PART TWO
Diagnostic Cytology
Fig. 8.52 Transformation zone.
The most distal part of the endocervical
columnar epithelial lining bordering the original stratified squamous
nonkeratinizing epithelium has been replaced by mildly atypical squamous
metaplastic epithelium (H&E x MP).
Cervical Intraepithelial Abnormalities
O rigin and Localization
Dysplastic lesions occur significantly more frequently on the
anterior than on the posterior lip of the uterine cervix22 and are
usually localized in the endocervical mucosa at the transforma-
tion zone in the region of the cervical os or in the epithelium
covering the ectocervix or portio vaginalis.
The majority of abnormal surface reactions begin within the
area of the endocervical-lining epithelium and mimic in an
abnormal fashion various stages in the process of squamous
metaplasia.73 There is some confusion about the exact site and
cells of origin of cervical intraepithelial abnormalities. Koss
identifies the site of origin of more than 90% of the intraepi-
thelial abnormalities to be the area of squamous epithelium
bordering the columnar epithelium, known as the squamo-
columnar junction or transformation zone94 (Fig. 8.52). The
remaining fewer than 10% of lesions are then thought to origi-
nate in the area of the columnar epithelium. This would mean
that the cell of origin of most of the intraepithelial lesions
would be the basal cell of the original ectocervical squamous
epithelium overlying an area without gland-bearing stroma.
This is in conflict with the observation by Reagan and Patten
that only 11.1% of a series of dysplasias were located in an area
of the cervix without underlying glands.95 In 48.9% of speci-
mens, the site of involvement was partially related to gland-
bearing stroma, and the remaining 40% of the lesions were
confined to a site with underlying glands.8 From these data,
it appears that in 88.9% of their specimens there had been
at least partial involvement of the arena in which squamous
metaplasia occurs as the basic reaction to injury of the colum-
nar epithelium. The latter distribution is more in line with
the experience from routine clinical practice that the major-
ity of intraepithelial changes and virtually all of the severe
intraepithelial abnormalities extend into the invaginations of
the columnar epithelium. It is a common observation that the
severity of the change in the invaginations is less than that of
the surface change.
M orphology Related to O rigin
From the spectrum of morphologic patterns of intraepithelial
abnormalities occurring on the ectocervix and in the epithelial
lining of the endocervical canal, it is evident that the potential of
reserve cells to differentiate into squamous epithelium through
an intermediate stage of immature squamous metaplasia gradu-
ally diminishes in the proximal direction along the canal. This
is reflected in the epithelial abnormalities originating at differ-
ent sites. The dysplastic lesions occurring close to the squamo-
columnar junction usually still demonstrate some maturation
into squamous-like epithelium in the superficial layers, whereas
abnormalities occurring proximally in the canal completely lack
this squamous differentiation and seem to be composed entirely
of undifferentiated primitive cells (atypical reserve cells). The
resemblance to squamous epithelium of the more distal lesions
does not necessarily mean that these, although often errone-
ously named "better differentiated" when compared with clas-
sic carcinoma in situ, would have a less malignant potential. In
this respect, the relatively large-cell severe dysplasia should be
considered of comparable severity as the more classic carcinoma
in situ and treated accordingly.
G rading
The current concept of dysplasia and carcinoma in situ is that
these form a continuous spectrum of a developing intraepithe-
lial abnormality. Many have believed such a continuum to be in
conflict with a subdivision into grades. However, on the basis of
histologic criteria, it is not only possible to grade the severity of
the change but also clinically relevant, because grading provides
a basis for the mode of treatment. Grading lesions also makes
these lesions accessible for retrospective and prospective stud-
ies, which are the only available means to achieve more insight
into the true nature of these changes. The fact that it has been
proved to be very difficult to diagnose these lesions accurately
and reproducibly can never be the reason to refrain from catego-
rizing these lesions.
Grading of dysplastic lesions may give more insight into the
morphologically different types of dysplasia as well as into the
biologic potential of these types.
The more closely the lesion resembles normal epithelium,
the less severe that lesion is thought to be. The more that primi-
tive cell types that lack signs of differentiation predominate, the
more severe a lesion is considered to be. Thus, it is possible to
apply the terms minimal, slight, moderate, and severe to dif-
ferentiate on a morphologic basis—phenotypically—one lesion
from another.
Unfortunately, the degree of morphologic abnormality does
not necessarily correlate with the biologic potential of the epi-
thelial change.12 Because of this frequent lack of correlation,
Friedell recommended a morphologic classification incorporat-
ing both qualitative and quantitative information.96
Fundamentally, the intraepithelial neoplastic—dysplastic—
reaction is characterized by premature keratinization of com-
ponent cells and abnormal differentiation of a variable number
of cell layers that, in the most severe forms, encompasses all
cell layers throughout the whole thickness of the mucosal
lining.
In all dysplastic changes, by definition, in the uppermost lay-
ers of the epithelium, cells that remain have features of normal
epithelial cells. This is usually more apparent in dysplasia orig-
inating in the original squamous epithelium than in changes
involving the squamous metaplastic epithelium.
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