IgG4-Positive Ocular Adnexal Extranodal Marginal Zone Lymphoma as an Aggressive Clinical Subtype: Evidence From a 377-Patient Cohort.

Objective

To investigate the clinicopathological characteristics of IgG4-positive ocular adnexal lymphoma (OAL).

Design

Retrospective clinical cohort study.

Participants

A total of 377 patients diagnosed with OAL between October 2014 and October 2024 were enrolled. Study data were analyzed from March 2025 to August 2025.

Methods

A comprehensive review of the medical records for all OAL patients was conducted. The distribution of IgG4-positive cases was assessed. Clinicopathological characteristics, as well as recurrence risk, were compared between IgG4-positive and IgG4-negative patients.

Main outcomes and measures: Differences in local and systemic involvement at baseline, and recurrence risk during follow-up.

Results

The highest proportion of IgG4-positive patients was observed in extranodal marginal zone lymphoma (EMZL) (23.3% [75/322]), with a significant higher frequency of involvement in the eyelid, lacrimal gland, optic nerve, superior/inferior orbital fissures, cavernous sinus, and Infratemporal fossa/pterygopalatine fossa compared with IgG4-negative EMZL patients. At presentation, T3-T4 stages were more frequently observed among IgG4-positive EMZL patients, while differences in systemic involvement showed no statistical significance after Benjamini-Hochberg adjustment. The Ki-67 index was higher in IgG4-positive EMZL patients (20.08 ± 6.56 vs 14.13 ± 5.03, P < .0001), and IgG4-positive plasma cells showed significant positive correlations with T-stage and Ki-67 index. Both IgG4-positive and IgG4-negative EMZL patients were primarily treated with radiotherapy following surgery. IgG4-positive EMZL patients experienced earlier recurrence (2.04 ± 1.21 years vs 3.71 ± 1.23 years, P = .002) and a lower cumulative proportion without recurrence or reoperation (All P < .01). Cox regression analysis revealed a strong association between IgG4-positive EMZL and recurrence in multivariate model (HR, 2.04, 95% CI, 1.07-3.91, P = .031). IgG4-positive plasma cells in tissue were significantly negatively correlated with the time to recurrence (rs = -0.605, P < .0001).

Conclusions

IgG4-positive EMZL represents a more aggressive clinical subtype, characterized by more widespread local involvement and an increased risk of recurrence, thereby warranting more intensive management and long-term follow-up for disease surveillance. Targeted management strategies need to be established to achieve optimal disease control.