14
Alimentary Tract (Esophagus, Stomach, Small Intestine, colon, Rectum, Anus, Biliary Tract)
Table 14.2 Cytologic Differential Diagnosis of Esophageal Viral Infections
Feature
HSV
CMV
Cell type infected
Squamous
Stromal, glandular
Multinucleation
+
-
Ground-glass chromatin
+
-
Cytoplasmic inclusions
-
+
%
Fig. 14.5
Aspergillus.
Compared to
Candida,
the hyphae of Aspergillus
are thicker and cyanophilic, and show true septation and 45° acute angle
branching (Papanicolaou x HP),
Other Infections
Primary bacterial infections seem to be infrequent causes of
clinically apparent esophagitis.53 Usually, the causative organ-
isms are saprophytes that affect individuals who have been on
long-term antibiotic therapy or who are immunosuppressed.
In cytologic specimens, specific identification cannot be made.
Bacteria are also seen in smears from individuals with esophagi-
tis due to other causes. Whether these bacteria are simple con-
taminants or are contributing to the pathogenesis of disease is
unknown. It is prudent to mention in the cytology report that
bacteria are present in the smears.
Candida
aside, it is rare for
other fungi to produce clinical esophagitis. Rare cases of esopha-
geal
Aspergillosis
in cytologic brushings have been reported in
immunocompromised patients (Fig. 14.5).68 Additionally a rare
case report of esophageal disease resulting from trichomonias in
AIDs patients has also been published.69
The role of human papillomavirus (HPV) in the pathogenesis
and diagnosis of premalignant disorders of the female genital
tract is well known to all practicing cytologists. Recently, squa-
mous cell lesions of the esophagus have been associated with
HPV infection.70,71 Rarely, the cytomorphologic features of HPV
infection of the esophagus have been reported.72
Radiation and chemotherapy-Associated
esophagitis
Inflammation of the esophagus is an unfortunate but frequent
complication of radiation therapy to the chest and mediasti-
num.73 Although susceptibility varies from patient to patient,
the severity of injury is generally related to the total dose of radi-
ation given, the fraction delivered per treatment session, and the
time course over which the therapy is provided.1
Many cytotoxic
f §
*
Fig. 14.6 Radiation atypia. Scattered cells from radiation atypia are
characterized by nuclear and cytoplasmic enlargement with low N/C ratios
and degenerative changes (Papanicolaou x MP.)
chemotherapeutic agents may also injure the esophagus in a
similar manner. In fact, the effects of radiation and chemother-
apy may potentiate each other, lowering the threshold for injury.
The histopathologic picture of radiation and chemotherapy-
associated esophagitis includes the presence of large, bizarre-
appearing squamous epithelial cells characterized by increased
volumes of cytoplasm and nucleoplasm with the retention of
a relatively normal N/C ratio. With toxic radiation exposure,
the chromatin typically appears pale or washed-out rather than
hyperchromatic. Nucleoli also tend to be minimally developed.
Conversely, both hyperchromasia and huge nucleoli are more
likely with certain chemotherapy agents. Within the epithelial
layer, the number of mitotic figures are increased compared with
normal. In addition, they may be present in higher than nor-
mal positions in the epithelium and may have abnormal con-
figurations. Additionally, highly atypical-appearing stromal cells
characterized by enlarged, hyperchromatic, and irregular nuclei
may populate the lamina propria and the muscle layers.
The
cytomorphologic
features
of radiation
esophagitis
include prominent but relatively proportionate nucleomegaly
and cytomegaly with a retention of a relatively normal N/C
ratio.1
Vacuolization of the nuclei and cytoplasm, irregularities
in the nuclear membranes, and multinucleation all are features
that may be seen in cytologic specimens (Fig. 14.6). For the most
part, chromatin is very finely granular or almost structureless
and pale staining. On the other hand, in chemotherapy-related
esophagitis, nucleoli may be quite prominent and the chroma-
tin more coarsely granular and darkly stained. In both of these
therapeutic situations, the N/C ratios may fall within the range
of those seen in well- to moderately differentiated squamous
cell carcinomas. On a cell-for-cell basis, individual elements in
smears from such patients without carcinoma may be indistin-
guishable from malignant epithelial elements. In this situation,
these elements must be examined in the context of the entire
specimen and integrated with a good clinical history.
Key features of radiation esophagitis
• Nucleomegaly and cytomegaly with relatively normal
N/C ratios;
• Cytoplasmic and nuclear vacuoles;
• Multinucleation; and
• Irregularities in nuclear outlines.
379
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