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Bronchogenic Carcinoma in Young Patients at Risk for Acquired Immunodeficiency Syndrome

1993; Elsevier BV; Volume: 103; Issue: 3 Linguagem: Inglês

10.1378/chest.103.3.862

1931-3543

Thomas Chan, Conrado P. Aranda, William N. Rom,

Plant Virus Research Studies

Several case reports have suggested that bronchogenic carcinoma occurs more frequently in young patients who are human immunodeficiency virus (HIV) seropositive. We investigated the incidence of bronchogenic carcinoma and its clinical presentations in young patients at risk for HIV infection. The tumor registry of Bellevue Hospital was reviewed, and 261 cases of bronchogenic carcinoma during the period from 1976 to 1979 (pre-AIDS period) and 232 during the period from 1987 to 1990 (AIDS period) were identified. These cases were stratified into age groups: 45 or younger, 46 to 55, 56 to 65, and 66 years or older. All patients aged 45 years or younger in the AIDS period were subdivided by HIV risk, and clinical characteristics were compared among the subgroups. Results revealed no increased incidence of bronchogenic carcinoma from the pre-AIDS period compared with the AIDS period. These results suggest that HIV seropositivity is not a risk factor for bronchogenic carcinoma. Several case reports have suggested that bronchogenic carcinoma occurs more frequently in young patients who are human immunodeficiency virus (HIV) seropositive. We investigated the incidence of bronchogenic carcinoma and its clinical presentations in young patients at risk for HIV infection. The tumor registry of Bellevue Hospital was reviewed, and 261 cases of bronchogenic carcinoma during the period from 1976 to 1979 (pre-AIDS period) and 232 during the period from 1987 to 1990 (AIDS period) were identified. These cases were stratified into age groups: 45 or younger, 46 to 55, 56 to 65, and 66 years or older. All patients aged 45 years or younger in the AIDS period were subdivided by HIV risk, and clinical characteristics were compared among the subgroups. Results revealed no increased incidence of bronchogenic carcinoma from the pre-AIDS period compared with the AIDS period. These results suggest that HIV seropositivity is not a risk factor for bronchogenic carcinoma. human immunodeficiency virus Acquired immunodeficiency syndrome is associated with an increased incidence of neoplasia, with an increase in the incidences of Kaposi's sarcoma and non-Hodgkin's lymphoma established.1Fauci A Macher A Longo D Lane H Rook A Masur H et al.Acquired immunodeficiency syndrome: epidemiologic, clinical immunologic, and therapeutic considerations.Ann Intern Med. 1984; 100: 92-106Crossref PubMed Scopus (614) Google Scholar, 2Biggar R Burnett W Mikl J Nasca P Cancer among New York men at risk of acquired immunodeficiency syndrome.Int J Cancer. 1989; 43: 979-985Crossref PubMed Scopus (97) Google Scholar, 3Longo D Steis R Lane H Malignancies in the AIDS patient: natural history, treatment strategies and preliminary results.Ann NY Acad Sci. 1984; 437: 421-430Crossref PubMed Scopus (43) Google Scholar, 4Safai B Dias B Schwartz J Boulier I HIV-associated malignancies.Antibiot Chemother. 1991; 43: 69-95Crossref Google Scholar, 5Penn I Tumors of the immunocompromised patient.Annu Rev Med. 1988; 39: 63-73Crossref PubMed Scopus (196) Google Scholar, 6Beckstead J The acquired immunodeficiency syndrome and neoplasia.Prog AIDS Pathol. 1989; 1: 201-212Google Scholar, 7Buonaguro F Beth-Giraldo E Giraldo G Prospected etiopathogenic mechanisms of AIDS-associated tumors.Antibiot Chemother. 1991; 43: 96-114Crossref PubMed Google Scholar Recent reports of bronchogenic carcinoma occurring in young patients who are human immunodeficiency virus (HIV)-seropositive8Braun M Killam D Remick S Ruckdeschel J Lung cancer in patients seropositive for human immunodeficiency virus.Radiology. 