Female Genital Tract
Glandular Lesions of the Uterine Cervix
David C Wilbur
In tro d u c tio n
A ty p ic a l R e p a ir
E n d o c e rv ic a l C a n a l N o rm a l H is to lo g y a n d C y t o lo g y
I n t r a u t e r in e D e v ic e E ffe c t
D ir e c t S a m p lin g o f E n d o m e t r iu m
H u m a n P a p illo m a v iru s (H P V ), O th e r C o fa c to rs , a n d T h e ir R o le
E n d o c e rv ic a l p o ly p s
in E n d o c e rv ic a l C a rc in o g e n e s is
D ia g n o s tic A c c u ra c y o f C e rv ic a l C y t o lo g y R e g a rd in g G la n d u la r L e s io n s
E n d o c e rv ic a l A d e n o c a rc in o m a in Situ
M a n a g e m e n t o f G la n d u la r N e o p la stic L e s io n s a n d A ty p ic a l
E n d o c e rv ic a l A d e n o c a rc in o m a
G la n d u la r C e lls
A ty p ic a l G la n d u la r C e lls
C o n c lu d in g R e m a rk s
B e n ig n a n d N o n -G la n d u la r N e o p la stic P ro ce sse s th a t M im ic
E n d o c e rv ic a l a n d E n d o m e tria l N e o p la sia
T u b a l M e ta p la s ia
H ig h -G r a d e S q u a m o u s D y s p la s ia s p re s e n tin g as A ty p ic a l G la n d u la r C e lls
The relevance of lesions derived from the glandular portions
of the endocervical canal has increased in recent years. There
has been a reported increase in incidence of preneoplastic and
neoplastic endocervical lesions, both absolute and relative,
when compared to the more common squamous lesions. In a
study of 9 US SEER databases, incidence rates of squamous and
adenocarcinomas of the cervix compared to a variety of demo-
graphic factors, such as age and race, were studied.1 Of 27,016
invasive carcinomas reported between 1976 and 2000, 19,703
were squamous, 3,895 were adenocarcinoma (a ratio of about
5 to 1), 956 were adenosquamous, and 2,457 were other types
or types not specified. During this period, invasive squamous
carcinomas declined by about 2 0 %, while in situ squamous car-
cinomas increased by about 140%. This phenomenon related to
squamous lesions is most consistent with an effect of improved
screening. Adenocarcinoma in situ (AIS) also increased in both
black and white populations by about sevenfold, while inva-
sive adenocarcinomas increased about twofold in whites and
remained about equal in blacks.1 This increase in incidence of
endocervical glandular lesions reported in the SEER databases is
undoubtedly real, as numerous additional reports from many
countries have found similar results on review of their own data-
bases.2-7 However, this phenomenon is not universal with a small
number of countries showing actual declines (Finland, France,
Italy) and others showing no change.2 *
* Any increase in incidence
of endocervical glandular lesions is undoubtedly multifactorial.
Rising incidence of preinvasive AIS may be linked, in part, as in
squamous lesions, to better recognition of precursor lesions via
improved sampling, better preparation techniques, changes in
nomenclature, evolving methods of treatment, and advancing
understanding of the morphologic features, and hence criteria
for diagnosis of early dysplastic lesions. In addition, changing
patterns of hormone use in the modern population may also
account for increases in glandular neoplasia. This phenomenon
has been noted as a "birth cohort" effect.8 Possible biologic
mechanisms for the link between hormone use and the rise of
glandular carcinomas will be detailed later.
This chapter will detail the histology of the normal endo-
cervical canal, followed by the epidemiology and pathogenesis
of endocervical glandular neoplastic lesions. Well-established
morphologic criteria for cytologic diagnosis will be discussed.
One of the byproducts of improved sampling of the upper
portions of the endocervical canal has been the emergence of
new patterns of cytologic appearance of benign and reactive cells
that may be present in these areas. This leads to a discussion of
glandular "atypias," which are described in the Bethesda System
nomenclature as "atypical glandular cells" with several subcate-
gorizations.9 These cellular presentations can lead to significant
confusion with regard to not only interpretation, but also with
clinical management algorithms. The approach to differential
diagnostic possibilities and the morphologic features that may
help in their discrimination will be presented.
Endocervical Canal Normal Histology
and Cytology
In order to recognize the cytologic appearance of endocervical
glandular neoplasia with maximal sensitivity and specificity, a
solid understanding of the normal and variant normal morphol-
ogy of the epithelial surface of the canal is necessary. The normal
endocervical canal has multiple histologic patterns depending
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