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C
ytopathologic
evaluation
of
patients
submitted
to
radiotherapy
for
uterine
cervix
cancer
R
ev
A
ssoc
M
ed
B
ras
2017; 63(4):379-385
383
true that radiotherapy is associated with unsatisfactory
samples. According to Wright et al.,
33
liquid-based cytol-
ogy considerably reduced the occurrence of unsatisfac-
tory results in the studies performed by them, with only
2.7% of the cytopathological exams (8 of 294) being de-
scribed as unsatisfactory. They concluded that the use
of ThinPrep to perform post-irradiation Pap smears is
associated with a high satisfactory cytology rate. Other
studies using the SurePath method also corroborated
these results.
29,31,36-41
However, the method is still too
expensive to be used applied on a large scale.
29
Cells with actinic effects may be confused with dyskary-
otic atypia and produce false-positive results. False-negatives
may also occur as a result of actinic changes, as well as dif-
ficulty in collecting adequate samples because of changes in
the anatomy of the cervix and vaginal canal, especially with
brachytherapy, leading to inadequate treatment. It is a con-
sensus among professionals who performmicroscopic ana-
lyzes (cytopathologists, cytologists and cytotechnicians)
42
that it is often difficult to differentiate actinic alterations in
normal cells from cellular atypia in recurrent tumors.
2
R
esults
Post-radiotherapy cytopathologic diagnosis
Several methods have already been used to test the radio-
sensitivity of cervical cancer. Some measure the tumor
response and others measure host response, such as the
cytopathologic method.
43
The quantitative and qualitative
analysis of SR-sensitive and RR-resistant cells, as described
by Graham,
44
served as a parameter for post-radiotherapy
diagnosis for a long time, but today it is no longer used
in most services.
2,9,34
Several authors have didactically
classified cytological changes caused by radiation as im-
mediate or chronic, delimited in annual periods,
34,45
or
acute, intermediate or chronic.
9
Although the morphology generates difficulties to de-
fine all the cytological changes induced by radiation, it is
still considered by several authors an effective means of
post-therapeutic control.
45,46
In order to improve cytological
diagnosis, methods such as computerized cytometry, spe-
cific immunoreactions, immunocytochemistry, and other
techniques have been used. However, to date there is no
effective protocol to predict the biological behavior of some
cell types found in post-radiotherapy smears.
45-48
Post-radiotherapy cytopathologic criteria
In general, almost all cells undergo radiation-induced
changes.
45
Cellular alterations, despite the previously
mentioned pattern, can display, depending on gravity, a
wide and complex series of morphological modifications,
with the appearance of bizarre cytological formations
that are difficult to interpret.
49
Table 1 shows the main
cytological findings in post-radiotherapy smears.
2,9,34,43-49
TABLE 1
Main cytological findings induced by radiation
in cervicovaginal smears.
Increased cytoplasm
Cytoplasmic vacuolization
Cytoplasmic degeneration
Cytoplasmic pallor
Cellular atrophy
Cellular gigantism
Amphophilia
Dyskeratosis
Pleomorphism
Nuclear increase (without compromising the nuclear-cytoplasmic
ratio)
Nuclear vacuolization
Nuclear degeneration
Nuclear pallor
Hyperchromasia
Dyskaryosis (present in malignant cells)
Mitosis (typical or atypical)
Binucleation
Multinucleation
Karyorrhexis
Nuclear pyknosis
Anisokaryosis
Necrosis
Leukocyte infiltrate
Multinucleated giant cells
Repair cells
Macro and multiple nucleoli
Anisonucleolosis
C
onclusion
To date, a protocol has not been established to precisely
differentiate the morphological characteristics of benign
cells with actinic effects from recurrent malignant cells on
post-radiotherapy smears. However, there are several studies
aimed at minimizing occasional diagnostic difficulties. The
information presented here allows for a critical and reflexive
analysis of the knowledge about the impact of radiotherapy
on epithelial cells, allowing us to point out difficulties,
limitations and potentialities that affect the medical prac-
tice and the care provided during cytopathological follow-
-up of patients submitted to cervical cancer radiotherapy.
The most incident actinic cytopathological alterations
as described in the literature are: cellular gigantism, nuclear