Anti-Homer3 antibody-positive autoimmune cerebellar ataxia (ACA) is a rare immune-mediated neurological disorder whose association with malignancy remains unclear. We report a 70-year-old female who presented with subacute cerebellar ataxia, fever, elevated D-dimer, and multiple cerebral infarctions. Serum testing confirmed anti-Homer3 antibodies (1:30, cell-based assay). Biopsy of a thigh mass revealed diffuse large B-cell lymphoma (DLBCL). The patient declined immunotherapy and chemotherapy and received zanubrutinib only as palliative lymphoma-directed therapy. At six-month follow-up, her ataxia improved, and no recurrent stroke occurred; however, this improvement cannot be attributed to zanubrutinib and may reflect spontaneous fluctuation of ACA or other nonspecific factors. This is the second pathologically confirmed case of anti-Homer3 antibody-positive ACA associated with malignancy worldwide, and the first linked to DLBCL. Although most such cases are idiopathic, this report raises the possibility of a paraneoplastic context and suggests that lymphoma should be considered during tumor screening in anti-Homer3-positive patients, particularly those with systemic inflammatory responses or hypercoagulability. However, a causal relationship remains unproven, and a chance co-occurrence cannot be excluded.
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