LAUSR

OBJECTIVE To retrospectively identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) among male patients with bone marrow vacuolization using a clinically applicable, targeted-screening approach. METHODS Bone marrow reports from 1 May 2014 through 18 Feb 2022 were reviewed for documentation of cytoplasmic vacuolization. Patients with acute leukaemia, lymphoma, metastatic solid tumor, amyloidosis, or POEMS were excluded as were those without clinical records available for direct chart review. Cases were rated for suspicion of VEXAS syndrome using a 5-point scale based on the presence of laboratory findings, clinical features, and treatment response. Patients with available DNA material and moderate (3 pts) or high (4-5 pts) suspicion were tested for somatic UBA1 variants associated with VEXAS syndrome. RESULTS 315 reports from 292 unique patients included documentation of vacuolization. Following exclusion criteria, 64 patients underwent direct medical chart review to assess likelihood of VEXAS syndrome for which 21 patients met moderate to high suspicion. Available DNA was present in 8 patients of which 7 (87.5%) had a pathogenic somatic UBA1 variant consistent with VEXAS syndrome. The distribution of cytoplasmic vacuolization in the bone marrow biopsy reports among patients with VEXAS syndrome were erythroid and myeloid precursors (6/7), erythroid precursors only (1/7), and myeloid precursors only (0/7). CONCLUSION In this study, the utilization of a clinically applicable targeted-screening approach to test bone marrow specimens (with vacuolization) for the presence of previously undiagnosed VEXAS syndrome resulted in a positive detection rate of 87.5%.