Diagnostic Cytology
Fig. 11.21 Cytology of anal LSIL. Large pleomorphic cells with enlarged
single, binucleated, or multinucleated nuclei and abundant orangophilic
cytoplasm (Papanicolaou xHP).
Fig. 11.22 Cytology of anal HSIL. Atypical squamous cells with slightly
enlarged irregular nuclei and higher N/C ratio (Papanicolaou xHP).
cells were prevalent, found in 62% of the specimens. These atyp-
ical parakeratotic cells initially contributed to overdiagnosis as
SCC of some anal cases. Therefore, the diagnosis of AIN should
be based on the presence of nonkeratinizing cells with altered
N/C ratios and nuclear abnormalities such as hyperchromasia,
coarse chromatin, and irregular nuclear contours.104,106
totic cells,
on the other hand, although frequently observed were
not helpful in the diagnosis of anal SIL, a finding supported by
Friedlander et al. who observed parakeratotic cells in 84% of
their study cases. Similar studies in cervical smears have shown
that parakeratosis in otherwise negative Pap smears, is not a reli-
able marker for cervical intraepithelial neoplasia.107
Although a line of studies has demonstrated that anorectal
cytology may be as sensitive as a cervical Pap smear in the early
detection of neoplastic processes, special attention must be given
potential pitfalls.
The cytologic diagnosis of dysplasia should
be based on nuclear alterations and N/C ratios rather than on
cytoplasmic features. It is noteworthy that koilocytosis is not as
frequent as is seen in cervicovaginal cytology. In addition, reactive
epithelial changes associated with infection, such as herpes sim-
plex infection, should be approached with care to avoid a misdi-
agnosis of malignancy, especially in HIV-positive patients, who
are prone to multiple infectious diseases.
Grading of AIN
on anal cytology did not always correspond to the histologic
grade.105,108 Thus, the presence of any abnormal anal cytologic
finding indicates a potential for HSIL on histologic examina-
tion.104 Anoscopy is important in confirming the presence of a
lesion, particularly high-resolution methods.109 Nonetheless, only
a biopsy can accurately determine the grade of an AIN lesion.
Anorectal cytology has a relatively high sensitivity (up to 94%),
particularly in high-risk individuals, but relatively low specificity
(below 50%) in the evaluation of anal dysplasia.104,105,108 A recent
study showed that a diagnosis of ASC-H or HSIL accurately pre-
dicted the presence of AIN II/III in 90% of cases.108 However,
a cytologic diagnosis of ASC-US or LSIL also held a 46-56%
chance that a high-grade AIN would be present on biopsy.
This figure is high when compared to cervical cytology where
ASC-US and LSIL have been associated with only 5-17% chance
of HSIL on biopsy based on recent ALTS and other studies.110-112
As in cervical cytology,
reflex testing has been applied to
anal cytology. Walts et al. have correlated cytological diagnoses
and HPV DNA (Digene Hybrid Capture HC-II assay) in anal spec-
imens collected in SurePath liquid medium from 118 patients.
They found that 54.8% of cases diagnosed as ASC-US and 87.8%
diagnosed as LSIL or above tested positive for high-risk HPV
DNA.113 Studies suggest that reflex HPV DNA testing might be
helpful in triaging patients diagnosed with ASC-US, enhancing
the specificity of anal cytology.99 However, patients diagnosed
with LSIL or above should go directly to anoscopic biopsy.
Key features of AIN in anal PAP:
• Essentially similar to features of cervical LSIL and
• Atypical keratinized squamous cells are more com-
monly seen in anal PAP; and
• Nonkeratinized squamous cells with higher N/C ratio
are required for anal HSIL diagnosis.
Adequacy and Sample Collection Methods
Collecting anal cytologic specimens is similar to collecting
cervical Pap materials. The anal "Pap smear" can be collected
from the anal canal by swabbing all surfaces of the anus and
distal rectum. The cytologic slide can be made by direct smears
or by liquid-based cytologic techniques. However, because of
the convenience of HPV testing, liquid-based cytologic col-
lection is recommended. It has been shown that detection of
abnormalities in liquid-based collection is more effective than
conventional preparations,103,106 and anal liquid-based collec-
tion contained glandular cells twice as often as conventional
smears.104,106 In one study, 92% of liquid-based collections
contained a glandular component in contrast to 33% of con-
ventional smears. More importantly, it has been shown that
liquid-based collection detects almost eight times as many SIL
cases than conventional smears. In addition, SIL is diagnosed
significantly more often in liquid-based collections containing
t-zone elements when compared with those that do not contain
these elements.103,104,106 Other studies indicate that specimens
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