Risk and Type of Malignancy in Primary Immunodeficiencies

Primary immunodeficiencies (PIDs) are genetic disorders that predispose to frequent and severe infections, autoimmunity and cancer. The expanded life span of such patients increases the overall risk for developing cancer, which is now estimated at 4-25% . The type of malignancy depends on the primary immunodeficiency, the age of the patient and possible viral infection, suggesting that different pathogenetic mechanisms are implicated in each case. NonHodgkin’s lymphomas predominate, accounting for 60% of cases. The PIDs known to be associated with increased incidence of malignancy are: common variable immunodeficiency, IgA deficiency and DNA repair disorders. During recent years other types have also been included, such as severe combined immunodeficiency (SCID) and Wiskott Aldrich syndrome (WAS). Immunodeficiencies are genetic or acquired diseases that predispose to frequent and severe infections, autoimmunity and cancer. Patients with immunodeficiencies have an increased risk of developing malignancy due to a defective immunity towards cancer cells. Some types of immunodeficiencies, however, especially those with defective cellular immunity, predispose more frequently to cancer. The expanded life span of patients with primary and secondary immunodeficiency, due to recent therapeutic procedures and supportive care, has been connected with an increased risk for malignancies. The incidence of primary immunodeficiencies (PIDs) is 1:10.000 births. Secondary immunodeficiencies are associated with infection with human T-cell lymphotropic virus (HTLV), immunosuppressive medication and posttransplantation immune dysfunction and although they are the most frequent, they are not addressed in this review. Risk and Type of Malignancy in Primary Immunodeficiencies The overall risk for children with congenital immunodeficiency of developing malignancy is estimated at 4-25% (1). The type of malignancy is highly dependent on the primary immunodeficiency, the age of the patient and probably viral infection, suggesting that different pathogenetic mechanisms are implicated in each case (1). Non-Hodgkin’s lymphomas predominate, accounting for 60% of cases (1). However, in only a few of them have distinctive features been described using current diagnostic approaches (2). Prognostic factors are not well known as yet. There are only a few studies in the literature regarding the incidence of malignancy in primary immunodeficiencies, the histopathological types and prognosis. Filipovich et al. have reported the results of their research on tumours in the Immunodeficiency Cancer Registry (3). The median age of diagnosis was 7.1 years with a male predominance, due to an increased frequency of X-linked disorders. Diseases more often associated with cancer were common variable immunodeficiency (CVID), Wiskott Aldrich syndrome (WAS), ataxia-telangiectasia (AT) and severe combined immunodeficiency (SCID). Canioni et al. performed an interesting study from 1981-1997 among 18 children with primary immunodeficiency that developed lymphoproliferative disease (2). The patients were diagnosed as having AT, X-linked lymphoproliferative disease, combined immunodeficiency, CVID and hyper-IgM syndrome. The immunological status of the patients, as indicated by low T-cell numbers (<1000/mm3) and poor to absent lymphocyte proliferative response to mitogens, was investigated in 33% and 47% , respectively. The morphological, immunochemical and molecular findings were classified as classical lymphoma, while the others were more morphologically heterogeneous. 1263 Correspondence to: Ariadni Mavrou, Department of Medical Genetics, Athens University, “Aghia Sofia” Children’s Hospital, 11527 Athens, Greece. Tel: 210 7467463, Fax: 210 7795554, email: [email protected]