Guess the Diagnosis: Case 1 - Episode 10

Frits van Rhee, MD, PhD: Potential Treatment Options

What are the potential treatment options?

Frits van Rhee, MD, PhD, University of Arkansas for Medical Sciences, says the treatment options for multicentric Castleman’s disease first include steroids. Steroids will control the disease for a while, but usually patients need to take quite high dose steroids; this is not tolerable for longer periods of tim, due to the side effects. There are antibodies, which have been used for lymphoma as well. One of them is called rituximab, and it targets cells in the lymph nodes. This sometimes can provide temporary relief. The actual experience of this antibody therapy in what one would call HHV8-negative or idiopathic multicentric Castleman’s disease is very limited, so its efficacy is not very well known. Other more novel therapies target a molecule called interleukin-6. Interleukin-6 is made by the Castleman’s disease lymph nodes, and that is what gives rise to the symptoms in the patient. It’s not specific for Castleman’s disease, but it can also occur in other disorders. For instance, if one has the flu and he or she feels sick and miserable and may have a fever, it’s actually interleukin-6, which is responsible for that. Patients who have multicentric Castleman’s disease have a chronic flu-like syndrome, which can become quite severe, and they can, in fact, succumb to their disease. IL-6 is quite critical to the pathology and pathogenesis of Castleman’s disease, and targeting it directly with an antibody is very effective. There are currently two antibodies available. One was developed in Japan. It targets the interleukin-6 receptor and is called tocilizumab. This drug is approved in Japan for Castleman’s disease. There is another antibody called siltuximab, which has undergone a worldwide randomized trial and was found to be effective. Siltuximab is an important new treatment for Castleman’s disease. This would be Dr. van Rhee’s first choice of treatment for this particular patient.

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