Guess the Diagnosis: Case 1 - Episode 3

David Fajgenbaum, MD, MBA, MSc: Patient's Diagnostic Workup

Dr. David Fajgenbaum, Perelman School of Medicine, University of Pennsylvania, says pathology alone cannot render a diagnosis of MCD. A diagnosis of MCD re- quires (a) the presence of pathology consistent with MCD; (b) exclusion of oth- er disorders, which can give rise to similar pathology; and (c) enlargement of multiple lymph node stations. EBV, lymphoma, and autoimmune disorders are especially important to rule out. Testing for these disorders was negative in this patient.

Next, it is crucial to establish whether or not the patient has active HHV-8 replication. This can be established by quantitative polymerase chain reaction (PCR) for HHV-8 on the peripheral blood, which can be ob- tained through large reference laboratories or academic centers that have an interest in MCD and other HHV-8—related disorders. PCR for HHV-8 was negative in this patient. The other gold standard for assessing HHV-8 sta- tus is LANA-1 staining for the lymph node. There have been reports of cases with negative LANA-1 staining that had replicating HHV-8 by PCR. In addition, one should rule out HIV infection by serology. HHV-8 serology is not informative, because as approximately 10% to 20% of the US popu- lation have been in contact with the HHV-8 virus and are latently infected, but the virus is well controlled by their immune system.

Both HHV-8—positive and HHV-8–negative patients with MCD can exhibit a spectrum of clinical features, ranging from mild flu-like symptoms to multi- organ failure. It is important to distinguish the two variants of MCD because they require different therapeutic approaches.

What other tests are important in her diagnostic workup?

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