Clinicopathological characteristics, diagnostic challenges, and systemic implications of metastatic tumors to the eyelid: a systematic review

Abstract

Abstract Background Metastatic tumors to the eyelid are rare but clinically significant, often indicating advanced systemic malignancy or presenting as the first sign of an occult primary. Histopathology is the diagnostic cornerstone, yet the spectrum of clinicopathological patterns, immunohistochemistry, and common diagnostic pitfalls has not been systematically synthesized at the patient level. Methods We conducted a PRISMA 2020–compliant systematic review (protocol registered on the Open Science Framework). PubMed/MEDLINE, Embase, and Scopus were searched on 7 March 2026 without date restrictions, supplemented by Google Scholar citation tracking. Case reports and case series of histopathologically confirmed eyelid metastases were eligible. We performed a descriptive case-level systematic synthesis; proportions are reported with 95% Wilson confidence intervals. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Reports. Results Seventy-three studies (95 patients; 52/95, 54.7% female; median age 61 years, range 21–92) were included. Breast carcinoma was the most frequent primary site (39/95; 41.1%), followed by gastrointestinal tumors (15/95; 15.8%), renal cell carcinoma (9/95; 9.5%), and lung carcinoma (8/95; 8.4%). Metachronous presentation predominated (58/92; 63.0%; median interval 36 months, range 2–288), followed by synchronous (27/92; 29.3%) and occult presentation (7/92; 7.6%). Among 62 patients with documented preoperative impressions, 41/62 (66.1%) received a benign misdiagnosis; pyogenic granuloma was the most frequent mimic. Immunohistochemistry was reported in 61/73 studies (83.6%). BAP1 loss was observed in 2 of 3 evaluable uveal melanoma cases and was intact in all 6 cutaneous melanoma cases [18, 20]. Overall, 61/89 (68.5%; 95% CI 58.6–77.0%) had synchronous distant organ metastases at eyelid biopsy; eyelid biopsy identified an occult primary in 11/95 (11.6%) and altered oncologic management in 13/95 (13.7%). Conclusions Eyelid metastases commonly mimic benign conditions, supporting a low threshold for biopsy of atypical or refractory lesions. Site-directed immunohistochemistry, including BAP1 for melanoma subtype attribution, can be diagnostically informative and should inform staging and management decisions.