A Systematic Review on Predisposition to Lymphoid (B and T cell) Neoplasias in Patients With Primary Immunodeficiencies and Immune Dysregulatory Disorders (Inborn Errors of Immunity)

Abstract

Primary immunodeficiencies and immune dysregulatory disorders (PIDDs; now referred to as inborn errors in immunity) are rare disorders with a prevalence of 41. 4 or 50.5 per 100,000 persons ( 1 ). The incidence of malignancy in PIDD patents is the second-highest cause of death in children as well as adults, after infection, and is higher in certain PIDDs compared to others. We performed a systematic review of the literature to identify reports of B cell and T cell neoplasias in PIDDs and clustered them based on their classification in the IUIS schema. As would be expected, higher susceptibility to malignancies are typically reported in patients with Common Variable Immunodeficiency (CVID), combined immunodeficiencies affecting cellular immunity, in particular, DNA repair defects, or in the context of impaired immune regulatory control. There is not much evidence of increased risk for cancer in patients with innate immune defects, indicating that not all types of infection or genetic susceptibility predispose equally to cancer risk. Viral infections, in particular EBV, HHV and HPV, have been shown to increase susceptibility to developing cancer, but also patients with defects in immune regulation, such as Autoimmune Lymphoproliferative Syndrome (ALPS), activated p110delta syndrome (APDS type 1) and IL-10 receptor deficiency among others have a higher incidence of neoplastic disease, particularly lymphomas. In fact, lymphomas account for two-thirds of all malignancies reported in PIDD patients ( 2 ), with either a combined immunodeficiency or DNA repair defect predominating as the underlying immune defect in one registry, or antibody deficiencies in another ( 3 ). The vast majority of lymphomas reported in the context of PIDDs are B cell lymphomas, though T cell lymphomas have been reported in a few studies, and tend to largely be associated with chromosomal breakage disorders ( 4 ) or Cartilage Hair Hypoplasia ( 5 ). There appears to be a much higher prevalence of T cell lymphomas in patients with secondary immunodeficiencies ( 6 ), though this could reflect treatment bias. We reviewed the literature and summarized the reports of B and T cell lymphoma in PIDD patients to survey the current state of knowledge in this area.

Serum Free Light Chains in Common Variable Immunodeficiency Disorders: Role in Differential Diagnosis and Association With Clinical Phenotype

“…One of these two patients, in particular, initially presented a reduction of both light chains and subsequently developed a significant increase of circulating lambda chain, with no detectable paraprotein and was eventually diagnosed a NHL. This suggests that sFLC assay might also be an effective tool in the follow-up strategy in a population with a well-known risk of hematological malignancies (4,24,25).…”

T-cell lymphoma with a granulomatous lesion of the lungs after autologous hematopoietic stem cell transplantation for Epstein–Barr virus-positive diffuse large B-cell lymphoma: a unique rare case of metachronous B-cell and T-cell lymphoma

“…Monogenic and other genetic defects of the immune system are categorized as PIDs, which affect various components of the immune system with susceptibility to infections but also to malignancies, including lymphoma [2,6,35,36]. Recent investigations reported that the risk of lymphoma is increased tenfold in PID patients and that EBV is associated with 30-60% of lymphoma cases in PIDs [4,5].…”

“…The risk of lymphoma increases up to 10 times in PID patients, and EBV is associated with 30-60% of lymphoma cases in PIDs [4,5]. In PIDs, the most frequently reported lymphoma types are diffuse large B-cell lymphoma (DLBCL; 33.5%) and Burkitt's lymphoma (7.1%), but the incidence of T-cell lymphoma is rare [1,6,7].…”

Serum Free Immunoglobulins Light Chains: A Common Feature of Common Variable Immunodeficiency?

“…The type of malignancy seems to be highly dependent on the specific PID, the age of the patient, and chronic infectious stimuli or dysbiosis involving complex pathogenic mechanisms (35). Cancer is 1.4 to 5-fold higher in registrybased PID studies respect to general population (36,37), from which 70% corresponds to lymphoid malignancy (38,39). Individuals with CVID are at 5 to 10-fold higher risk of developing hematological malignancies (36,37,40), while unexpectedly lower incidence on most common cancers than general population has been described (41,42).…”