You are on page 1of 6

CONSENSUS STATEMENT

The 2001 Bethesda System


Terminology for Reporting Results of Cervical Cytology
Diane Solomon, MD Objectives The Bethesda 2001 Workshop was convened to evaluate and update
Diane Davey, MD the 1991 Bethesda System terminology for reporting the results of cervical cytology.
A primary objective was to develop a new approach to broaden participation in the
Robert Kurman, MD consensus process.
Ann Moriarty, MD Participants Forum groups composed of 6 to 10 individuals were responsible for
Dennis O’Connor, MD developing recommendations for discussion at the workshop. Each forum group in-
cluded at least 1 cytopathologist, cytotechnologist, clinician, and international repre-
Marianne Prey, MD sentative to ensure a broad range of views and interests. More than 400 cytopatholo-
Stephen Raab, MD gists, cytotechnologists, histopathologists, family practitioners, gynecologists, public
health physicians, epidemiologists, patient advocates, and attorneys participated in the
Mark Sherman, MD workshop, which was convened by the National Cancer Institute and cosponsored by
David Wilbur, MD 44 professional societies. More than 20 countries were represented.
Thomas Wright, Jr, MD Evidence Literature review, expert opinion, and input from an Internet bulletin board
were all considered in developing recommendations. The strength of evidence of the
Nancy Young, MD scientific data was considered of paramount importance.
for the Forum Group Members and Consensus Process Bethesda 2001 was a year-long iterative review process. An
the Bethesda 2001 Workshop Internet bulletin board was used for discussion of issues and drafts of recommenda-
BACKGROUND tions. More than 1000 comments were posted to the bulletin board over the course
of 6 months. The Bethesda Workshop, held April 30-May 2, 2001, was open to the
The Bethesda System for reporting the public. Postworkshop recommendations were posted on the bulletin board for a last
results of cervical cytology was devel- round of critical review prior to finalizing the terminology.
oped as a uniform system of terminol-
Conclusions Bethesda 2001 was developed with broad participation in the consen-
ogy that would provide clear guidance
sus process. The 2001 Bethesda System terminology reflects important advances in
for clinical management.1 The first biological understanding of cervical neoplasia and cervical screening technology.
workshop was held in 1988, to reduce JAMA. 2002;287:2114-2119 www.jama.com
widespread confusion among labora-
tories and clinicians created by the use
tation.3 Currently, more than 90% of US considered an opportune time to re-
of multiple classification systems and
laboratories use some form of the 1991 evaluate the Bethesda System.
inconsistently defined numerical grad-
Bethesda System in reporting cervical cy-
ing conventions.
tology.4 With the increased utilization Bethesda 2001 Process
The most important contribution of
of new technologies and recent find- Eight months prior to the Bethesda
the Bethesda System was the creation of
ings from research studies, 2001 was 2001 Workshop, 9 forum groups (listed
a standardized framework for labora-
tory reports that included a descriptive Author Affiliations: Division of Cancer Prevention, Na- Financial Disclosure: Dr Wright was the principal in-
diagnosis and an evaluation of speci- tional Cancer Institute, Bethesda, Md (Dr Solomon); De- vestigator of the clinical trials investigating HPV DNA
partment of Pathology and Laboratory Medicine, Uni- testing and liquid-based cytology funded by Digene
men adequacy. While not everyone versity of Kentucky Medical Center, Lexington (Dr Corp and Cytyc Corp via formal grants to Columbia
agreed with every detail of that initial ef- Davey); Departments of Gynecology and Obstetrics and University. Dr Wright has no financial or equity inter-
fort, the recommendations of the 1988 Pathology, Johns Hopkins Hospital, Baltimore, Md (Dr est in, ongoing consultancy with, or membership on
Kurman); AmeriPath Indiana, Indianapolis (Dr Mori- the scientific advisory board of Digene Corp, which
workshop received widespread accep- arty); Clinical Pathology Associates, Louisville, Ky (Dr makes the only FDA-approved HPV DNA test in the
tance in practice.2 A second workshop O’Connor); Quest Diagnostics Incorporated, St Louis, United States. Dr Wright currently serves on the speak-
Mo (Dr Prey); Department of Pathology, Allegheny Hos- er’s bureau of Cytyc Corp and Tripath Inc, which make
was held in 1991 to modify the Bethesda pital, Pittsburgh, Pa (Dr Raab); Division of Cancer Epi- liquid-based cytology test kits.
System based on actual laboratory and demiology and Genetics, National Cancer Institute, Forum Group Members are listed at the end of this
Bethesda, Md (Dr Sherman); Department of Pathol- article.
clinical experience after its implemen- ogy, Massachusetts General Hospital, Boston (Dr Wilbur); Corresponding Author and Reprints: Diane
Department of Pathology, Columbia University, New Solomon, MD, EPN Room 2130, 6130 Executive
See also pp 2120 and 2140. York, NY (Dr Wright); and Department of Pathology, Blvd, Bethesda, MD 20892 (e-mail: ds87v@nih
Fox Chase Cancer Center, Philadelphia, Pa (Dr Young). .gov).

