Correspondence
Body-Cavity–Based Lymphoma in an HIV-Seronegative Patient without Kaposi's Sarcoma–Associated Herpesvirus-Like DNA Sequences
N Engl J Med 1996; 334:272-273January 25, 1996
- Article
To the Editor:
Moore et al. (May 4 issue)1 found herpesvirus-like DNA sequences in Kaposi's sarcoma lesions, both in patients infected with the human immunodeficiency virus (HIV) and in HIV-seronegative patients.1 In the same issue, Cesarman and coworkers reported having found the footprint of this new agent in all eight patients with peculiar AIDS-related non-Hodgkin's lymphoma based in body cavities.2 Body-cavity–based non-Hodgkin's lymphomas seem to occur very rarely in HIV-seronegative patients.3,4 In the October 5 issue of the Journal, however, Nador and colleagues reported a body-cavity–based lymphoma in an HIV-seronegative patient in which Kaposi's sarcoma–associated herpesvirus (KSHV) DNA sequences were detected.5 On the basis of this finding, they suggested that, as in Kaposi's sarcoma, KSHV is involved in all body-cavity–based lymphomas regardless of the patient's HIV status. Thus, it is interesting to investigate whether or not KSHV DNA sequences are found in the tumor cells of all body-cavity–based non-Hodgkin's lymphomas in HIV-seronegative patients.
We studied a 52-year-old HIV-seronegative white woman who met all the criteria for having a body-cavity–based lymphoma. She reported no risk factors for HIV infection and had no detectable HIV antibodies according to enzyme-linked immunosorbent assay or the Western blot assay. No HIV p24 antigen was detectable in her serum. She was admitted to the hospital with massive pericardial and pleural effusions. Her clinical examination, including an examination of the skin, was normal. Abdominal and chest computed tomographic scanning did not reveal any enlargement of lymph nodes, spleen, or liver. Pericardial and bone marrow biopsies and analysis of cerebrospinal fluid showed no tumor cells. In contrast, the cytologic analysis of the pericardial and pleural effusions revealed numerous large cells with one to three large prominent nucleoli. These cells expressed CD45, CD22, CD19, CD20, and DR antigens. The B-cell lineage of the tumor cells was confirmed by the finding of a clonal rearrangement of immunoglobulin genes. Epstein–Barr virus (EBV) was absent from the tumor cells when they were assessed by the polymerase chain reaction (PCR) and in situ hybridization with an EBER probe. Amplifiable DNA (positive for β-globin on PCR) from lymphoid neoplastic cells was analyzed for KSHV after PCR with two different sets of specific primers, as described by Moore et al.1 No KSHV DNA sequences were detectable, even after hybridization with internal oligonucleotide probes.
Therefore, we disagree with the conclusion of Nador and coworkers. Our case demonstrates that KSHV is not related to all body-cavity–based lymphomas in HIV-negative patients. Further studies are needed to assess the frequency of such lymphomas and to understand their pathophysiology, particularly the role of KSHV.
5 ReferencesOlivier Hermine, M.D.
Marc Michel, M.D.
Agnès Buzyn-Veil, M.D.
Hôpital Necker, 75743 Paris, FranceAntoine Gessain, M.D., Ph.D.
