Benign Proliferative Reactions, intraepithelial Neoplasia, and invasive Cancer of the Uterine Cervix
advocated to differentiate as much as possible between severe
dysplasia and carcinoma in situ, in routine diagnosis such a strict
separation is not very relevant. Both changes are considered to
be of a high potential for progression to an invasive lesion, and
clinical management is usually identical. In view of the influ-
ence of local environmental factors and because of the origin
from different stem cells, a markedly dysplastic change, which
usually still shows some maturation of the most superficial lay-
ers into squamous cells, originating in the original ectocervical
squamous epithelium, is likely to be fully comparable to the
characteristic carcinoma in situ, originating in the endocervical
canal through a squamous metaplastic interphase and charac-
teristically showing no sign of maturation, even in the most
superficial layers.
Approximately 80% of carcinomas in situ coexist with dys-
plasia. Graphic distribution of these lesions suggests that when
coexistence occurs, dysplasia lies distal from carcinoma in situ.12
Both dysplasia and carcinoma in situ occur more frequently on
the anterior lip of the cervix.
A possible explanation is that the anterior lip is more fre-
quently traumatized. The radial extent of CIN on the portio
epithelium is greatest in the population with carcinoma in
situ. Also, the size and distribution of carcinoma in situ on
the exposed portion of the cervix are more constant than in
Of patients with carcinoma in situ, 45% had only dysplasia
on the exposed portion of the cervix. The difference in the distri-
bution of carcinoma in situ and dysplasia may be accounted for
by the increased size of the lesion in patients with carcinoma in
situ22 and by the age-related size differences between dysplasia
and carcinoma in situ.95
The hypothesis that dysplasia represents a younger (smaller
and less extensive) precursor of carcinoma in situ is supported
by the colposcopic and cytologic observation in the individual
case. The lesions are not biologically different, but a patient with
a carcinoma in situ has a lesion that has been present for a longer
time and involves a larger area of the cervix. Our knowledge of
the biologic behavior of carcinoma in situ is still incomplete; an
untreated lesion may develop into an invasive cancer, regress to
a less severe lesion, completely disappear, or persist for an inde-
terminate time.79 Both dysplasia and carcinoma in situ occur in
the area of the transformation zone.
Co-occurrence of Squamous and Columnar
Intraepithelial Abnormalities
Carcinogenic changes in the uterine cervix can be considered to
be part of a field carcinogenic process. This means that the car-
cinogenic stimulus does not exert its action on an isolated cell
that becomes the stem cell of a malignant proliferation but on
a larger area of the epithelium. This may be the explanation for
the common observation that next to a severe lesion, changes
of different, often lesser severity are found. It also explains the
common multifocal occurrence of epithelial abnormalities.
This field stimulus apparently influences not only squamous
and squamous metaplastic epithelium but also the columnar
epithelium of the endocervical canal. The co-occurrence of
abnormal columnar cell changes together with abnormalities of
the squamous and squamous metaplastic epithelium is becom-
ing increasingly frequent.
The reduction in the incidence of squamous cell carcinoma
of the uterine cervix and mortality from cervical cancer is a
result of cytological screening and the subsequent detection and
Fig. 8.88 Mild-to-moderate atypia of endocervical columnar
epithelium. Pseudostratified columnar epithelium with irregular
arrangement of nuclei, variation in nuclear size, and scattered nuclear
hyperchromasia (H&E x HP).
removal of precursor lesions. The diagnosis of cervical glandular
cell lesions or combined squamoglandular cell lesions is based
on the same cytological principles.
In a series of 42,863 first cervical smears, minimally to
severely atypical columnar cell changes were observed in 69%
of cases of severe dysplasia, carcinoma in situ, and microinva-
sive and invasive cancer (Figs 8.88 and 8.89). In 13% of cases,
this atypia was diagnosed as an adenocarcinoma in situ (Figs
8.90 and 8.91).
The increased prevalence of these atypical columnar cell
changes may be due to a new factor that also causes colum-
nar cell abnormalities but is more likely caused by screeners'
increased sensitivity to columnar cell changes, correlated with a
growing awareness of the significance of endocervical columnar
cells as a quality parameter for cervical smears.72,151
Nevertheless published results indicate that glandular cell
abnormalities were frequently overlooked or underestimated
in the cytological specimen.152-161 This is at least in part due to
glandular abnormalities being less common than cervical squa-
mous cell lesions. Furthermore many cytotechnologists and
cytopathologists are focused on the cytological characteristics of
squamous cell lesions, whereas characteristics of glandular cell
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