The authors present a gamut or pattern approach to the diagnosis of esophageal diseases. They discuss the varied radiographic findings that can be used, with consideration of the clinical history, to determine the correct diagnosis or a graded differential diagnosis.
Dr. Rubesin is a Professor of Radiology and member of the
Gastrointestinal Radiology Section, and Dr. Levine is a
Professor of Radiology and Chief of the Gastrointestinal
Radiology Section at the Hospital of the University of
Pennsylvania in Philadelphia, PA.
This review article will present a gamut or pattern approach to
the diagnosis of esophageal diseases.
For most patients, analysis of the radiographic findings in
combination with consideration of the clinical history leads to the
diagnosis or a graded differential diagnosis.
The normal esophagus is a muscular tube covered by
nonkeratinized squamous epithelium. The esophagus lies in the neck
and mediastinum. The aorta, left mainstem bronchus, and posterior
border of the heart impress upon the wall of the esophagus. During
double-contrast esophagography, the barium-etched contour is
visible as a smooth, white line (figure 1). En face, the
barium-coated esophageal mucosa is smooth and featureless, fading
The squamocolumnar junction with the stomach may be seen as a
zigzag line, also known as the Z line.
Small esophageal ulcers
A wide variety of diseases are associated with small esophageal
ulcers <1 cm in diameter (Table 1).
The most common causes of radiographically diagnosed small
esophageal ulcers are viral-induced esophagitis, drug-induced
esophagitis, and reflux esophagitis.
Herpes simplex virus type I most frequently causes esophagitis
in immunosuppressed patients, although immunocompetent patients are
affected occasionally. On barium studies, small, discrete
superficial ulcers are seen on a background of normal mucosa
The ulcers may have a round, stellate, linear, or serpentine
configuration. Rarely, herpes esophagitis may develop in
immunocompetent patients. In this self-limited form of herpes
esophagitis, the ulcers manifest as smaller, punctate collections
Drug-induced esophagitis is primarily a contact esophagitis
caused by a variety of medications, including tetracycline or its
derivatives, quinidine, potassium chloride, non-steroidal
anti-inflammatory agents, and alendronate sodium. If little or no
water is used during ingestion of these medications, pills may
transiently lodge in the esophagus at the level of normal extrinsic
impressions, including the aortic arch, the left mainstem bronchus,
and the left atrium. Typically, small, shallow ulcers will be
clustered together in the mid-esophagus.
These ulcers usually heal within 7 to 10 days after cessation of
the offending medication.
In patients with small esophageal ulcers, the clinical history
provides the key to the diagnosis. Patients with herpes esophagitis
are usually immunosuppressed. If drug ingestion is the cause of the
ulcer, a clinical history of using the offending medication can
usually be elicited. Finally, patients with reflux-induced ulcers
usually have a history of heartburn, and the ulcers are usually
located in the distal esophagus near the esophagogastric junction.
These patients also usually have other radiographic findings of
Large esophageal ulcers
The most common causes of large esophageal ulcers, those >1
cm in diameter, are human immunodeficiency virus (HIV) and
cytomegalovirus (CMV) in immunocompromised patients, primarily
patients with acquired immunodeficiency syndrome (AIDS).
HIV ulcers sometimes occur near the time of clinical presentation
and seroconversion. The ulcers in CMV and HIV esophagitis (figure
3) tend to be large, flat, ovoid-shaped barium collections or
Endoscopic biopsy specimens are necessary to distinguish CMV or HIV
ulcers, as the treatment for each of these infections is different.
Esophageal ulceration due to HIV is a diagnosis of exclusion, so
this diagnosis can be made only when endoscopic biopsies,
brushings, and cultures are negative for CMV.
Other common causes of large esophageal ulcers include carcinoma
(figure 4), drug-induced ulcers, or Barrett's esophagus
(Table 1). However, these ulcers tend to be deeper than
viral-induced ulcers, and their edges are frequently thickened and
lobulated. In such cases, biopsy specimens may be necessary to
Mucosal nodules and plaques
Mucosal nodules and plaques are elevated lesions of varying
size. Plaques are usually discrete, irregular or ovoid elevations
that barely protrude above the mucosal surface. Nodules are smaller
elevations and are more rounded than plaques. The morphology of the
elevations in combination with the clinical history allows a
specific diagnosis to be made in most patients (Table 2).
esophagitis most frequently manifests as numerous small, discrete,
ovoid or linear plaque-like elevations aligned parallel to the
longitudinal folds of the esophagus (figure 5).
esophagitis, the plaques are separated by intervening segments of
normal mucosa. In more severe cases, the plaques may carpet the
esophagus. In even more severe cases, confluent plaques,
pseudomembranes, and barium burrowing beneath the inflammatory
detritus may produce a grossly irregular appearance of the contour
in profile and the mucosal surface en face, the so-called "shaggy
esophagus." When plaques and pseudomembranes slough, large ulcers
may form, but these are almost always present on a background of
diffuse plaque formation.
is the most common cause of infectious esophagitis.
Immunosuppression is the most frequent predisposing factor.
