Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disorder associated with significant immune dysregulation, recurrent infections, and autoimmunity. While the association between inborn errors of immunity (IEI) and cancer is being increasingly recognized, data on gastric cancers in this context are limited. Here, we present a case of metastatic gastric adenocarcinoma in an LRBA-deficient patient, highlighting the potential oncogenic implications of IEI and reviewing relevant literature.
A 19-year-old male with LRBA deficiency had a lifelong history of recurrent infections, enteropathy, and severe nutritional and electrolyte deficiencies. Due to the lack of a matched donor, he did not undergo stem cell transplantation, and his family declined treatment with intravenous immunoglobulin and Abatacept. He was diagnosed with metastatic gastric adenocarcinoma at the age of 19. Given his poor performance status and malnutrition, he was deemed unfit for chemotherapy and was transitioned to palliative care. He succumbed to the disease one month after the diagnosis.
Gastric cancer incidence in IEI patients is notably higher when compared to the general population. Like many other IEI, cancer link to LRBA deficiency is unproven. To date, only three cases of malignancies in LRBA-deficient patients have been reported—two involving CNS tumors and one with multifocal gastric cancer and melanoma. Our patient is the second documented case of early-onset gastric cancer with LRBA deficiency. Although not fully understood, LRBA dysregulation can impact CTLA4, an immune checkpoint receptor that might be implicated in neoplastic predisposition.
IEI, including LRBA deficiency, should be recognized as a potential risk factor for early-onset gastric malignancies. Larger-scale studies are needed to elucidate underlying mechanisms and improve early detection and management.