1990; 175: 341-343Crossref PubMed Scopus (62) Google Scholar, 9Francois T Igual J Cadranel J Bronchial cancer in patients infected with human immunodeficiency virus.Rev Pneumol Clin. 1990; 46: 99-102PubMed Google Scholar led us to speculate that the tumor also may be associated with AIDS. Acquired immunodeficiency syndrome is predominantly a disease of the younger age groups; 85 percent of AIDS occurs in men 20 to 49 years old.1Fauci A Macher A Longo D Lane H Rook A Masur H et al.Acquired immunodeficiency syndrome: epidemiologic, clinical immunologic, and therapeutic considerations.Ann Intern Med. 1984; 100: 92-106Crossref PubMed Scopus (614) Google Scholar, 2Biggar R Burnett W Mikl J Nasca P Cancer among New York men at risk of acquired immunodeficiency syndrome.Int J Cancer. 1989; 43: 979-985Crossref PubMed Scopus (97) Google Scholar Although bronchogenic carcinoma is more prevalent in the elderly, it was also known to occur in the younger patients before the HIV epidemic.10Pemberton J Nagorney D Gilmore J Taylor W Bernatz P Bronchogenic carcinoma in patients younger than 40 years.Ann Thorac Surg. 1983; 36: 509-515Abstract Full Text PDF PubMed Scopus (83) Google Scholar, 11Putnam J Lung carcinoma in young adults.JAMA. 1977; 238: 3536Crossref Scopus (47) Google Scholar It is possible therefore that these reported cases of bronchogenic carcinoma in the young HIV-infected patients do not reflect an increased incidence but rather are coincidental diseases. We compared the incidences of bronchogenic carcinoma in young patients between the pre-AIDS and the AIDS periods; we also evaluated the clinical characteristics of bronchogenic carcinoma in young patients at risk for HIV infection and in young patients without HIV risks during the AIDS period. Records in the tumor registry of Bellevue Hospital, New York, were reviewed, and all cases of bronchogenic carcinoma during the period from 1976 to 1979 (pre-AIDS period) and from 1987 to 1990 (AIDS period) were identified. Bellevue Hospital is a 1,200-bed municipal hospital which has had a large number of HIV-positive patients ever since the AIDS epidemic, and about 30 percent of its medical inpatients had HIV-related diseases during the period 1987 to 1990. Therefore, the patient population of Bellevue serves well as an indicator of changes in the risk of neoplasia emerging in HIV-at-risk patients. The time from 1976 to 1979 was chosen as the pre-AIDS period because no HIV-related diseases had been seen in this institution before 1980. The registry revealed 261 cases of bronchogenic carcinoma in the pre-AIDS period and 232 in the AIDS period. These cases were stratified into four different age groups: 45 years or younger, 46 to 55, 56 to 65, and 66 years or older. The incidences of bronchogenic carcinoma in the different age groups in the pre-AIDS period were compared with the ones in the AIDS period. In addition, all patients aged 45 years or less in the AIDS period were subdivided by HIV risk, and clinical characteristics were compared among the subgroups. Chi square was used to test for any differences in the age distribution among patients in the pre-AIDS period versus the AIDS period. The independent-samples t test was used to determine any significant difference in mean ages between the two groups. The incidences of bronchogenic carcinoma in pre-AIDS (1976-1979) and AIDS (from 1987 to 1990) periods are shown in Table 1. There were 261 patients in the pre-AIDS period: 16 (6.1 percent) were in the age range of 45 years or younger, 58 (22.2 percent) were in the 46- to 55-year range, 83 (31.8 percent) were in the 56- to 65-year range and 104 (39.8 percent) were in the group of those greater than 65 years old. From 1987 to 1990 (AIDS period), there were 232 patients: 19 (8.2 percent) were in the age range of 45 years or younger, 59 (25.4 percent) were in the 46- to 55-year range, 71 (30.6 percent) were in the 56- to 65-year range and 83 (35.8 percent) were in the group of those greater than 65 years old. There was no significant difference (χ2Biggar R Burnett W Mikl J Nasca P Cancer among New York men at risk of acquired immunodeficiency syndrome.Int J Cancer. 