David Fajgenbaum, MD, MBA, MSc: Initial Impression of Patient

What does the patient’s initial presentation suggest to you?

This is a very, very sick gentleman. Over the course of just a couple of weeks, he went from being totally healthy to being hospitalized in the intensive care unit. This patient at this time is on a ventilator getting continuous dialysis, and there is no diagnosis. Of course, the treating team is thinking that this could be either a malignancy, an autoimmune disease, or a disseminated infection. At the top of their list is a viral infection. They’re considering this could be EBV. They’re also considering that there could be pneumonia due to a productive cough that he has right now. In addition, inflammatory disorders like a potential first flare or presentation of lupus or Multicentric Castleman Disease are on the differential.

Finally, based on his age, they’re certainly very concerned that this could be a malignancy—multiple myeloma/lymphoma sort of malignancy. But the patient is very, very sick. Judging by his low albumin, his crashing platelet counts, his anemia, this is a patient that we need to get a diagnosis right away.

The treating physicians are thinking about this from 3 areas: autoimmune, malignancy, viral, or bacterial infection. Based on the data, we really can’t say with certainty what it is. But I can say that the next thing that needs to be done is a lymph node biopsy. We know that he has enlarged lymph nodes, both in his cervical and his inguinal regions. So we need to get one of those lymph nodes out and we need to look to see is there a malignancy in there or are there signs of an inflammatory disorder that we haven’t yet picked up.

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.