Institut Pasteur, 75724 Paris, France1
Moore PS ,Chang Y . Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and those without HIV infection. N Engl J Med 1995;332:1181-1185
Full Text | Web of Science | Medline2
Cesarman E ,Chang Y ,Moore PS ,Said JW ,Knowles DM . Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 1995;332:1186-1191
Full Text | Web of Science | Medline3
Walts AE ,Shintaku IP ,Said JW . Diagnosis of malignant lymphoma in effusions from patients with AIDS by gene rearrangement. Am J Clin Pathol 1990;94:170-175
Web of Science | Medline4
Harris NL ,Jaffe ES ,Stein H , et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994;84:1361-1392
Web of Science | Medline5
Nador RG ,Cesarman E ,Knowles DM ,Said JW . Herpes-like DNA sequences in a body-cavity-based lymphoma in an HIV-negative patient. N Engl J Med 1995;333:943-943
Full Text | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: At first glance, the report by Hermine et al. of a KSHV-negative lymphomatous effusion in an HIV-seronegative patient appears to contrast with our published studies. We identified KSHV in all 8 AIDS-related1 and 1 non–AIDS-related2 body-cavity–based lymphomas, but not in 185 other lymphomas. In those reports we stated that these lymphomas have a unique constellation of clinical, morphologic, immunophenotypic, and molecular genetic characteristics. These include morphologic features bridging immunoblastic and anaplastic large-cell lymphomas, the frequent absence of B-cell antigens, and the presence of EBV. The patient described by Hermine and colleagues differs in that her tumor-cell morphology may correspond to that of a large-cell lymphoma, three pan-B-cell antigens were expressed, and EBV was absent. Another very important feature, not mentioned by Hermine et al., is the uniform absence of c-myc gene rearrangement in all the body-cavity–based lymphomas that we have analyzed. Therefore, we strongly disagree with these authors' statement that their patient's lymphoma met our criteria for a body-cavity–based lymphoma.
Nevertheless, Hermine et al. raise issues that deserve comment. We have now identified and characterized 19 malignant lymphomatous effusions occurring in the absence of a contiguous tumor mass (unpublished data), 2 of which developed in HIV-seronegative patients. We identified KSHV in 15 of these 19 cases, so KSHV-negative body-cavity–based lymphomas clearly exist. However, all 4 KSHV-negative patients differed from the 15 KSHV-positive patients in that their tumor cells had small, non-cleaved-cell morphologic features and c-myc gene rearrangements and thus probably represented small, non-cleaved-cell lymphomas occurring in body cavities. All 15 KSHV-positive lymphomatous effusions had the distinctive morphologic features mentioned above but no c-myc gene rearrangements. Eleven of these 15 patients had no B-cell antigens, and cells from 14 of the 15 contained EBV. Therefore, we believe that KSHV-positive malignant lymphomatous effusions are a distinct clinicopathologic and biologic entity and that several criteria must be satisfied for a case to be classified in this category. Furthermore, we suggest that these lymphomas be designated “primary effusion lymphomas” rather than body-cavity–based lymphomas to avoid being confused with other lymphomas that may occur or arise within the body cavities.
Nonetheless, we have no doubt that exceptions will occur and that an occasional case will not readily fall into a precise category. We also agree that further studies are needed to clarify the pathogenetic role of KSHV in primary effusion lymphomas, as well as in other diseases.
2 ReferencesEthel Cesarman, M.D., Ph.D.
Roland Nador, M.D.
Daniel M. Knowles, M.D.
New York Hospital–Cornell Medical Center, New York, NY 100211
Cesarman E ,Chang Y ,Moore PS ,Said JW ,Knowles DM . Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 1995;332:1186-1191
Full Text | Web of Science | Medline2
Nador RG ,Cesarman E ,Knowles DM ,Said JW . Herpes-like DNA sequences in a body-cavity-based lymphoma in an HIV-negative patient. N Engl J Med 1995;333:943-943
Full Text | Web of Science | Medline
- Citing Articles (24)
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Graham S. Taylor, David J. Blackbourn. (2011) Infectious agents in human cancers: Lessons in immunity and immunomodulation from gammaherpesviruses EBV and KSHV. Cancer Letters 305:2, 263-278
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Yutaka Kobayashi, Yuri Kamitsuji, Junya Kuroda, Sei Tsunoda, Nobuhiko Uoshima, Shinya Kimura, Katsuya Wada, Yosuke Matsumoto, Kenichi Nomura, Shigeo Horiike, Chihiro Shimazaki, Toshikazu Yoshikawa, Masafumi Taniwaki. (2007) Comparison of Human Herpes Virus 8 Related Primary Effusion Lymphoma with Human Herpes Virus 8 Unrelated Primary Effusion Lymphoma-Like Lymphoma on the Basis of HIV: Report of 2 Cases and Review of 212 Cases in the Literature. Acta Haematologica 117:3, 132-144
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