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Uncommon Hematologic Malignancies

CASE 1. PLASMABLASTIC LEUKEMIA IN HIV-ASSOCIATED MULTICENTRIC CASTLEMAN’S DISEASE

Department of Oncology and Hematology, Medizinische Klinik and Department of Infectious Diseases, Medizinische Poliklinik, Klinikum Innenstadt; and Department of Clinical Chemistry–Großhadern, Ludwig Maximilians University, Munich, Germany

A 41-year-old male with a history of Kaposi’s sarcoma presented with fever, weight loss, anemia, and a giant spleen, associated with a severe systemic inflammatory response syndrome, thrombocytopenia, and shock. Splenectomy was performed and upon histologic examination, human herpesvirus-8 associated multicentric Castleman’s disease (MCD) was diagnosed. Subsequently, two cycles of liposomal encapsulated doxorubicin, etoposide, and bleomycin were administered. Two weeks after the last cycle, the patient developed fever, chills, leukocytosis of 66,000/µL, and a lactate dehydrogenase level of 724 U/L. In a peripheral blood smear, approximately 50% of the mononuclear cells had an immature, pleomorphic, and blastic appearance (Fig 1A). The large cells (approximately 1.5 to two-fold in size compared with neutrophils) were round shaped to oval, with a dispersed nuclear chromatin and prominent nucleoli, a high nuclear-cytoplasmic ratio, and a perinuclear hof in a basophilic cytoplasm, identifying them as plasmablasts. There was a large number of mitotic figures (Fig 1B) as well as cytoplasmic inclusions of immunoglobulin (Russel body–like appearance; Fig 1C). Flow cytometry studies revealed a monophenotypic population of 47% of all circulating mononuclear cells expressing CD19 and light chains, as well as CD 45 and little CD38; however, there was no CD138.

View larger version (98K): [in this window] [in a new window]   Fig 1.

MCD is a lymphoproliferative disorder of unknown etiology associated with an inflammatory syndrome and interleukin-6 (IL-6) dysregulation.² In the setting of HIV infection, MCD is associated with a 1.5-fold incidence of development of secondary B-cell lymphoma, often showing a rapidly fatal outcome.³ It has been previously suggested that proliferation of naive B-cells into monotypic (IgM) but polyclonal (no Ig rearrangement) plasmablasts, which may develop into microlymphomas or into frank monoclonal lymphomas, is triggered by HHV-8 infection.¹ Furthermore, there seems to be a major role for IL-6 in perpetuating the differentiation of naive B-cells into plasmablasts or lymphoproliferative lesions. HHV-8 encodes a viral IL-6 that acts analogously to its human counterpart (hIL-6).⁴

So far, there is no uniform treatment for MCD. Various chemotherapeutic regimens have been studied, but because of the low number of affected patients, no standard combination has been established. Except in frank lymphoma or plasma cell leukemia, treatment may not need to be dose intense. There seems to be a significant improvement on the clinical course of MCD after splenectomy. Furthermore, monoclonal anti-IL-6 antibodies have been shown to alleviate the manifestations of MCD.^5,6

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

REFERENCES

1. Du MQ, Liu H, Diss TC, et al: Kaposi sarcoma-associated herpesvirus infects monotypic (IgM lambda) but polyclonal naive B cells in Castleman disease and associated lymphoproliferative disorders. Blood 97:2130–2136, 2001[Abstract/Free Full Text]

2. Yoshizaki K, Matsuda T, Nishimoto N, et al: Pathogenetic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease. Blood 74:1360–1367, 1989[Abstract/Free Full Text]

3. Oksenhendler E, Boulanger E, Galicier L, et al: High incidence of Kaposi sarcoma-associated herpesvirus-related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease. Blood 99:2331–2336, 2002[Abstract/Free Full Text]

4. Osborne J, Moore PS, Chang Y: KSHV-encoded viral IL-6 activates multiple human IL-6 signaling pathways. Hum Immunol 60:921–927, 1999[CrossRef][Medline]

5. Beck JT, Hsu SM, Wijdenes J, et al: Alleviation of systemic manifestations of Castleman’s disease by monoclonal anti-interleukin-6 antibody. N Engl J Med 330:602–605, 1994[Free Full Text]

6. Nishimoto N, Sasai M, Shima Y, et al: Improvement in Castleman’s disease by humanized anti-interleukin-6 receptor antibody therapy. Blood 95:56–61, 2000[Abstract/Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Jung, C. P. Articles by Goebel, F. D. Search for Related Content PubMed PubMed Citation Articles by Jung, C. P. Articles by Goebel, F. D. Social Bookmarking                            What's this?