2114 JAMA, April 24, 2002—Vol 287, No. 16 (Reprinted) ©2002 American Medical Association. All rights reserved.

Downloaded from jama.ama-assn.org by guest on February 5, 2012


THE 2001 BETHESDA SYSTEM

at the end of the article) were estab-


lished to draft recommendations for BOX 1. Bethesda 2001 Workshop Cosponsors
modifying the Bethesda System. A American Cancer Society*
primary objective was to broaden American College Health Association*
participation by using the Internet American College of Obstetricians and Gynecologists*
in the premeeting development pro- American Social Health Association*
cess. A dedicated Web site (http:// American Society of Cytopathology*
bethesda2001.cancer.gov) with an elec- American Society for Colposcopy and Cervical Pathology*
American Society of Clinical Pathologists*
tronic bulletin board was established to
American Society for Cytotechnology*
seek input and critiques of draft rec- Asociación Mexicana de Patologos
ommendations. In total, more than Association of Reproductive Health Professionals
1000 individual comments were posted Association of Women’s Health, Obstetric and Neonatal Nurses
to the bulletin board. Australian Society of Cytology
The workshop was held April 30- British Society for Clinical Cytology
May 2, 2001, with more than 400 par- Canadian Society of Cytology – Société Canadienne de Cytologie*
ticipants, including pathologists, cyto- Centers for Disease Control and Prevention
technologists, clinicians, and patient Chinese Society of Cytopathology
advocates. Forty-four professional so- College of American Pathologists*
cieties, representing more than 20 coun- Deutsche Gesellschaft für Zytologie
Food and Drug Administration
tries, were cosponsors (BOX 1). More
Gynecologic Oncology Group, ACOG*
than 20 national and international so- Health Care Financing Administration
cieties have endorsed the 2001 Bethesda International Academy of Cytology
System at this writing. The following International Society of Gynecological Pathologists
summary highlights the most clinically Irish Association for Clinical Cytology*
relevant changes to the Bethesda Sys- Japanese Society of Clinical Cytology
tem (BOX 2); a more detailed text will Korean Society for Cytopathology
be published in specialty journals. Magyar Onkológusok Társasága-Cytodiagnosztikai Sectio
National Committee for Clinical Laboratory Standards
THE 2001 BETHESDA SYSTEM Nurse Practitioners in Women’s Health
Specimen Adequacy Öesterreichische Gesellschaft fuer Zytologie*
Papanicolaou Society of Cytopathology*
Evaluation of specimen adequacy is Planned Parenthood Federation
considered by many to be the single Romanian Society of Cytology
most important quality assurance com- Sociedad Argentina de Citologia
ponent of the Bethesda System. Origi- Sociedad Chilena de Citologia
nally, in 1988, specimen adequacy was Sociedad Española de Citologia*
categorized as “satisfactory,” “less than Sociedad Peruana de Citologia
optimal” (renamed “satisfactory but Sociedade Boliviana de Citologia
limited by . . . ” in 1991), or “unsatis- Sociedade Brasileira de Citopatologia
factory.” The middle category was used Società Italiana di Anatomia Patologica e Citopatologia Diagnostica
most often for cases lacking endocer- Société Belge de Cytologie Clinique—Belgische Vereniging voor Klinische
Cytologie*
vical or squamous metaplastic cells as
Société Française de Cytologie Clinique*
evidence of transformation zone sam- Society of Gynecologic Oncologists*
pling, but which were otherwise “sat- Suid Afrikaanse Vereniging vir Kliniese Sitologie—South African Society of
isfactory.” The 2001 Bethesda System Clinical Cytology*
maintains the “satisfactory for evalua- *Indicates that the society has endorsed the 2001 Bethesda System.
tion” and “unsatisfactory for evalua-
tion” categories, but eliminates “satis-
factory but limited by . . . ” because the
term was considered confusing to many Minimal squamous cellularity require- niques for evaluating cellularity will be
clinicians and prompted unnecessary ments for a specimen to qualify as “sat- presented in future publications.
repeat testing. Nevertheless, provid- isfactory” differ depending on speci- A notation is made regarding the
ing information on transformation zone men type: an estimated 8000 to 12000 presence or absence of an endocervical/
sampling has value in improving over- well-visualized squamous cells for con- transformation zone component for
all specimen quality and encourages ef- ventional smears and 5000 squamous specimens with adequate squamous cel-
forts to optimize sample collection. cells for liquid-based preparations. Tech- lularity. The numeric criterion for a
©2002 American Medical Association. All rights reserved. (Reprinted) JAMA, April 24, 2002—Vol 287, No. 16 2115

