Benign Proliferative Reactions, Intraepithelial Neoplasia, and Invasive cancer of the Uterine cervix
been related to an earlier onset of sexual activity but may at least
in part be attributed to more intense cytologic screening.
In our own registry the age-distribution curve showed a
bimodal pattern, with peak incidences at 35 and 50 years.76 139 145
These peaks were correlated with peak incidences of invasive
squamous cancer at about 48 years and after 60 years of age.
The subjective nature of morphologic classification criteria
initially caused a wide variation in the spectrum of histologic
substrates diagnosed as carcinoma in situ. However, experience
in the classification of carcinoma in situ combined with clini-
cally correlated studies has increasingly narrowed the histologic
spectrum to a point of relatively uniform agreement on certain
morphologic patterns.12
The best description of the characteristic cytomorphologic
and architectural changes of carcinoma in situ is given in the
definition adopted by the International Committee on Histo-
logical Terminology for Lesions of the Uterine Cervix in Vienna
in 196180: "Only those cases should be classified as carcinoma
in situ”
that, in the absence of invasion, show a surface epithe-
lium in which, throughout its whole thickness, no differentia-
tion takes place (Fig. 8.81). The process may involve the cervical
glands without creating a new group.
It is recognized that the cells of the uppermost layers may
show some flattening [Fig. 8.82]. The very rare case of an
otherwise characteristic carcinoma in situ that shows a greater
degree of differentiation belongs to the exception for which no
classification can provide.80
The WHO definition of a carcinoma in situ is "a lesion in
which all or most of the epithelium shows the cellular fea-
tures of carcinoma.”81 This definition also includes an epithe-
lial abnormality with some evidence of maturation in the most
superficial layers and thus also encompasses a lesion that many
pathologists would regard as severe dysplasia.
In general, the term carcinoma in situ is used to describe a
reaction replacing the normal surface epithelium or the epithe-
lium of the invaginations of the surface epithelium or both, in
which all the layers of the epithelium are composed of abnor-
mal poorly differentiated or largely undifferentiated cells.12
The lesion may be composed of large or small cells, but essen-
tial in the classification of a lesion as carcinoma in situ is that
the entire thickness of the epithelium is composed of poorly
differentiated cells virtually without signs of maturation (differ-
entiation) toward the surface (see Fig. 8.82). Continuous with
the surface lesion, it is not unusual to find in the endocervical
invaginations an epithelial change that shows better maturation,
with the more superficial layers composed of cells recognizable
as squamous (metaplastic).
Thus, together with a characteristic carcinoma in situ on the
surface of the endocervical canal, it is not unusual to find mod-
erate-to-severe dysplasia (of squamous metaplastic type) in the
invaginations of the endocervical canal.12 Both normal and
atypical mitoses are present at all levels of the epithelial reac-
tion (see Fig. 8.82). This contrasts with moderate and severe
dysplastic lesions, in which mitoses usually are absent in the
most superficial layers. On a histologic and cytologic basis, Rea-
gan and Hamonic14 proposed a subclassification of carcinoma
in situ into small- and large-cell carcinoma
in situ.
useful in recognizing morphologic variations and studying
Fig. 8.81 Carcinoma
in situ.
Almost complete lack of maturation and
parallel arrangement of cells throughout the entire epithelium. Disturbed
palisade arrangement of cells in the most basal layers (H&E x MP).
the morphogenesis of these lesions, this classification has not
provided significant information on the biologic potential of
these lesions.12 Patten subdivides carcinomas in situ into large-
cell type, intermediate type, and small-cell type.73 The inter-
mediate type seemed to be the dominant morphologic variant
in his material. The large-cell type, although relatively rare,
appeared to be increasing in frequency. The once-dominant
cell type of small-cell carcinoma in situ was observed with
decreasing frequency.
At the time of his reporting, it was not yet evident whether
this change in the distribution of morphologic variants of car-
cinoma in situ was paralleled by a change in the distribution of
morphologic variants of invasive cancer. The lesion is charac-
teristically located in the area of the transformation zone. The
overall extent and distribution of carcinoma in situ are com-
parable to that observed for reserve cell hyperplasia and imma-
ture squamous metaplasia. Extension of the surface change into
the invaginations occurs in more than 90% of cases.146 Richart
observed that extension into the portio vaginalis occurred in
about 55% of cases and that 3% of cancers in situ had extension
into the vaginal fornix.22
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