FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 332:12-18 January 5, 1995 Number 1 Next

	Full Text PDF Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Children with the acquired immunodeficiency syndrome (AIDS) have an unusually high incidence of smooth-muscle tumors (leiomyomas and leiomyosarcomas) in addition to malignant lymphomas. We tested the hypothesis that the smooth-muscle tumors in these children are associated with the Epstein–Barr virus (EBV).

Methods Tissue specimens of five leiomyosarcomas and two leiomyomas from five children and one young man with AIDS were studied for evidence of the human immunodeficiency virus (HIV) and EBV by in situ hybridization and quantitative polymerase chain reaction (PCR). Comparison specimens included samples of leiomyosarcoma and leiomyoma from HIV-negative children. EBV clonality of leiomyosarcomas was determined by Southern blot analysis with oligonucleotide probes for EBV terminal-repeat fragments. Tumor specimens were tested by immunoperoxidase staining for infiltration by B lymphocytes and expression of the EBV receptor. Serologic testing for EBV was performed.

Results In situ hybridization showed EBV genomes in all muscle cells of the five leiomyosarcomas and the two leiomyomas from the six HIV-infected patients. Quantitative PCR demonstrated strikingly high levels of EBV in tumor tissue, with as many as 4.3 genome copies per cell. Two colonic leiomyosarcomas obtained from different sites at different times from one patient contained different episomal EBV clones, signifying the presence of distinct monoclonal EBV-related tumors. We found biclonal EBV infection in the leiomyosarcoma of another patient. No EBV was detected in normal muscle or tumor specimens from HIV-negative patients. Immunostaining for the EBV receptor was strongly positive in six of the seven leiomyomas and leiomyosarcomas from the patients with AIDS.

Conclusions EBV can infect smooth-muscle cells, at least in patients with AIDS, and it may contribute to the pathogenesis of leiomyomas and leiomyosarcomas in patients with AIDS. EBV seems to play no part in smooth-muscle tumors in HIV-negative patients.

Source Information

From the Department of Pediatrics, Baylor College of Medicine, Houston (K.L.M.); the Department of Pediatrics, University of Texas Health Science Center at San Antonio (C.T.L., H.B.J.); the Department of Pathology and Laboratory Medicine, East Carolina University, Greenville, N.C. (V.V.J.); the Department of Pediatrics, University of Florida College of Medicine, Gainesville (B.H.P.); Carolinas Medical Center, Charlotte, N.C. (R.T.P.); the Department of Pathology, Children's Hospital of New Jersey, Newark (F.J.D.); and the Department of Pediatrics, Northwestern University Medical School and the Children's Memorial Hospital, Chicago (E.G.C., S.B.M.).

Address reprint requests to Dr. McClain at the Texas Children's Hospital, Children's Cancer Center MC 3-3320, 6621 Fannin St., Houston, TX 77030.

Full Text of this Article

Related Letters:

More on Reaction to a Foreign Body after Hip Replacement
Jacobs J. J., Urban R. M., Péoc'h M., Pasquier B.
Extract | Full Text  
N Engl J Med 1996; 335:1690-1691, Nov 28, 1996. Correspondence

This article has been cited by other articles:

