Alimentary Tract (Esophagus, Stomach, Small Intestine, colon, Rectum, Anus, Biliary Tract)
who have received systemic chemotherapy and/or irradiation
for treatment of malignancy. Other common groups of patients
include those who have received steroids or a transplanted organ.
Endoscopically and microscopically,
typically produces
a pseudomembrane that covers and is attached to the squamous
mucosa. Varying degrees of neutrophilic infiltrates and damage
to the epithelium may also be seen in biopsy specimens. It is
not infrequent that biopsies contain only inflammatory exudate
without any evidence of fungus or intact mucosa. Usually, the
cytologic diagnosis of
esophagitis is straightforward in
that the pseudohyphae are easily recognized.1,53 In Papanicolaou-
stained smears, the pseudohyphae are delicate and magenta, and
lack true septation. Rather, indentations along their long axes
("sausage-link chains") may be apparent. The smaller round
budding yeast cells are more difficult to find but are typically
present. In addition to lying free within the smear, the fungal
elements may be found trapped within an acute inflammatory
exudate and/or infiltrating the squamous epithelium (Fig. 14.3).
The changes of repair are often but not invariably present in the
smear background. One should almost never need to resort to a
methanamine silver stain for their detection. When the clinical
picture or presentation is suspicious for
infection but
the fungal elements are not evident in the smears, one should
very carefully search the necroinflammatory debris.
Key features of
C a n d id a
• Pseudohyphae and/or budding yeast;
• Acute inflammation (examine carefully); and
• Repair.
Compared with malignant neoplasms, it is not nearly as
widely recognized that biopsies and cytology are diagnostically
complementary in the evaluation of patients with inflammatory
esophageal conditions. However, the two sampling techniques
each provide important data in these non-neoplastic condi-
tions. Generally, cytologic preparations are more sensitive for
the detection of
than are concurrently obtained biop-
sies probably as
typically is concentrated at or near the
mucosal surface and thus is readily accessible to sampling by the
Fig. 14.3
A loose cluster of benign squamous cells is punctured
by pseudohyphae of
organisms. Scattered yeast forms
(spores) are present in the background (Papanicolaou x HP).
Herpes Esophagitis
The most frequent known cause of viral esophagitis is herpes
simplex virus (HSV). Predisposing conditions include mucosal
trauma (e.g. nasogastric intubation), cancer (especially lym-
phoreticular malignancies), treatment with cytotoxic agents,
radiation, and other immunodeficiency conditions including
the acquired immunodeficiency syndrome (AIDS).1,62 Occasion-
ally, symptomatic herpetic esophagitis is diagnosed in other-
wise apparently healthy individuals. Herpes esophagitis often
resolves spontaneously, even in immunocompromised individ-
uals. The classic endoscopic appearance of herpes esophagitis is
that of multiple small, shallow ulcers with sharply punched-out
edges in the distal third of the esophagus. In other instances,
there may be more extensive mucosal sloughing or a nonspe-
cific inflammatory picture. It is important for the endoscopist to
sample the edges of ulcers to diagnose a herpes infection.
Squamous epithelial cells are the prime target of HSV, and
therefore the major alterations are evident within these cells.
Basically, two types of viral cytopathic changes may be evident
in biopsies. In one, classic Cowdry type A eosinophilic inclusion
bodies are separated from a thick nuclear membrane by a clear
zone or halo. The other virocyte is characterized by a homoge-
neous, faintly basophilic chromatin appearance. In both types
of virocytes, the nuclei and the cytoplasm are increased in vol-
ume, but the N/C ratios are not always elevated. Furthermore,
multinucleation of the infected squamous cells is also character-
istic. Within these elements, the nuclei are typically compressed
against one another. Only a small proportion of all of the squa-
mous cells present may be so altered, requiring a careful search.
The cytologic diagnosis of herpes esophagitis is generally
straightforward in that the cytomorphologic picture mirrors that
seen in the tissue specimens.1,53 The virocytes appear as enlarged
squamous epithelial cells, both singly and in flat groups. The
enlarged nuclei may contain inclusion bodies. Typically, these
inclusions are round to irregular in shape and centrally posi-
tioned. The nuclear membrane is thickened and may appear
beaded, presumably a sign of degeneration. A broad clear halo
occupies the space between the membrane and the inclusion
body. More commonly, the chromatin has a smooth or homo-
geneous, pale basophilic appearance (Fig. 14.4). At times, it has
an almost refractile presentation, resulting in the "ground-glass"
descriptive terminology. Multinucleated squamous cells are fre-
quently seen in the smears and show characteristic compression
or molding of the enlarged nuclei. The cytoplasm of the infected
squamous cells may appear scanty, dense, and cyanophilic. As
ulcers are frequently present, the changes of a well-developed
reparative atypia are also often present. Neutrophils in granular
necrotic debris complete the picture.
Key features of herpes esophagitis
• Squamous cells with increased cytoplasmic
and nuclear volumes;
• Intranuclear inclusion bodies surrounded by a halo
and thickened nuclear membrane;
• Ground-glass chromatin; and
• Multinucleation, nuclear molding.
Owing to the large size of the virocytes and their nuclei, the
cytomorphologic differential diagnosis of herpes esophagitis
includes squamous cell carcinoma. In the virally infected cells,
the ground-glass chromatin is actually pale and agranular,
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