Lacrimal Sac and Nasolacrimal Duct Tumors Mimicking Chronic Inflammation: A Systematic Review

Background and Objectives: Lacrimal sac/nasolacrimal duct (LS/NLD) tumors may present as primary acquired nasolacrimal duct obstruction (PANDO), raising debate over routine versus selective dacryocystorhinostomy (DCR) biopsy. We systematically reviewed (i) biopsy yields in routine versus selective strategies, (ii) clinical/imaging red flags for neoplasia, and (iii) outcomes of malignant LS/NLD tumors. Materials and Methods: Following a preregistered PRISMA 2020-compliant protocol, we searched PubMed/MEDLINE, Web of Science, and Scopus (1970–2025) for adult cohorts reporting histopathology, imaging, or oncologic outcomes in PANDO/DCR or LS/NLD tumors. Eligible designs included comparative, cohort, cross-sectional, and diagnostic accuracy studies with histology as a reference. Results: Across 16 cohorts, routine DCR series reported “any specific pathology” in 0–7.91% of specimens and malignant yields generally ≤0.73%. In Anderson, 7.91% of 316 patients had significant pathology and 4.43% neoplasia, with 2.53% unsuspected pre-/intra-operatively. Selective biopsy or tumor-enriched cohorts showed higher malignant burdens; pooled modern data yielded ~72.8% squamous cell carcinoma and ~21.4% lymphoma among malignancies. Imaging red flags included bone erosion (50% malignant vs. 11% benign) and infiltrative patterns (63% vs. 0%), while sac masses were present in 88% of tumors in one recent series. In LSSCC-only cohorts, contemporary multimodal therapy achieved 5-year overall survival of 87.6% and progression-free survival of 76.3%. Conclusions: Malignancy is rare in unselected PANDO but clinically significant when present. A tiered strategy combining bedside red flags, targeted CT/MRI, and selective biopsy appears to balance oncologic safety with resource stewardship and supports histology-directed epithelial versus lymphoma care pathways.