8
Benign Proliferative Reactions, intraepithelial Neoplasia, and invasive Cancer of the Uterine Cervix
Years
30%
25%
20%
15%
10%
5%
0%
17
22
27
32
37
42
47
52
57
62
67
72
77
82
87
Years
Fig. 8.53 Moderate dysplasia.
Histologic diagnoses. Age distribution-
average age is 36.8 years (SD 9.1) and
n
= 420. (Data from the Nijmegen
Registry of Cervical Cytology, 1978-1987.)
Fig. 8.54 Severe dysplasia.
Histologic diagnoses. Age distribution-
average age is 35.7 years (SD 8.7) and
n
= 609. (Data from the Nijmegen
Registry of Cervical Cytology, 1970-1987.)
Cells in the upper layers of dysplasia have features reflect-
ing differentiation. However, the nuclei are usually enlarged and
more hyperchromatic than in normal squamous epithelial cells,
and the nuclei of the cells show remarkable variation, in con-
trast to the rather uniform size and shape of nuclei in normal
epithelial cells at a comparable level.
In lesions involving mature squamous epithelium, individ-
ual cell keratinization and keratohyalin pearl formation are not
uncommon.
Mitoses are usually found. In less severe lesions, mitoses,
both normal and abnormal forms, are confined to the lower half
or lower two-thirds of the epithelium. In more severe changes,
mitoses can also be found in the upper third of the mucosal
lining.
O ccurrence
The mean age at which cervical intraepithelial lesions are diag-
nosed seems to be gradually decreasing. This might be related
to changes in sexual behavior within Western countries and
a younger age of first sexual activity. Although several observ-
ers have reported that invasive cancers are also diagnosed with
greater frequency in younger women,69 this has so far not resulted
in a greater mortality from cervical cancer in women in younger
age groups. The reported increased frequency of intraepithelial
lesions in younger women may in part be due to an increased
frequency of cytologic testing and may not be a true increase in
the number of intraepithelial abnormalities.
On the basis of cellular evidence of dysplasia, Patten
reported a prevalence of 0.98% in 57,469 nongravid women.13
Reagan and co-workers reported a prevalence of 0.77% in a
study of 10,533 women.97 On the basis of histologic evidence,
the prevalence has been reported to vary between 1.298 and
3.2%.97 In our own experience with women ages 35 through
55 years, mild and moderate dysplasia was found in 1.6% and
severe dysplasia and carcinoma in situ in 0.3% of women at
first screening.76
A ge at Detection
The stages of evolution of the dysplastic process might be reflected
in the age at detection. Based on cellular evidence of dysplasia,
the mean age at detection was 34.7 years.9 Patients with slight
dysplasia were found to have a mean age of 32.0 years. With
moderate dysplasia, the mean age was 35.7 years, and in patients
with severe dysplasia, the mean age was 38.4 years.9
Reagan and associates reported a mean age of 34.2 ± 1.6 years
in women having only minimal-to-slight dysplastic lesions and
of 41.4 ± 3.0 years in reactions classified as severe dysplasia.97 In
our own series, the average age of detection of moderate dyspla-
sia was 36.8 years and of severe dysplasia 35.7 years (Figs 8.53
and 8.54).
Histology
In the dysplastic lesion, abnormal cells are present through-
out all layers of the epithelium. Signs of differentiation occur
in inverse relation to the severity of the lesion, from the basal
layers to the surface. The morphology of cells composing the
superficial layers of a dysplastic lesion is related to the sever-
ity of the dysplastic lesion. The dysplastic lesion is character-
ized by premature keratinization of component cells, abnormal
differentiation of the cells composing the epithelial lining, and
abnormally large nuclei in association with various degrees of
cytoplasmic maturation (usually various degrees of abnormal
maturation of the cytoplasm).
Cells present in the upper layers of the mucosa reflect in their
morphology the entire cascade of maturation steps throughout
the epithelium. The more dedifferentiated the cell in the most
basal layers, the less influence maturation stimuli have during
this cell's passage through the layers of the epithelium, and the
greater the remaining abnormality of the cell that finally reaches
the superficial layers. From the morphology of these superficial
cells, which are mechanically removed from the superficial lay-
ers of the mucosa, an experienced cytopathologist can rebuild
an image of the histopathologic appearance of the mucosal lin-
ing at the site of the scrape and thus give an impression of the
severity of the abnormality at that site.
Cytology
Shortly after Ayre introduced the spatula for making cervical
smears,99,100 it was reported that precancerous and cancerous
changes still confined to the mucosa of the cervix could be
detected in these cytologic samples.100-103 The number of abnor-
mal cells in a cell preparation taken from epithelial lesions
157
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