Diagnostic Cytology
diffuse variant is a more aggressive neoplasm. Early carcinoma,
on the other hand, is an eminently curable tumor, even when
lymph node metastases are present.
From a cytomorphologic viewpoint, it is advisable to con-
sider the intestinal and diffuse variants separately.1,140 In smears,
the intestinal form basically mirrors adenocarcinomas occur-
ring in Barrett's esophagus (Fig. 14.18). Smears usually contain
numerous malignant cells manifesting reductions in cohesion
and polarity. Thus, there may be large numbers of individually
dispersed tumor cells and small three-dimensional aggregates
with frayed margins. Within the latter, the malignant nuclei are
crowded, compressed, and overlapped. Variability in cellular
and nuclear sizes and appearances is evident.1
Most neoplastic
cells possess a solitary nucleus that is large, round to elongated,
and hyperchromatic. The nuclear membranes are thick, with
minor contour irregularities. Chromatin is variably granulated,
and one or more nucleoli are apparent. Cytoplasm varies in
quantity and may be obviously vacuolated or granular and frag-
ile. Its fragility may result in the presence of numerous stripped
atypical nuclei in the smears. A diagnosis of carcinoma should
not be rendered solely on the presence of such nuclei. At least a
few intact isolated cells need to be present. As with benign pep-
tic ulcers, granular necrotic debris and neutrophils are present in
the smear background.
Key features of adenocarcinoma, intestinal type
• Reduction of intercellular cohesion;
• Reduction of polarity;
• Enlarged nuclei with irregular contours and
hyperchromatic chromatin; and
• Prominent nucleoli.
Overall, it is more difficult to diagnose cytologically the dif-
fuse form as fewer malignant cells are typically present due to
the host desmoplastic response and malignant features may not
be immediately recognizable.1
Signet ring carcinoma cells due to the host desmoplastic
response are usually dispersed as single elements and small very
loosely cohesive groups (Fig. 14.19). The cytoplasm is dominated
by a single, large mucin vacuole or is densely granular. Only a thin
rim of cyanophilic cytoplasm may separate the vacuole from the
cell membrane. The vacuole appears sharply delineated and may
be either optically clear or somewhat granular and pale-stained.
Nuclear appearances may be remarkably heterogeneous. Some
are obviously malignant with thick irregular contours, darkly
stained chromatin, and nucleoli. Typically, the vacuole impinges
on the nucleus, producing a concave configuration with sharply
pointed tips and angles. Long flat nuclear surfaces are another
frequent presentation. A proportion of the nuclei may not be
obviously malignant. These are characterized by delicate mem-
branes, pale chromatin, and inapparent nucleoli. Mitotic figures
may be present. Some authors could not reliably distinguish
the two major histologic forms of adenocarcinoma.50 With the
exception of the relatively clean smear background, the cyto-
morphologic presentation of early gastric carcinoma does not
differ from that of more advanced tumors.
Key features of adenocarcinoma, signet-ring type
• Variable numbers of generally dispersed solitary tumor
• Rounded cells with clear to foamy cytoplasm, a single
eccentric nucleus, and at times a low N/C ratio;
• Cytoplasmic mucin vacuoles displace and distort
• Hyperchromatic nuclei vary from bland to obviously
• Contours may be sharply angulated or pointed; and
• Variable nucleoli.
The differential diagnosis of the intestinal variant basically
consists of benign peptic ulcers, which may yield cellular smears
with a dirty necrotic background. However, as in repair else-
where, intercellular cohesion and polarity are relatively well
maintained. Thus, only rare isolated atypical glandular cells may
be present, and prominent crowding and overlapping of nuclei
within the aggregates are not evident. Although huge nucleoli
may be seen in repair, the chromatin remains finely granular,
evenly distributed, and not truly hyperchromatic.1,45,50,52,129,134
Normal mucus-producing columnar and goblet cells may be
seen in cytologic specimens of the stomach. These need to be
distinguished from signet ring carcinoma cells. Although some
of the latter may have bland nuclear features, a proportion
possess obviously malignant nuclear characteristics. The nuclei
of neither histiocytes nor benign glandular cells should have
Fig. 14.18 Gastric carcinoma intestinal type. Brushings are composed of loosely cohesive groups of malignant cells with loss of polarity. The tumor cells
have hyperchromatic, irregular nuclei with prominent nucleoli (Papanicolaou x HP).
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