testing and radiographic imaging.

Prognosis
Most patients with UCD who undergo complete surgical resection of affected lymph nodes achieve long-term disease-free survival, with an observed 10-year mortality of 4% in the largest case series to date.

History
Castleman disease was first described by Dr. Benjamin Castleman in 1954.

Castleman Disease Collaborative Network
The Castleman Disease Collaborative Network (CDCN) is the largest organization related to Castleman disease. It is a global collaborative network focused on Castleman disease research and patient support.