Niraj Kumar Yadav, Priyanshi Priya, Neha Verma, Tapan Tapan, Reshma Ragunath, Eesha Agarwal
Background: Lacrimal gland malignancies are rare orbital tumors characterized by diverse histopathological subtypes and aggressive clinical behavior. Despite their low incidence, these tumors pose significant diagnostic and therapeutic challenges due to delayed presentation, high recurrence rates, and the potential for distant metastasis. Advances in molecular biology, imaging technologies, and multimodal treatment strategies have improved understanding of their pathogenesis and clinical management.Objective: This systematic review evaluates emerging trends in lacrimal gland malignancies reported between 2000 and 2026, focusing on epidemiology, molecular pathogenesis, diagnostic approaches, and therapeutic strategies.Materials and Methods: A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and Embase for studies published between January 2000 and March 2026 following PRISMA 2020 guidelines. Eligible studies included observational studies, cohort studies, case series, and molecular investigations reporting clinical, diagnostic, and therapeutic data on lacrimal gland malignancies. Relevant data on tumor subtype, diagnostic methods, treatment strategies, and survival outcomes were systematically extracted and analyzed.Results: A total of 40 studies involving more than 2,500 patients were included. Adenoid cystic carcinoma was the most common malignant subtype (40–60%) and was associated with poor prognosis due to perineural invasion and recurrence. Molecular studies identified key pathways including MYB–NFIB fusion, NOTCH, PI3K/AKT, and EGFR signaling. Surgical excision with adjuvant radiotherapy remains the primary treatment approach.Conclusion: Lacrimal gland malignancies remain rare but aggressive tumors requiring multidisciplinary management and further molecular research to improve diagnosis and treatment outcomes.