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Emerging of dual AIDS associated neoplastic diseases in the era of highly active antiretroviral therapy
  1. R Manfredi,
  2. L Calza,
  3. F Chiodo
  1. Department of Clinical and Experimental Medicine, Division of Infectious Diseases, University of Bologna “Alma Mater Studiorum”, S. Orsola Hospital, Bologna, Italy
  1. Correspondence to:
    Dr Roberto Manfredi, Department of Clinical and Experimental Medicine, Division of Infectious Diseases, University of Bologna, S Orsola Hospital, Via Massarenti 11, I-40138 Bologna, Italy;
    manfredi{at}med.unibo.it

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Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical cancer remain the only AIDS associated malignancies, according to the 1993 CDC definition, but other neoplasms were reported throughout AIDS pandemic (Hodgkin’s lymphoma, oropharyngeal, oesophageal, gastric, anal, lung, and brain cancer, testicular-ovarian neoplasms, melanoma, skin and thyroid malignancies, multiple myeloma, leiomyosarcomas, angiosarcomas, smooth muscle tumours), with an increasing frequency despite HAART introduction.1–,4

Among 711 AIDS patients notified since 1985, 66 (9.3%) were diagnosed because of an AIDS defining cancer, and 51 more patients (7.2%) developed a malignancy with AIDS, but dual AIDS associated neoplasms were never seen until 2000. A rare combination of lethal Kaposi’s sarcoma plus non-Hodgkin’s lymphoma was recently observed. Two homo/bisexual men had received multiple antiretroviral lines since 1990–2, but complete viral suppression was achieved by the first patient for a limited 6 month period, while elevated viraemia (with peaks of 210 000 and 270 000 HIV-RNA copies/ml, respectively), lasted for the past 5 years. An appreciable degree of HIV related immunodeficiency was expressed by a CD4+ count of 42–255 cells × 106/l in the first patient, and 68–355 cells × 106/l in the second case. A first AIDS related neoplasm (a cutaneous-mucous Kaposi’s sarcoma), was identified 2 and 5 years before death, respectively. Repeated cytotoxic treatment with adriablastine-bleomycin-vincristine, followed by liposomal daunorubicin, reduced disease progression, while a number of HIV related opportunistic infections occurred: oesophageal candidiasis and cryptosporidiasis in the first patient, and pneumonia, zoster, plus wasting syndrome in the second subject. Eleven and 5 months before the lethal outcome, respectively, a Burkitt’s B cell lymphoma involving multiple skin sites and complicated by bone marrow, gastroduodenal, gingivobuccal, and pulmonary localisations was detected in the first patient, while the second subject had a high grade non-Hodgkin’s lymphoma involving axillary-mediastinal lymph nodes, lungs, and pleura. Notwithstanding therapeutic attempts (methotrexate-zidovudine, followed by MNCOP-B), a rapidly fatal course occurred.

The introduction of HAART determined a profound modification of the evolution of HIV disease, but improved patient survival, persisting immune system abnormalities, and co-infection with potentially oncogenic viruses may be responsible for the increased incidence of neoplasms during the HAART era.1–,4 This phenomenon seems to extend beyond typical AIDS defining neoplasms, since other malignancies were reported with an incidence greater than that of the general population, and that of the pre-HAART era,3,4 although they may be largely underestimated, owing to the unchanged CDC AIDS classification system. This trend is not uniform for Kaposi’s sarcoma,2,5 probably because of the favourable effects of antiretroviral-antiherpetic medications. The occurrence of dual AIDS associated malignancies remains exceptional: only two patients with a rare and aggressive non-Hodgkin’s null cell lymphoma and prior Kaposi’s sarcoma were described by Ascoli.6 Although our patients developed “typical” AIDS defining neoplasms, this phenomenon may become of increasing concern, when involving rare cancers. The increased life expectancy of HAART treated patients, a direct involvement of HIV itself, or abnormalities driven by oncogenic viruses, including EBV, HSV-8, and papillomavirus,1,2 might explain the tendency to develop a broader spectrum of long term neoplastic complications. In our experience, a persistent HIV associated immunodeficiency and an incomplete virological response to HAART, possibly had a pathogenetic role. Clinicians should maintain an elevated clinical suspicion for a broad spectrum of HIV associated cancer, even after a first diagnosis of AIDS related neoplasm. Epidemiological studies should give a reliable estimate of the frequency of all HIV associated tumours, and recognise eventual dual AIDS associated cancers. The pathogenesis underlying AIDS related malignancies (especially neoplasm immunity and viral oncogenesis) deserve careful insight.

Contributors

RM collected and interpreted data and literature evidences, and drafted the entire work; LC collected clinical and laboratory data and literature evidences, and revised both data evaluation and discussion; FC proposed and supervised the report, read and corrected the draft, and participated in the discussion of both data and literature references

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