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Diffuse, Undifferentiated Non-Hodgkins Lymphoma among Homosexual Males -- United States

A recent outbreak of Kaposi's sarcoma, Pneumocystis carinii pneumonia, and other opportunistic infections (KSOI) involving homosexual males and associated with an acquired cellular immunodeficiency syndrome has been described (1,2). While the pathogenesis of these disorders among homosexual males in San Francisco was being studied, 4 cases of diffuse, undifferentiated non-Hodgkins lymphoma (DUNHL) were diagnosed between March 1981 and January 1982. Because of the rarity of this malignancy and the potential relationship of these cases to the KSOI syndrome, they are reported here.

Patient 1: A 28-year-old hospital clerk complained of back and shoulder pain starting in early March 1981. Within a few days he had swelling of the right eye and an unsteady gait, and he was hospitalized on March 21. "Shotty" peripheral lymphadenopathy was present. A biopsy of an orbital mass and an enlarged cervical lymph node disclosed DUNHL. A myelogram revealed a T4-T6 block by an extradural mass. Radiation and chemotherapy led to complete remission. In September 1981, another tumor in the spinal cord was treated with radiation. The ensuing remission was temporary, and the patient died with disseminated DUNHL on January 15, 1982.

Patient 2: A 33-year-old nurse developed a tumor in his left lower jaw in October 1981. Penicillin was given for a suspected abscess, but the mass enlarged. A biopsy on November 24 disclosed DUNHL. Tumor cells contained surface IgM, kappa type, indicating a B-cell tumor. The tumor involved a left axillary lymph node, the retroperitoneum, the bone marrow, and the meninges. Generalized "reactive" lymphadenopathy and mild splenomegaly were present. Systemic and intrathecal chemotherapy led to temporary tumor regression; the patient relapsed and died in March 1982.

Patient 3: A 35-year-old janitor developed an enlarged cervical lymph node in October 1981. A dental extraction was performed for a suspected abscess, but lymphadenopathy persisted. A biopsy on December 12 revealed DUNHL. Tumor cells contained surface IgM, kappa type. Tumor was detected in the mediastinum, retroperitoneum, both kidneys, bone marrow, and meninges. Moderate generalized lymphadenopathy and splenomegaly were present. Systemic and intrathecal chemotherapy led to rapid tumor regression; however, this patient has recently relapsed.

Patient 4: A 24-year-old clerk developed backache and fatigue in November 1981. On January 21, 1982, an exploratory laparotomy showed DUNHL with extensive retroperitoneal involvement. Tumor cells contained surface IgM, kappa type. Combination chemotherapy has led to complete remission.

All these patients were homosexual males living in San Francisco. They had no known contact with each other, had no known sexual partners in common, and had no known contact with patients with Kaposi's sarcoma (KS). Each gave a history of a life style that included use of such drugs as nitrite inhalants, amphetamines, and marijuana. Medical histories indicated that all 4 patients had had 1 or more of such infections as hepatitis B, anal warts, gonorrhea, and syphilis. All patients had generalized lymphadenopathy, and 3 had splenomegaly of uncertain duration. Detailed virology and immunology studies are in progress. Reported by JL Ziegler, MD, G Wagner, MD, VA Medical Center, San Francisco, JS Greenspan, BDS, PhD, MRC Path, EJ Shillitoe, BDS, PhD, D Greenspan, BDS, J Beckstead, MD, C Cassavant, PhD, D Abrams, MD, W Chan, DDS, S Silverman, DDS, F Lozada, DDS, University of California San Francisco, School of Medicine and Dentistry, L Drew, MD, E Rosenbaum, MD, R Miner, BS, L Mintz, MD, J Gershow, MD, R Weiss, MD, Mt. Zion Hospital, San Francisco, K Yamamoto, MD, K Chick, MD, St Mary's Hospital, San Francisco, S Dritz, MD, MPH, Dept of Public Health, San Francisco, D Austin, MD, MPH, Dept of Health Svcs, Berkeley, J Chin, MD, State Epidemiologist, California Dept of Health Svcs; W McGuire, MD, University of Illinois Hospital, I Iossifides, MD, Abraham Lincoln School of Medicine, Chicago, BJ Francis, MD, State Epidemiologist, Illinois State Dept of Public Health; J Costa, MD, National Cancer Institute, National Institutes of Health; Chronic Disease Div, Center for Environmental Health, Center for Infectious Diseases, the Task Force on Kaposi's Sarcoma and Opportunistic Infections, CDC.

Editorial Note

Editorial Note: Since July 1981, CDC has received reports of 162 cases of Kaposi's sarcoma among young homosexual males; the above report documents the possible appearance of a second unusual malignancy among this group of young males--i.e., DUNHL, a B-cell lymphoma (3).

