Immunohistochemical and Molecular Profiles of Eyelid Sebaceous Gland Carcinoma: A Narrative Review

Purpose: To assess the immunohistochemical (IHC) and molecular/genetic profiles of eyelid sebaceous gland carcinoma (SGC) and to examine correlations between clinical features and IHC and molecular/genetic alterations. Methods: This narrative review identified published studies reporting IHC and molecular/genetic findings in eyelid SGC. Eligible studies were reviewed, and extracted data included demographic characteristics, clinical and histopathologic tumor features, IHC biomarker expression, genetic and molecular alterations, and evaluated correlations between IHC or molecular findings and clinical behavior. Results: A total of 38 studies published between 2000 and 2025 were included, encompassing 1564 patients with eyelid SGC. Lymph node invasion or metastasis was reported in 15.9% of cases, and the mortality rate was 6.3%. Among diagnostic biomarkers, adipophilin was identified as a reliable marker for distinguishing SGC from other periocular neoplasms. With respect to tumorigenesis, multiple molecular pathways were implicated, including dysregulation of cholesterol metabolism, aberrant retinoic acid receptor expression, EGFR (epithelial growth factor receptor) overexpression, and androgen receptor signaling. Regarding tumor invasion, metastatic potential, and survival, associations involving Sonic hedgehog (SHH) signaling, the miR-200 family, and epithelial–mesenchymal transition (EMT)–related markers (ZEB2, vimentin, and E-cadherin) appeared to play critical roles. Conclusion: This review highlights adipophilin as a valuable diagnostic marker for eyelid SGC, particularly in diagnostically challenging cases. In addition, androgen-related pathways and EMT-associated mechanisms appear to contribute significantly to both the pathogenesis and aggressive behavior of eyelid SGC. These pathways warrant further investigation, especially for their potential relevance in the development of future targeted therapeutic strategies.