Downloaded from jama.ama-assn.org by guest on February 5, 2012


THE 2001 BETHESDA SYSTEM

Comments on quality indicators such


BOX 2. The 2001 Bethesda System (Abridged) as partially obscuring inflammation or
SPECIMEN ADEQUACY
blood may also be added to the “satis-
factory” designation. A specimen is con-
Satisfactory for evaluation (note presence/absence of endocervical/
transformation zone component) sidered “partially obscured” when 50%
Unsatisfactory for evaluation . . . (specify reason) to 75% of the epithelial cells cannot be
Specimen rejected/not processed (specify reason) visualized. Specimens with more than
Specimen processed and examined, but unsatisfactory for evaluation of 75% of epithelial cells obscured are “un-
epithelial abnormality because of (specify reason) satisfactory.”
GENERAL CATEGORIZATION (Optional) Specimens that cannot be acces-
Negative for intraepithelial lesion or malignancy sioned by the laboratory, if unlabelled
Epithelial cell abnormality for example, are also designated as “un-
Other satisfactory”; these are distinguished
from specimens that have been pro-
INTERPRETATION/RESULT
cessed by the laboratory and deter-
Negative for Intraepithelial Lesion or Malignancy
mined to be unsatisfactory following
Organisms
Trichomonas vaginalis microscopic evaluation.
Fungal oganisms morphologically consistent with Candida species
Shift in flora suggestive of bacterial vaginosis General Categorization
Bacteria morphologically consistent with Actinomyces species The “general categorization” is an op-
Cellular changes consistent with herpes simplex virus tional component of the Bethesda Sys-
Other non-neoplastic findings (Optional to report; list not comprehensive) tem, designed to allow clinicians and/or
Reactive cellular changes associated with their staff to triage reports readily. The
inflammation (includes typical repair) previous category headings of “within
radiation normal limits” and “benign cellular
intrauterine contraceptive device
changes” have been combined into a
Glandular cells status posthysterectomy
Atrophy
single category “negative for intraepi-
Epithelial Cell Abnormalities thelial lesion or malignancy.”In this way,
Squamous cell reactive changes are more clearly des-
Atypical squamous cells (ASC) ignated as “negative.” “Other” has been
of undetermined significance (ASC-US) added as a category for cases in which
cannot exclude HSIL (ASC-H) there are no morphological abnormali-
Low-grade squamous intraepithelial lesion (LSIL) ties in the cells per se; however, the find-
encompassing: human papillomavirus/mild dysplasia/cervical ings may indicate some increased risk:
intraepithelial neoplasia (CIN) 1 for example, benign-appearing “endo-
High-grade squamous intraepithelial lesion (HSIL) metrial cells in a woman ⱖ40 years of
encompassing: moderate and severe dysplasia, carcinoma in situ;
age” (see below).
CIN 2 and CIN 3
Squamous cell carcinoma These categories are mutually exclu-
Glandular cell sive; therefore, if several findings
Atypical glandular cells (AGC) (specify endocervical, endometrial, or not are present, the general categorization
otherwise specified) is based on the most clinically sig-
Atypical glandular cells, favor neoplastic (specify endocervical nificant result (eg, epithelial cell
or not otherwise specified) abnormality).
Endocervical adenocarcinoma in situ (AIS)
Adenocarcinoma Interpretation/Result
Other (List not comprehensive) The workshop participants unani-
Endometrial cells in a woman ⱖ40 years of age
mously supported the view that cervi-
AUTOMATED REVIEW AND ANCILLARY TESTING (Include as appropriate) cal cytology is primarily a screening test,
EDUCATIONAL NOTES AND SUGGESTIONS (Optional) which in some instances may serve as
a medical consultation by providing an
interpretation that contributes to a di-
agnosis. However, a patient’s final di-
transformation zone component is un- preserved endocervical or squamous agnosis, and therefore management,
changed from the 1991 Bethesda Sys- metaplastic cells; however, clusters are must integrate clinical and laboratory
tem—there should be at least 10 well- no longer required. results. Therefore, in the 2001 Bethesda
2116 JAMA, April 24, 2002—Vol 287, No. 16 (Reprinted) ©2002 American Medical Association. All rights reserved.

