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Multicentric Castleman Disease Case Studies

David Fajgenbaum, MD, MBA, MSc: Pathology Report Findings

David Fajgenbaum, MD, MBA, MSc
Published Online:Aug 07, 2015
Lisa B. is a 47-year-old female store owner from St. Louis, with a 10-month history of fatigue, night sweats, and weight loss.

Guess the Diagnosis: Case 1

What are the relevant findings from her pathology report? 

Dr. David Fajgenbaum, Perelman School of Medicine, University of Pennsylvania, says the pathology from the lymph nodes is not consistent with lymphoma, and negative light chain restriction studies of the plasma cells and the absence of B-cell clonality support this notion. The regressed germinal centers with hyperplastic follicles and expanded mantle zones with interfollicular plasmacytosis and prominent vasculature are consistent with a diagnosis of multicentric Castleman disease (MCD), plasmacytic variant. The negative EBER excludes Epstein-Barr virus (EBV)–related lymphoproliferation, and the immunoglobulin G4 (IgG4) stain rules out IgG4–related lymphadenopathy. The negative latency-associated nuclear antigen (LANA-1) stain, which is constitutively expressed in all human herpes virus 8 (HHV-8) infected cells, indicates that this is HHV-8-negative MCD, [also referred to as] idiopathic MCD (iMCD).
In HHV-8–positive MCD, HHV-8 signals for viral interleukin-6 (IL-6), hu- man IL-6, and other proinflammatory cytokines that drive the characteristic lymph node changes, systemic features, and organ dysfunction. Most patients with HHV-8–positive MCD are infected with HIV or have another cause for immunosuppression. In HHV-8–negative MCD, the cause for the hypercytokinemia is unknown.

Guess the Diagnosis: Case 1

Lisa B. is a 47-year-old female store owner from St. Louis, with a 10-month history of fatigue, night sweats, and weight loss.
  • She presents to her PCP with generalized lymphadenopathy, most prominent in the cervical region; there is no polyneuropathy, and patient does not report joint pain. She is referred to a hematologist to rule out lymphoma
  • Medical history is unremarkable; family history relevant for a mother with systemic lupus erythematous and father who died with prostate cancer at 65 years old
  • Her physical exam is notable for bilateral cervical lymphadenopathy (1-2 cm), mild splenomegaly, and mild edema
  • Laboratory findings: anemia (Hgb 11 gm/dL), elevated CRP (35 mg/L) and ESR (80mm/hr), elevated platelets (400,000/mK), Igs (IgG: 4500 mg/dL, IgM: 1500 mg/dL, IgA: 300mg/dL)
  • PET scan showed generalized lymphadenopathy with a maximum SUV of 4.5; FNA of the lymph node is uninformative; she was referred to a general surgeon for excisional lymph node biopsy
Lisa’s pathology report shows the following findings:
  • Regressed germinal centers, scattered hyperplastic follicles, preserved architecture with patent peripheral sinuses and florid interfollicular plasmacytosis with no light chain restriction
  • Prominent vascularization and hyalinization is present
In view of these findings, the hematologist orders further tests, which yield the following results:
  • Lymph node: negative EBER, LANA-1, and IgG4 stains; negative PCR for B-cell clonality
  • Additional laboratory work: negative ANA, negative dsDNA, anti-Smith and anti-phosholipid antibodies; monospot negative
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