David Fajgenbaum, MD, MBA, MSc: Important Diagnostic Tests

What other tests are important in her diagnostic workup?

In this patient, based on the pathology features that were seen, we’re thinking that this could be Multicentric Castleman Disease. So the first thing that we need to do is LANA-1 staining. LANA-1 will tell us if this patient is HHV-8-positive. HHV-8 or KSHV is a virus that typically replicates and can cause a systemic inflammatory syndrome which results in Multicentric Castleman Disease. We know that this typically occurs in patients who are immunocompromised, whether it’s through the HIV virus or for some other reason. So the first step is to figure out is this patient HHV-8-positive or negative. In HHV-8-positive MCD, we know that the HHV-8 virus typically replicates in B-cells and then secretes cytokines. It causes a cytokine storm in the lymphoproliferation. That is Castleman Disease. It’s the viral replication in the virus that’s driving the disease.

Now, in HHV-8-negative Multicentric Castleman Disease, there’s a very similar cytokine storm and also lymphoproliferation, but we’re not sure what’s causing the cytokine storms. So that’s why we call it HHV-8-negative or idiopathic Multicentric Castleman Disease. So it’s really important to do that LANA-1 stain and then if it’s LANA-1 negative, you’re leaning towards idiopathic Multicentric Castleman Disease. But it’s really important to still consider some additional diseases that can overlap or mimic Multicentric Castleman Disease, and that’s Hodgkin lymphoma, non-Hodgkin lymphoma. You want to perform a bone marrow biopsy to make sure there’s no clonality within the bone marrow. But, at this stage, we’re really thinking, based on the previous labs and the lymph node pathology that this is idiopathic Multicentric Castleman Disease of what’s called the plasmacytic subtype.

Multicentric Castleman Disease: Case 1

Mary is a 13-year old female who presents with a 10-month history of night sweats, fatigue, and weight loss. She presents to urgent care with complaints of flu-like symptoms. Her physical exam is notable for bilateral cervical lymphadenopathy (1-2 cm), mild splenomegaly, and mild edema. She has no neuropathy and no joint pain. She is referred to a hematologist to rule out lymphoma. Her medical history is unremarkable. Her family history is relevant for a mother with systemic lupus erythematous and father who died from colon cancer at 65 years old.

At the hematology office, the following laboratory abnormalities are noted:

• Anemia (Hgb 11 gm/dL), elevated CRP (35mg/L) and ESR (80mm/hr), elevated platelets (400,000/mK), Igs (IgG: 4500 mg/dL, IgM: 1500mg/dL, IgA: 300mg/dL).
• Negative ANA, negative dsDNA, anti-Smith and anti-phosholipid antibodies; monospot negative.
• 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.