Downloaded from jama.ama-assn.org by guest on February 5, 2012


THE 2001 BETHESDA SYSTEM

System the term “diagnosis” has been gued for elimination of the ASCUS cat- Squamous Intraepithelial Lesions. The
replaced by “interpretation” or “re- egory. However, the participants 1988 Bethesda System introduced a
sult” to convey that cervical cytology decided that it was essential to main- 2-tiered terminology, LSIL and HSIL, for
provides an interpretation of morpho- tain an equivocal category because of reporting the spectrum of noninvasive
logical findings that must be inte- the large number of women with un- squamous cervical abnormalities.
grated into a clinical context. derlying CIN 2 and 3 who are discov- After thorough consideration by the
Negative for Intraepithelial Lesion ered through a workup for an equivo- Bethesda 2001 Workshop, the 2-tiered
or Malignancy. Specimens for which no cal cytological reading. Estimates LSIL /HSIL terminology remains un-
epithelial abnormality is identified are suggest that 10% to 20% of women with changed.
reported as “negative for intraepithe- ASC have underlying CIN 2 or 3 and The dichotomous division of SIL re-
lial lesion or malignancy.” Reporting that 1 in 1000 may have invasive can- flects the substantial virological, mo-
non-neoplastic findings, other than the cer.6 The elimination of an equivocal lecular, and clinical evidence that LSIL
listed organisms, is optional; Box 2 in- cytology category seemed imprudent is generally a transient infection with
cludes a partial list of findings. given the high expectations for very sen- HPV, while HSIL is more often associ-
Epithelial Cell Abnormalities. Atypi- sitive cervical cytological screening in ated with viral persistence and higher
cal Squamous Cells. The 1988 Bethesda the United States. risk for progression.10-13 In addition,
System included the term “atypical The 2001 Bethesda System differs in data from the ASCUS LSIL Triage Study
squamous cells of undetermined sig- several fundamental ways with regard to demonstrate the following: (1) LSIL vs
nificance” (ASCUS) to designate “cel- reporting equivocal results. First, “atypi- HSIL is a fairly reproducible diagnos-
lular abnormalities that were more cal squamous cells” are now qualified tic breakpoint, (2) subdividing cyto-
marked than those attributable to re- as “of undetermined significance logical HSIL into moderate and severe
active changes but that quantitatively (ASC-US)” or “cannot exclude HSIL” dysplasia or CIN 2 and 3 is not very re-
or qualitatively fell short of a defini- (ASC-H). The qualifier “undetermined producible, and (3) HPV cytopathic
tive diagnosis of ‘squamous intraepi- significance” was retained to empha- effect cannot be reliably separated from
thelial lesion’ (SIL).” Pathologists were size that some cases of ASC-US are as- mild dysplasia or CIN 1 (M. Schiff-
encouraged to qualify ASCUS with re- sociated with underlying CIN 2 or 3. Sec- man, written communication, 2001).
spect to whether a reactive process or ond, ASC is not a diagnosis of exclusion; However, the 3-tiered CIN 1-2-3 des-
SIL was favored. In practice, patholo- all ASC is considered to be suggestive ignations may be helpful in managing
gists reported a significant proportion of SIL. Accordingly, the category of some individual patients, in correlat-
of smears as “ASCUS, not otherwise “ASCUS, favor reactive” was elimi- ing cytopathologic and histopatho-
specified.” nated. Pathologists are encouraged to logic findings, or in reporting cytol-
When the 1988 Bethesda System was judiciously downgrade to “negative for ogy results outside the United States.
drafted, clinical management in the intraepithelial lesion or malignancy” a Some members of the European cyto-
United States focused on identifying all portion of the cases previously termed pathology community in particular fa-
SIL, including low-grade SIL (LSIL), “ASCUS favor reactive.” vor use of CIN terminology. As in pre-
based on the view that all grades of SIL The new term “ASC-H” is thought to vious versions of the Bethesda System,
represented closely linked precursors include approximately 5% to 10% of CIN or dysplasia terminology can be
that required colposcopy and treat- ASC cases overall.7-9 This category re- used, either as a substitute for SIL or
ment. However, there has been a shift flects a mixture of true HSIL and its as an additional descriptor.
in the United States with regard to man- mimics. Although the interpretation is Atypical Glandular Cells.The classi-
agement based on the recognition that not highly reproducible among patholo- fication of glandular abnormalities has
most LSIL, especially in young women, gists, studies suggest that ASC-H has a been significantly revised in the 2001
represents a self-limited human papil- positive predictive value for histologi- Bethesda System, reflecting a reap-
lomavirus (HPV) infection.5 Accord- cal CIN 2 or 3 that is intermediate be- praisal of the strengths and weak-
ingly, the current emphasis is on de- tween ASC-US and HSIL. It is hoped nesses of cytology in assessing these
tection and treatment of histologically that by highlighting such cases, ASC-H findings.
confirmed high-grade disease (particu- will aid in more rapid detection and The term “atypical glandular cells of
larly cervical intraepithelial neoplasia treatment of some cases of CIN 2 and undetermined significance” (AGUS) has
[CIN] 3). Therefore, it is logical for the 3. However, the equivocal nature of the been eliminated to avoid confusion with
ASC category qualifiers to emphasize ASC-H designation should encourage ASC-US. Glandular cell abnormalities
the importance of detecting high- comprehensive review of all pathol- are classified as “atypical endocervi-
grade SIL (HSIL), which has emerged ogy and colposcopic findings prior to cal, endometrial, or glandular cells.”
as the central purpose of screening. performing a diagnostic loop electro- In the majority of cases, morpho-
At the 2001 workshop, a small mi- surgical excision procedure in women logical features permit differentiation
nority of workshop participants ar- with negative histology results. between atypical endometrial and en-
©2002 American Medical Association. All rights reserved. (Reprinted) JAMA, April 24, 2002—Vol 287, No. 16 2117