Patients usually complain of dysphagia or odynophagia. Thrush in
the oral cavity or pharynx is seen in about one-half of patients.
esophagitis may also develop in patients with severe esophageal
motility disorders, such as scleroderma, or in patients with
esophageal obstruction and stasis due to achalasia or
Small nodules and plaques of varying sizes may also be seen in
the esophagus in patients with glycogenic acanthosis, a common
However, the plaques of glycogenic acanthosis are usually seen in
the upper or midesophagus in a random distribution. In this
disorder, glycogen is accumulated in the cytoplasm of cells in the
upper portion of the squamous epithelium. Glycogenic acanthosis
typically occurs in elderly individuals who have no esophageal
symptoms and who do not have a history of immunosuppression or a
condition predisposing to stasis. In contrast, patients with
esophagitis are usually symptomatic, and the plaques tend to be
more linear in shape and aligned longitudinally along the
In some patients with reflux esophagitis, tiny mucosal nodules
are seen (figure 6).
However, these nodules are more ill-defined and less discrete than
the plaques in
esophagitis. The nodules of reflux esophagitis also are more
confluent and are located in the distal esophagus, usually in
patients with gastro-esophageal reflux and hiatal hernias. Reflux
esophagitis is more frequently characterized by poorly defined tiny
mucosal elevations, termed mucosal "granularity" (figure 6B).
This granularity may be associated with tiny or linear ulcers and
thickened, nodular folds. These changes are also usually associated
with a hiatal hernia and fluoroscopically detected gastroesophageal
reflux. Some patients with reflux esophagitis have such severe
inflammation that plaque-like pseudomembranes may eventually form.
A focal area of confluent mucosal nodularity may be worrisome
for superficial spreading carcinoma, a cancer confined to the
mucosa and submucosa (figure 7).
However, the nodules are not as discrete as those in
esophagitis, nor are they separated by normal intervening mucosa.
Although most focal areas of mucosal irregularity will probably be
caused by glycogenic acanthosis, an area of focal mucosal
nodularity should be biopsied to exclude superficial spreading
It is also difficult to distinguish a focal area of mucosal
nodularity from the surface pattern termed "reticular mucosa,"
which is seen in Barrett's esophagus.
Barrett's esophagus is an acquired condition in which there is
progressive columnar metaplasia of the esophagus due to
long-standing gastroesophageal reflux disease. The reticular
mucosal pattern resembles the areae gastricae of the stomach, with
a fine, net-like web of barium-filled grooves surrounding small
tufts of mucosa (figure 8).
Abnormal esophageal folds
The longitudinal folds of the esophagus are composed of mucosa
and submucosa and are best seen when the esophagus is
underdistended. Therefore, abnormalities of folds reflect disease
in the mucosa and submucosa (Table 3). In patients with reflux
esophagitis, thickened esophageal folds are frequently seen when
the esophagus is collapsed.
These patients usually have other findings of reflux disease,
including gastro-esophageal reflux, a granular mucosa, and hiatal
hernia. In contrast, esophageal varices are serpentine, with a
smooth surface (figure 9). Varices may change in size with varying
degrees of esophageal distention and patient position. If the folds
are rigid, fixed, or irregular, however, the varicoid form of
squamous cell carcinoma must be excluded (figure 10).
The differential diagnosis of an esophageal stricture depends on
the morphology and location of the stricture as well as on the
clinical history. Benign strictures typically manifest as smooth,
tapered areas of concentric narrowing (figure 11).
Asymmetric scarring may result in sacculation, flattening, or other
deformity of the wall. In contrast, malignant strictures are
manifest as eccentric narrowings, thicker on the side where the
The mucosal surface is irregular, with nodules of varying size
disrupting the surface and barium being trapped in areas of
ulceration. The margins of malignant strictures often appear abrupt
and shelf-like (figure 12). Unlike malignant lesions in the colon,
however, malignant esophageal lesions may have sloped or tapered
margins, as the soft esophageal submucosa and muscularis propria
provide little resistance to the longitudinal spread of tumor. In
some patients, a plaque-like indentation of the lumen is seen
(figure 13). If any mucosal irregularity or plaque-like flattening
is identified in the region of an esophageal stricture, endoscopy
and biopsy are required to exclude carcinoma.
The most common causes of short distal esophageal strictures are
gastroesophageal reflux and carcinoma (Table 4; figures 11 and 14).
Long distal esophageal strictures are often due to severe acid
exposure related to Zollinger-Ellison syndrome, prolonged
nasogastric intubation, or alkaline reflux esophagitis (Table 4).
Some patients with Crohn's disease may also develop long distal
esophageal strictures. A wide variety of conditions cause
midesophageal strictures (Table 4).
The combination of the clinical history, physical examination
findings, and radiographic appearance of the strictures often
enables a specific diagnosis.
Strictures related to reflux esophagitis are usually seen in the
distal esophagus. Some reflux-induced strictures are smooth and
tapered (figure 11). However, other reflux-induced strictures are
associated with enough asymmetric scarring to cause sacculation in
the area of tapering. These sacculations due to scarring should not
be confused with ulcers. Other reflux-induced strictures may be
associated with such severe scarring and esophageal shortening that
a hiatal hernia is even present in the erect position.