• Spunt, S. L., Skapek, S. X., Coffin, C. M. (2008). Pediatric Nonrhabdomyosarcoma Soft Tissue Sarcomas. The Oncologist 13: 668-678 [Abstract] [Full Text]  
• Delecluse, H-J, Feederle, R, O'Sullivan, B, Taniere, P (2007). Epstein Barr virus-associated tumours: an update for the attention of the working pathologist. J. Clin. Pathol. 60: 1358-1364 [Abstract] [Full Text]  
• Perrine, S. P., Hermine, O., Small, T., Suarez, F., O'Reilly, R., Boulad, F., Fingeroth, J., Askin, M., Levy, A., Mentzer, S. J., Di Nicola, M., Gianni, A. M., Klein, C., Horwitz, S., Faller, D. V. (2007). A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood 109: 2571-2578 [Abstract] [Full Text]  
• Scadden, D. T., Muse, V. V., Hasserjian, R. P. (2006). Case records of the Massachusetts General Hospital. Case 30-2006. A 41-year-old man with dyspnea, fever, and lymphadenopathy.. NEJM 355: 1358-1368 [Full Text]  
• Yokoi, S., Iizasa, T., Hiroshima, K., Saitoh, Y., Fujisawa, T. (2006). Pulmonary artery leiomyosarcoma expressing epstein-barr virus in an immunocompetent individual.. Ann. Thorac. Surg. 81: 1897-1899 [Abstract] [Full Text]  
• Clark, M. A., Fisher, C., Judson, I., Thomas, J. M. (2005). Soft-Tissue Sarcomas in Adults. NEJM 353: 701-711 [Full Text]  
• Thompson, M. P., Kurzrock, R. (2004). Epstein-Barr Virus and Cancer. Clin. Cancer Res. 10: 803-821 [Abstract] [Full Text]  
• Bellezza, G., Sidoni, A., Cavaliere, A., Scheibel, M., Bucciarelli, E. (2004). Primary Cutaneous Leiomyosarcoma: A Clinicopathological and Immunohistochemical Study of 7 Cases. INT J SURG PATHOL 12: 39-44 [Abstract]  
• Tateishi, U., Gladish, G. W., Kusumoto, M., Hasegawa, T., Yokoyama, R., Tsuchiya, R., Moriyama, N. (2003). Chest Wall Tumors: Radiologic Findings and Pathologic Correlation: Part 2. Malignant Tumors. RadioGraphics 23: 1491-1508 [Abstract] [Full Text]  
• Tulvatana, W., Pancharoen, C., Mekmullica, J., Thisyakorn, U., Tinnungwattana, U., Keetacheeva, K., Shuangshoti, S., Shuangshoti, S. (2003). Epstein-Barr Virus-Associated Leiomyosarcoma of the Iris in a Child Infected With Human Immunodeficiency Virus. Arch Ophthalmol 121: 1478-1481 [Full Text]  
• Ferri, L., Fraser, R., Gaboury, L., Mulder, D. (2003). Epstein-Barr virus-associated pulmonary leiomyosarcoma arising twenty-nine years after renal transplantation. J. Thorac. Cardiovasc. Surg. 126: 877-879 [Full Text]  
• Pollock, B. H., Jenson, H. B., Leach, C. T., McClain, K. L., Hutchison, R. E., Garzarella, L., Joshi, V. V., Parmley, R. T., Murphy, S. B. (2003). Risk Factors for Pediatric Human Immunodeficiency Virus-Related Malignancy. JAMA 289: 2393-2399 [Abstract] [Full Text]  
• Feng, W.-h., Westphal, E., Mauser, A., Raab-Traub, N., Gulley, M. L., Busson, P., Kenney, S. C. (2002). Use of Adenovirus Vectors Expressing Epstein-Barr Virus (EBV) Immediate-Early Protein BZLF1 or BRLF1 To Treat EBV-Positive Tumors. J. Virol. 76: 10951-10959 [Abstract] [Full Text]  
• Jenson, H. B., Ench, Y., Zhang, Y., Gao, S.-J., Arrand, J. R., Mackett, M. (2002). Characterization of an Epstein-Barr virus-related gammaherpesvirus from common marmoset (Callithrix jacchus). J. Gen. Virol. 83: 1621-1633 [Abstract] [Full Text]  
• Feng, W.-h., Israel, B., Raab-Traub, N., Busson, P., Kenney, S. C. (2002). Chemotherapy Induces Lytic EBV Replication and Confers Ganciclovir Susceptibility to EBV-positive Epithelial Cell Tumors. Cancer Res. 62: 1920-1926 [Abstract] [Full Text]  
• Caselli, D., Klersy, C., de Martino, M., Gabiano, C., Galli, L., Tovo, P. A., Arico, M. (2000). Human Immunodeficiency Virus-Related Cancer in Children: Incidence and Treatment Outcome--Report of the Italian Register. JCO 18: 3854-3861 [Abstract] [Full Text]  
• Young, L S, Dawson, C W, Eliopoulos, A G (2000). The expression and function of Epstein-Barr virus encoded latent genes. Mol. Pathol. 53: 238-247 [Abstract] [Full Text]  
