Cervical inlet patch: case series and literature review.

Abstract: Heterotopic gastric mucosa patch (HGMP) has been reported to occur in various parts of the gastrointestinal system from mouth to anus. Extra-gastrointestinal locations have also been reported. Presence of ectopic gastric mucosa has been associated with complications such as ulceration, bleeding, perforations and malignant transformations. Most complications are probably related to acid production. Meckel diverticulum is the most commonly reported ectopic location. Similarly, esophageal HGMP, also known as cervical inlet patch (CIP), has been increasingly reported. Nonspecific oropharyngeal symptoms are common and thought to be due to laryngopharyngeal reflux. CIP is often missed due to its location in the esophagus, just distal to the upper esophageal sphincter, making endoscopic evaluation difficult. Hence the condition is most likely to be under-reported. This article presents a series of five cases of CIP and discusses the pathogenesis, clinical presentations and management of this interesting entity.

Key Words: heterotopic gastric mucosa, presentations, complications, malignant transformations, laryngopharyngeal reflux

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Heterotopic gastric mucosal patches (HGMP) are congenital gastrointestinal anomalies and have been reported to occur anywhere along the gastrointestinal system from mouth to anus. (1,2) The presence of this ectopic gastric mucosa has been associated with ulceration, bleeding, and malignant transformations. (3-5) Esophageal HGMP, also known as cervical inlet patch (CIP), is usually located just distal to the upper esophageal sphincter. CIP has been increasingly associated with oropharyngeal symptoms. Due to its postcricoid location, CIP is often missed during endoscopy. Similarly, many endoscopists may not be aware of this condition. This article presents a series of five patients with CIP and reviews the literature on the pathogenesis, clinical manifestations and their managements.

Case Reports

Patient 1

A 48-year-old woman was referred with symptoms of sore throat, dyspepsia and retrosternal discomfort that were relieved by belching. She had a negative cardiac evaluation with an exercise stress test. She did not have any underlying past medical history except for an anxious personality. Upper gastrointestinal endoscopy (EGD) showed a flat salmon-colored patch postcricoid suggestive of HGMP (Fig. 1). Biopsy confirmed the presence of fundic type gastric mucosa. She was negative for Helicobacter pylori (H pylori) on rapid urease test (CLOTest, Delta West Ltd, Bentley, West Australia). She was started on omeprazole 20 mg twice a day and domperidone 10 mg three times a day. Her symptoms only improved slightly. She was referred to the Ear, Nose and Throat (ENT) department for further evaluation. Endoscopic examination did not show any significant abnormalities except for mild congestion of the vocal cords and the laryngeal mucosa. She was started on a small dose of anxiolytic in addition to her acid suppression. Her symptoms improved significantly. She remained well on maintenance acid suppression therapy on follow-up with occasional throat symptoms.

Patient 2

A 58-year-old Chinese man was referred from the ENT department with suspected gastroesophageal reflux disease (GERD). He had been seeing the ENT department with a 6 month history of throat discomfort, dryness and chronic cough that had not responded to medications. Chest radiography and electrocardiogram examinations were normal. Endoscopic examination of the oropharyngeal space only showed congestion of the laryngeal mucosa and vocal cord, consistent with laryngopharyngeal reflux (LPR). EGD showed mild gastritis and two flat salmon-colored mucosal patches just distal to the upper esophageal sphincter (Fig. 2). Biopsies from these patches confirmed the presence of fundic type gastric mucosa. He was H pylori negative by rapid urease test. He was treated with a course of acid suppression (omeprazole 20 mg twice daily) and pro-kinetic (domperidone 10 mg three times a day). His symptoms improved significantly. Repeat EGD showed that these mucosal patches had reduced in size. He is currently on maintenance acid suppression.

Patient 3

A 61-year-old man was referred for evaluation of constipation and dyspepsia. There were no warning symptoms. Examination did not reveal any abnormalities. He had underlying diabetes mellitus. EGD showed pangastritis with mucosal atrophy. In the proximal esophagus, there was a flat patch of salmon-colored mucosa located at 18 cm from the incisors. Proper visualization of the entire patch was difficult as it was extending proximally over the upper esophageal sphincter (Fig. 3). Biopsy from the distal part of the patch showed gastric mucosa. His gastric biopsy was H pylori positive by rapid urease test. He was treated with a one-week course of triple therapy (omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and tinidazole 500 mg twice daily). Repeat EGD posteradication showed similar findings. Repeat testing for H pylori by histology was negative. On direct inquiry, the patient admitted to having long-standing mild throat discomfort and occasional cough. However, this had not troubled him enough to seek medical attention. He was started on acid suppression therapy on an as required basis. There were no new complaints apart from the constipation which was responding to supplemental fiber.