Downloaded from jama.ama-assn.org by guest on February 5, 2012


THE 2001 BETHESDA SYSTEM

docervical cells.14 The management of menstrual/menopausal status, exog- tive, consistent with clinical follow-up
patients with glandular abnormalities enous hormone therapy, and other guidelines published by professional or-
may vary significantly depending on cell clinical risk factors are often un- ganizations, and phrased in the form of
type and justifies making this distinc- known or unclear. Although usually a suggestion. A qualifying phrase (eg,
tion when possible. The term “atypi- benign in nature, identification of “as clinically indicated”) should gen-
cal epithelial cells” may be used for endometrial cells, particularly if not as- erally be added since the pathologist
cases where a squamous vs glandular sociated with menses or after meno- may be unaware of other pertinent clini-
origin cannot be determined. pause, may indicate risk for an endo- cal information. One study has shown
The finding of atypical glandular cells metrial abnormality.22-25 As noted above, that including suggestions for further
(AGC) is important clinically because this finding is categorized as “other.” evaluation improves the likelihood that
the percentage of cases associated with It is important to emphasize that cer- appropriate follow-up occurs.26 Pro-
underlying high-grade disease is higher vical cytology is primarily a screening viding references for consensus clini-
than for ASC-US. On follow-up, high- test for squamous epithelial lesions and cal follow-up guidelines for abnormal
grade lesions (either squamous or glan- squamous cancer. It is unreliable for the cervical cytology results published by
dular) may be seen in 10% to 39% of detection of endometrial lesions and medical organizations (eg, American
such cases.15-17 Based on such data, the should not be used to evaluate sus- College of Obstetricians and Gynecolo-
qualifier “favor reactive” was consid- pected endometrial abnormalities. gists, American Society for Colpos-
ered misleading and it has been elimi- copy and Cervical Pathology) may also
nated: such cases are now included in Automated Review be helpful.27
the AGC category. and Ancillary Testing
In the 1991 terminology, adenocar- “Automated review and ancillary test- SUMMARY
cinoma in situ (AIS) was included in ing” are elements of the report that are The goal of the Bethesda System is to
“AGUS, probably neoplastic.” Since that included as appropriate. For slides promote more effective communica-
time, studies have clearly documented scanned by automated computer sys- tion of cervical cytology results from the
predictive value and reproducibility of tems, the instrumentation used and the laboratory to clinicians. The 2001 re-
properly applied cytological criteria for automated review result should be in- vision of the terminology was devel-
this interpretation.18-20 “Endocervical ad- cluded in the cervical cytology report. oped through a process designed to in-
enocarcinoma in situ” is therefore now If an ancillary molecular test has been corporate new scientific data and
a separate category. However, there is performed, the type of assay should be encourage input from a broad range of
