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The New Bethesda System for

Reporting Results of Smears of

the Uterine Cervix

Leopold G. Koss*

Over 40 years have elapsed since the large-scale introduction

of the cervical-cancer smear as a cancer detection tool. The

smear, which consists of a sample of cells from the epithelial

surfaces of the uterine cervix, is colloquially known as the "Pap

test," after its discoverer, George N. Papanicolaou. The test is

performed annually on many millions of women. It has contrib-

uted in a statistically sign ificant way to the reduction of mo rbidity

and mortality rates from invasive carcinoma of the uterus in

appropriately screened populations {1-4). However, the test is

prone to disturbing failures (5).

Theoretically, at least, the test is quite simple: the cell samples,

placed on microscope slides and appropriately stained, are stud-

ied under the microscope by trained cytotechnologists. The

presence of precancerous lesions is heralded by the appearance of

nuclear and cytoplasmic abnorm alities. Tissue biopsies, prefera-

bly obtained with the colposcope, a magnifying instrument,

provide further information on the scope and size of the lesion,

which is subsequently removed or destroyed to prevent its

progression to invasive cancer.

In practice, there are several problems with the Pap test. They

are (a) the adequacy of the samples, (b ) the difficulty of micro-

scopic screening, based on recognizing few abnormal cellsamong many thousands of cells in each sample, and (c) the

compliance of patients with testing at appropriate intervals or

with follow-up procedures. T hese problems have been the subject

of considerable concern in the lay press and in scientific publica-

tions (5). The failure to discover a precancerous lesion before it

becomes malignant has resulted in invasive cancer and death of

some young patients.

Measures to improve the quality of screening have been

recently proposed (Amendment to the Clinical Laboratory Im-

provement Act: pending), but, without adequate funding, the

implementation and results of these measures are uncertain.

One of the key issues in providing adequate care to patients at

risk for cervical cancer is the manner in which the smears arereported to the primary care physicians and gynecolog ists. Papa-

nicolaou, who was not a trained pathologist, recognized early in

his work that he was not qualified to render diagnostic verdicts

based on smears. He therefore devised a system of reporting

based on five classes. C lass I smears were entirely benign, hence

normal. Class II smears disclosed minor cell abnormalities

("atypia" ), thoug ht to be benign. Class III smears corresponded to

cell abnormalities that were "suspicious," but not definitely

cancerous. Class IV smears were "most likely malignant," and

Class V smears were unequivocally malignant and diagnostic of

cancer.

This reporting system was widely adopted in the United States

and abroad but was rarely used as originally intended . Instead, the

significance of classes was often modified. In some laboratories,

Class II smears w ere considered to be susp icious, C lass III smears

were considered to indicate precancerous lesions, and Class IV

smears were considered to indicate invasive cancer. Other labo-

ratories used only three classes. Still further variations in the

theme existed, including subdivision of the classes by letters,

such as III A and IIIB .

The issue became even m ore complicated once tissue patholo-gists entered the act. It was recognized fairly early in the

mass-screening process that the rate of discovery of precancerous

lesions of the cervical epithelium was much higher than the true or

projected incidence of invasive cancer. Hence, there were at least

some precancerous lesions that did not have the potential for

progression to invasive cancer. Some observers thought that the

cytologic and histologic appearance of these lesions might pro-

vide the clue to their behavior. Thus, despite some dissenting

voices {6,7), the lesions were divided into two broad categories:

dysplasia and carcinoma in situ. Dysplasia referred to lesions

with a lower degree of abnorm ality that w ere implicitly less likely

to progress to invasive cancer. Carcinoma in situ referred to

lesions that were implicitly more likely to progress to invasivecancer. Dysplasia was further subdivided into three grades (mild,

moderate, and severe) that were presumed to reflect the potential

for "good" or "w orse" behavior {8). It was also proposed that one

could accurately interpret the cervical smear in terms of the

underlying tissue pattern.

These additional classifications had a profound impact on the

reporting system. Because of significant peer pressure, patholo-

gists felt co mpel led to add a comment on the nature, and hence the

probable behavior, of the underlying lesion to every abnormal

smear report. This system of reporting was based on the premise

that the interpretation of smears and biopsies was reproducible.

Unfortunately, in spite of some efforts {8), the precancerous

lesions known as dysplasias have never been objectively defined.