Patient 4

A 34-year-old woman with a history of throat discomfort, coughing and persistent throat clearing was referred for endoscopic evaluation. She also had symptoms consistent with GERD. Multiple ENT endoscopic examinations showed mucosal congestion of the larynx and vocal cords consistent with laryngophanyngeal reflux. She had been treated with intermittent courses of omeprazole with some relief. EGD showed two large flat patches of salmon-colored mucosa just distal to the upper esophageal sphincter at 19 cm from the incisors, characteristic of CIP. The patches measured 2 to 3 cm in size. There was also endoscopic esophagitis at the gastroesophageal junction (Los Angeles Grade B) and mild gastritis. She was negative for H pylori with rapid urease test and histology. She was started on an eight-week course of acid suppression (omeprazole 20 mg twice daily, with marked improvement of her symptoms). She required maintenance acid suppression therapy to control her symptoms. Her acid suppression therapy was switched to esomeprazole (Nexium, AstraZeneca) 40 mg daily due to intermittent breakthrough throat symptoms. At last follow up, she was only experiencing mild infrequent symptoms.

Patient 5

An 83-year-old man was referred for EGD for suspected upper gastrointestinal bleeding. He was known to have long-standing gout and had needed regular nonsteroidal analgesia. EGD showed a geographic gastric ulcer on the lesser curve. He also had a submucosal lesion with normal overlying gastric mucosa on the lesser curve, consistent with a lipoma. Upon extubation, there were two patches of salmon-colored mucosa measuring 1 to 3 cm noted in the postcricoid area (Figs. 4 and 5). The edge of the larger proximal patch was raised and the center of the patch looked atrophic. Biopsies only showed body type gastric mucosa consistent with HGMP. There was no evidence of malignant changes on either the esophageal or gastric ulcer biopsies. H pylori testing by rapid urease test and histology was negative. The patient denied ever having any esophageal or throat symptoms. A computed tomography scan confirmed a submucosal lesion consistent with a lipoma. He was treated with a course and later maintained acid suppression with omeprazole. He remained well on follow up.

Discussion

HGMP of the esophagus, or the cervical inlet patch, was first described by Schmidt (6) in 1805 as an aberrant gastric fundus-type epithelium located in the proximal esophagus. This ectopic mucosal patch is usually separated by 15 to 20 cm of normal squamous-lined esophagus from the gastroesophageal junction. At endoscopy, the ectopic gastric mucosa appears as a mainly flat or slightly raised, well circumscribed red-orange salmon-colored patch. This is mainly a solitary patch but can be multiple, measuring from a few millimeters to several centimeters. (7,8) Three of our patients had two patches. In cases with multiple patches, they tend to be found on the opposite wall.

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The reported incidence of CIP in the endoscopic literature ranged from 0.29 to 10%, but incidence of up to 70% has been reported in autopsy studies. (9-11) There may be an element of underestimation of the true incidence, as the condition is commonly missed during endoscopy due to their proximal location and difficulty in examining this area. One study showed that the prevalence was higher when endoscopists were made aware and assessed for CIP compared with when endoscopists were not aware (2.27% versus 0.29% respectively). (9) Retrospective review of endoscopy done in our center showed that there was no case of CIP diagnosed until the first case was documented in 2003. Since then, there have been four additional cases documented and confirmed by histology. Three of these cases were documented in a prospective series of 392 patients undergoing upper gastrointestinal endoscopy over a period of 15 months by a single endoscopist. This gives a prevalence of 0.7% in our local setting. This is in agreement with previous reports that suggest underreporting is contributed to by unawareness of this entity by the endoscopists. (9)

The origin of HGMP is thought to be congenital in nature and CIP is thought to represent esophageal columnar embryologic remnants that had failed to transform to squamous lining during the fetal development period. Microscopically, gastric mucosa containing either cardiac, antral and potentially acid-secreting fundic mucosa can be found. (7) HGMP has been reported to occur in almost any part of the gastrointestinal tract, including the tongue, esophagus, duodenum, gallbladder, jejunum, Meckel diverticulum, rectum and anus. (12-16) Extragastrointestinal locations such as the scrotum have also been reported. (17) The most commonly reported site of HGMP is in the Meckel diverticulum. There are also reports that CIP is associated with increased risk for Barrett esophagus, suggesting a possible link. It is speculated that acid reflux causing esophagitis leading to Barrett esophagus can cause formation of CIP. (18) However, many studies have not found evidence of endoscopic Barrett in patients found to have CIP. Similarly, in our series, there was no Barrett esophagus in any of our patients. Only one of our patients had endoscopic evidence of esophagitis.

