Alimentary Tract (Esophagus, Stomach, Small Intestine, colon, Rectum, Anus, Biliary Tract)
Table 14.4 Cytomorphologic Differential Diagnosis of Glandular Lesions in Barrett's Esophagus and the Stomach
Adenocarcinoma (intestinal type)
Cellular aggregates
Large, smooth edges, normal polarity
Small, frayed edges, altered polarity
Small, frayed edges, altered polarity
Individual cells
Rare to absent
Few to many
Nuclear contours
Smooth, round to oval
Slight irregularities, elongated
Slight to prominent irregularities
Large, prominent, smooth
Large, angulated
N/C ration
Normal to slightly increased
Slightly to moderately increased
Slightly to greatly increased
correlated with increasing grade of dysplasia in patients with
Barrett's esophagus.91 This may be useful in surveillance of
selected populations.
Key features of Barrett's glandular dysplasia and
• Reduced intercellular cohesion: small cellular
aggregates with frayed borders, individually dispersed
abnormal cells;
• Loss of polarity with irregular distribution of crowded,
overlapped nuclei;
• Indistinct cell borders;
• Nuclei: thickened membranes with contour
irregularities, pleomorphism, hyperchromasia, large
nucleoli; and
• Greater degrees of changes in carcinoma than in
dysplasia, including increased numbers of single ab-
normal cells.
The diagnostic accuracy of cytology for esophageal adenocar-
cinoma ranges from 72 to 100%, with a weighted mean yield
of 84% in published series.80,92,93 These corresponding biopsies
have diagnostic accuracies from 67 to 100% with a weighted
mean yield of 79%. When both cytology and biopsies are com-
bined, the yield ranged from 88 to 100% with a combined
weighted mean yield of 91%. Another recent study by Saad et al.
supports the high degree of diagnostic accuracy of cytology for
the diagnosis of Barrett's associated high-grade dysplasia and/or
carcinoma and moderate sensitivity for Barrett's esophagus.94
It is the recognition that benign Barrett's metaplasia progresses
through an intermediate morphologic stage of glandular dys-
plasia prior to developing into early and advanced adenocarci-
noma that has led to the development of surveillance programs
in patients with Barrett's esophagus.77,79,81,95,96 To date, almost all
of these have involved numerous endoscopic biopsies procured
throughout the length of the metaplastic esophageal segment.
Only a minority of these programs have included brushing
cytology as well. The authors believe that brushing cytology has
considerable use in this setting because it allows for greater sam-
pling of the mucosal surface than more directed surgical biop-
sies.37,97 Utilization of nonendoscopic abrasive sampling of the
esophagus in this patient population has been considered.37
Squamous cell carcinoma
The most frequent malignant neoplasm in the esophagus is
squamous cell carcinoma, accounting for approximately 85%
of all malignancies of this organ. In the United States, there is
an incidence of approximately 2.5 cases per 100,000 individuals
in the population, yielding an incidence of nearly 12,000
cases each year. Within this country, demographic groups dif-
fer greatly in their risk for developing this tumor. Blacks are 4.5
times more likely to develop this cancer than are whites, and
this racial difference appears to be widening even further. Men
are also more likely than women to develop this malignancy.
In whites, the male-to-female ratio is 3:1; in blacks it is 4:1. In
the United States, this cancer is highly lethal, with 5-year sur-
vival rates approximately 10%, largely because these tumors are
usually detected late in their course.
Worldwide, there is a remarkable variation in incidence rates.
Over half of all cases occur in China, but even within that nation,
there are marked regional variations. Similarly, both high and
low rates are intermingled in South Africa and Iran. Epidemi-
ologic studies have pointed to environmental factors as being
crucial in the development of most instances of this neoplasm.
High levels of dietary nitrates and nitrites are suspected etiologic
factors. Both can be enzymatically converted by the body to car-
cinogenic nitrosamines. Low dietary levels of vitamins A, C, E,
and riboflavin are especially prevalent in the regions of China
with the highest cancer rates. Low levels of zinc and selenium
have also been implicated. In many parts of the Western world,
including the United States, heavy tobacco use and alcohol abuse
are strongly implicated as etiologic factors. The risk of cancer
increases as the amount of alcohol and the number of cigarettes
consumed increases. Caustic injury to the mucosa, as may occur
with lye ingestion, increases long-term risk. Recently, it has been
suggested that HPV may also have a role in some individuals.
Although most common in the middle portion of the esopha-
gus, squamous cell carcinoma may arise at any site along the
entire length of the organ. Endoscopically, they may present as
large fungating polyploid masses, deep irregular ulcers, or flat
mucosal elevations. Frequently, the luminal caliber is markedly
reduced; the stenosis may be so tight that biopsy forceps may
not be able to reach the neoplasm adequately.
Histologically, squamous cell carcinoma can be divided
into three grades, with the well-differentiated neoplasms
most closely resembling normal squamous epithelium. The
presence of voluminous cytoplasm, well-developed keratini-
zation, and distinct intercellular bridges correlate with better
differentiated neoplasms. In the well-differentiated carcino-
mas, many of the nuclei have a dense pyknotic-like chromatin
pattern. In the more poorly differentiated squamous carcino-
mas, the chromatin is more finely granular with areas of chro-
matin clearing. Furthermore, large prominent nucleoli tend to
occur in the more poorly differentiated malignancies. Overall,
N/C ratios are much higher in the high-grade carcinomas. As
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