PART TWO
Diagnostic Cytology
in the uterine cervix, when carcinoma does not invade into
the underlying lamina propria, the diagnosis of carcinoma in
situ is made.
The cytologic picture in brushings from
patients with
squamous cell carcinoma reflects the underlying histologic
grade.1,43,53 In well-differentiated carcinomas, intercellular cohe-
sion is relatively well maintained. Accordingly, smears contain
sizable aggregates of large tumor cells that have abundant dense-
appearing cytoplasm (Fig. 14.10A). With the Papanicolaou
reaction, many of the neoplastic cells may have orangeophilic
cytoplasm. Typically, their nuclei are centrally positioned and
have sharply angulated contours. The chromatin is character-
istically very hyperchromatic and coarsely granular or almost
pyknotic in quality. Keratin pearls, elongated cellular configura-
tions (tadpole cells), and numerous anucleated squames may be
present as well. In the less differentiated squamous cell carcino-
mas, the smears typically contain smaller cellular aggregates and
often numerous individually dispersed neoplastic cells, reflect-
ing reduced cohesion. Cytoplasm remains dense but is much
more frequently cyanophilic. Lower volumes of cytoplasm
translate into higher N/C ratios (Fig. 14.10B). Pyknotic chroma-
tin is less frequent as well; rather, the chromatin appears finely
to coarsely granular. Nucleoli are also more apparent as were
focally dyshesive single tumor cells.
Key features of squamous cell carcinoma
• Variability in cellular size and shape;
• Optically opaque cytoplasm, varying from oran-
geophilic to cyanophilic; well-defined cell borders;
• Centrally positioned angulated nuclei;
• Obviously hyperchromatic chromatin, typically
coarsely granular to structureless;
• Variable nucleoli; and
• Variable intercellular cohesion.
In some parts of the world, especially China, large-scale sur-
veillance programs are in effect to detect early squamous cell
carcinoma and its precursors.38,41-43 Early detection is critical for
survival because the most important prognostic factor is the
depth of invasion by carcinoma into the wall of the esophagus.
The progression of squamous dysplasia and carcinoma in situ to
invasive carcinoma mirrors the morphologic evolution of this
neoplasm in the uterine cervix to a remarkable extent. There-
fore, the cytologic diagnosis of preinvasive and early invasive
squamous cell carcinoma can be rendered. For screening pro-
grams to be technically and financially feasible, nonendoscopic
(blinded) sampling methodologies using various types of abra-
sive instruments have been developed. Prior to the development
of these surveillance procedures, the cytologic diagnosis of squa-
mous cell dysplasia was only very rarely made.98 The success of
these surveillance programs in high-risk populations is now
well documented.36,39,41,43 Although in some studies the mor-
phologic features of preinvasive disease have been subdivided
into a number of categories, the two-tier division presented by
Shu seems more practical.42 The application of such surveillance
programs to the general population in the United States and
other parts of the Western world seems unlikely due to the rela-
tively low incidence of this neoplasm in the general population.
However, in individuals deemed to be at higher risk, such
methodology may be successful39,40 (Table 14.3).
Small-Cell Carcinoma
Neuroendocrine neoplasms of the esophagus are very uncom-
mon, constituting less than 5% of all malignancies of this
organ. In contrast to the remainder of the GI tract, carcinoids
are not the most frequent tumor type in this category. Rather, it
is the rare, highly lethal small-cell carcinoma. With somewhat
more than 100 reported examples of this carcinoma, the litera-
ture suggests that this neoplasm accounts for about 2% of all
esophageal cancers.99,100
Although young adults may be affected, this tumor typically
occurs in the middle or distal portion of the esophagus in mid-
dle-aged or older individuals. Dysphagia is the most common
clinical presentation. Histologically, these highly cellular neo-
plasms are composed of small uniform-appearing malignant
cells. Each possesses a solitary ovoid to elongated nucleus, very
darkly stained chromatin, and exceedingly high N/C ratios.
Obviously, it is important to exclude small-cell carcinoma aris-
ing elsewhere in the body, especially the lung, with extension or
metastases to the esophagus. Rare cases of small-cell carcinoma
arising in Barrett's esophagus have been reported.101
384
Fig. 14.10 (A) Well-differentiated squamous cell carcinoma. Loose clusters of keratinized malignant cells are characterized by dense orangeophilic
cytoplasm with irregular shapes and enlarged hyperchromatic nuclei (Papanicolaou x MP, HP). (B) Poorly differentiated squamous cell carcinoma. Extreme
hyperchromatin, very high N/Cs, and cyanophilic cytoplasm are present (Papanicolaou x MP, HP).
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