Most cases of CIP are discovered incidentally during endoscopic evaluations for other symptoms. In our series, clinical symptoms ranged from asymptomatic to protracted oropharyngeal symptoms. The characteristics and findings of our patients are shown in the Table. Symptoms were protracted in three patients and only responded to prolonged acid suppression. CIP is increasingly being recognized as a cause of nonspecific throat symptoms that is believed to be due to LPR. Acid production by the mucosal patch has been described and this can lead to localized ulceration leading to complications. (3,7,19) Nonspecific throat and esophageal symptoms such as cricopharyngeal spasm, upper esophageal spasm and odynophagia are usually reported.

Management of CIP depends on the symptoms and is probably related to acid secretion. (7) It is important to look for CIP in patients with protracted throat symptoms who have not responded to therapy, as prolonged potent acid suppression is effective in most cases. Trial of acid suppression with proton pump inhibitor should be given, however, the duration is not defined. In the presence of response, the patient can be put on maintenance therapy or on an as required basis. To date, there is no report as to whether treatment has any impact on the size of the CIP. The mechanism is unknown but may be due to the acid suppression leading to reduction in inflammation with subsequent regeneration of the squamous esophageal lining. For patients without response to prolonged acid suppression, they should undergo further evaluation to rule out other pathologies, especially if there are warning signs and symptoms. Often these patients have a long history of troublesome throat symptoms that may impact on their quality of life.

H pylori has been detected within the patch in up to 73% of patients who were also positive for H pylori in the stomach. The presence of H pylori in CIP has been shown to correlate with a high bacterial load in the stomach. (20) However, this is the only study that specifically assessed the presence of H pylori in the CIP. Eradication therapies should be given as the infection can lead to inflammation and ulceration. Rare complications include bleeding, stricture, perforation, fistula and esophageal malignant transformation. (4,5,21-23) In cases where there is evidence of dysplasia, management includes endoscopic mucosal resection, argon plasma coagulation and surgical resection. (24,25)

Conclusions

Cervical inlet patch is not uncommon, but is under-recognized due to its location in the proximal esophagus, in addition to physicians being unaware of the condition. CIP should be looked for particularly in patients with chronic cough and nonspecific oropharyngeal symptoms. Endoscopists should be aware of this condition and carefully assess the proximal esophagus just distal to the upper esophageal sphincter during endoscopy in patients with throat symptoms. This is particularly true as CIP can be associated with significant complications and rarely can lead to malignant transformation.

References

1. Wetmore RF, Bartlett SP, Papsin B, et al. Heterotopic gastric mucosa of the oral cavity: a rare entity. Int J Pediatr Otorhinolaryngol 2002;66:139-142.

2. Steele SR, Mullenix PS, Martin MJ, et al. Heterotopic gastric mucosa of the anus: a case report and review of the literature. Am Surg 2004;70:715-719.

3. Byrne M, Sheehan K, Kay E, et al. Symptomatic ulceration of an acid producing esophageal inlet patch colonized by helicobacter pylori. Endoscopy 2002;34:514.

4. Bataller R, Bordas JM, Ordi J, et al. Upper gastrointestinal bleeding: a complication of 'inlet patch mucosa' in the upper esophagus. Endoscopy 1995;27:282.

5. Noguchi T, Takeno S, Takahashi Y, et al. Primary adenocarcinoma of the cervical esophagus arising from heterotopic gastric mucosa. J Gastroenterol 2001;36:704-709.

6. Schimdt FA. De mammalium esophagus alque werticulo. Inaugural dissertation. Halle, in office, Bathenea, 1805.

7. Jabbari M, Goresky CA, Lough J, et al. The inlet patch: heterotopic gastric mucosa in the upper esophagus. Gastroenterology 1985;89:352-356.

8. Lauwers GY, Wahl SJ, Urmacher CD. Multifocal ectopic gastric mucosa of the cervical esophagus. Am J Gastroenterol 1991;86:793-794.

9. Maconi G, Pace F Vago L, et al. Prevalence and clinical features of heterotopic gastric mucosa in the upper oesophagus (inlet patch). Eur J Gastroenterol Hepatol 2000;12:745-749.

