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Case Study: 32-Year-Old Man with Adenopathy and Systemic Symptoms

A board-style question with an explanation and a link to a relevant article is a recurring feature of TraineE-News. The goal of the case study is to clarify specific and timely teaching points in the field of hematology. The following case study focuses on a 32-year-old man who is admitted to the hospital after the onset of fevers, fatigue, 10-pound weight loss, and diffuse lymphadenopathy. Examination reveals palpable splenomegaly and laboratory evaluation reveals a Cr of 2.5 mg/dL, hematocrit 22 percent, and C-reactive protein of 97 mg/L. HIV serology is negative. A right cervical lymph node biopsy is performed on the second hospital day and reveals atypical plasmablasts within the mantle zone of the lymph node follicle, which stain positive for human herpesvirus-8 (HHV-8).

Which of the following cytokines has been implicated in the pathogenesis of this disease?

  1. Interleukin-2
  2. Interleukin-6
  3. Interferon-gamma
  4. Interleukin-17

Answer

  1. Interleukin-6.

Explanation

This patient presents with constitutional symptoms, lymphadenopathy, splenomegaly, renal dysfunction, and elevation of CR-P-all of which support a diagnosis of multicentric Castleman disease (MCD). This diagnosis is confirmed by the findings on a lymph node biopsy of a plasmablastic infiltrate, and many cases are associated with HHV-8 (KSHV).1,2 The symptoms of MCD have been correlated with increased IL-6 production in the host3, as well as viral-IL-6 production in HHV-8 positive cases. Therapy directed at the IL-6 receptor4,5 as well as monoclonal antibodies directed against IL-6 itself have shown clinical activity5-7 in MCD.

None of the other listed cytokines are implicated in MCD. IL-2 is used as a therapeutic in melanoma and renal cell carcinoma, interferon-γ has been shown to correlate with severity of acute graft-versus-host disease,8 and IL-17 is implicated in the pathogenesis of autoimmune conditions such as aplastic anemia.9

References

  1. Soulier J, Grollet L, Oksenhendler E, et al. . Blood. 1995;86:1276-1280.
  2. Gessain A, Sudaka A, Briere J, et al.  Blood. 1996;87:414-416.
  3. Yoshizaki K, Matsuda T, Nishimoto N, et al.  Blood. 1989;74:1360-1367.
  4. Nishimoto N, Kanakura Y, Aozasa K, et al.  Blood. 2005;106:2627-2632.
  5. Song SJ, Tomosugi N, Kawabata H, et al.,  Blood. 2010;116:3627-3634.
  6. van Rhee F, Fayad L, Voorhees P, et al.,  J Clin Oncol. 2010;28:3701-3708.
  7. Beck JT, Hsu SM, Wijdenes J, et al.  N Engl J Med. 1994;330:602-605.
  8. Xu J, Wei J, Zhu X, et al. Biol Blood Marrow Transplant. 2013;19:196-201.
  9. de Latour RP, Visconte V, Takaku T, et al.  Blood. 2010;116:4175-4184.

Question written by Matthew Ulrickson, MD, MD Anderson Cancer Center.

Case study submitted by Mark A. Walshauser, MD, Loyola University Medical Center.

Citations