**2. Pathogenesis**

HGMP is widely considered to be congenital in nature, as result of incomplete esophageal squamous epithelization during the embryogenic development stage (von Rahden et al., 2004). Reports of HGMP in the esophagus of young children and even babies support this theory (Boybeyi et al., 2008; Georges et al., 2011; Macha et al., 2005; Surana et al., 1993). However, it has also been proposed to be acquired in nature, similar to Barrett's esophagus (Avidan et al., 2001; Lauwers et al., 2005). There are based on similarities in the mucin and staining characteristics with CK7 and CK20 (Bogomoletz et al., 1988; Lauwers et al., 2005) between Barrett's esophagus and HGMP/CIP. Reports of higher incidence of Barrett's esophagus in patients with HGMP/CIP also suggested a link. Some has even proposed that the origins of HGMP/CIP may be different, congenital in children and acquired in adult (Lauwers et al., 2005). A recently proposed hypothesis suggested that HGMP/CIP developed from rupture retention cyst of the proximal esophagus (Meining & Baubouj, 2010).

#### **2.1 Origin of heterotopic gastric mucosal patch of the proximal esophagus 2.1.1 Congenital origin theory**

#### *Embryogenesis of the esophagus*

The development of the esophagus starts at the beginning of embryogenesis (Lieberman-Meffert et al., 2002). The upper aerodigestive tract (oro, naso and largyngopharynx), respiratory tract, esophagus and stomach and duodenum arise from the same embryogenic segment. The stages of development are correlated with the length of the embryo. At 3 mm crown-rump length, the esophagus is mainly lined with columnar mucosa and during development at 110 CR length (equivalent to 24 weeks gestation), the squamous lining begin to replace the columnar lining starting at the mid esophagus, migrating in both directions. The cervical region of the esophagus is the last area to get stratification and this account for the common findings of HGMP in the proximal esophagus. The embryogenic development of the esophagus is shown in Figure 1.
