UCD is diagnosed based on patient history, physical exam, laboratory testing, radiologic imaging, and microscopic analysis (histology) of biopsied tissue from an enlarged lymph node. There are no widely accepted diagnostic criteria for UCD; however, diagnosis generally requires enlargement of lymph nodes limited to a single region of lymph nodes (typically confirmed with radiologic imaging), biopsy of an enlarged lymph node demonstrating characteristic features of Castleman<unk> , and exclusion of other<unk> s that can mimic UCD. Classification Castleman<unk>  describes a group of at least 3 distinct disorders—unicentric Castleman<unk>  (UCD), human herpesvirus 8 associated multicentric Castleman<unk>  (HHV-8-associated MCD), and idiopathic multicentric Castleman<unk>  (iMCD). Identifying the correct subtype of the<unk>  is important, as the three disorders vary significantly in symptoms, clinical findings,<unk>  mechanism, treatment approach, and prognosis. * In<unk>  enlarged lymph nodes with characteristic microscopic findings are present in only a single lymph node region. * In the multicentric subtypes of Castleman<unk> , enlarged lymph nodes with characteristic findings are present in multiple lymph node regions. The multicentric variants of Castleman<unk>  are further classified by known causes of the<unk> . * HHV-8-associated MCD is caused by uncontrolled infection with human herpesvirus 8 (HHV-8, also known as Kaposi sarcoma-associated herpesvirus). * In idiopathic multicentric Castleman<unk>  (iMCD) the cause of the<unk>  is unknown (idiopathic). Testing for HHV-8 must be negative to diagnose iMCD. Medical imaging Radiologic imaging shows 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). Laboratory testing Laboratory testing is typically normal, including blood counts, metabolic tests, and inflammatory markers; however, in some people with UCD, laboratory testing may show abnormalities more commonly seen in HHV-8-associated MCD or iMCD. These abnormal tests include elevated C-Reactive Protein, decreased hemoglobin levels (anemia), low albumin levels, elevated creatinine (kidney dysfunction), increased immunoglobulin levels, abnormal platelet counts, and elevations of molecules involved in inflammation (cytokines), such as interleukin 6 (IL-6). Pathology The microscopic appearance (histology) of biopsied tissue from an enlarged lymph node must demonstrate a constellation of features consistent with Castleman<unk> . There are three patterns of characteristic histologic features associated with UCD: * 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. * Plasmacytic – increased number of follicles with large hyperplastic germinal centers and sheetlike plasmacytosis (increased number plasma cells). * Mixed - features of both hyaline vascular and plasmacytic patterns 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<unk>  by histologic features is uncertain, as histologic subtypes do not consistently predict<unk>  severity or treatment response. Staining with latency-associated nuclear antigen (LANA-1), a marker for HHV-8 infection, must be negative to diagnose UCD.<unk> s to be excluded Diagnosis of UCD requires ruling out other<unk> s that can present with enlarged lymph nodes limited to a single region of lymph nodes and histologic findings similar to UCD on microscopic analysis of biopsied lymph nodes. This include infectious causes, such as toxoplasma lymphadenitis, and cancers, including Hodgkin lymphoma, follicular dendritic cell sarcoma, and plasmacytoma.
Unicentric Castleman disease
Idiopathic multicentric Castleman disease
Follicular lymphoma
Follicular dendritic cell sarcoma
Progressive nodular histiocytoma
Thymic carcinoma
Marginal zone B-cell lymphoma
Progressive nodular histiocytosis