Diagnostic Cytology
In the United States, adenocarcinoma of the large bowel is one
of the more common malignancies in both men and women,
accounting for a relatively large portion of cancer-related deaths.
Nearly 150,000 new cases are diagnosed annually. It appears as
if many patients have an inherited predisposition to the carcino-
genic action of environmental, predominantly dietary, factors.
Two of the more important implicated dietary components are
a high animal fat intake and a low consumption of fiber. Predis-
posing conditions include the polyposis syndromes, especially
familial adenomatosis coli, Lynch syndromes I and II, chronic
inflammatory bowel disease, prior pelvic irradiation, and pre-
existing adenomas.
Although carcinoma may occur at almost any age, it is most
frequent in individuals in the fifth and sixth decades. Com-
mon clinical presentations include rectal bleeding or anemia,
obstruction, or an alteration in bowel habits. Although the rela-
tive distribution of carcinoma varies from study to study, more
than half probably occur in the rectosigmoid portion. In general,
left-sided neoplasms grow as a napkin ring luminal constric-
tion, whereas the right-sided lesions produce bulky exophytic
masses. Histologically, the majority represent variably differen-
tiated gland-forming adenocarcinomas. A small but significant
portion is dominated by abundant extracellular mucin (colloid
carcinomas), which portend a worse prognosis. The 5-year sur-
vival rate is approximately 50-55%. The single most important
prognostic factor is the surgical stage.
Brushing cytology is not the procedure of choice in the
diagnosis of adenocarcinoma as many tumors cannot be dis-
tinguished from adenomas. A major use of brushing cytology,
however, is to identify potentially malignant colonic strictures.
Biopsy forceps may not be able to reach the neoplasm ade-
quately, whereas the brush has a greater opportunity to obtain
diagnostic material. For example, Mortensen and associates
evaluated a large series of patients with obstructive lesions.169
Their series included 55 patients with malignant strictures and
24 patients with benign strictures. Endoscopic brushings were
more sensitive than biopsies for the detection of adenocarci-
noma. Neither diagnostic modality in their study resulted in a
false-positive diagnosis.
However, the use of brushing cytology may not be restricted
solely to stenotic lesions. For example, Marshall and co-workers
evaluated 70 consecutive patients with masses that could not be
removed by endoscopic polypectomy.170 For each lesion, brush-
ing cytology and ten endoscopic biopsies were procured. Of the
60 cancers, carcinoma was identified in 78% of the biopsies and
77% of the brushings; the overall combined yield was 92%. In
other words, brushings and biopsies are diagnostically comple-
mentary in the large bowel.
Usually, brushing smears are highly cellular and include
both individually dispersed malignant cells and variably sized
neoplastic aggregates.1,68,171,172 The latter are generally small and
three-dimensional and have irregular borders. Individual cells
tend to have a rounded configuration, solitary large hyperchro-
matic nuclei, and well-developed nucleoli; cytoplasmic mucin is
highly variable (Fig. 14.29B, Table 14.7).
Normal Histology and Cytology
The mucosal lining of the anal canal can be divided into two
types. Nonkeratinizing stratified squamous epithelium con-
stitutes most of the length of the canal. The more proximal
portion of the anus, that is, the portion that borders the rectum,
is referred to as the transitional zone. The type of epithelium lin-
ing the transitional zone varies among individuals. Most often,
it consists of a stratified epithelium somewhat reminiscent of
that in the urinary bladder. Cuboidal epithelial cells constitute
most of the thickness, but the most superficial layer may be flat,
cuboidal, or columnar.
Most or all of the cells in a cytology sample from the anal
canal resemble normal intermediate squamous cells. Depend-
ing on the composition of the transitional zone, columnar cells
may be present, or there may be elements resembling umbrella
cells of the urinary bladder.
Squamous Cell Lesions
The use of anal cytology has increased in recent years due to the
arising incidence of HPV-related lesions; squamous cell dyspla-
sia, and carcinoma.173 Abnormal proliferations of the squamous
mucosa include condyloma, dysplasia, and carcinoma. Many
of these lesions appear to be related to infection by human
papillomavirus.174,175 HPV types 6 and 11 are most often associ-
ated with condyloma and low-grade squamous dysplasia. Types
16 and 18 have a stronger association with carcinoma and high-
grade dysplasia. However, there is overlap among HPV types
and the histologic diagnosis. Squamous cell carcinoma of the
anus is an uncommon form of GI malignancy in the general
population. Among heterosexual individuals, it is more fre-
quent in women than in men. The incidence of anal squamous
cell dysplasia and carcinoma is greatly increased in homosex-
ual men. This increase prevails independent of their serologic
status for human immunodeficiency virus (HIV). Major risk
factors for dysplasia and carcinoma in all individuals include
HPV infection and anoreceptive intercourse.74 HPV also appears
Table 14.7 Cytomorphologic Differential Diagnosis of Colonic Brushing Cytology
Cellular aggregates
Large, flat, smooth edges, normal
Large, three-dimensional, smooth
edges, altered polarity
Small, three-dimensional, frayed
edges, altered polarity
Individual cells
Moderate to many
Cell contours
Columnar to polygonal
Columnar (needle)
Round, smooth, euchromatic
Elongated, hyperchromatic
round to irregular, hyperchromatic
Small, inconspicuous
Small to large
Small to large
Greatly reduced
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