In the presence of a hiatal hernia and gastroesophageal reflux,
a benign-appearing midesophageal stricture or reticular pattern
should be strongly suggestive of Barrett's esophagus.
Strictures associated with Barrett's esophagus are more frequently
seen in the distal esophagus, however. Patients with distal
esophageal strictures and reflux changes have a moderate risk of
Barrett's esophagus, between 20% and 40%.
Patients with reflux esophagitis alone have about a 10% risk of
Conversely, a very low risk of Barrett's esophagus is present if
the esophageal mucosa is smooth, if a stricture is not seen, and if
only gastroesophageal reflux or a hiatal hernia is present.
Schatzki rings are of unknown etiology, possibly related to
gastro-esophageal reflux. They are thin (1 to 3 mm in thickness),
symmetric rings at the esophagogastric junction, frequently seen
above a small hiatal hernia (figure 15).
Schatzki rings are best demonstrated in the prone position and are
sometimes detected only with a solid bolus.
Rings <13 mm in luminal diameter invariably cause dysphagia,
whereas rings 13 to 20 mm in luminal diameter may or may not cause
Acute radiation damage causes small ulcers, mucosal granularity,
and abnormal peristalsis.
Chronic radiation strictures are usually smooth and tapered.
Caustic ingestion can result in one or more long strictures in
esophagus or diffuse esophageal narrowing. Stricture formation
occurs as early as 4 to 6 weeks after ingestion of a caustic agent.
Any irregularity in a long-standing lye stricture should be
suspicious for esophageal carcinoma until proven otherwise.
In the classic form of esophageal intramural
pseudodiverticulosis, numerous 1- to-3-mm flask-shaped outpouchings
are associated with a long cervical or upper thoracic esophageal
stricture (figure 16).
In the more common form of esophageal intramural
pseudodiverticulosis, however, the outpouchings are associated with
a short, distal, reflux-induced stricture.
Primary or metastatic cancers are frequent causes of
midesophageal strictures. Some squamous cell carcinomas have an
elongated, circumferentially infiltrating appearance (figure 12).
An eccentric, annular lesion may be seen with a coarsely lobulated
contour and barium trapped within tumor nodules. Adenocarcinomas of
the esophagus arise in dysplastic columnar epithelium within
Barrett's mucosa. Adenocarcinomas are found most frequently in the
distal esophagus. Adenocarcinomas can have an infiltrative (figure
14), plaque-like (figure 13), ulcerative, or polypoid appearance.
Unlike squamous cell carcinomas, adenocarcinomas have a marked
tendency to invade the gastric cardia and fundus. Metastases to the
esophagus most frequently involve the subcarinal region due to
direct invasion by tumor from subcarinal lymph nodes (figure 17) or
from the left mainstem bronchus.
Polypoid intraluminal masses
A wide variety of polypoid masses are seen in the esophagus
Polypoid masses are demonstrated radiographically as radiolucent
filling defects in the barium pool (figure 18) or as barium-etched
lines within the esophageal lumen. Polypoid masses must first be
distinguished from foreign bodies (figure 19). The clinical history
is crucial for the diagnosis of foreign bodies. These patients
typically complain of abrupt-onset dysphagia or odynophagia during
eating and the sensation that food is stuck in the substernal
region. The polypoid filling defect of the foreign body may be
associated with an irregular meniscus of barium superiorly.
Perforation is uncommon, usually occurring after the impaction has
been present longer than 24 hours. A repeat esophagram should be
performed after the foreign body has been removed to exclude an
esophageal stricture or motor disorder as the cause of the food
Squamous papillomas are the most common benign mucosal tumor of
the esophagus (figure 18), appearing as small, sessile, slightly
lobulated polyps. The esophagus is one organ of the
gastrointestinal tract in which true leiomyomas form. Most tumors
arising in the mesenchyme are undifferentiated gastrointestinal
stromal tumors of unknown malignant potential. Leiomyomas, however,
are true proliferations of smooth muscle and are the most common
submucosal mass in the esophagus. Granular cell tumors are another
rare cause of submucosal masses in the esophagus.
Polyps at the esophagogastric junction are frequently related to
chronic gastroesophageal reflux disease, termed "inflammatory
esophagogastric" or "sentinel" polyps.
These polyps are smooth-surfaced enlargements atop a thickened
rugal fold at the gastric cardia. If any surface irregularity is
seen, however, endoscopy must be performed to exclude a malignant
tumor at the cardia or in Barrett's esophagus.
Some squamous cell carcinomas have a polypoid (figure 20) rather
than infiltrating appearance.
Small cell carcinomas are rare tumors that typically manifest as
small, centrally ulcerated masses in the midesophagus.
Spindle cell carcinomas are usually large, polypoid masses that
expand the esophageal lumen without causing significant
Despite the relatively noninfiltrating appearance of spindle cell
carcinomas, 5-year survival rates in these patients are as dismal
as in those patients with squamous cell carcinomas. Rarely, primary
malignant melanoma of the esophagus may be manifest as a bulky,
polypoid intraluminal mass indistinguishable from spindle cell