considerable morphological overlap be- specified in addition to the results. Ide- individuals involved in cervical can-
tween AIS and well-differentiated inva- ally, cytology and ancillary testing re- cer screening. Management guide-
sive endocervical adenocarcinoma; a per- sults should be reported concur- lines for women with abnormal cytol-
centage of cases interpreted as AIS will rently; however, this may not always be ogy results, based on the 2001 Bethesda
demonstrate invasion on histological possible. System, have been developed at a con-
evaluation. sensus conference sponsored by the
For cases showing some features sug- Educational Notes and Suggestions American Society for Colposcopy and
gestive of, but not sufficient to reach an Written comments regarding the va- Cervical Pathology.28 Such collabora-
interpretation of AIS, an intermediate lidity and significance of a cytology re- tive and integrated development of re-
category of “atypical endocervical cells, sult are the responsibility of the pa- porting terminology and management
favor neoplastic” conveys a significant thologist and are directed to the guidelines should provide more uni-
level of concern. There is no basis for es- clinician who requested the test. The form, evidence-based care of women
tablishing a category of “endocervical laboratory should avoid communi- with cervical abnormalities.
glandular dysplasia” or “low grade glan- cating results directly to the patient, as
dular intraepithelial lesion.”21 A mor- this may interfere with the patient- The Forum Group Members include the following:
Specimen Adequacy: Diane D. Davey, MD, George
phological spectrum of bona fide pre- clinician relationship. Direct contact be- Birdsong, MD, Henry W. Buck, MD, Teresa Darragh,
cursors of AIS has not been identified for tween the patient and the laboratory MD, Paul Elgert, CT(ASCP), Michael Henry, MD,
Heather Mitchell, MD, Suzanne Selvaggi, MD; Be-
endocervical glandular lesions. may be acceptable, however, if specifi- nign Cellular Changes and Infections: Nancy Young,
Other. In the previous version of the cally requested by the clinician. MD, Marluce Bibbo, MD, Sally-Beth Buckner, CT
Bethesda System, the finding of endo- The use of educational notes or sug- (ASCP), Terence Colgan, MD, Dorothy Rosenthal, MD,
Edward Wilkinson, MD; ASCUS: Mark Sherman, MD,
metrial cells was reported only for post- gestions is optional. If used, the for- Fadi Abdul-Karim, MD, Jonathan Berek, MD, Patri-
menopausal women. However, in the mat and style may vary depending on cia Braly, MD, Robert Gay, CT(ASCP), Celeste Pow-
ers, MD, Mary Sidawy, MD, Sana Tabbara, MD; AGUS:
2001 Bethesda System, endometrial the preferences of the laboratory and its David Wilbur, MD, David Chhieng, MD, J. Thomas
cells are noted if the woman is 40 years clinicians. Nevertheless, any com- Cox, MD, Jamie Covell, BS, CT(ASCP), Barbara Gui-
dos, SCT(ASCP), Kenneth Lee, MD, Dina Mody, MD;
of age or older, regardless of the date ments should be carefully and thought- HPV Triage: Stephen Raab, MD, Karen Allen, CT
of the last menstrual period, because fully crafted, concise but not direc- (ASCP), Christine Bergeron, MD, PhD, Diane Harper,

