138 Pathologic Hallmarks of VEXAS Syndrome: Insights from a Seven-Case Series

Introduction/Objective VEXAS syndrome is an autoinflammatory disorder caused by somatic UBA1 mutations, with characteristic bone marrow findings. Methods/Case Report We retrospectively reviewed cases diagnosed with VEXAS syndrome between 2020 and 2025, evaluating clinical data, bone marrow findings, molecular profiles, and outcomes. Results Seven male patients (ages 56–72; median 62) were identified. Diagnosis was prompted by marrow vacuolations (n = 2) or clinical symptoms such as polychondritis, vasculitis, or dermatitis (n = 5). All had hypercellular marrow with increased and vacuolated granulopoiesis and erythropoiesis. Dysgranulopoiesis was present in 3/7 and dyserythropoiesis in all cases. Megakaryocytes were normal (2/7), hypolobated (3/7), or atypical (2/7). Plasma cells were increased in 5/7 (up to 7%), and blasts in 1/7 (up to 8%). All patients harbored UBA1 p.E264X mutations; co-mutations included TET2, DNMT3A, TP53, NOTCH1, and del(20q). Two patients died (with TP53 and DNMT3A mutations); five remain alive (follow-up: 8–34 months). Conclusion VEXAS syndrome is characterized by multilineage dysplasia, vacuolated precursors, and increased plasma cells. Co-mutations may impact prognosis. Timely recognition and comprehensive genetic testing are critical for accurate diagnosis and appropriate management.