Castleman Disease Differential Diagnoses

Updated: Jan 09, 2023
  • Author: Geneva E Guarin, MD, MBA; Chief Editor: Emmanuel C Besa, MD  more...
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Diagnostic Considerations

The differential diagnosis of unicentric Castleman disease (UCD) includes other disorders that can present as a solitary enlarged lymph node and/or systemic symptoms. As a general rule, it is unusual for patients with other causes of reactive lymphadenopathy to present with enlargement of a solitary lymph node, or to have lymph node enlargement to sizes greater than 2 to 3 cm, clues that can be helpful when the histologic appearance raises the possibility of UCD. However, the "CD-like" histopathological features can be seen in other disorders.

The differential diagnoses for the hyaline vascular histopathological subtype of UCD include the following:

  • Toxoplasma lymphadenitis
  • Burned-out HIV lymphadenitis
  • Follicular hyperplasia of any cause
  • Non-Hodgkin lymphoma subtypes with nodular growth patterns
  • Follicular dendritic cell (FDC) sarcoma
  • Autoimmune lymphoproliferative syndrome (ALPS)

The differential diagnoses for the plasma cell histopathological subtype of UCD include the following:

The differential diagnosis of human herpesvirus 8–associated multicentric Castleman disease (HHV-8–associated MCD), which presents as the plasmablastic histopathological subtype, includes the same disorders as HHV-8–negative MCD (below), as well as the following:

  • HIV lymphadenitis
  • Kaposi sarcoma inflammatory cytokine syndrome (KICS)
  • Kaposi sarcoma

Diagnosis of HHV-8–negative/idiopathic multicentric Castleman disease (iMCD) requires exclusion of disorders that can mimic iMCD. In addition to the diseases listed above, these include the following [10] :

  • Human herpesvirus 8 (HHV-8)–associated MCD - Can be excluded by negative latency-associated nuclear antigen–1 (LANA-1) staining in a diagnostic lymph node
  • Epstein-Barr virus (EBV)–associated lymphoproliferative disorders (eg, infectious mononucleosis or chronic active EBV infection); however, low levels of EBV are not necessarily exclusionary
  • Inflammation and adenopathy caused by other uncontrolled infections (eg, acute cytomegalovirus, toxoplasmosis, HIV, acute tuberculosis)
  • Adult-onset Still disease
  • ALPS
  • Juvenile idiopathic arthritis
  • Lymphoma
  • Primary lymph node plasmacytoma
  • FDC sarcoma