Review

Acta Cytologica 2015;59:121–132 Received: December 27, 2014
Accepted: December 27, 2014
DOI: 10.1159/000381842
Published online: May 19, 2015

The Pap Test and Bethesda 2014
“The reports of my demise have been greatly exaggerated.”
(after a quotation from Mark Twain)

Ritu Nayar a, b David C. Wilbur c, d
   

a Department of Pathology, Northwestern University, Feinberg School of Medicine, b Northwestern Medicine,
Chicago, Ill.,c Department of Pathology, Massachusetts General Hospital, and d Department of Pathology, Harvard
 

Medical School, Boston, Mass., USA

Key Words Introduction
The Bethesda System · Bethesda atlas · Pap test ·
Cervical cytology · Reporting One snowy weekend in December 1988, a small group
of individuals with expertise in cytopathology, histopa-
thology, and patient management met at the National In-
Abstract stitutes of Health in Bethesda, Maryland [1]. This meet-
The history of ‘The Bethesda System’ for reporting cervical ing, which became the first Bethesda workshop, was
cytology goes back almost 3 decades. This terminology and chaired by Robert Kurman and focused on addressing the
the process that created it have had a profound impact on issues related to the wide variability in reporting results
the practice of cervical cytology for laboratorians and clini- of cervical cytology when cytologists used either the nu-
cians alike. The Bethesda conferences and their ensuing out- meric ‘Pap Class’ system or the ‘dysplasia’ terminology.
put have also set the stage for standardization of terminol- The objective was to establish terminology that would
ogy across multiple organ systems, including both cytology provide clear-cut thresholds for management and de-
and histology, have initiated significant research in the biol- crease interobserver variability. During the 2 days of that
ogy and cost-effective management for human papillomavi- historic workshop, 3 fundamental principles emerged
rus-associated anogenital lesions, and, finally, have fostered that have guided The Bethesda System (TBS) to this day:
worldwide unification of clinical management for these le- 1. Terminology must communicate clinically rele-
sions. Herein, we summarize the process and rationale by vant information from the laboratory to the patient’s
which updates were made to the terminology in 2014 and health care provider.
outline the contents of the new, third edition of the Bethes- 2. Terminology should be uniform and reasonably
da atlas and corresponding website. © 2015 S. Karger AG, Basel reproducible across different pathologists and laborato-
ries and also flexible enough to be adapted in a wide vari-
ety of laboratory settings and geographic locations.
This article is jointly published in Journal of the American Society of Cy- 3. Terminology must reflect the most current un-
topathology, Cancer Cytopathology, Journal of Lower Genital Tract Dis- derstanding of cervical neoplasia.
ease and Acta Cytologica by the American Society of Cytopathology, On the basis of these principles, in 1988, the first itera-
the American Cancer Society, the American Society for Colposcopy tion of TBS recommended a 2-tiered reporting system for
and Cervical Pathology, and the International Academy of Cytology.
©
2015 American Cancer Society Inc., American Society of Cytopa- squamous intraepithelial lesions (SILs): low-grade SIL
thology, American Society for Colposcopy and Cervical Pathology, (LSIL) and high-grade SIL (HSIL). This terminology re-
and International Academy of Cytology. flected the up-to-date understanding of human papillo-
179.7.140.208 - 5/12/2017 6:28:51 AM

© 2015 S. Karger AG, Basel Correspondence to: Prof. Ritu Nayar
0001–5547/15/0592–0121$39.50/0 Northwestern University Feinberg School of Medicine
Northwestern Memorial Hospital
Downloaded by:

