AIM: To determine the prevalence, demographic, clinical and histopathologic features of heterotopic gastric mucosa (HGM) in Chinese patients.

METHODS: Patients referred to three endoscopy units were enrolled in this study. The macroscopic characteristics of HGM were documented. Biopsies were obtained and observed using hematoxylin and eosin staining. Helicobacter pylori colonization was examined by Whartin-Starry staining.

RESULTS: HGM was observed in 420 Chinese patients, yielding a prevalence of 0.4%. The majority of patients had a single patch (300/420; 71.4%), while the remainder had two (84/420; 20%) or multiple patches (36/420; 8.6%). The size of the patches and the distance from the patch to the frontal incisor teeth varied significantly. The large majority of HGM patches were flat (393/420; 93.6%), whereas the remaining patches were slightly elevated. The primary histological characteristic was fundic-type (216/420; 51.4%) within the HGM patch, and antral- (43/420; 10.2%) and transitional-type (65/420; 15.5%) mucosa were also observed. The prevalence of intestinal metaplasia was 3.1% (13/420) and the prevalence of dysplasia was 1.4% (6/420), indicating the necessity for endoscopic follow-up in patients with HGM. Esophageal and extraesophageal complaints were also observed in patients with HGM. Dysphagia and epigastric discomfort (odds ratios: 6.836 and 115.826, respectively; Ps < 0.05) were independent risk factors for HGM.

CONCLUSION: Clinical complaints should be considered to improve the detection rate of HMG. The prevalence of intestinal metaplasia and dysplasia also indicates a need for endoscopic follow-up.

Heterotopic gastric mucosa (HGM) is an area of heterotopic columnar mucosal islands located in the postcricoid portion of the cervical esophagus or below the level of the upper esophageal sphincter[1]. The majority of researchers consider HGM to be the remnant of the esophageal columnar embryologic lining due to underdevelopment of squamous epithelium during the fetal period. However, some researchers consider that HGM may share a similar pathogenesis to that of Barrett’s esophagus and is associated with gastroesophageal reflux[2]. A possible explanation for the origin of HGM was recently postulated, suggesting that HGM might develop from mucus gland cysts within the cervical esophagus after eruption[3]. The symptoms of esophageal HGM are diverse and primarily comprised of chest pain, throat discomfort, dysphagia, globus sensation, and laryngopharyngeal or supraesophageal symptoms[4-7]. Although most esophageal HGM patches do not lead to obvious health problems, a few case reports have indicated that these lesions can further develop into a web, stricture, ulcer, perforation, esophagotracheal fistula, Barrett’s esophagus or adenocarcinoma[8-12].

The endoscopic prevalence of HGM ranges from 0.1 to 11%, with the majority of reports indicating the prevalence to be between 1% and 2%[5,13-16]. The significant discrepancy may be the result of differences in the experience and special interests of endoscopists[17]. The clinical significance and prevalence of esophageal HGM are still largely uncertain due to the limited number of subjects in most studies and the discrepant focus on these lesions by endoscopists. Here we present a prospective, multicenter cohort study to determine the prevalence of esophageal HGM in a Chinese population, identify the macroscopic and histologic features, and evaluate the associations of HGM with demographic and clinical characteristics.

The clinical significance of HGM has recently been discussed in numerous published reports. However, most studies only included a limited number of patients, due to lack of persuasion. To our knowledge, our study includes the largest number of subjects in the literature. An HGM prevalence rate of 0.4% was observed in our study, which is consistent with the 0.3%-0.4% reported in a previous study conducted by Wang et al[18] in China. HGM patches are always located near the upper esophageal sphincter and are easily ignored by endoscopists if the endoscope is withdrawn quickly and without care[15]. Maconi et al[17] demonstrated a prevalence of 2.27% when endoscopists were informed about the presence of HGM patches, and a prevalence of 0.3% when they were not informed about these lesions. Thus, the low prevalence of HGM in our study may partly be due to the fact that endoscopists were not instructed to search for HGM lesions. Furthermore, HGM patches were equally distributed between male and female patients in our study, and there was no significant difference in the mean age of patients with and without HGM, consistent with previous reports[6,19].

