Frits van Rhee, MD, PhD: Most Likely Diagnosis

What is the most likely diagnosis for this patient?

Frits van Rhee, MD, PhD, University of Arkansas for Medical Sciences, says that in order to make a diagnosis of multicentric Castleman’s disease, one must have the correct pathology in the correct context, so the symptoms are compatible with the disease. Then, one must exclude the other disorders, which is very important. The next step is to be sure that there are lymph nodes present in more than one area, such as the armpits, chest, belly, or in the groins. In order to diagnose what is called multicentric Castleman’s disease, one must have lymph nodes in multiple areas. Lastly, it’s crucial to make a distinction as to whether or not the disease is driven by a virus. There’s a virus called Human Herpesvirus type 8, which can actively replicate and cause a very similar picture. This is referred to as HHV8 associated multicentric Castleman’s disease. If this virus is not present and not actively replicating and dividing in the bloodstream for patients, it is called idiopathic multicentric Castleman’s disease. The distinction is really important because the treatment is very different.

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