E-Mail karger@karger.com
Chicago, IL 60611 (USA)
www.karger.com/acy
E-Mail r-nayar @  northwestern.edu

ample illustrations depicting mimics and SIL terminology. histograms from the BIRST [6]. and previously posed a significant clinical management tories that offered cervical cytology testing. Af. which then brought together over 400 par. By early 2003.140. Areas in Cytopathology and Histopathology tion by providing an interpretation that contributes to a diagnosis. ation test. leading to billions of dollars in colposcopic fol- Bethesda atlas addressed all of these considerations. was the ue of the screening process. and results of other laboratory tests to the biology of cervical cancer and exploring new ap- such as cervical biopsy’ [2. Because ASCUS is the most common cytologic abnor- 3. sent sources of poor interobserver agreement [6]. In addition to the pretive criteria. Downstream Events That Significantly Influenced cal cytology report. Between 1991 and 2001.1159/000381842 Downloaded by: . The final diagnosis and management plan Initiation of Research and Clinical Trials should integrate the cervical cytology with patient histo.mavirus (HPV) biology – squamous epithelium is affect.7. 2001 and to improve reproducibility.5/12/2017 6:28:51 AM 122 Acta Cytologica 2015. by extension. and (ii) to identify specific cyto- criteria for TBS interpretive categories and diagnostic morphologic features and cytologic categories that repre- terms and for the determination of specimen adequacy. 4. reproducibility of the various Bethesda categories. ditional images beyond those available in the print atlas. more detailed inter- tion or as viral-associated precancer. for over a million results annually in the United States ing were introduced and increasingly utilized in labora. to finalize the 2001 Bethesda System taken the self-test alone. 4]. Terminology [4]. Implementation of TBS Initiated Several mended instead of ‘diagnosis’ in the heading of the cervi. duction of ancillary studies to improve the predictive val- The next Bethesda workshop. clinical findings. addition. held in 2001. this monograph quickly became a has led to further progress in education and to the intro- worldwide reference for the practice of cervical cytology. but before publication of the ment [2]. proaches and strategies for patient management. In conjunction with the print atlas. it accounts automation. This site has been extensively used – over ticipants. develop the web-based Bethesda Interobserver Repro- ther advances in scientific knowledge. cells of undetermined significance’ (ASCUS) highlighted genital tract. Also Impacted Terminology Development for Other which in some instances may serve as a medical consulta. corresponding atlas. Over 2. and the adoption of TBS in the international cytopathology Noteworthy Points from the 2001 Bethesda Update community had produced a significant impact [8]. histologic correlation.59:121–132 Nayar/Wilbur DOI: 10. The terms ‘interpretation’ or ‘result’ were recom. 85. an important quality-assurance ele.208 . ducibility Study (BIRST). computer-assisted imaging. The in- 2. subsequent Bethes. a subset of atlas images were used to After experience using TBS in clinical practice and fur. because it was believed that cervical Cervical Cancer Screening and Management and cytology should be viewed primarily as a ‘screening test. To deter- 179. to facilitate widespread implementation of TBS- ed by the virus in essentially 2 ways: either as viral infec. A major to evaluate concordance among participants with varied recommendation from the 1991 workshop was to develop training and experience.000 unique individuals from all over the world have dozen countries. Although TBS was developed primarily for cervi. could also be the inherent limitations of morphologic interpretation. and sample reports were ment of adequacy’ as an integral component of the report added [5]. The 2004 problem. pitfalls. and HPV test.5% of laboratories in the United States had implemented Bethesda 2001 terminology. The re- These deliberations and the codification of criteria led to sults of that study highlighted important issues about the the production of the first Bethesda atlas in 1994 [3]. In low-up and/or treatment of these women [1]. an education- pathology community an opportunity to offer input to al Bethesda website [7] was established that provides ad- the refinements proposed by the forum work groups. specimens from other sites in the lower ano.000 Internet comments were considered before images. reported using this terminology. such as the vagina and anus. and. 5. and a self-evalu- the meeting. Included the Following 1. mality reported on Papanicolaou (Pap) tests. TBS played a vital role in facilitating research related ry. troduction of TBS terminology of ‘atypical squamous cal cytology. After TBS-2001. first to use the Internet to provide the international cyto. liquid-based cytology. the objectives of which were: (i) da workshops were convened in 1991 and 2001. including representatives from more than 2 60. which ter its publication. TBS-1988 also incorporated a ‘state.