1989; 43: 979-985Crossref PubMed Scopus (97) Google Scholar=1.86; p = 0.60) in the age distributions of patients in the pre-AIDS period versus the AIDS period. The mean age of all patients in the pre-AIDS period was 62 ± 11 (SD) years with a range from 24 to 90 years, and the mean age in the AIDS period was 61 ± 12 years with a range from 34 to 80 years. No significant difference between the mean ages was detected (t value =1.094, p = 0.27). Also, the mean ages of the 45 or younger groups in both periods were 40 ± 6 and 40 ± 4 years, respectively, with no significant difference (t value = 0.080, p = 0.94).Table 1Age Distribution of Patients With Bronchogenic Carcinoma in the Pre-AIDS vs AIDS Period*χ 2 = 1.86; p = 0.60.AgeRange, yrNo. of PatientsPre-AIDS Period (%)AIDS Period (%)≤4516 (6.1)19 (8.2)46-5558 (22.2)59 (25.4)56-6583 (31.8)71 (30.6)≥66104 (39.8)83 (35.8)Total261 (100)232 (100)* χ 2Biggar R Burnett W Mikl J Nasca P Cancer among New York men at risk of acquired immunodeficiency syndrome.Int J Cancer. 1989; 43: 979-985Crossref PubMed Scopus (97) Google Scholar = 1.86; p = 0.60. Open table in a new tab Of the 19 patients aged 45 or younger in the AIDS period, 17 had medical records available for review. Eight patients had no HIV risk factors, and nine were at risk (all due to intravenous drug abuse). Of these nine HIV-at-risk patients, four tested HIV-positive, two were HIV-negative and three were not tested. Their clinical characteristics are shown in Table 2.Table 2Demographic and Clinical Characteristics of Bronchogenic Carcinoma in AIDS Period in 17 Patients Aged 45 Years or Younger*HIV(?) = HIV not tested.HIV StatusNo.Mean Age, yrSexHistologySmokingNo HIV risk8433M6 adenocarcinoma4 nonsmokers5F2 small cell carcinoma4 smokersHIV-at-risk†All due to intravenous drug abuse.HIV(+)4383M3 adenocarcinoma4 smokers1F1 small cell carcinomaHIV(–)2371M2 large cell2 smokers1FcarcinomaHIV(?)3393M1 adenocarcinoma3 smokers1 large cell carcinomaI poorly differentiatedcarcinoma* HIV(?) = HIV not tested.† All due to intravenous drug abuse. Open table in a new tab In the non-HIV-risk group, there were three males and five females with a mean age of 43 ± 2 years and a range of 39 to 45 years. Of these, four were smokers (average, 27 pack-years) and, strikingly, four were lifelong nonsmokers. Six had adenocarcinomas: one, stage I; two, stage III; and three, stage IV. Two had small cell carcinomas that were in the extensive stage. In the HIV-at-risk group, there were seven males and two females with a mean age of 38 ± 3 years and a range of 34 to 44 years. They were all smokers (average, 26 pack-years). Four had adenocarcinomas, three large cell and one poorly differentiated. One patient had stage II disease; four, stage III; and three, stage IV. Another one had a small cell carcinoma presenting in limited stage. The demographics of the two groups were similar, and the stage of bronchogenic carcinoma was advanced in the majority of patients. An immunodeficiency state has been shown by many studies to increase the risk of cancer in humans. Primary immunodeficiency diseases such as WiskottAldrich syndrome, ataxia telangiectasia, X-linked Bruton's type of agammaglobulinemia, and X-linked lymphoproliferative syndrome are associated with an increased incidence of neoplasia.6Beckstead J The acquired immunodeficiency syndrome and neoplasia.Prog AIDS Pathol. 1989; 1: 201-212Google Scholar, 7Buonaguro F Beth-Giraldo E Giraldo G Prospected etiopathogenic mechanisms of AIDS-associated tumors.Antibiot Chemother. 1991; 43: 96-114Crossref PubMed Google Scholar Secondary immunodeficiency induced by immunosuppressive drugs for organ transplantation also has been established to predispose humans to the development of malignancy. The malignancies most increased in these patients are primarily non-Hodgkin's lymphoma.5Penn I Tumors of the immunocompromised patient.Annu Rev Med. 1988; 39: 63-73Crossref PubMed Scopus (196) Google Scholar, 6Beckstead J The acquired immunodeficiency syndrome and neoplasia.Prog AIDS Pathol. 1989; 1: 201-212Google Scholar, 7Buonaguro F Beth-Giraldo E Giraldo G Prospected etiopathogenic mechanisms of AIDS-associated tumors.Antibiot Chemother. 