• Westphal, E. M., Blackstock, W., Feng, W., Israel, B., Kenney, S. C. (2000). Activation of Lytic Epstein-Barr Virus (EBV) Infection by Radiation and Sodium Butyrate in Vitro and in Vivo: A Potential Method for Treating EBV-positive Malignancies. Cancer Res. 60: 5781-5788 [Abstract] [Full Text]  
• Cohen, J. I. (2000). Epstein-Barr Virus Infection. NEJM 343: 481-492 [Full Text]  
• Quintanilla-Martinez, L., Kumar, S., Fend, F., Reyes, E., Teruya-Feldstein, J., Kingma, D. W., Sorbara, L., Raffeld, M., Straus, S. E., Jaffe, E. S. (2000). Fulminant EBV+ T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome. Blood 96: 443-451 [Abstract] [Full Text]  
• Antonescu, C. R., Elahi, A., Healey, J. H., Brennan, M. F., Lui, M. Y., Lewis, J., Jhanwar, S. C., Woodruff, J. M., Ladanyi, M. (2000). Monoclonality of Multifocal Myxoid Liposarcoma: Confirmation by Analysis of TLS-CHOP or EWS-CHOP Rearrangements. Clin. Cancer Res. 6: 2788-2793 [Abstract] [Full Text]  
• Ambinder, R. F. (2000). Gammaherpesviruses and ""Hit-and-Run"" Oncogenesis. Am. J. Pathol. 156: 1-3 [Full Text]  
• Brenner, M., Rossig, C., Sili, U., Young, J. W., Goulmy, E. (2000). Transfusion Medicine: New Clinical Applications of Cellular Immunotherapy. ASH Education Book 2000: 356-375 [Abstract] [Full Text]  
• Franchini, G., Ambinder, R. F., Barry, M. (2000). Viral Disease in Hematology. ASH Education Book 2000: 409-423 [Abstract] [Full Text]  
• Bonnet, M., Guinebretiere, J.-M., Kremmer, E., Grunewald, V., Benhamou, E., Contesso, G., Joab, I. (1999). Detection of Epstein-Barr Virus in Invasive Breast Cancers. JNCI J Natl Cancer Inst 91: 1376-1381 [Abstract] [Full Text]  
• Mueller, B. U. (1999). Cancers in Children Infected With the Human Immunodeficiency Virus. The Oncologist 4: 309-317 [Abstract] [Full Text]  
• Westphal, E.-M., Mauser, A., Swenson, J., Davis, M. G., Talarico, C. L., Kenney, S. C. (1999). Induction of Lytic Epstein-Barr Virus (EBV) Infection in EBV-associated Malignancies Using Adenovirus Vectors in Vitro and in Vivo. Cancer Res. 59: 1485-1491 [Abstract] [Full Text]  
• Edinger, J. W., Bonneville, M., Scotet, E., Houssaint, E., Schumacher, H. R., Posnett, D. N. (1999). EBV Gene Expression Not Altered in Rheumatoid Synovia Despite the Presence of EBV Antigen-Specific T Cell Clones. J. Immunol. 162: 3694-3701 [Abstract] [Full Text]  
• Mueller, B. U. (1998). Cancers in Human Immunodeficiency Virus-Infected Children. J Natl Cancer Inst Monogr 1998: 31-35 [Abstract] [Full Text]  
• Scadden, D. T., Howard, W. W. (1998). AIDS-Related Malignancies. The Oncologist 3: 119-123 [Abstract] [Full Text]  
• Kanegane, H., Bhatia, K., Gutierrez, M., Kaneda, H., Wada, T., Yachie, A., Seki, H., Arai, T., Kagimoto, S.-i., Okazaki, M., Oh-ishi, T., Moghaddam, A., Wang, F., Tosato, G. (1998). A Syndrome of Peripheral Blood T-Cell Infection With Epstein-Barr Virus (EBV) Followed by EBV-Positive T-Cell Lymphoma. Blood 91: 2085-2091 [Abstract] [Full Text]  
• Evans, J A, Gibb, D M, Holland, F J, Tookey, P A, Pritchard, J, Ades, A E (1997). Malignancies in UK children with HIV infection acquired from mother to child transmission. Arch. Dis. Child. 76: 330-333 [Abstract] [Full Text]  
• Jenson, H. B., Leach, C. T., Montalvo, E. A., Lin, J.-C., Murphy, S. B. (1996). Absence of Herpesvirus in AIDS-Associated Smooth-Muscle Tumors. NEJM 335: 1690-1690 [Full Text]  
• van Gelder, T., Vuzevski, V.D., Weimar, W. (1995). Epstein-Barr Virus in Smooth-Muscle Tumors. NEJM 332: 1719-1719 [Full Text]  
• Liebowitz, D. (1995). Epstein-Barr Virus -- An Old Dog with New Tricks. NEJM 332: 55-57 [Full Text]  
• Phiel, C. J., Gabbeta, V., Parsons, L. M., Rothblat, D., Harvey, R. P., McHugh, K. M. (2001). Differential Binding of an SRF/NK-2/MEF2 Transcription Factor Complex in Normal Versus Neoplastic Smooth Muscle Tissues. J. Biol. Chem. 276: 34637-34650 [Abstract] [Full Text]