Female Genital Tract
Benign Proliferative Reactions,
Intraepithelial Neoplasia, and Invasive Cancer
of the Uterine Cervix
G. Peter Vooijs, Anniek JM van Aspert-van Erp, and Johan Bulten
In tro d u c tio n
In v a s iv e C a n c e r o f th e U te rin e C e rv ix
T h e N o rm a l U te rin e C e rv ix
E p id e m io lo g y
H is t o lo g y a n d C y t o lo g y
M ic r o in v a s iv e C a rc in o m a
B e n ig n P ro life ra tiv e R e a c tio n s
E ffic a c y o f C e rv ic a l C y t o lo g y in th e D e te c tio n o f C e rv ic a l
H y p e rk e ra to s is
A b n o rm a litie s
P a r a k e ra to s is
S q u a m o u s M e ta p la s ia
A ty p ia
R e a c tiv e a n d R e g e n e r a tiv e C h a n g e s
S q u a m o u s In tra e p ith e lia l N e o p la sia
R e v ie w
T e r m in o lo g y
C o n c lu d in g R e m a rk s
P a p a n ic o la o u C la s s ific a tio n
D y s p la s ia
C e rv ic a l I n t r a e p ith e lia l N e o p la s ia
Diagnostic cytology of the uterine cervix was not the first appli-
cation of cytology in clinical diagnosis of diseases, but it is defi-
nitely the most widespread and best known. In its early days,
vaginal cytology was primarily directed at the diagnosis of inva-
sive cancer of the uterine cervix and of the endometrium, but
cytologists later began to realize that cervical lesions were best
recognized in direct scrapes of the cervical mucosa. The concept
that invasive carcinoma of the cervix is antedated by an intraepi-
thelial neoplastic change—carcinoma
in situ
—was postulated at
the beginning of the 20th century.1
These intraepithelial changes
were believed to be potentially progressive precursors of inva-
sive cancer. It subsequently became known that the spectrum
of abnormal changes of the epithelial lining of the uterine cer-
vix was much wider than previously thought. Cytologists soon
became aware that these noninvasive epithelial abnormalities
of the uterine cervix could also be diagnosed in the direct scrap-
ings. With meticulous comparison between the characteristics
of the cells in cytologic smears and the histologic changes found
in the same patients, the cytologic characteristic of intraepithe-
lial lesions of the cervix became better defined and the accuracy
of cervical cytology in predicting the histopathologic change
All epithelial abnormalities of squamous character derive
from ectocervical squamous basal cells and endocervical reserve
cells. Depending on the strength of the negative stimulus on
the differentiating and maturing basal cells and endocervical
reserve cells and, in a later stage, immature metaplastic cells,
the ultimately resulting cells have a more or less differentiated
aspect. This explains not only common morphologic features in
the different variants of dysplasia and ultimately in the most de-
differentiated intraepithelial variant, carcinoma in situ, but also
the extremely common co-occurrence of carcinoma in situ and
dysplastic changes of different severity.
Despite a relatively high proportion of incorrect diagnoses,
in large-scale population-screening programs, cervical cytol-
ogy has proved to be the most effective tool for the diagnosis of
cervical cancer. After an initial increase in the number of severe
epithelial lesions diagnosed in the population, the majority of
lesions diagnosed are of slight-to-moderate severity. It is well
known that the majority of these lesions regress to a less abnor-
mal change after a variable time. In this respect, it is justified
to monitor these changes cytologically, when the cytodiagnostic
service is of high quality.
For correct interpretation of abnormalities,
a thorough
knowledge of the cytologic and histologic characteristics of
cervical cancer and its potential precursor lesions is necessary.
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