2118 JAMA, April 24, 2002—Vol 287, No. 16 (Reprinted) ©2002 American Medical Association. All rights reserved.

Downloaded from jama.ama-assn.org by guest on February 5, 2012


THE 2001 BETHESDA SYSTEM

MD, Walter Kinney, MD, Alexander Meisels, MD; En- mined significance: baseline results from a random- nificance as defined by the Bethesda System. Am J Ob-
dometrial Cells: Ann Moriarty, MD, Edmund Cibas, ized trial. J Natl Cancer Inst. 2001;93:293-299. stet Gynecol. 1997;177:1188-1195.
MD, Gary Gill, CT(ASCP), Meg McLachlin, MD, Ellen 7. Sherman ME, Solomon D, Schiffman M, for the 18. Betsill WL, Clark AH. Early endocervical glandu-
Sheets, MD, Theresa Somrak, CT(ASCP), Rosemary ALTS Group. Qualification of ASCUS: a comparison lar neoplasia, I: histomorphology and cytomorphol-
Zuna, MD; LSIL /HSIL: Tom Wright, MD, Richard De- of equivocal LSIL and equivocal HSIL cervical cytol- ogy. Acta Cytol. 1986;30:115-126.
May, MD, Rose Marie Gatscha, CT(ASCP), Lydia How- ogy in the ASCUS LSIL Triage Study. Am J Clin Pathol. 19. Lee KR, Manna EA, Jones MA. Comparative cy-
ell, MD, Ronald Luff, MD, MPH, Volker Schneider, MD, 2001;116:386-394. tologic features of adenocarcinoma in situ of the uter-
Leo Twiggs, MD; Computer-Assisted Diagnosis: Mari- 8. Quddus MR, Sung CJ, Steinhoff MM, et al. Atypi- ine cervix. Acta Cytol. 1991;35:117-126.
anne Prey, MD, Mike Facik, CT(ASCP), Albrecht Reith, cal squamous metaplastic cells: reproducibility, out- 20. Biscotti CV, Gero MA, Toddy SM, Fischler DF, Ea-
MD, Max Robinowitz, MD, Mary Rubin, NP, PhD, Sue come, and diagnostic features on ThinPrep Pap test. sley KA. Endocervical adenocarcinoma in situ: an analy-
Zaleski, SCT(ASCP); Recommendations, Educational Cancer. 2001;93:16-22. sis of cellular features. Diagn Cytopathol. 1997;17:
Notes, and Disclaimers: Dennis O’Connor, MD, Mar- 9. Sherman ME, Tabbara SO, Scott DR, et al. “ASCUS, 326-332.
shall Austin, MD, PhD, Lisa Flowers, MD, Blair rule out HSIL”: cytologic features, histologic corre- 21. Farnsworth A, Laverty C, Stoler MH. Human pap-
Holladay, PhD, CT(ASCP), Dennis McCoy, JD, Paul lates and human papillomavirus detection. Mod Pathol. illomavirus messenger RNA expression in adenocar-
Krieger, MD, Gabriele Medley, MD, Jack Nash, MD, 1999;12:335-343. cinoma in situ of the uterine cervix. Int J Gynecol
Mark Sidoti, JD; Electronic Bulletin Board Program- 10. Park TJ, Richart RM, Sun X-W, et al. Association Pathol. 1989;8:321-330.
mer: Lomi Kil, BA. between HPV type and clonal status of cervical squa- 22. Montz FJ. Significance of “normal” endometrial
mous intraepithelial lesions (SIL). J Natl Cancer Inst. cells in cervical cytology from asymptomatic post-
1996;88:355-358. menopausal women receiving hormone replacement
REFERENCES
11. Wright TC, Kurman RJ. A critical review of the mor- therapy. Gynecol Oncol. 2001;81:33-39.
1. National Cancer Institute Workshop. The 1988 phologic classification systems of preinvasive lesions 23. Ng ABP, Reagan JW, Hawliczek S, Wentz BW. Sig-
Bethesda System for reporting cervical/vaginal cyto- of the cervix: the scientific basis for shifting the para- nificance of endometrial cells in the detection of en-
logic diagnoses. JAMA. 1989;262:931-934. digm. Papillomavirus Rep. 1994;5:175-182. dometrial carcinoma and its precursors. Acta Cytol.
