American Journal of Gastroenterology
C ?2004 by Am. Coll. of Gastroenterology
Published by Blackwell Publishing
Heterotopic Gastric Mucosa of the Esophagus:
Literature-Review and Proposal of a Clinicopathologic
Burkhard H. A. von Rahden, M.D., Hubert J. Stein, M.D., F.A.C.S., Karen Becker, M.D.,
Dorothea Liebermann-Meffert, M.D., F.A.C.S., and J. R¨ udiger Siewert, M.D., F.A.C.S.
Department of Surgery; and Department of Pathology, Klinikum rechts der Isar, Technical University Munich,
The prevalence of heterotopic gastric mucosa (HGM) in the cervical esophagus is frequently
underestimated. Tiny microscopic foci have to be distinguished from a macroscopically visible
patch, also called “inlet patch.” Symptoms as well as morphologic changes associated with HGM
are regarded as a result of the damaging effect of acid, produced by parietal cells in the mostly
fundic type of HGM.
We herein review the literature and propose a new clinicopathologic classification of esophageal
HGM: Most of the carriers of esophageal HGM are asymptomatic (HGM I). Some individuals with
HGM in the esophagus complain of dysphagia, odynophagia, or “extraesophageal manifestations”
(hoarseness and coughing), without further morphologic findings (HGM II). Still fewer patients are
symptomatic due to morphologic changes, i.e., esophageal strictures, webs, or esophagotracheal
fistula (HGM III). Malignant transformation via dysplasia (intraepithelial neoplasia, HGM IV) to
cervical esophageal adenocarcinoma (HGM V) is exceedingly rare (only 24 reported cases). In
contrast to Barrett’s esophagus, HGM should not be regarded as a precancerous lesion.
Symptoms are more likely to occur in patients with inlet patch, whereas malignant transformation
and adenocarcinogenesis can also occur in microscopic HGM foci. Asymptomatic HGM requires
neither specific therapy nor endoscopic surveillance. Only in symptomatic cases treatment, i.e.,
dilatation for (benign) strictures or acid suppression for reflux symptoms, can be recommended.
Patients with low-grade dysplasia in HGM might be candidates for surveillance strategies, whereas
in cases of high-grade dysplasia and invasive adenocarcinoma oncological treatment strategies
must be employed.
it can be responsible for local morphologic alterations (e.g.,
webs, strictures, ulcers, fistula) causing local symptoms (es-
pecially pain and dysphagia). Furthermore, in exceedingly
rare cases, HGM can be the origin of malignant progression
to cervical esophageal adenocarcinoma.
HGM is not exclusively found in the esophagus as it has
trointestinal tract, like the tongue (1), the duodenum (2), the
jejunum (3), the gall bladder (4), and the rectum (5).
macroscopically visible areas of red or salmon-colored vel-
vety patches. Predominant localization of esophageal HGM
ter. Such patches of macroscopically visible HGM are also
called “inlet patches.”
Although the first description of a gastric inlet patch in the
esophagus dates back 200 yr when Schmidt in 1805 was the
ology, pathophysiology, and treatment remain unanswered.
Selection of articles for this review was based on a comput-
erized MEDLINE database search for relevant literature, us-
ing the search terms “ectopic gastric mucosa,” “heterotopic
gastric mucosa,” “gastric inlet patch,” and “gastric hetero-
topia.” Articles were checked and included if relevant new
information on the topic were provided. The literature search
encompassed the years available online. Additionally, prior
articles cited in the papers were included if relevant.
Epidemiologic data concerning HGM are scarce. The ex-
act prevalence, the frequency of symptomatic cases, and the
544 von Rahden et al.
incidence of malignant progression to cancer are vaguely
Historical investigations revealed a prevalence of 0.67%
(7) to 70% when microscopically visible foci were included
Rector and Connerly revealed abberant gastric mucosa in the
upper esophagus in 4.5% of the cases (9). Unfortunately this
interesting question has not been addressed in more recent
of the cases (10–14), but the frequency tends to be clinically
The latter is due to the predominant localization in the re-
area is not easily accessible by endoscopy as it is just below
the scope of the otolaryngologist and exploration by flexible
upper gastrointestinal endoscopy is difficult: The region is
quickly passed protruding the endoscope over the sphincter’s
an inlet patch be detected (12, 13).
to 0.3 cm to 3 × 4 cm (12). They can be unique or multiple,
round or oval, can extent transversally or circumferentially.
The surface can be flat, slightly raised, or depressed, some-
times with heaped margins (15) (see Figs. 1 and 2)
The histologic appearance of HGM is fairly characteris-
tic (see Figs. 3 and 4) although esophageal mucosal glands
can be mistaken for HGM (16). Mostly the gastric mucosa
is uniformly of the fundic-type, containing parietal cells
(10, 12). Less frequently, histopathologic examination of
HGM shows a “transitional” cell type with random admix-
Figure 1. Development of the Mucosa in the human esophagus (from (17)).
by the absence of chief cells and only few parietal cells (10).
(infiltration of inflammatory cells) may be present and varies
in extent (10, 15). Infiltration with granulocytes as well as
common is the coexistence of esophagitis in the squamous
mucosa adjacent to the HGM (12).
Inherited Condition or Metaplastic Change?
Esophageal HGM is generally regarded as a congeni-
tal condition, resulting from an incomplete embryologic
esophageal epithelization process: The columnar epithelium
of the embryo’s esophagus is gradually replaced by squa-
mous cell epithelium. This process starts in the mideso-
phagus and extents vertically in both directions with the
cervical esophagus being the last region to get stratified
(17, 9, 18). If the squamous epithelization remains incom-
plete, the persisting columnar-lined area differentiates to
The development of the esophageal lumen and the pattern
of epithelization is illustrated in Figure 5. Cell types (colum-
nar/squamous cells), cell layers and special features of the
cells (vacuoles/cilia/glands), and the size of the esophageal
lumen at the certain stages of mucosal development are il-
lustrated. The features are correlated with the length of the
Barrett’s esophagus has formerly also been regarded as a
congenital condition, but nowadays it is generally accepted
that it is an acquired metaplastic change due to chronic gas-
troesophageal reflux. Repeatedly attempts have been under-
taken to find an association between Barrett’s esophagus and
HGM (19, 14). Avidan et al. judged from their findings in
a large case control study (53 patients with inlet patch and
4,882 control subjects) that the coincidence of the cervical
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