1991; 43: 96-114Crossref PubMed Google Scholar The surveillance theory of tumorigenesis by the immune system has been proposed in that the immune system acts as a powerful mechanism against neoplasms especially those related to oncogenic viruses.7Buonaguro F Beth-Giraldo E Giraldo G Prospected etiopathogenic mechanisms of AIDS-associated tumors.Antibiot Chemother. 1991; 43: 96-114Crossref PubMed Google Scholar, 12Burnet F The concept of immunological surveillance.Prog Exp Tumor Res. 1970; 13: 1-27Crossref PubMed Google Scholar, 13Klein G Immunosurveillance-a powerful mechanism with a limited range.Natl Cancer Inst Monogr. 1981; 44: 109-110Google Scholar Clinical observations suggest that this theory applies to the HIV as well. Of the 2,008 cases of AIDS reported to Centers for Disease Control in 1983, nearly 40 percent developed a malignancy during the course of their illness.1Fauci A Macher A Longo D Lane H Rook A Masur H et al.Acquired immunodeficiency syndrome: epidemiologic, clinical immunologic, and therapeutic considerations.Ann Intern Med. 1984; 100: 92-106Crossref PubMed Scopus (614) Google Scholar, 3Longo D Steis R Lane H Malignancies in the AIDS patient: natural history, treatment strategies and preliminary results.Ann NY Acad Sci. 1984; 437: 421-430Crossref PubMed Scopus (43) Google Scholar Kaposi's sarcoma and non-Hodgkin's lymphoma were the most common neoplasms observed. The etiopathogenesis of Kaposi's sarcoma in AIDS patients frequently is associated with cytomegalovirus6Beckstead J The acquired immunodeficiency syndrome and neoplasia.Prog AIDS Pathol. 1989; 1: 201-212Google Scholar, 7Buonaguro F Beth-Giraldo E Giraldo G Prospected etiopathogenic mechanisms of AIDS-associated tumors.Antibiot Chemother. 1991; 43: 96-114Crossref PubMed Google Scholar and non-Hodgkin's lymphoma with Epstein-Barr virus.4Safai B Dias B Schwartz J Boulier I HIV-associated malignancies.Antibiot Chemother. 1991; 43: 69-95Crossref Google Scholar, 6Beckstead J The acquired immunodeficiency syndrome and neoplasia.Prog AIDS Pathol. 1989; 1: 201-212Google Scholar, 7Buonaguro F Beth-Giraldo E Giraldo G Prospected etiopathogenic mechanisms of AIDS-associated tumors.Antibiot Chemother. 1991; 43: 96-114Crossref PubMed Google Scholar Other tumors like squamous cell carcinoma of the oral cavity and cloacogenic carcinoma of the anorectum also have been reported to occur in AIDS patients.4Safai B Dias B Schwartz J Boulier I HIV-associated malignancies.Antibiot Chemother. 1991; 43: 69-95Crossref Google Scholar, 5Penn I Tumors of the immunocompromised patient.Annu Rev Med. 1988; 39: 63-73Crossref PubMed Scopus (196) Google Scholar, 6Beckstead J The acquired immunodeficiency syndrome and neoplasia.Prog AIDS Pathol. 1989; 1: 201-212Google Scholar, 7Buonaguro F Beth-Giraldo E Giraldo G Prospected etiopathogenic mechanisms of AIDS-associated tumors.Antibiot Chemother. 1991; 43: 96-114Crossref PubMed Google Scholar Findings of bronchogenic carcinoma in young HIV-positive patients led to suggestions that the tumor also may be related to AIDS. The results of our study, however, suggest otherwise. They revealed no increased incidence of bronchogenic carcinoma from 1976 to 1979 (pre-AIDS period) to the period from 1987 to 1990 (AIDS period) and no change in the age distribution. There were also no differences noted in the clinical presentations of the tumor between HIVat-risk (including HIV-positive) patients and non-HIVrisk patients aged 45 years or younger. These results suggest that bronchogenic carcinoma in young HIV-positive patients is likely not related to HIV infection, but they are rather coincidental diseases. One possible explanation for no increased incidence of bronchogenic carcinoma in AIDS is that the tumor is not related to oncogenic viruses in contrast to Kaposi's sarcoma and non-Hodgkin's lymphoma. Therefore, the impaired immunologic surveillance in AIDS is less important for the etiopathogenesis of bronchogenic carcinoma. We wish to thank Ms. Alice Weiss and Dr. Rita Demopoulos for their assistance in the tumor registry and Dr. John Concato for his assistance in statistical analysis.