PART TWO
Diagnostic Cytology
Table 8.1
Main different reporting systems for cervical cytological squamous epithelial abnormalities
Papanicolaou
WHO
CIN
Bethesda
Class I
Negative for intraepithelial lesion
or malignancy
Class II
Atypical squamous cells
Mild dysplasia
CIN 1
Low-grade SIL
Class III
Moderate dysplasia
CIN 2
High-grade SIL
Severe dysplasia
CIN 3
High-grade SIL
Class IV
Carcinoma
in situ
CIN 3
High-grade SIL
Class V
Carcinoma
Carcinoma
Carcinoma
C IN , c e r v ic a l in t r a e p it h e lia l n e o p la s ia ; S IL , s q u a m o u s in t r a e p it h e lia l le s io n .
Very slight epithelial
abnormalities—conditions between
"negative" and true intraepithelial lesions (LSIL and HSIL)—are
placed into a fourth category as "atypical squamous cells (ASC).
This fourth category was chosen because everybody agreed
that the presence of (slightly) atypical squamous cells of "unde-
termined significance" implied a significant risk for an underly-
ing high-grade cervical intraepithelial lesion (SIL).
Abnormalities of glandular cells, as well as ASC, LSIL, and
HSIL, are placed in the group of (intra)epithelial cell abnor-
malities and subdivided as "atypical glandular cells," "cervical
adenocarcinoma in situ," and "adenocarcinoma."
Finally, in 2001 Bethesda introduced a new category, "other,"
in which disorders such as the presence of endometrial cells in a
postmenopausal woman can be placed.78 For further details on
the Bethesda System see Chapter 6.
It was thought that using these four categories would reduce
the present inconsistencies in terminology. The proposed ter-
minology is related to the expected clinical behavior of the
epithelial abnormalities and is management oriented in that
it includes a recommendation for the preferred follow-up pro-
cedure in an individual case. The new classification is thought
to provide a basis for communicating the diagnostic interpre-
tation of a specimen in unambiguous descriptive or diagnos-
tic terms that have clear implications for proper treatment of
patients.74,75
Not all countries have adopted the Bethesda System in their
screening programs. Several countries continue using the World
Health Organization (WHO) terminology (mild, moderate, and
severe dysplasia; carcinoma in situ; and carcinoma) or the CIN
categories (CIN 1, 2 and 3; invasive carcinoma).
The Bethesda System terminology can be easily translated
into these two other systems of categorization.
For an overview of all currently used classification systems see
Table 8.1 (Papanicolaou, WHO, CIN, Bethesda).
Dysplasia
The term
dysplasia
means "disordered form" (disordered dif-
ferentiation). Reagan and associates introduced the term
dysplasia to describe these disordered growth patterns and
reported that the majority of these intraepithelial changes
would regress spontaneously or persist unchanged if left
untreated.79
In the uterine cervix, the term dysplasia is applied to a
spectrum of heteroplastic reactions involving stratified
squamous or squamous-like (metaplastic) epithelium.
As
the term implies, this group of reactions is characterized
by malformation or disordered development, manifested
morphologically by variations in cytoplasmic maturation in
association with certain nuclear abnormalities.9-12
The definition of dysplasia is derived from the definition
of carcinoma in situ, which is defined as "an intraepithe-
lial abnormality in which throughout its whole thickness, no
differentiation takes place."
All other disturbances of differentiation in the squamous
epithelial lining, the glands, or covering of the surface are to
be classified as dysplasia. They may be characterized as a high
or a low degree, terms that are preferable to suspicious and
nonsuspicious, as the proposed terms describe the histologic
appearance and do not express an opinion.80
In the definition of the World Health Organization, dysplasia
is "a lesion in which part of the thickness of the epithelium is
replaced by cells showing varying degrees of atypia." The lesions
were further graded as mild, moderate, and severe.81 Most pathol-
ogists determine these grades of dysplasia on the basis of the
proportion of the epithelial thickness occupied by the abnor-
mal cells, taking into account the degree of atypia of these cells.
The latter grading has stimulated much discussion, because a
number of investigators do not believe that this grading is suf-
ficiently correlated to biologic behavior. The dual terminology
has led gynecologists to assume that dysplasia and carcinoma
in situ are two biologically distinct entities with different pro-
gressive potential and that dysplastic lesions may not require
treatment.82 Some studies have shown that the behavior of these
intraepithelial lesions cannot be predicted with accuracy and
that even mildly abnormal changes, when left untreated, may
progress to carcinoma in situ and invasive cancer.83,84 Burghardt
reported on the direct development of invasive cancer from dys-
plasia with an interphase of carcinoma in situ.85
The marked variation in morphology, even from one site to
another within the same cervix, is undoubtedly the cause for the
confusion in terminology and the difficulties in evaluating the
biologic significance of these reactions.
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