The sebaceous gland is closely related to the hair follicle, forming the pilosebaceous apparatus, most commonly in the face and scalp, but occasionally in aberrant areas. Ectopic sebaceous glands were first reported in 1896 as small yellow nodules of the mouth and lips, and they were named as Fordyce’s spots [1]. Since then, they have been reported in the genitalia, eyes and orbits, nipples, palms, soles, and parotid glands [2]. Ectopic sebaceous glands of the esophagus are a very rare condition. The first report of the gross findings was based on the 200 autopsies in 1962, which revealed ectopic sebaceous glands in approximately 2% of the total cases [3]; the first endoscopic observation was reported in 1978 [4]. To date, a total of seven cases have been reported in the Korean literature [5-11]. Herein, we report two cases of esophageal ectopic sebaceous glands found incidentally during endoscopy with magnifying endoscopic findings.

Ectopic sebaceous glands of the esophagus are very rare findings and found incidentally on endoscopy. Recently, reports of cases with esophageal ectopic sebaceous glands have been increasing owing to an increase in heath-checkup endoscopy. According to a study of 215,046 patients in Taiwan, the incidence and prevalence rates were 0.00465% and 0.41 per year, respectively [12], and in a recent Korean literature, ectopic esophageal sebaceous glands were identified in 0.05% of asymptomatic subjects [13].

The origin of ectopic sebaceous glands in the esophagus has not been elucidated. The most interesting aspect is that the esophagus originates from the endoderm, whereas the sebaceous gland is the structure of the ectodermal origin. The mechanism of their development is unclear; however, it is presumed to be caused by congenital misplacement or metaplastic change. Since esophageal ectopic sebaceous glands have never been reported in children and are more prevalent in older individuals [14,15], the metaplastic theory is more plausible. Some authors have argued that an association with reflux esophagitis and smoking and drinking habits exists [2,10] but have not yet shown any clear correlation. Our patients did not drink or smoke, and endoscopic findings suggesting reflux esophagitis were not found. Considering these, there is limited evidence favoring the roles of irritations, such as gastroesophageal reflux or smoking/alcohol consumption, on the occurrence of esophageal ectopic sebaceous glands. Although our patients had non-specific symptoms, such as mild dyspepsia or reflux symptoms, the association between these symptoms and the development of ectopic sebaceous glands seems to be weak.

The endoscopic findings may appear as yellowish papules or nodules with an irregular surface, occasionally with a small tubular opening in the center, which may appear as a small white protuberance [10]. The size and number of the lesions vary, ranging from 1 to 20 mm and from single to more than a hundred, respectively [16,17]. The most prevalent anatomical location has not been established; however, to date, ectopic sebaceous glands have been reported to occur most frequently in the mid-to-lower esophagus. In our cases, the lesion in the first case was in the mid-esophagus, and that in the second case was in the lower esophagus. Their endoscopic findings were similar as multiple yellowish patches or plaques. A differential diagnosis is needed in the presence of other yellowish lesions in the esophagus, such as carcinoid tumor, granular cell tumor, or xanthoma. Xanthoma is most likely to be confused with ectopic sebaceous glands. Macroscopically, esophageal xanthoma often manifests as white-to-yellowish, granular or verruciform lesions [18]. Therefore, it is not easy to distinguish xanthoma from ectopic sebaceous glands before the confirmation of endoscopic biopsy; at that time, ME-NBI might help distinguish them. In fact, the excretory ducts of the sebaceous glands were seen very clearly on ME-NBI, and they were surrounded by circular microvessels in both cases. The circular microvessels seen on ME-NBI may have occurred because of the displacement of the vessels by the presence of subepithelial components (ectopic sebaceous glands) in the lamina propria mucosae. To our knowledge, this is the first report on ME-NBI for esophageal ectopic sebaceous glands.

In several studies, esophageal ectopic sebaceous glands were followed up for years, and there were some fluctuations in their appearance; nevertheless, no change in the number and size of the lesions was eventually observed [15,19,20]. In addition, no report on malignant transformation has been conducted to date. Therefore, they usually have a good prognosis and do not require treatment.

In conclusion, we report two rare cases of esophageal ectopic sebaceous glands with characteristic ME-NBI findings. On endoscopy, the esophageal ectopic sebaceous glands appeared as yellowish papules or nodules in the mid-to-lower esophagus, and on ME-NBI, the excretory ducts of the sebaceous glands were surrounded by circular microvessels. These characteristic features are helpful in differentiating ectopic sebaceous glands from other yellowish lesions, such as carcinoid tumor, granular cell tumor, or xanthoma.