Frits van Rhee, MD, PhD: Patient's Diagnosis

What is the most likely diagnosis for this patient?

Frits van Rhee, MD, PhD, University of Arkansas for Medical Sciences, says the first point to make is that a false positive screen for autoimmune disease occurs in about 30% of patients. If one finds that this test is positive, it is necessary to do more sophisticated blood testing, and this was completed in this patient. Very specific tests for lupus were conducted, and they were negative, so lupus was ruled out. Lymphoma was ruled out as well. A stain on the lymph node ruled out Epstein-Barr Virus infection, and then the patient was found to have generalized lymphadenopathy. In that constellation, one needs to seriously consider that the correct diagnosis is multicentric Castleman’s disease.

Guess the Diagnosis: Case 2

Mark F. is a 25-year-old law school student from Florida with a 3-week history of severe fatigue, night sweats, and weight loss; he has also reported high fevers for the past week. He did not complain of joint pain.

• He presents to the emergency department complaining of abdominal pain. His past medical history is notable for enlarged thyroid incidentally found 5 years before; family history relevant for an aunt with rheumatoid arthritis
• Physical exam was notable for generalized lymphadenopathy (1-2 cm), hepatosplenomegaly, bilateral pleural effusions, ascites, and 4+ peripheral edema. Laboratory findings show anemia (7 gm/dL), elevated CRP (150 mg/L), ESR (120mm/hr), creatinine (3.0 mmol/L), Albumin of 2.1 g/dL and normal immunoglobulin levels (IgG: 1100 mg/dL, IgA: 300 mg/dL, IgM 200 mg/dL), low platelets (50,000/mL), positive ANA 1:160 with a speckled pattern. RhF was negative. Coagulation screen was not suggestive of DIC. LDH was normal

The patient was admitted for further assessment.

• Regressed germinal centers, scattered hyperplastic follicles, preserved architecture with patent peripheral sinuses and florid interfollicular plasmacytosis with no light chain restriction
• Rheumatologist diagnosed the patient with SLE and treated with high-dose steroids; this did not result in a major improvement in symptoms, laboratory parameters or lymphadenopathy

Mark’s SLE diagnosis was reviewed and further testing was performed:

• The patient was believed to be too sick to be taken to the OR to undergo a lymph node biopsy, so a bone marrow biopsy was performed. Bone marrow showed a hypercellular marrow with mild increase in polyclonal plasma cells and moderate reticulin fibrosis
• Laboratory work: Negative dsDNA, anti-Smith and anti-phopsholipid antibodies with normal complement levels; ANCA and anti-streptolysis O titer are negative. No M protein on protein electrophoresis. 24-hour urine showed mild proteinuria. Monospot negative. TSH, T4, and T3 normal. Normal thyroglobulin and thryoid peroxidase antibodies. Urinary sediment is negative as are urine and blood cultures. IL-6 is 6 pg/mL
• CT-PET: generalized lymphadenopathy with low-positive FDG uptake
• Without a clear diagnosis, a lymph node biopsy was performed of the cervical chain: Regressed germinal centers, scattered hyperplastic follicles, preserved architecture with patent peripheral sinuses; florid interfollicular plasmacytosis, prominent vascularization with absence of light chain restriction. Negative LANA-1, IgG4, and EBER stains. Negative PCR for B-cell clonality