Extranodal marginal zone B-cell lymphoma (EMZL) of mucosa associated lymphoid tissue (MALT) that affect the ocular adnexa, also known as ocular adnexal MALT lymphomas (OAML), are low grade lymphomas that mostly affect elderly individuals. This study was conducted to explore the genetic and microbial drivers of OMAL, and unique morphometric phenotypes associated with these mutations and infections. In this study we performed targeted deep sequencing of 8 OAML cases to identify its potential genetic and microbial drivers. We additionally performed computational digital image analysis of cases to determine if morphologic features corresponded to genetic mutations and disease biology. We identified as recurrently mutated in OAML (4/8), and mutations in several other oncogenes, tumor suppressors, transcription regulators and chromatin remodeling genes. Morphologically, OAML cases with mutations in showed lymphoma cells with significantly lower circularity and solidity by computational digital image analysis (p-value < 0.0001). Additionally, cases of OAML with mutations in showed equivalent or increased vascular density compared to cases without mutations in . Finally, we did not find any infectious microbial organisms associated with OAML. Our study showed recurrent mutations in is associated with unique morphometric phenotypes in OMAL cases. Additionally, mutations in genes associated with methylation status of histone 3, nuclear factor (NF)-κB pathway, and NOTCH pathway were enriched in OMAL cases. Our findings have biologic and clinical implications as mutations in and other genes have the potential to be used as markers for the diagnosis of OAML, and also demonstrate a specific biologic phenotypic manifestation of mutations.

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