AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME WITH INITIAL PRESENTATION OF HODGKIN'S LYMPHOMA

Abstract

<h3>Introduction</h3> Autoimmune lymphoproliferative syndrome (ALPS) is characterized by disruption of lymphocyte apoptosis generally attributable to germline FAS mutation. Disease manifests in early life with splenomegaly, lymphadenopathy, and autoimmunity. Patients are at increased risk of lymphoma, typically developing in adulthood. We describe a case of FAS-ALPS with initial presentation of Hodgkin's lymphoma (HL). <h3>Case Description</h3> An 8-year-old previously healthy male was diagnosed with stage-IV mixed-cellularity HL and underwent chemoradiation. Two years later, adenopathy recurred with PET demonstrating FDG-avid nodes. Pathology revealed follicular and paracortical hyperplasia without immunophenotypic evidence of HL. Concern thus existed for primary immunodeficiency, specifically ALPS. Genetic testing revealed a pathogenic variant in exon 7, affecting a donor splice-site resulting in disrupted FAS-protein, confirming FAS-ALPS. <h3>Discussion</h3> Our case is unique in that ALPS generally manifests earlier (median age 2.5), and lymphoma is rarely a presenting feature (median age 24.5). Few reports detail lymphoma at diagnosis. In a French cohort, presence of lymphoma ultimately led to diagnosis in two patients, however, each had displayed symptoms in early life. A case-report describes a 34-year-old with lymphoma and no reports of childhood symptoms. Three years later, his son was diagnosed with ALPS, thus his diagnosis was revisited and he too was found to have ALPS. Splenomegaly is seen in >90% of ALPS and autoimmunity in >70%, thus their absence in our patient is also unusual. <h3>Discussion</h3> This case demonstrates that ALPS should be considered in the differential for lymphoma, histology should be carefully reviewed, and disease should not be ruled out based on absence of autoimmunity or splenomegaly.