Am J Clin Pathol 2005;123:699-706 699
© American Society for Clinical Pathology
Anatomic Pathology / ATYPICAL SQUAMOUS LESIONS OF THE CERVIX
Histologic and Immunohistochemical Characteristics
of Neoplastic and Nonneoplastic Subgroups of Atypical
Squamous Lesions of the Uterine Cervix
Chisa Aoyama, MD,1,3Paul Liu, PhD, MD,1,3Nora Ostrzega, MD,1,3
and Christine H. Holschneider, MD2,3
Key Words: Atypical squamous lesions; Ki-67; p16; High-grade squamous intraepithelial lesion; HSIL; Uterine cervix
A b s t r a c t
Atypical squamous lesion (ASL), a histologic
diagnosis of unclear significance in the uterine cervix,
can be divided into neoplastic and nonneoplastic groups.
We aimed to determine the morphologic characteristics
of these 2 groups. Histologic and immunohistochemical
features were evaluated on the original biopsy specimen
from 37 ASL cases, and the results were compared
between neoplastic (19 cases) and nonneoplastic (18
cases) groups, which were determined based on the
follow-up histopathologic findings.
Mitosis, vertical nuclear growth pattern, no
perinuclear halo, indistinct cytoplasmic border,
primitive cells in the upper third of the squamous layer,
p16+ cells in the upper two thirds of the squamous
layer, and Ki-67+ cells in the upper two thirds of the
squamous layer were significant indicators for
neoplastic ASLs. Of the 19 neoplastic ASLs, 16 (84%)
had 5 or more of these 7 indicators. The majority
(16/18 [89%]) of the nonneoplastic ASLs had 2 or
fewer indicators. Determination of the histologic and
immunohistochemical characteristics is useful for
distinguishing neoplastic and nonneoplastic ASLs.
Although it is not well-defined, the diagnosis of atypical
squamous lesion (ASL) often is used by pathologists to
describe histologically borderline conditions, including neo-
plastic and nonneoplastic processes in the uterine cervix.1-3
The category of ASL includes various conditions, such as
atypical repair or reactive changes, atrophy, atypical immature
metaplasia, transitional metaplasia, and dysplasia or carcino-
ma with metaplastic changes. Some of these conditions are
still under study in terms of their cause, biologic behavior, and
relationship to human papillomavirus (HPV) infections.1,4-6
Besides the fact that ASLs are loosely defined, their biologic
behavior often is difficult to predict by histopathologic exam-
ination because of a lack of morphologic criteria for distin-
guishing neoplastic from
Accordingly, ultimate final evaluation of individual ASL cases
usually depends on the subsequent diagnostic histopathologic
findings, clinical follow-up data, or both.
Continuous efforts have been made to describe histologic
and cytologic features that potentially could separate neoplas-
tic (or malignant) from nonneoplastic (or benign) groups in
ASLs.4,7,8These features include atypical nuclei, nuclear
enlargement, hyperchromatism, increased nuclear/cytoplas-
mic ratio, irregular nuclear contours, obvious mitotic activity,
atypical mitosis, nuclear vertical orientation, lack of matura-
tion, perinuclear halos, and nuclear grooves.
Some investigators use HPV detection and subtyping for
discriminating neoplastic from nonneoplastic groups in
ASLs.1,5However, it is well known that more than 20% of the
female population is estimated to harbor HPV without devel-
oping significant disease, malignant or benign.9Recent studies
show that HPV-related overexpression of p16INK4A, a cyclin-
dependent kinase inhibitor, is critical in developing cervical
Am J Clin Pathol 2005;123:699-706
© American Society for Clinical Pathology
Aoyama et al / ATYPICAL SQUAMOUS LESIONS OF THE CERVIX
#5K12HD00849 and the American Board of Obstetrics and
Gynecology (ABOG-National Institute of Child Health and Human
Development Fellow of the Reproductive Scientist Development
Program [Dr Holschneider]).
Address reprint requests to Dr Aoyama: Dept of Pathology,
Room 1A 120, Olive View-UCLA Medical Center, 14445 Olive
View Dr, Sylmar, CA 91342.
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