In the present study, the presence of a single patch under endoscopy was more common than that of double or multiple patches within the upper esophagus, which is consistent with previous studies[14,20]. The size of patches (0.3-3.0 cm) and their distance from the frontal incisor teeth (14-22 cm) varied significantly, but were in accordance with previous publications[5,16,21]. The patch surface may be smooth and flat, slightly raised or depressed with a heaped margin[21]. The patch can appear as a sessile polyp in rare cases[22]. Our study showed that the majority of HGM patches appeared flat, while only a small portion were identified as slightly elevated.

The histopathology of HGM is usually observed as fundic-type, characterized by oxyntic features other than antral- or transitional-type[21], which is in accordance with the results of our study where more than half of the heterotopic patches were identified as fundic-type. Although intestinal metaplasia or malignant transformation of HGM patches are considered rare events and have only been published as case reports[23-25], the prevalence of intestinal metaplasia and dysplasia in our series of 420 patients suggests that these are not infrequent events.

H. pylori colonization within HGM is considered to be part of H. pylori-positive gastritis. There are no reports of exclusive H. pylori colonization in HGM. The prevalence of H. pylori colonization within HGM is more frequent in the proximal esophagus, and ranges between 5.3% and 18% in the literature[26,27]. Although we did not detect H. pylori colonization in the gastric mucosa in our study, the prevalence was 10% in patients with HGM, which is in accordance with previous studies[13,28]. In addition, chronic inflammation is reportedly present within most of the cervical inlet patches[5,14]. Our findings similarly revealed that more than half of patients with HGM patches suffered from chronic inflammation.

Acid production and/or H. pylori colonization within HGM patches can potentially lead to esophageal web, stricture, ulcer, perforation or bleeding, which are rarely reported in the literature[10,29,30]. In our study, no such complications were observed in patients with HGM patches. Although mucosal atrophy is very rarely observed within HGM patches, we observed a prevalence of 8.3% in our study. The factors leading to such a high prevalence of mucosal atrophy within HGM patches are unknown and may be associated with chronic inflammation, H. pylori infection, and even racial difference.

The results of this study showed a significant difference between patients with and without HGM regarding heartburn and regurgitation, throat discomfort, dysphagia and epigastric discomfort, but not retrosternal pain. Previous studies indicated that esophageal symptoms (e.g., heartburn, regurgitation, chest pain, dysphagia, and globus sensation) and extraesophageal symptoms (e.g., cough, asthma, and wheezing) differ between those with and without patches[19,20]. Although these symptoms are not specific for the diagnosis of HGM, they are potentially regarded as evidence for further endoscopic examination. It is important to investigate the association between HGM and these symptoms from a clinical point of view. It is known that dysphagia, globus sensation and respiratory symptoms (e.g., cough, hoarseness) are commonly observed with HGM[7,31-33]. In our study, dysphagia and epigastric discomfort were identified as independent risk factors for HGM; however, male gender was associated with a reduced risk of HGM. Other symptoms, such as throat discomfort, heartburn, regurgitation and retrosternal pain were not associated with the presence of HGM.

Although our study indicated a relatively high occurrence of intestinal metaplasia and malignant transformation, a very small number of these lesions have been reported in other studies. Therefore, whether patients with HGM require follow-up by endoscopy is still a controversial issue and requires further consideration.

In conclusion, the prevalence of HGM patches is an infrequent anomaly based on our multicenter prospective cohort study in a Chinese population, although the endoscopists were not instructed to focus on these lesions. Because it is easy to ignore HGM patches in the upper esophagus, an endoscopic examination should be thorough and performed carefully. Biopsy was reasonable once the HGM patch was identified. Although malignant transformation of a heterotopic patch is rare, the prevalence of intestinal metaplasia and dysplasia indicates a need for endoscopic follow-up in patients with HGM. Clinical complaints should be a focus of attention to increase the rate of HGM detection in light of our findings.