Primary Aggressive Oral Lymphomas (PAOL): A Narrative Review of Diagnosis, Molecular Features, Therapeutic Approaches, and the Integrated Role of Dentists and Hematologists

Primary aggressive oral lymphomas (PAOL) are a rare subset of extranodal non-Hodgkin lymphomas arising in the oral cavity without evidence of other systemic involvement at diagnosis. PAOL accounts for only about 2–3% of all lymphomas. They most commonly belong to aggressive B-cell subtypes such as Diffuse large B-cell lymphoma (DLBCL) and plasmablastic lymphoma (PBL), with occasional cases of Burkitt lymphoma and T-cell/NK-cell lymphomas. Clinically, these malignancies often present with non-specific symptoms (e.g., swelling, pain, ulceration, tooth mobility) that mimic benign dental conditions, leading to diagnostic delays. An integrated diagnostic approach—combining thorough oral examination, imaging (CT, MRI, PET), and definitive biopsy with immunohistochemistry and genetic studies—is critical for accurate diagnosis and staging. Treatment typically involves systemic chemotherapy, often combined with rituximab for CD20+ tumors and adjunctive radiotherapy for localized disease. Ongoing research into the genomic and microenvironmental landscape of PAOL is paving the way for novel targeted therapies to improve outcomes. In HIV+ or transplant patients, PAOL are often driven by viral co-infections (EBV, HHV-8) and may require tailored therapy, including optimization of immune status. The dentist’s role encompasses not only diagnosis but also active participation in cancer therapy through preventive and supportive dental care, and persists thereafter by monitoring for recurrence and treating chronic treatment sequelae. This review provides a comprehensive overview of PAOL‘s epidemiology, clinical-pathologic and molecular features, current and emerging treatments, and the essential collaborative role of dentists and hematologists in patient care.