Rare Autoimmune Cerebellar Ataxia Linked to Lymphoma in New Case Report

A 70-year-old woman with subacute cerebellar ataxia, fever, elevated D-dimer and multiple cerebral infarctions turned out to have anti-Homer3 antibody-positive autoimmune cerebellar ataxia (ACA) alongside diffuse large B-cell lymphoma (DLBCL), according to a case report published in Frontiers in Hematology. The report, authored by Miao Sun, Xingyang Wang and Yingjie Dai of the Department of Neurology, General Hospital of Northern Theater Command in Shenyang, China, describes what the authors identify as only the second pathologically confirmed case of anti-Homer3 antibody-positive ACA associated with malignancy worldwide, and the first linked to DLBCL.

The association between this antibody and malignancy has remained unclear, and the authors note that most such cases are idiopathic, meaning no underlying cause is identified.

In this case, serum testing confirmed anti-Homer3 antibodies at a titer of 1:30 using a cell-based assay. The diagnostic picture was complicated by systemic findings: the patient presented with fever and elevated D-dimer, a marker of hypercoagulability, and imaging revealed multiple cerebral infarctions. Biopsy of a thigh mass ultimately revealed diffuse large B-cell lymphoma.

Treatment decisions in the case were constrained by the patient’s own choices. She declined both immunotherapy directed at the neurological condition and conventional chemotherapy for the lymphoma. Instead, she received zanubrutinib, a targeted drug, as palliative lymphoma-directed therapy only.

At six-month follow-up, her ataxia had improved and no recurrent stroke had occurred. The authors are explicit, however, that this improvement cannot be attributed to zanubrutinib. They suggest it may reflect spontaneous fluctuation of ACA or other nonspecific factors, and they caution that no causal relationship between the lymphoma and the neurological syndrome has been proven; a chance co-occurrence cannot be excluded.

The authors suggest that lymphoma should be considered during tumor screening in anti-Homer3-positive patients, particularly those who show systemic inflammatory responses or evidence of hypercoagulability.

In this patient, the combination of cerebellar signs, fever, elevated D-dimer and cerebral infarctions pointed in several directions at once before the thigh mass biopsy clarified the picture.

The report is a single-patient case study, and its conclusions are correspondingly limited. With only one pathologically confirmed DLBCL association and one prior malignancy-linked case worldwide, no firm epidemiological or causal inference can be drawn. The authors themselves frame the finding as raising a possibility rather than establishing an association with confidence, and they emphasize that the neurological improvement observed during follow-up may have occurred independently of any lymphoma-directed treatment.

Nevertheless, the case adds to the sparse literature on anti-Homer3 antibody-positive ACA and its possible systemic associations. For clinicians, the practical message offered by the authors is that when patients test positive for this rare antibody, particularly in the presence of systemic inflammatory signs or hypercoagulability, lymphoma deserves a place on the differential diagnosis during tumor screening. For researchers, the case underscores that the association between anti-Homer3 antibody-positive ACA and malignancy remains unclear, and the authors note that a causal relationship remains unproven.

The article was received on 13 August 2026 and accepted on 15 October 2026, and appears in the journal’s Blood Cancer section as an open-access case report.

Subject of Research: A case report of anti-Homer3 antibody-positive autoimmune cerebellar ataxia associated with diffuse large B-cell lymphoma.

Article Title: Anti-Homer3 antibody-positive autoimmune cerebellar ataxia associated with diffuse large B-cell lymphoma: a case report

Article References: Sun, M., Wang, X., & Dai, Y. (2026). Anti-Homer3 antibody-positive autoimmune cerebellar ataxia associated with diffuse large B-cell lymphoma: a case report. Frontiers in Hematology, 5, Article 1967079. https://doi.org/10.3389/frhem.2026.1967079

Image Credits: AI Generated

DOI: 10.3389/frhem.2026.1967079

Keywords: anti-Homer3 antibody, autoimmune cerebellar ataxia, diffuse large B-cell lymphoma, paraneoplastic syndrome, case report, cerebellar ataxia, zanubrutinib, cerebral infarction, neuroimmunology, hematology, Anti-Homer3, antibody-positive