Numerous surveys among expert pathologists clearly showed that

the diagnostic system was no t reproducible and that one person's

dysplasia was another pe rson's carcinoma and vice versa {9,10).

Further, long-term follow-up studies documented that the behav-

ior of precancerous lesions could not be predicted by morphology

(6).

The clinicians at the receiving end of the cytologic reports were

often unaware of the substance and nature of the controversy and

acted (or failed to act) according to their interpretation of the

classes and verbal comments. There is evidence that women with

Class III smears or "dysplasia" were not always treated and

subsequently developed invasive cancer {11). Because of thediagnostic chaos, it became impossible to compare the results

from laboratories and individual pathologists.

Received May 1, 1990; accepted May 2, 1990.

*Correspondence to: Leopold G. Koss. M.D., Department of Pathology,

Montefiore Medical Center and Albert Einstein College of Medicine . H I E .

210th St.. Bronx, NY 10467.

Journal of the National Cancer Insti tute



Richart's introduction of the concept of "cervical intraepithe-

lial neoplasia" (CIN) (12), encomp assing all of the precancerous

lesions of the epithelium of the uterine cervix, constituted a major

breakthrough. Many gynecologists recognized that reports on

cervical smears were not always accurate and that many women

with "atypia" or "mild dysplasia" have precancerous lesions

requiring colposcopy and treatment. This knowledge, however,

did not necessarily drift down to the primary care physicians or

alleviate the need for a uniform reporting system of cervical

smears.

A group of expe rts, representing a broad spectrum of interested

professional organizations, met in Bethesda, Md, under the

auspices of the National Cancer Institute on December 12 and 13,

1988. They met in an attempt to redefine the reporting system of

the cervical smears and to address several other pertinent issues

(13). The resulting document, now known as The Bethesda

System (table 1), was adopted by consensus and, hopefully, will

introduce order and uniformity into the diagnostic chaos that

prevailed until now.

The key points of the Bethesda System are as follows:

I. The cytology report is a medical consultation. This state-

ment separates the cervical smear from machine-generated clini-

cal laboratory tests and proposes a different role for the smear in

the cancer prevention system. It holds clinician responsible forobtaining an adequate sample and for providing an adequate

medical history. It obligates the cytopathologist to assess the

adequacy of the sam ple, that is, whether it is representative of the

status of the cervical epithelium. The statement also obligates the

Table 1. The 1988 Bethesda System for reporting cervical/vaginal cytological diagnoses.

Statement on Specimen Adequacy

Satisfactory for interpretationLess than optimalUnsatisfactory

Explanation for less than optimal/unsatisfactory specimen:

—Scant cellularity

—Poor fixation or preservation—Presence of foreign material (e.g., lubricant)—Partially or completely obscuring inflammation

—Partially or completely obscuring blood—Excessive cytolysis or autolysis—No endocervical component in a premenopausal woman who has a

cervix—Not representative of the anatomic site—Other

General Categorization

Within normal limits

Other:

Se e descriptive diagnoses

Further action recommended

Descriptive Diagnoses

INFECTIONFungal

Fungal organisms morphologically consistent with Candida speciesOther

Bacterial

Microorganisms morphologically consistent with Gardnerella speciesMicroorganisms morphologically consistent with Actinomyces speciesCellular changes suggestive of Chlamydia species infection, subject

to confirmatory studiesOther

Protozoan

Trichomonas vaginalisOther

Viral

Cellular changes associated with cytomegalovirusCellular changes associated with herpesvirus simplexOther

(Note: for human papillomavirus IHPVJ, refer to "Epithelial CellAbnormalit ies , Squamous Cell")

Other

REACTIVE AND REPARATIVE CHANGES

Inflammation

Associated cellular changes

Follicular cervicitisMiscellaneous (as related to patient history)

Effects of therapy

Ionizing radiationChemotherapyEffects of m echanical devices (e.g., intrauterine contraceptive device)

Effects of nonsteroidal estrogen exp osure (e.g., diethylstilbestrol)Other

EPITHELIAL CELL ABNORMALITIES

Squamous Cell• Atypical squamous cells of undetermined significance

(recommended follow-up and/or type of further investigation:specify)

• Squamous intraepithelial lesion (SIL) (comm ent on presence ofcellular changes associated with HPV if applicable)

Low-grade squamous intraepithelial lesion, encompassing:Cellular changes associated with HPVMild (slight) dysplasia/cervical intraepithelial neoplasia

grade 1 (CIN I)High-grade squamous intraepithelial lesion, encompassing:

