David Fajgenbaum, MD, MBA, MSc: Important Tests

What other tests are important in this diagnostic workup?

It’s very important to perform a LANA-1 stain to look to see if this patient has HHV-8-positivity in the lymph node. It’s also important to perform an EBER test. If it’s HHV-8-positive, you’re going to now think that this is HHV-8-positive Multicentric Castleman Disease which has different treatments with rituximab. Now, if you find out that it’s LANA-1-negative, so HHV-8-negative Multicentric Castleman Disease, we’re still thinking this is idiopathic MCD. Now, if you don’t EBER statin regardless of whether it’s positive or negative, this still would be called idiopathic MCD. At this stage, we don’t know the exact role that Epstein Barre plays in the potential of MCD. Of course, with such a high percentage of individuals that are infected with EBV at some stage in their life, we would not rule out idiopathic MCD based on EBER positivity.

Right now, we’re looking at staining of the lymph node to confirm the exact diagnosis, and also we’re going to want to continue to exhaust our battery of tests systematically. We want to make sure to test for HIV. We want to make sure to continue to do an exhaustive rheumatoid panel, rheumatology panel, and also perform tests for malignancy. We want to look to see: are there Reed-Sternberg cells in the lymph node, are there additional stains that would suggest that this could be Waldenström’s macroglobulinemia or that this could be lymphoma? So really at this stage we’re thinking that it’s HHV-8-negative MCD with TAFRO syndrome, but we always want to exclude other diseases that can act like mimics.

Multicentric Castleman Disease: Case 2

Garrett is a 47-year old male carpenter who was formerly a Marine, with a 4-week history of fatigue, night sweats, and weight loss. He reported difficulty breathing for 2 weeks, and 1 week of fevers. He also reported that he’s noted fluid in his legs. He presented to the emergency department for a work-up. His past medical history was only notable for Raynaud’s phenomenon. His family history included a mother that died from a myocardial infarction at 71 and a father who died from lung cancer at 61. His physical exam was notable for bilateral cervical and inguinal lymphadenopathy (1-2 cm), moderate edema (10 lb weight gain in past 7 days), and pleural effusions.

Laboratory findings showed anemia (Hgb: 11 gm/dl), low platelets (109k), and elevated alkaline phosphatase levels. The patient was admitted with a presumed viral illness and then moved to MICU when the patient began experiencing severe difficulty breathing, transaminitis, and increased fluid gain (30 lbs). Further testing showed his CRP >300 mg/L, albumin 1.2 g/dL, renal dysfunction, and Hgb trending downward (now 9 gm/dl), and PLTs trending downward (now 35k). His infectious workup was pan-negative, except for possible EBV infection (8/29/10: EBV PCR positive). He was diagnosed with acute EBV mononucleosis early in admission, but the diagnosis was rescinded when he was found to be EBV IgG+. A rheumatology workup was negative except for a positive ANA (1:120).

The patient was started on 125mg BID of solumedrol without improvement. His hematology/oncology workup was notable for: .

• Elevated B-2-microglobulin
• CT scan: diffuse LAD, splenomegaly
• PET: patchy FDG uptake in SI only (while on high dose steroids)
• Normal Igs (IgG: 930, range: 650-2000; IgM 63, range: 40-270; IgA: 202, range: 50-500)
• Normal/moderately elevated IL-6 (6, nml <5)
• No light chain restriction
• Negative SPEP and UPEP

A bone marrow biopsy reported:

• Hypercellular marrow (90%) with myeloid and megakaryocytic hyperplasia, and emperipoesis.
• Small perivascular lymphohistiocytic aggregate
• Reticulin fibrosis was also noted with &ldquo;cytological atypia of the megakaryocyte lineage (FVIII+, CD61+)&hellip;&rdquo;
• &ldquo;increased CD68+ macrophages (10%)&hellip;&rdquo;
• &ldquo;myeloid: erythroid ratio of 6:1&rdquo;
• &ldquo;Large CD34- cKit+ blasts.&rdquo;
• &ldquo;Rare macrophages and megakaryocytes that contain red and white blood cells.&rdquo;

A lymph node biopsy was scheduled to be performed.