The difficulty in distinguishing DUNHL histologically from Burkitt's lymphoma (BL) (3), a tumor often associated with Epstein-Barr virus, and the lack of consensus on the classification of non-Hodgkin's lymphoma (NHL) (4) make the precise determination of incidence difficult. About 0.7%-2.4% of all cases of NHL are DUNHL (4,5)--for a crude incidence rate of 0.06-0.21/100,000 population/year. No cases of DUNHL and only 1 case of BL were reported in 1977-1980 among 20-39 year olds to the Surveillance Epidemiology and End Results Cancer Registry in the San Francisco-Oakland-Standard Metropolitan Statistical Area, emphasizing the unusual occurrence of 4 cases within 10 months in the San Francisco homosexual male population. CDC has also recently received a report from Chicago of another case of DUNHL affecting a young homosexual male.

Underlying immune deficiency appears to be the common denominator for the development of the opportunistic infections and tumors associated with the KSOI syndrome (6-8). A similar syndrome, with an increased risk for NHL but a different time course and spectrum of opportunistic diseases, appears among renal allograft recipients (4,9). Lymphoreticular tumors also occur much more frequently among patients with primary immunodeficiency disorders (4). The cause of the acquired cellular immunodeficiency among homosexual males is being studied.

This report of DUNHL suggests that more than one kind of tumor may occur in association with the KSOI syndrome; assessment of these patients' immunologic findings will help to document the relationship between such tumors and the KSOI syndrome. The full range of potential outcomes (i.e., opportunistic tumors and infections) is probably only now being elucidated. There have also been recent case reports of other malignancies affecting the homosexual population, including carcinoma of the anorectum (10) and squamous cell carcinoma of the oral cavity (11,12). The excess of carcinoma of the anus and anorectum appears to antedate the onset of KSOI syndrome (13). The relationship between these malignancies and the KSOI syndrome is uncertain.

Many homosexual males with persistent, unexplained, generalized lymphadenopathy and biopsies reportedly demonstrating only reactive hyperplasia have also been reported to CDC and are under active investigation (14). Homosexual males with clinical findings similar to DUNHL or lymphadenopathic KS (15) should be carefully evaluated and followed.


  1. Durack DT. Opportunistic infections and Kaposi's sarcoma in homosexual men. N Eng J. Med 1981;305:1465-7. Editorial.

  2. Centers for Disease Control Task Force on Kaposi's Sarcoma and Opportunistic Infections. Epidemiologic aspects of the current outbreak of Kaposi's sarcoma and opportunistic infection. N Eng J Med 1982;306:248-52.

  3. Grogan TM, Warnke RA, Kaplan HS. A comparative study of Burkitt's and non-Burkitt's "undifferentiated" malignant lymphoma. Cancer 1982;49:1817-28.

  4. Greene MH. Non-Hodgkin's lymphoma and mycosis fungoides. In: Cancer Epidemiology and Prevention. M Schottenfeld, JF Fraumeni, eds, WB Saunders, Philadelphia 1982:754-78.

  5. National Cancer Institute. Surveillance epidemiology end results. Incidence and mortality data: 1973-1977. Monograph 57. U.S. Department of Health and Human Resources. NIH Publication No. 81-2330. National Cancer Institute. Bethesda, Maryland 20205. 1981.

  6. Gottlieb MS, Schroff R, Schauker HM, et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Eng J Med 1981;305:1425-3l.

  7. Masur H, Michelis MA, Greene JB, et al. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestations of cellular immune dysfunction. N Eng J Med 1981;305:1431-8.

  8. Siegal FP, Lopez C, Hammer GS, et al. Severe acquired immunodeficieny in male homosexuals, manifested by chronic perianal ulcerative Herpes simplex lesions. N Eng J Med 1981;305:1439-44.

  9. Penn I. Malignant lymphomas in organ transplant recipients. Transplant Proc 1981;13:736-8.

  10. Leach RD, Ellis H. Carcinoma of the rectum in male homosexuals. J R Soc Med 1981;74:490-1.

  11. Conant MA, Volberding P, Fletcher V, Lozada FI, Silverman S. Squamous cell carcinoma in sexual partner of Kaposi sarcoma patient. Lancet 1982;1:286. Letter.

  12. Lozada F, Silverman S, Conant MA. New outbreak of oral tumors, malignancies and infectious diseases strikes young male homosexuals. Journal of California Dental Association 1982;10:39-42.

  13. Daling JR, Weiss NS, Klopfenstein LL, Cochran LE, Chow WH, Daifuku R. Correlates of homosexual behavior and the incidence of anal cancer. JAMA 1982;247:1988-90.

  14. CDC. Persistent, generalized lymphadenopathy among homosexual males. MMWR 1982;31:249-51.

  15. Scully RE, Mark EJ, McNeely BU. Case records of the Massachusetts General Hospital. N Eng J Med 1982;306:657-68.

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