10. Borhan-Manesh F, Farnum JB. Incidence of heterotopic gastric mucosa in the upper oesophagus. Gut 1991;32:968-972.

11. Schridde H. Uber Magenschleimhaut-Inseln vom Bau der Cardialdrusenzone und Fundusdrusenregion und den unteren, oesophagealen Cardial-drusen gleichende Drusen im obersten Oesophagusabschnitt. Virchows Arch A Pathol Arat Histopathol 1904;175:1-16.

12. Melato M, Ferlito A. Heterotopic gastric mucosa of the tongue and the oesophagus. ORL J Otorhinolaryngol Relat Spec 1975;37:244-254.

13. Lessells AM, Martin DF. Heterotopic gastric mucosa in the duodenum. J Clin Pathol 1982;35:591-595.

14. Wakiyama S, Yoshimura K, Shimada M, et al. Heterotopic gastric mucosa in a gallbladder with an anomalous union of the pancreatobiliary duct: a case report. Hepatogastroenterology 1998;45:1488-1491.

15. Emamian SA, Shalaby-Rana E, Majd M. The spectrum of heterotopic gastric mucosa in children detected by Tc-99m pertechnetate scintigraphy. Clin Nucl Med 2001;26:529-535.

16. De Angelis P, Trecca A, Francalanci P, et al. Heterotopic gastric mucosa of the rectum. Endoscopy 2004;36:927.

17. Khan MA, Fitzgerald RJ. Heterotopic gastric tissue in the scrotum. J Urol 1996;155:2061.

18. Avidan B, Sonnenberg A, Chejfec G, et al. Is there a link between cervical inlet patch and Barrett's esophagus? Gastrointest Endosc 2001;53:717-721.

19. Galan AR, Katzka DA, Castell DO. Acid secretion from an esophageal inlet patch demonstrated by ambulatory pH monitoring. Gastroenterology 1998;115:1574-1576.

20. Gutierrez O, Akamatsu T, Cardona H, et al. Helicobacter pylori and heterotopic gastric mucosa in the upper esophagus (the inlet patch). Am J Gastroenterol 2003;98:1266-1270.

21. Yarborough CS, McLane RC. Stricture related to an inlet patch of the esophagus. Am J Gastroenterol 1993;88:275-276.

22. Sanchez-Pernaute A, Hernando F, Diez-Valladares L, et al. Heterotopic gastric mucosa in the upper esophagus ('inlet patch'): a rare cause of esophageal perforation. Am J Gastroenterol 1999;94:3047-3050.

23. Kohler B, Kohler G, Riemann JF. Spontaneous esophagotracheal fistula resulting from ulcer in heterotopic gastric mucosa. Gastroenterology 1988;95:828-830.

24. Pech O, May A, Gossner L, et al. Early stage adenocarcinoma of the esophagus arising in circular heterotopic gastric mucosa treated by endoscopic mucosal resection. Gastrointest Endosc 2001;54:656-658.

25. Klaase JM, Lemaire LC, Rauws EA, et al. Heterotopic gastric mucosa of the cervical esophagus: a case of high-grade dysplasia treated with argon plasma coagulation and a case of adenocarcinoma. Gastrointest Endosc 2001;53:101-104.

Vui Heng Chong, MRCP, FAMS, and Anand Jalihal, MBBS, DM

From the Gastroenterology Unit, Department of Medicine, Raja Isteri Pengiran Anak Saleha (RIPAS) Hospital, Brunei Darussalam

Reprint requests to Vui Heng Chong; Gastroenterology Unit, Department of Medicine, Raja Isteri Pengiran Anak Saleha (RIPAS) Hospital, Bandar Seri Begawan BA 1710, Brunei Darussalam. Email: [e-mail]

Accepted April 19, 2006.

RELATED ARTICLE: Key Points

* Cervical inlet patch or heterotopic gastric mucosa of the esophagus is not uncommon, but is an under-recognized condition.

* Symptoms are mainly related to acid production.

* Management consists of acid suppression therapy.

* It is associated with significant complications such as bleeding, ulcerations, perforations and malignant transformations.

Table. Characteristics of patients, endoscopic findings and responses
to treatment

                     No. of
Patient  Age/gender  patches  Histology    Symptoms          Response

1        48/female   1        Fundic type  Sore throat       Partial
                                                             response
2        58/male     2        Fundic type  Sore throat       Good
                                           Chronic cough     response
3        61/male     1        Body type    Minimal symptoms  NA
4        34/femae    2        Not biopsy   Sore throat       Good
                                           Throat clearing   response
                                           Cough
5        84/male     2        Body type    Asymptomatic      NA

NA, not applicable.