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:

Rheumatoid arthritis
Plasmacytoma
Non-Hodgkin lymphoma subtypes with prominent plasma cells

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)
Systemic lupus erythematosus
Rheumatoid arthritis
Adult-onset Still disease
ALPS
Juvenile idiopathic arthritis
Lymphoma
Multiple myeloma
Primary lymph node plasmacytoma
FDC sarcoma

Workup

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Author

Geneva E Guarin, MD, MBA Resident Physician, Department of Internal Medicine, Einstein Medical Center Philadelphia

Disclosure: Nothing to disclose.

Coauthor(s)

Claudia M da Costa Dourado, MD Clinical Assistant Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Program Director, Hematology and Medical Oncology Fellowship Program, Attending Physician, Division of Hematology and Medical Oncology, Department of Medicine, Einstein Medical Center Philadelphia

Claudia M da Costa Dourado, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David C Fajgenbaum, MD, MSc, MBA Research Assistant Professor of Medicine, Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania; Associate Director, Patient Impact, Orphan Disease Center, Division of Medical Genetics, Hospital of the University of Pennsylvania

David C Fajgenbaum, MD, MSc, MBA is a member of the following medical societies: American Society of Hematology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: EUSA Pharma<br/>Received research grant from: EUSA Pharma.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Neetu Radhakrishnan, MD Medical Oncologist, Kettering Cancer Care

Neetu Radhakrishnan, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Castleman Disease Differential Diagnoses

Diagnostic Considerations

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