2. Davey DD, Nielsen ML, Rosenstock W, Kline TS. 12. Einstein MH, Burk RD. Persistent human papil- 1974;18:356-361.
Terminology and specimen adequacy in cervicovagi- lomaviral infection: definitions and clinical implica- 24. Yancey M, Magelssen D, Demaurez A, Lee RB.
nal cytology: the College of American Pathologists’ tions. Papillomavirus Rep. 2001;12:119-123. Classification of endometrial cells on cervical cytol-
interlaboratory comparison experience. Arch Pathol 13. zur Hausen H. Papillomaviruses causing cancer: ogy. Obstet Gynecol. 1990;76:1000-1005.
Lab Med. 1992;116:903-907. evasion from host-cell control in early events in car- 25. Gondos B, King EB. Significance of endometrial
3. The 1991 Bethesda System for reporting cervical/ cinogenesis. J Natl Cancer Inst. 2000;92:690-698. cells in cervicovaginal smears. Ann Clin Lab Sci. 1977;
vaginal cytologic diagnoses: report of the 1991 14. Wilbur DC. The cytology of the endocervix, endo- 7:486-490.
Bethesda Workshop. JAMA. 1992;267:1892. metrium, and upper female genital tract. In: Bonfiglio 26. Jones BA, Novis DA. Follow-up of abnormal gy-
4. Davey D, Woodhouse S, Styer P, Stastny J, Mody TA, Erozan YS, eds. Gynecologic Cytopathology. Phila- necologic cytology: a College of American Patholo-
D. Atypical epithelial cells and specimen adequacy: cur- delphia, Pa: Lippincott-Raven; 1997:107-156. gists Q-Probes study of 16,132 cases from 306 labo-
rent laboratory practices of participants in the Col- 15. Jones BA, Novis D. Cervical biopsy-cytology cor- ratories. Arch Pathol Lab Med. 2000;124:665-671.
lege of American Pathologists interlaboratory com- relation: a College of American Pathologists Q- 27. Smith-McCune K, Mancuso V, Constant T, Jack-
parison program in cervicovaginal cytology. Arch Pathol Probes study of 22,439 correlations in 348 laborato- son R. Management of women with atypical Papani-
Lab Med. 2000;124:203-211. ries. Arch Pathol Lab Med. 1996;20:523-531. colaou tests of undetermined significance by board-
5. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. 16. Soofer S, Sidawy M. Atypical glandular cells of un- certified gynecologists: discrepancies with published
Natural history of cervicovaginal papillomavirus in- determined significance: clinically significant lesions and guidelines. Am J Obstet Gynecol. 2001;185:551-556.
fection in young women. N Engl J Med. 1998;338: means of patient follow-up. Cancer Cytopathol. 2000; 28. Wright TC Jr, Cox JT, Massad LS, Twiggs LB,
423-428. 90:207-213. Wilkinson EJ, for the 2001 ASCCP-sponsored Con-
6. Solomon D, Schiffman M, Tarone R, for the ALTS 17. Eddy GL, Stumpf KB, Wojtowycz MA, Piraino PS, sensus Conference. 2001 Consensus guidelines for the
Group. Comparison of three management strategies Mazur MT. Biopsy findings in five hundred thirty one management of women with cervical cytological ab-
for patients with atypical squamous cells of undeter- patients with atypical glandular cells of uncertain sig- normalities. JAMA. 2002;287:2120-2129.

©2002 American Medical Association. All rights reserved. (Reprinted) JAMA, April 24, 2002—Vol 287, No. 16 2119

Downloaded from jama.ama-assn.org by guest on February 5, 2012

You might also like