5 There are several risk factors for NHL including congenital and acquired immunodeficiency states, infection with chronic antigen stimulation, autoimmune disorders, and environmental factors.6

According to the comprehensive database from the Immunodeficiency Cancer Registry, the most common tumors in primary immunodeficiencies are lymphomas.7 Immunodeficiency is the strongest described risk factor for NHL.8 The incidence of NHL is increased 10-100 or more in people with acquired or Inhibitors,research,lifescience,medical congenital immunodeficiency.8,9 Such an association is not surprising, because the immune system plays a critical role in the recognition and destruction of malignant cells, and successful elimination of these cells requires an intact immune surveillance system. Therefore, excessive generation of malignant cells coupled with immunodeficiency may result in the increased risk of cancer.10 Inhibitors,research,lifescience,medical Some immune defects are associated with abnormalities in other organs. These syndromic immunodeficiencies present more with other symptoms rather than immune abnormalities.11 The present patient with SIOD Inhibitors,research,lifescience,medical is an example of a syndromic immunodeficiency that presented with edema and poor growth; however, immunodeficiency was not the major clinical problem. The mechanism by which SMARCAL1 protein deficiency causes SIOD is still unknown. The arginine residue at position 561 is located in a conserved

SNF2 motif (IIa) that contributes to the enzyme active site, and is in close proximity to Walker B magnesium binding site. Therefore, we suspect that the nonconservative substitution of histidine for arginine affects function of the active site and possibly DNA binding.12 Patients with SIOD have T cell deficiency, which generally affects CD4+ cells

in the most Inhibitors,research,lifescience,medical severe manner.13 Although our patient had episodic Inhibitors,research,lifescience,medical lymphopenia, low CD3, CD4, CD4/CD8 ratio, and low IgG level, he did not have prominent symptoms of immunodeficiency such as recurrent infections prior to presenting with large B cell lymphoma at the age of eight. The only reported case of SIOD with lymphoproliferative disorder in the literature is a 5-year-old Saudi Arabian boy who presented fever of unknown old origin and EBV-related non-Hodgkin lymphoma.14 In contrast, lymphoma in our patient was EBV negative. The cause of this difference is not clear; however, it might be due to a milder immunodeficiency state in our patient. It has been suggested that milder, but measurable immunodeficiency, is mostly unrelated to EBV infection.15 The other possibilities include unknown lymphotrophic virus and PF-2341066 dysregulation of B cell proliferation with resultant malignant proliferation. Also, given the recent findings of a role for SMARCAL1 in DNA repair and replication,16 SIOD patients may have an increased cancer risk, although their short lifespan limits the manifestation of such a risk. The poor prognosis of NHL in immune deficiency states is accompanied by increased risk of complications such as sepsis following chemotherapy.