Esophageal Ectopic Sebaceous Gland: A Case Series and Literature Review of Clinical, Endoscopic, and Pathological Features

Abstract Esophageal ectopic sebaceous gland (EESG) is a rare lesion that can be challenging to differentiate from other upper gastrointestinal endoscopic findings. The origin of EESG remains debated, with hypotheses ranging from embryologic misplacement to metaplasia of esophageal epithelium or glands. The aim of our study is to further investigate the clinicopathological features and pathogenesis of EESG. Our study systematically reviewed 87 cases reported in the literature and analyzed an additional 21 cases from our institution. Demographic data (gender, age), lesion location, endoscopic features, and clinical presentations were summarized. Additionally, immunohistochemical staining for androgen receptor (AR), Kiel 67 (Ki-67), and cytokeratin 14 (CK14) was performed on nine cases. A normality test was conducted to determine whether the age distribution of male and female patients followed a normal distribution. Correlation coefficients and principal component analysis (PCA) were applied to further analyze the characteristics of case onset. The estimated prevalence of EESG was approximately 0.105‰. Lesions were more frequent in males than in females (nearly 2:1 ratio) and predominantly occurred in middle-aged and elderly individuals (mean age: 56.9 years). Most lesions were located in the middle and/or lower esophagus in both genders (99.6% variance explained by PCA). Endoscopically, EESG presented as distinctive “whitehead acne-like” structures with protrusions corresponding to sebaceous duct openings. Immunohistochemistry showed positive AR expression in all cases (9/9, 100%). Ki-67 and CK14 expression patterns indicated a close association between ectopic lesions and the basal layer of the esophageal squamous epithelium. EESG typically presents after puberty with a male predominance. Given that sebaceous glands are androgen-responsive, androgens are likely involved in lesion development. The anatomical proximity of ectopic lesions to the basal layer of the squamous epithelium supports the hypothesis that pubertal androgens may drive aberrant differentiation of basal stem cells toward sebaceous gland lineage.