Clinical Features and Outcomes of Localized Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma: A Dual-Center Retrospective Observational Study with a Long-Term Follow-up
Authors: Yoshida Kikuaki , Iwaki Noriko , Yamauchi Nobuhiko , Koba Yusuke , Shirouchi Yuko , Ishihara Yuko , Mishima Yuko , Makita Shinichi , Fukuhara Suguru , Munakata Wataru , Inoue Norihito , Tsuyama Naoko , Taguchi Senzo , Terauchi Takashi , Tsuji Hideki , Miyagi-Maeshima Akiko , Suzuki Shigenobu , Igaki Hiroshi , Takeuchi Kengo , Izutsu Koji , Maruyama Dai 
Published: December 2024

Background: Since ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) is rare, several clinical questions remain unclear, including the optimal treatment strategy, particularly the validity of watchful waiting (WW), the incidence of systemic progression, histological transformation, and survival outcomes. Therefore, the present study investigated the clinical features and outcomes of patients (pts) with localized OAML.

Methods: We retrospectively analyzed consecutive pts with histopathologically diagnosed OAML in the Cancer Institute Hospital between 2000 and 2022 and the National Cancer Center Hospital between 1997 and 2022. WW was defined as observations without treatment after the initial diagnosis for more than 6 months, while treatment failure was defined as the commencement of second-line treatment, including systemic chemotherapy or radiation therapy (RT). This study was approved by the Institutional Review Board of each hospital.

Results: In total, 283 pts were identified as subjects. Median age was 62 years (range, 14-92), 134 pts were males, and 149 pts were females. The most frequently involved site was the conjunctiva (148 pts). RT was the most common initial treatment (237 pts, 84%), followed by WW (40 pts, 14%), immunochemotherapy (5 pts, 2%), and additional surgical resection (1 pt). WW pts were more likely to have had their tumors completely resected at the diagnosis. RT doses of 30-40 Gy were used for 149 pts, 16-24 Gy for 70, and 4-8 Gy for 18, with the selection of lower RT doses being more common in recent years. With a median follow-up of 7.9 years (range, 0.3-23.7), the cumulative incidence of treatment failure using death as a competing risk was 11.5% (95% CI, 7.7-16.1) at 5 years and 17.7% (95%CI, 12.5-23.6) at 10 years. Pts who initially received RT had a higher likelihood of not receiving second-line treatment in the first 5 years than those on WW (HR, 0.33; 95%CI, 0.15-0.71). Intra- and extra-ocular adnexal progression was observed in 28 (10%) and 21 pts (7%), respectively. The cumulative incidence of extra-ocular adnexal progression was 5.5% at 5 years and 10.7% at 10 years. Extra-ocular adnexal progression sites were the lymph nodes (12 pts), extranodal lesions (6 pts), and both (3 pts). Histological transformation was observed in 6 pts with a cumulative incidence of 1.4% at 5 years and 3.2% at 10 years, and all progressed to the lymph nodes. Progression-free survival (PFS) and overall survival (OS) in all 283 pts were 81.1 and 98.3% at 5 years and 72.2 and 91.9% at 10 years, respectively. PFS was worse in WW pts than in RT pts (HR, 2.62; 95% CI, 1.40-4.88), while no significant difference was observed in OS (HR 2.85; 95% CI, 0.97-8.39). In the RT group, the complete response rate was 94%. Twenty-seven pts received second-line treatment, which included RT (13 pts, 11 with contralateral ocular adnexa and 2 with lymph nodes) and immunochemotherapy (13 pts, including 10 with rituximab monotherapy or the R-CHOP(-like) regimen). In the WW group, 9 pts received second-line treatment, which mainly included RT (7 pts). Seventeen pts died during the study period, and the causes of death were as follows: other malignancies (5 pts), transformed lymphoma (1 pt), pneumonia (1 pt), and unknown (10 pts).

Conclusion: The present results demonstrated that pts with localized OAML had favorable outcomes. Histological transformation and death associated with lymphoma were rare regardless of the initial treatment approach.