Alimentary Tract (Esophagus, Stomach, Small Intestine, colon, Rectum, Anus, Biliary Tract)
Fig. 14.16 Chemotherapy-induced glandular atypia. A gastric brushing.
The enlarged nuclei have distinct but rather smooth membranes, vesicular
chromatin, and prominent nucleoli. The voluminous cytoplasm contains
large cytoplasmic vacuoles (Papanicolaou x HP).
Fig. 14.17 Adenomatous polyp—gastric. This brushing from an
adenoma includes cells with elongated, pseudostratified hyperchromatic
nuclei (Papanicolaou x MP).
and the chromatin was uniformly dispersed. Another common
nuclear feature was the presence of one or more huge nucleoli.
The atypical cells were frequently multinucleated.
Although a number of benign exophytic lesions occur in the
stomach, the two most important ones are hyperplastic polyps
and adenomas. The former are small, benign, non-neoplastic
lesions. They may be solitary or more often multiple and are
associated with only a minimally increased risk for carcinoma.
Histologic features include elongation of the pits, prolifera-
tion of slender smooth muscle cells, and eroded tips; the last
feature is associated with regenerating epithelium and acute
inflammation. Brushing smears contain glandular cells with
prominent reparative atypia, neutrophils, and necrotic debris.
The smears are indistinguishable from those obtained from
the edge of a peptic ulcer. Adenomas, on the other hand, are
composed of dysplastic glandular cells and are associated with
a significantly increased risk of adenocarcinoma. In brushings,
the dysplastic elements should fully resemble those that may be
seen in atrophic gastritis. Large cohesive papillary-like fragments
of these cells are present. In cytologic brushings the nuclei are
hyperchromatic, elongated, and pseudostratified (Fig. 14.17).
Although the incidence of gastric adenocarcinoma is declin-
ing worldwide, it remains one of the more common forms of
malignancy.137 In the 1930s, it was the number one form of
cancer in the United States, but its frequency has declined pro-
gressively since then. Its exact etiology and the reasons for these
reductions are unknown. It is quite possible that the causes and
pathogenesis of carcinoma occurring in the gastric cardia dif-
fer from those occurring more distally.76,137 Despite the overall
decline in incidence of this tumor in the stomach, the frequency
of carcinoma of the cardia is increasing.137 This latter form of
neoplasia appears to be closely related to Barrett's-associated
carcinoma.78,82 As with esophageal squamous carcinoma, there
is a marked variability in the incidence from country to coun-
try. Thus, mostly environmental and to a lesser extent heredi-
tary factors have been implicated. Dietary factors may be quite
important, especially diets high in salt content and consump-
tion of smoked meats. Predisposing conditions include atrophic
gastritis with intestinal metaplasia and a prior gastrectomy. The
latter situation may be related through the presence of atrophic
gastritis in the gastric stump. As in Barrett's esophagus, glandu-
lar dysplasia is probably the intermediate morphologic stage.
Although adenocarcinoma of the stomach may rarely occur
in children, this is predominantly a disease of middle-aged
and older adults. Symptoms, which are usually associated with
advanced tumors, are nonspecific and include nausea, heart-
burn, anorexia, and general weakness. In many instances, weight
loss accompanies the symptom complex. Early carcinomas are
Grossly and endoscopically, adenocarcinomas can be divided
into two major forms: early and advanced. Early carcinomas refer
to neoplasms confined to the mucosa or submucosa independ-
ent of the status of regional lymph nodes. Although uncommon
in most of the Western world, early carcinoma may represent up
to one-third or more of all tumors in Japan, where active surveil-
lance programs exist. Early carcinomas are generally small and
appear as only slightly elevated or excavated mucosa. Most of the
more advanced carcinomas present as either a polypoid mass or
an ulcer. It is the latter type that may be difficult to distinguish
from a peptic ulcer. As described by Lauren, there are two major
histologic forms of gastric adenocarcinoma.139 The intestinal or
gland-forming variant occurs much more frequently. It is charac-
terized by the growth of glandular structures lined by malignant
columnar cells. They are usually graded as well or moderately
differentiated. The less common diffuse form shows little in
the way of lumen-containing glandular structures. The majority
are composed of signet ring cells that infiltrate in small nests
and singly, often associated with a desmoplastic host response.
The individual cells are dominated by huge cytoplasmic mucin
vacuoles that displace and distort the single malignant nucleus
to one pole, forming a signet ring cell. Characteristically, the
vacuole indents the nucleus, creating sharply pointed tips. Both
histologically and cytologically, these malignant cells must
be distinguished from benign glandular cells and histiocytes.
Advanced gastric adenocarcinoma carries a poor prognosis, with
no more than 15% of patients surviving for 5 years. Overall, the