Alimentary Tract (Esophagus, Stomach, Small Intestine, colon, Rectum, Anus, Biliary Tract)
Cytologic specimens
are dominated by small
neoplastic cells.63,102 Each cell possesses a single round, ovoid,
or fusiform nucleus with inconspicuous nucleoli. Other char-
acteristic features include very darkly stained, finely to coarsely
granular, and evenly distributed chromatin and exceedingly
high N/C ratios. Both individual and aggregated neoplastic cells
may be present. The latter may include chains, densely packed
nests, and rarely rosette-like structures. Within the aggregates,
the nuclei are crowded and often appear to overlap one another
with indistinct cell borders. Compression of adjacent nuclei
may be evident. By immunocytochemistry, the malignant cells
are generally positive for both epithelial and neuroendocrine
The cytologic differential diagnosis of esophageal small cell
carcinoma includes metastases from elsewhere in the body,
high-grade squamous cell carcinoma, and malignant lympho-
mas. If a small-cell malignancy is known or suspected of hav-
ing originated in a different organ, then an esophageal origin
should not be ascribed. As metastases from the lung are more
common, a TTF-1 stain is a useful marker in this regard. How-
ever, the cytologic picture could be totally indistinguishable.
Lymphoma cells should have more discernible nucleoli but do
not manifest any evidence of intercellular cohesion or nuclear
molding. In poorly differentiated squamous cell carcinoma, at
least a small fraction of the neoplastic elements are larger, have
a greater volume of cytoplasm, have better developed nucleoli,
and manifest more pleomorphism than in small-cell carcinoma.
Neuroendocrine differentiation should not be evident in either
lymphoma or squamous cell carcinoma.
Miscellaneous Malignant Neoplasms
The initial presentation of a malignant lymphoreticular neo-
plasm in an esophageal cytologic specimen is most unusual.
Fulp et al. presented the clinical and morphologic features of
three adult patients with acute myeloblastic leukemia who pre-
sented with dysphagia unrelated to infections, reflux esophagitis,
or chemotherapy-induced mucocytis.103 During their evaluation,
the patients underwent both endoscopic biopsies and brush-
ings. In all three, the cytologic specimens contained numerous
isolated malignant leukocytes. Leukemic blasts were easily rec-
ognized by their round nuclei, prominent nucleoli, and very
high N/C ratios. Two of the patients had the M4 form of dis-
ease; a large proportion of the tumor cells had somewhat more
irregularly shaped nuclei and somewhat greater volumes of
cytoplasm, consistent with monocytoid differentiation. One to
four small nucleoli were apparent within the evenly distributed,
moderately stained chromatin. There was a distinct absence of
intercellular cohesion and nuclear molding. In all three patients,
the concurrently obtained biopsies also revealed leukemic infil-
trates of the esophageal mucosa.103 In the evaluation of brushing
specimens from patients with known or suspected leukemia, the
cytologist should look for the common morphologically iden-
tifiable causes of esophagitis, namely fungi and virocytes. How-
ever, the inflammatory infiltrates should not be ignored. Higher
magnification makes it possible to differentiate between benign
reactive and malignant leukocytes. If it is the latter, they may
explain the patient's symptoms.
Primary melanoma of the esophagus is an exceedingly unusual
neoplasm.104 The clinical presentation and endoscopic appear-
ance probably will not provide any specific clues. Cytologic sam-
ples, on the other hand, may be fully diagnostic.53,105 Cutaneous
melanomas metastatic to the esophagus may also rarely be
recognized in cytologic specimens.106,107 The cytologic presenta-
tion basically reflects the histologic diversity of melanoma but
usually is easily recognized as malignant. The smears may be cel-
lular and include both solitary cells and small loosely cohesive
clusters. The size of the neoplastic cells may vary tremendously.
Marked variations in cellular configurations may also be seen,
although the majority of the malignant cells are rounded. They
have distinct cellular borders and cyanophilic cytoplasm. When
recognizable, melanin appears as distinct dark brown intracy-
toplasmic granules or as minute particles that convey a dusky
appearance. The malignant melanocytes have one or more large
eccentrically positioned nuclei with thick nuclear membranes
and huge nucleoli. Nuclear pseudoinclusions, although infre-
quent, are characteristic (Fig. 14.11). The neoplastic cells should
be positive for melanoma markers (S-100 protein, HMB-45, and
Melan-A) by immunocytochemistry. Although the lack of cohe-
sion, eccentric nuclei, macronucleoli, and cytoplasmic pigment
granules all are quite suggestive of melanoma, in an individual
specimen, it may be very difficult to distinguish this rare neo-
plasm from either a high-grade adenocarcinoma or squamous
cell carcinoma.
Exceptionally, neoplasms resembling soft tissue sarcomas
and primary malignant germ cell tumors may present in esopha-
geal cytologic specimens.108,109 Metastases, sometimes clinically
unsuspected, may also be identified in smears.13,106
normal Histology and cytology
Through the use of grossly visible anatomic landmarks, the
stomach may be divided into four major regions. The cardiac
portion is immediately contiguous with the distal esophagus
and empties into the body of the stomach. It is controver-
sial whether the cardia is a normal part of the stomach or is
acquired in relation to inflammation.110 However, this specific
topic is beyond the realm of this chapter. The body constitutes
the greatest proportion of mucosal surface. The fundus is that
portion superior to an imaginary horizontal line drawn through
the cardiac opening. The distal-most portion of the stomach is
Fig. 14.11 Metastatic melanoma to esophagus. This brushing of
metastatic melanoma contains neoplastic spindle-shaped cells, many of
which contain chunky intracytoplasmic pigment (Papanicolaou x HP).
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