Diagnostic Cytology
Key features of repair
• Preservation of intercellular cohesion;
• Retention of polarity; streaming;
• Enlarged nuclei with smooth contours and finely
granular chromatin;
• Macronucleoli; and
• Mitotic figures.
Normal Histology and Cytology
Almost the entire length of the esophagus is lined by a non-
keratinizing stratified squamous epithelium. The distal most
1-2 cm may be lined by a simple columnar cell epithelium with
or without mucus production.58 Immediately beneath the epi-
thelium is the lamina propria, which consists of loose connec-
tive tissue. Throughout the entire length of the esophagus, the
lamina propria contains glandular structures that histologically
resemble those present in the cardiac portion of the stomach;
these secrete predominantly neutral mucins. The submucosa of
the esophagus contains glandular structures that empty their
secretions into the esophageal lumen via ducts lined by strati-
fied squamous epithelium; acidic mucins predominate. Goblet
cells are not present normally in the esophagus or stomach.
Accordingly, cytologic specimens from the esophagus are
dominated by squamous epithelial cells of the superficial and
intermediate types. The former are characterized by abundant
delicate eosinophilic cytoplasm, polygonal contours, and a
solitary centrally positioned pyknotic nucleus. Very infrequent
cells may also possess keratohyalin granules. According to Shen
and co-workers, the vast majority of the cells have an intermedi-
ate level of maturation.41 Their nuclei thus are larger and have
Table 14.1 Cytomorphologic Differential Diagnostic Features ofEpithelial
Repair Versus Malignancy in Gastrointestinal Cytology
Epithelial repair
Groups of cells
Groups of cells
Rare single cells
Many intact single cells
Flat metaplastic sheets
maintaining honeycomb
Syncytial arrangement pattern
Distinct cytoplasmic borders
Variable to indistinct cytoplasmic
Cellular polarity maintained
Loss of polarity
Enlarged nuclei
Enlarged nuclei
Round-to-oval nuclei with smooth
nuclear borders
Irregular nuclear borders
Uniform nuclei
Variably sized nuclei
Vesicular and hypochromatic to
mildly hyperchromatic with even
chromatin distribution
Opaque to hyperchromatic nuclei
with irregular chromatin distribution
and parachromatin clearing
Nucleoli may be prominent
Nucleoli often irregular in shape
Normal mitotic figures
Normal and abnormal mitotic
No diathesis unless ulcer is present
Clear background or tumor
finely granular chromatin and possibly small chromocenters.
Generally, nucleoli are not evident. Both types of squamous
cells are present in large flat sheets, in small clusters, in concen-
tric arrangements ("pearls"), and as solitary cells. Rarely, smears
may also contain parabasal cells, presumably the result of very
vigorous sampling. These typically appear as single cells with
round or ovoid contours with dense cyanophilic cytoplasm and
relatively high N/C ratios.
Glandular elements may also be present in normal esopha-
geal brushings, the consequence of either inadvertent sampling
of the stomach and/or procurement of columnar cells that may
normally be present in the distal most esophagus. These cells
are present in small to large, generally flat sheets with sharply
defined edges, distinct cellular borders, and small round nuclei
with finely granular, pale-staining chromatin and inconspicu-
ous nucleoli. Their cytoplasm is delicate and finely granular;
large vacuoles are not evident (Fig. 14.2).
Several contaminants may be seen in otherwise totally unre-
markable smears. These include ciliated respiratory columnar
cells, pigment-containing alveolar macrophages, meat fibers,
plant cells, and microbes from the oral cavity.
infectious Esophagitis
The most common forms of esophageal disorders that mani-
fest clinically are the various forms of inflammation.59 Patients
may present with dysphagia, odynophagia, heartburn, or severe
chest pain. By far, the most common cause of esophagitis is
gastroesophageal reflux disease (GERD). Although the clinical
and radiologic features may suggest a specific cause in a given
patient, the cytomorphologic findings of the esophagitides are,
for the most part, totally nonspecific. The major exceptions are
the infectious esophagitides that may produce characteristic
morphologic features in cytologic preparations.
By far,
Candida albicans
is the most frequent cause of clinically
significant infectious esophagitis. The vast majority of patients
with this infection are immunosuppressed. Commonly, it is
diagnosed in patients with leukemia or lymphoma or those
Fig. 14.2 Barrett's esophagus. Benign glandular cells on the right
compared with those showing reparative atypia on the left. In the latter, the
nuclei are larger, nucleoli more evident, cell borders indistinct, and N/C ratios
increased (Papanicolaou x HP).
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