**3. Histology**

HGMP/CIP consists of columnar mucosa found in the stomach (Figure 4). HGMP/CIP can contain glandular mucosa of different types similar to those found in the stomach. One study showed that the body or fundus mucosa type parietal cells is the most common accounting for 50 to 65% with the antral type and mixed transition type accounting for 20 to 25% respectively (Borhan-Manesh & Franum, 1991). Presence of acid producing parietal mucosa have been associated with acid production (Galan et al., 1998; Hamilton et al., 1986; Korkut et al., 2010; Yüksel et al., 2008). Mucin is also secreted (Bajbouj et al., 2009; Bogomoletz et al., 1988). The cytokeratin staining pattern of HGMP/CIP is similar to those seen with Barrett's esophagus with surface epithelium staining for CK7 and CK20 (Figure 5). The staining pattern of the esophagus and stomach is shown in Figure 6 (Latchford et al., 2001).

Fig. 4. High power view showing boundary between squamous esophageal mucosa and the glandular mucosa of the HGMP/CIP

Apart from CK, only one study had assessed the MUC protein profiles (Lauwers et al., 2005). This study showed that MUC5AC was strongly expressed on the surface and pits but not in the glands of HGMP/CIP and antral mucosa. In contrast, MUC5AC positivity was noted on the surface, pits and the glands of Barrett's esophagus. MUC6 similarly decorated the glands of HGMP/CIP and Barrett's esophagus. MUC2 was expressed rarely in HGMP/CIP with goblet cells but conspicuously on the surface and pits of Barrett's esophagus. MUC5B was seen in both HGMP/CIP and Barrett's esophagus and rarely in

Heterotopic Gastric Mucosal Patch of the Proximal Esophagus 131

A clinico-pathologic classification has been proposed by von Rahden *et al.* (von Rahden et al., 2004) which categorized patients with HGMP into five groups (I to V) based on the clinical, endoscopic and histological findings (Table 1). This classification also takes into account of small patches that may be only visible microscopically. Based on this classification, majority of the HGMP/CIP are categorized into types I and II, asymptomatic and mildly symptomatic respectively. One study found that the most common lesions are

**Category Description Symptoms/findings Frequency I** Asymptomatic None Common **II** Symptomatic Laryngopharyngeal reflux Common

**IV** Intra-epithelial dysplasia None/non-specific Uncommon **V** Malignant transformation Asymptomatic/dysphagia Reported

Adapted from von. Rahden *et al*. Heterotopic gastric mucosa of the esophagus: literature-review and

The majority of patients found to have HGMP/CIP are asymptomatic and the HGMP/CIP are usually detected incidentally while being evaluated with endoscopy for other gastrointestinal complaints. The clinical importance of HGMP/CIP remains controversial with some authors believe that they are benign and of no clinical relevance. Others have shown HGMP/CIP to be clinically important especially for a subset of patients with HGMP/CIP. For those who have symptoms attributable to the HGMP/CIP, most are mild and are detected only on direct inquiries. For a small proportion of patients, the symptoms can be prominent and patients may have many consultations before a diagnosis is made. The prevalence of any symptoms, typically those considered extra-esophageal symptoms complex of gastroesophageal reflux such as chronic cough, throat irritation or sore throat, regurgitation, globus pharyngeus, dysphagia or hoarseness ranges from very low to as high

HGMP/CIP like other ectopic gastric mucosal have been proven to be able to secrete acid in sufficient quantity to induce inflammatory changes and acid related symptoms (Baudet et al., 2006; Galan et al., 1998; Hamilton et al., 1986; Korkut et al., 2010; Nakalima et al., 1993; Yüksel et al., 2008). Acid is the main cause of symptoms in patients with HGMP/CIP. Given the proximity of the HGMP/CIP to the laryngopharyngeal area, it is not surprising that

a inlet patch (macroscopically visible patch of HGMP/CIP) b microscopic foci (only microscopically visible HGMP/CIP)

proposal of a clinicopathologic classification. Am J Gastroenterol. 2004; 99:543-51.

Table 1. Clinico-pathological classification for HGMP/CIP

as 75% (Chong & Jalihal, 2010; Maconi et al., 2000).

Strictures/webs/fistula/bleeding

\* Polyps Uncommon

**4. Classification** 

types I (73%) and II (27%) lesions.

**III** Symptomatic with

*Suffix* 

benign complications

\* Not included in the original classification

**5. Clinical manifestations** 

the antral mucosa. The authors concluded that the similarities between HGMP/CIP and Barrett's esophagus but not with normal antral mucosa fit with the hypothesis that both lesions may originate from sub-mucosal esophageal mucous glands. Despite this, there are differences seen between HGMP/CIP and Barrett's esophagus. Staining pattern was also different between HGMP/CIP and the embryogenic esophagus. The authors of this study suggested that HGMP/CIP etiology may be different, congenital in children or babies and acquired in adult.

Fig. 5. (a) Cytokeratin (CK) 7 staining of HGMP/CIP showing uptake in the surface glandular tissue similar to that seen in Barrett's esophagus (b). CK20 staining uptakes are similar in HGMP/CIP (c) and Barrett's esophagus (d)

The HGMP/CIP can also be colonized by *Helicobacter pylori* and the patches are subjected to changes that are seen in the stomach (Akbayir et al., 2004; Alagozlu et al., 2010; Borhan-Manesh & Franum, 1991 & 1993; Gutierrez et al., 2003; Jacobs et al., 1997; Maconi et al., 2000; Poyrazoglu et al., 2009; Tang et al., 2004; Yüksel et al., 2008). Chronic inflammatory changes can be seen and progression to atrophy, intestinal metaplasia, dysplasia and malignant transformation have been reported (Borhan-Manesh & Franum, 1991). The surrounding squamous cell mucosa can also show inflammatory changes similar to those seen in reflux esophagitis (Borhan-Manesh & Franum, 1991).
