The two major categories of malignant lymphoma are Hodgkin disease (which accounts for just under half of the total) and non-Hodgkin lymphoma. The latter is a heterogeneous group of disorders, most are of monoclonal B cell origin, and a lesser number are of T cell or non-T non-B type. Genetic disorders that predispose to malignant lymphoma are listed in Table (1). 11. Clearly, there is a strong association between genetic disorders that cause clinical immunodeficiency and the development of malignant lymphoma. Furthermore, the incidence of lymphoproliferative disorders is increased among patients with immunodeficiency secondary to therapeutic immunosuppression or human immunodeficiency virus (HIV) infection. Although many lymphomas in immune-deficient individuals are of B cell origin, some are derived from other cells such as T lymphocytes (Baumler et al. 2003).
Table 1 Genetic disorders predisposing to lymphoma
|Common variable immunodeficiency|
|Severe combined immunodeficiency|
|X-linked lymphoproliferative disease|
Tumours, especially lymphoproliferative disorders, are the second leading cause of death in immunodeficiency disorders, and it is estimated that 15–25 % of patients with the three major immunodeficiency syndromes (Wiskott– Aldrich syndrome, AT and common variable immunodeficiency) develop cancer. Approximately 60 % of cancers reported in patients with immunodeficiency disorders are lymphomas, and non-Hodgkin lymphoma is about six times as frequent as Hodgkin disease in these patients.
There is a slight increase in risk of lymphoma in the relatives of patients with hemopoietic malignancy (Chang et al. 2005; Altieri et al. 2006).
In patients with childhood onset of colonic adenocarcinoma, lymphoma, and brain Tumours, (Menko et al. 2004; Poley et al. 2007) homozygous germline mutations in the MSH6 gene have been identified, and in other patients, biallelic germline mutations in other genes involved in repair of microsatellite errors in DNA have been detected. Leukemia is thus a feature of the homozygous state for germline mutations in the “MMR” genes, which in heterozygous individuals cause Lynch syndrome (constitutional mismatch repair deficiency).
A subset of patients with lymphoma has been found to have germline mutations in the perforin gene. Patients with biallelic mutations in this gene may have familial hemophagocytic lymphohistiocytosis (HLH), but a few such patients have been found to have Hodgkin or non-Hodgkin lymphoma. (Clementi et al. 2005).