Moderate dysplasia/CIN IISevere dysplasia/CIN III

Carcinoma in situ/CIN III

• Squamou s cell carcinoma

Glandular Cell

• Presenc e of endom etrial cells in one of the followingcircumstances:

Out of phase in a menstruating womanIn a postmenopausal womanNo menstrual history available

• Atypical glandular cells of undetermined significance(recommended follow-up and/or type of further investigation:specify)

EndometrialEndocervicalNot otherwise specified

• AdenocarcinomaSpecify probable site of origin: endocervical, endometrial,

extrauterineNot otherwise specified

• Other epithelial malignant neoplasm: specify

NONEPITHELIAL MALIGNANT NEOPLASM: SPECIFY

HORMONAL EVALUATION (APPUES TO VAGINAL SMEARS ONLY)

• Hormo nal pattern compatible with age and history• Hormonal pattern incompatible with age and history: specify• Hormonal evaluation not possible

Cervical specimenInflammation

Insufficient patient history

OTHER

Vol. 82, No. 12, June 20, 1990 EDITORIAL



pathologist to provide guidance to the clinician in further evalu-

ation of the patient, if required.

II. The Papanicolaou reporting system of smear classes was

not considered adequate. The lack of uniformity and uncertainty

of the message conv eyed by classes was judged to be ill-suited to

the practice of preventive medicine.

III. A new reporting system was proposed. The proposed

reporting system is the heart of the Bethesda document because it

requires that each report should determine several aspects of the

cervical sample. (The Bethesda System proposal does not pre-clude the use of other nomenclature as an addendum to the

principal reporting system.) Requirements for the report are as

follows:

A. Adequacy of smea rs. The adequacy of each sample must be

assessed. If the sample is thought to be inadequate, an

explanation of the reasons for this judgment must be

provided. This provision has significant fiscal implica-

tions: for a smear to be judged as inadequate, it must be

processed and screened. The costs of this procedure must

be borne by the patients or third-party payers, and obtain-

ing another smear clearly implies additional costs. T hus, it

is in the interest of the clinicians and the patients to provideadequate smears on the first attempt. On the other hand,

rejecting a sme ar as inadequate requires good judgm ent by

the pathologist, and this decision must be based on solid

grounds. Because the makeup of the smear may vary

according to the clinical situation, sampling instruments,

age, and menstrual status of the patient, these factors must

be taken into account. Needless to say, reporting an

inadequate sm ear as negative in a patient who subsequently

develops invasive cervical cancer may have major legal

consequences.

B. Primary assessm ent. The reporting of the sample falls into

two categories: within normal limits and "other," which

calls for descriptive diag nosis.

C. Descriptive diagnosis of benign abnormalities. The de-

scriptive diagnosis of benign abnormalities includes a

broad variety of infections and infestations and reactive

changes.

D. Descriptive diagnosis of precancerous lesions. In reference

to the precancerous intraepithelial lesions, the significant

thrust of the Bethesda System is the classification of these

lesions into two categories: low-grade and high-grade. Th e

low-grade lesions include all neoplastic changes, previ-

ously classified as "mild dy splasia," CIN I, or lesions with

morphologic changes suggestive of human papillomavirus

infections (e.g., flat condylomas). The high-grade lesionscomprise all other precancerous events or lesions previ-

ously classified as moderate or marked dysplasia and

carcinoma in situ (CIN II and III). Thus, the reporting of

precancerous lesions is much simplified.

E. Descriptive diagnosis of cancer. Additional reporting cate-

gories have been provided to encompass other abnormali-

ties, including various types of invasive cancer that can be

recognized in the cervical samples.

The goal of the Bethesda System is to introduce a uniform

reporting system for cervical smears. This is an important first

step in introducing a national system of quality control. The

mandatory reporting of inadequate samples may have a major

impact on the quality of the smears. Patients' compliance with

testing at appropriate intervals and/or with follow-up procedures,

on the other hand, will not be directly affected, short of a major

media campaign.

Is the Bethesda System a final document that will once and for

all eliminate all problems with providing, screening, and report-

ing cervical smears? W ill it introduce uniform clinical han dling of

these lesions? And finally, will the system eliminate invasive

cervical cancer, w hich is a preventable disease? This writer hassome doubts about it. The reporting system as such is only one

part of a complex cancer detection process (5). The reproducibil-

ity of the diagn ostic sys tem, even with the simplified classifica-

tion of low-grade and high-grade precancerous lesions must still

be tested. While this subdivision is possible in the morphologic

sense, it still does not imply that the handling of the patients

should be different.

