Alimentary Tract (Esophagus, Stomach, Small Intestine, colon, Rectum, Anus, Biliary Tract)
epithelial cells with accentuated nuclei with thick membranes
and macronucleoli. Chromatin generally remains finely granu-
lar and is not truly hyperchromatic. Individually dispersed and
intact atypical elements are present in very low numbers.
The major challenge comes in distinguishing the benign reac-
tive alterations associated with active colitis from those due to
glandular dysplasia.151166 Dysplastic nuclei are enlarged, often
to an extent greater than expected in repair. The chromatin is
moderately to coarsely granular and hyperchromatic. The nuclear
envelopes may be fairly smooth but often manifest subtle altera-
tions in contour, e.g. notches. The dysplastic cells are present in
relatively small aggregates, with an obvious loss of normal polar-
ity. In other words, the abnormal nuclei are crowded, molded,
and overlapped. Nucleoli may be multiple and well developed.
The N/C ratios are accentuated. The overall impression of these
aggregates may be one of a syncytium. Although the borders of
these aggregates may appear frayed, individually dispersed dys-
plastic cells are not recognized to any extent (Fig. 14.28B).
Adenomas and Adenocarcinoma
Colorectal cytology has only a limited role in diagnostic medi-
cine. Its major purpose is to increase the diagnostic sensitivity for
the detection of neoplasms, especially adenocarcinoma. Adeno-
mas may be defined as localized elevated or exophytic masses
of dysplastic glandular cells. Potential causes and predisposing
conditions mirror those for colonic adenocarcinomas, which
are discussed later. Adenomas may be found anywhere in the
large intestine, but many are concentrated in the sigmoid and
rectum. Endoscopically and grossly, adenomas may be broadly
divided into those that are pedunculated and those that are ses-
sile; in the former, the adenomatous head is on a stalk, whereas
the latter is broad-based and lies flat on the mucosal surface.
Many adenomas are less than 1 cm in diameter, but others are
much larger. Histologically, they can be divided on the basis of
architectural pattern as tubular, villous, or mixed (tubulovil-
lous). Tubular adenomas are composed of lumen-containing
glandular structures of dysplastic cells, whereas finger-like papil-
lary fronds form the background of the villous adenomas. As
a generalization, smaller adenomas tend to be tubular in type,
and larger ones have a villous configuration. The level of dyspla-
sia can be divided into low and high.
The major importance of adenomas is that they are the
precursor for the vast majority of colorectal carcinomas. This
evolutionary pathway is referred to as the adenoma-carcinoma
sequence. Many adenomas are asymptomatic, but they may
yield symptoms, most commonly rectal bleeding. Although
uncommon in the first three decades, their incidence increases
progressively thereafter, peaking in individuals between the ages
of 50 and 70 years.
The cytologic diagnosis of colorectal adenomas is of lim-
In patients with adenomas amenable to removal by
polypectomy, cytology is unimportant. It may also be difficult to
distinguish cytomorphologically between cells derived from an
adenoma and those from a well-differentiated adenocarcinoma.
Yet, this differentiation may be of clinical value. In large masses,
biopsy may demonstrate only adenoma on the basis of random
sampling of the tumor, whereas smears may reveal obviously
malignant cells. Different therapeutic protocols might be initi-
ated by the different diagnoses.
Direct brushings of adenomas yield cellular smears with small
to large three-dimensional arrays of glandular cells.1,167,168 The
larger aggregates may have a branched papillary configuration
reminiscent of antlers (Fig. 14.29A). At low magnification, these
aggregates appear dark as a result of the constituent enlarged
nuclei and reduced cytoplasmic mucin. Characteristically, the
nuclei have an elongated (cigar-like) contour, finely to mod-
erately granular hyperchromatic chromatin, and one or more
nucleoli. These elongated elements were termed "needle cells"
by Thabet and MacFarlane.168 The nuclei may be so crowded that
cytoplasm is inapparent, although at times mucin vacuoles are
evident. Within the aggregates, the nuclei may form palisades
and be irregularly overlapped. An important negative finding is
the absence of individually dispersed abnormal cells resembling
those within the aggregates. The finding of single abnormal cells
to any extent favors adenocarcinoma.
Key features of adenomas
• Large three-dimensional aggregates, at times branched,
with well-defined edges and altered polarity;
• Few single abnormal cells;
• Columnar cells with variable mucin; and
• Enlarged, elongated hyperchromatic nuclei with
Fig. 14.29 (A) Colonic adenoma. This cohesive aggregate is composed of pseudostratified hyperchromatic nuclei. The nuclei are elongated, thin, and
cigar- to needle-shaped (Papanicolaou x HP). (B) Colonic adenocarcinoma. Loose cluster of malignant cells from colonic adenocarcinoma with focal signet
and ring cells are present.