Introduction: Anal lymphoma (AL) is a rare presentation of extranodal lymphomas, characterized by occurrence in the anal area and largely understudied due to its infrequency. This study aimed to address gaps in knowledge about AL’s demographic and clinical profiles, treatments, and survival outcomes, leveraging data from the SEER program. Methods: We conducted a retrospective analysis of 79 AL cases identified in the SEER database from 2000 to 2022; 36 stage I AL cases were identified and defined as localized primary anal lymphoma (L-PAL). Data on demographics, tumor specifics, treatment modalities, and survival were analyzed using the Kaplan-Meier method and Cox proportional hazards models. Results: The majority of AL cases were diffuse large B-cell lymphoma (70.9%). Other notable subtypes included anaplastic T-cell lymphoma, marginal zone lymphoma, B-cell non-Hodgkin lymphoma, Burkitt lymphoma/leukemia (each accounting for 6.3%), followed by follicular lymphoma and mantle-cell lymphoma (each at 1.3%). AL primarily affected younger males (median age 50), with a significant majority being Caucasian. Initial stages (I and II) were more commonly observed, and treatments varied, with chemotherapy being most prevalent (67.1%), followed by radiation (30.4%) and surgery (30.4%). The 5- and 10-year overall survival (OS) rates were 59.4% and 44.1%, respectively, while the corresponding cancer-specific survival (CSS) rates were 67.9% and 58.0%, respectively. Age was a significant prognostic factor for OS but not for CSS. Radiotherapy tended to improve CSS in the AL population. Conclusion: This research corresponds to the first in-depth analysis of AL, highlighting its distinct demographic patterns, clinical features, and responses to various treatments, distinguishing it from other types of anal cancers. Our results underscore the importance of developing specialized diagnostic and treatment strategies. To enhance our understanding and management of this uncommon form of lymphoma, future studies should aim for broader and more collaborative international research efforts.

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