Although there is fairly good evidence that many of the

low-grade lesions will disappear spontaneously, many exceptions

to this rule exist. F urther, no statistical analysis performed to date

indicates how many high-grade lesions are represented in the

smears classified as low-grade lesions. Anecdotal experience

suggests that this occurrence is not uncommo n. T hus, colposcopy

of all the lesions, whether low- or high-grade, is still the prudent

way to proceed.

Undoubtedly, with the passage of time, perhaps in the next

century, m olecular biologic probes will become available. These

probes will allow an accurate prediction of the behavior of

precancerous lesions, a task that unfortunately is not possible

today by morphologic examination of the cytologic samples or

tissue samples or by typing of human papillomaviruses (14).

However, the Bethesda System is a good beginning. As the

writers of the document stated, like any other human endeavor,

this document can be amended in the future. At this time, it is

worthy of a major trial on a national scale, provided that theresults are collated and evaluated. To my knowledge, no effort

has been made so far to create an agency that would assess the

results.

References

( /) BOYES DA: The value of a Pap smear program and suggestions for itsimplementation. Cancer 48:613-621, 1981

(2 ) MILLER A B , LINDSAY J, HILL GB: Mortality from cancer of the uterus inCanada and its relationship to screening for cancer of the cervix. Int J Cancer17:602-612, 1986

(3 ) GEIRSSON G: Organization of screening in technically advanced countries:

Iceland. In Screening for Cancer of the Uterine Cervix (Hakama M, MillerAB, Day NE, eds). Lyons: 1ARC, 1986, pp 239 -250

(4 ) HAKAMA M: Trends in the incidence of cervical cancer in the Nordiccountries. In Trends in Cancer Inciden ce, Causes and Practical Implications(Magnus K, ed). Washington, DC: Hemisphere 1988, pp 279-292

(5) Koss LG : The Papanicolaou test for cervical cancer detection: A triumphand a tragedy. JAMA 261:737 -743, 1989

(6) Koss LG, STEWART FW , FOOTE FW JR, ET AL: Some histologic aspects ofbehavior of epidermoid carcinom a in situ and related lesions of the uterinecervix: A long-term prospective study. Cancer 12:1171-1193, 1963

(7) Koss LG: Dysplasia: A real concept or a misnomer? Obstet Gynecol51:374-379, 1978

(8 ) PATTEN SF JR: Diagnostic Cytology of the U terine Cervix. 2nd ed. Basel: SKarger, 1978

(9 ) COCKER J, Fox H, LANCLEY FA: Consistency in the histological diagnosis ofepithelial abnormalities of the uterine cervix. J Clin PathoF 21:6 7-70 , 1968

Journal of the National Cancer Institute



(10) SEYBOLT JF , JOHNSON WD: Cervical cytodiagnostic problems: A survey.Am J Obstet Gynecol 109:1089-1103, 1971

( / / ) RYLANDER E: Negative smears in women developing invasive cervical

cancer. Acta Obstet Gynecol Scand 56:115-118, 1977(12) RICHART RM: Cervical intraepithelial neoplasia: A review. Pathol Annu

3:301-328, 1973

(13) NATIONAL CANCER INSTITUTE WORKSHOP: The 1988 Bethesda system for

reporting vaginal/cervical cytological diagnoses. JAMA 262:567-576,1989

(14) LORINCZ AT, LANCASTER WD, KURMAN RJ, ET AL : Characterization of

human papillomaviruses in cervical neoplasias and their detection in routineclinical screening. In Viral Etiology of Cervical Cancer: B anbury Report 21(Peto R, zur Hausen H, eds). Cold Spring Harbor, NY: Cold Spring HarborLaboratory, 1986, pp 225-237

Cancer Is Complex

Is Simple

For the lates t cance r informationfrom the National CancerInstitute's Cancer InformationService, write:

The N ational Cancer InstituteBuilding 31, Room 10A24Bethesd a, M aryland 20892-3100U.S.A.

Or Call:1-800-4-CANCER*

( 1 - 8 00 - 422 - 6237 )

Vol. 82, No. 12, June 20, 1990 EDITORIAL 9

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