appointed a task force (see Ap- Terminology in Pathology pendix). tional new information into a third edition of the Bethes- headed by the ASCCP. to accomplish the 2014 update. testing) and. Ritu Nayar. and experience in the United States. with increased incorporation of TBS provided the framework necessary for the devel. urine [15]. chaired by Dr. After the 2001 cytology has been proposed as a ‘reflex’ test or triage for Bethesda conference. primary hrHPV testing as ad- dorsed as the preferred management option for the ditional screening options. inherent loss of sensitivity when prevalence of the disease nology that correlated with both HPV biology and clini. no formal consensus meet- by the World Health Organization. equal management for equal risk [20]. These include the increased use of liquid-based ALTS established high-risk HPV (hrHPV) testing as the preparations. The draft recommendations were shared with the 179. 2014 was an cal management. and the ing was held in association with this update. 12]. non-16/18 HPV-positive screens.208 . evidence-based cervical cancer HPV testing is used alone for primary screening. colposcopy. When opment of systematic.59:121–132 123 DOI: 10. The groups performed anogenital tract [16–19]. The 2-tiered terminology minimal changes were anticipated to the terminology of LSIL and HSIL used in TBS is now also recommended recommended by TBS-2001.1159/000381842 Downloaded by: . clinicians. The results from agement. further insights into HPV bi- Bethesda category re-named as ASC-US. spear. the role of HPV guideline processes have incorporated the fundamental testing. creased prevalence of HPV16/18-associated lesions. David Wilbur (American Society On the basis of the key principles of TBS. information related to cervical cancer. Bethesda 2014: Why? copy. On the basis of all of these changes. With increased uptake copy and Cervical Pathology (ASCCP) held a consensus of HPV vaccination and its downstream effects of de- conference to tailor management strategies that con. pancreas [14]. is low.7. force was divided into 12 groups. HPV triage. idemiologists. hrHPV and genotyping for triage and follow-up. each of which was re- thology of HPV-associated squamous lesions of the lower sponsible for 1 of 12 atlas chapters.140. a literature review and proposed new and expanded con- tent. results from subse- quent clinical trials. evidence-based consensus characteristics of cytology. more recently. including thyroid [13]. and implementation of prophylactic HPV vaccines.5/12/2017 6:28:51 AM The Pap Test and Bethesda 2014 Acta Cytologica 2015. the ASCCP. The task College of American Pathologists for reporting histopa.mine the best course of management (immediate colpos. ology. additional insight into HPV biology. approval egory of atypical squamous cells (ASC) in 2001 [10]. This was en. comprised of a rela- terminology systems have been developed for cytology of tively small group of cytopathologists. Because and. most recently. cer- formed to the Bethesda reporting categories. the American Society for Colpos. under the cat. and the biology/management of HPV-related principles of balancing harms and benefits and providing cervical lesions. and incorporation of revisions and addi- dozens of organizations and professional societies. This meet. With continued development of da atlas for cervical cytology [21]. prevention. and ditional assessment of the ALTS database resulted in nu. The results of ALTS and other clinical appropriate time for a review and update of the 2001 research formed the basis for development of the 2001 Bethesda System terminology. or conservative management) for equivocal and low-grade abnormalities. and ep- other body sites. and man- Study (ALTS). Ad. the US National The past decade has witnessed several changes in the Cancer Institute sponsored the ASCUS/LSIL Triage realm of cervical cancer screening. Management guidelines for abnormal cervical cytology results were up- Alignment of Management with Terminology dated in 2006 and 2012. which began in 1997 [9]. these management guidelines were subsequently updated Bethesda 2014: Process in 2006 and 2012 [11. vical cytology will become even more challenging with ing was also a significant historic event because it was the respect to locator and interpretation skills because of the first time that there was coordination of reporting termi. which have provided a great deal of ical management. cervical screening and management guidelines. President of the American Society of TBS as a Prototype for Standardized Reporting Cytopathology in 2014. including the Over the past few years. the addition of co-testing (Pap and hrHPV most cost-effective triage test for ASCUS. updated guidelines for cervical cancer screening and clin- merous publications. Dr. refinements of morpho- clinical management algorithms – a process that involved logic criteria. standardized of Cytopathology President in 2002). changes in histopathology terminology.

current management guide- and public comment consensus. the predictive value for endometrial hy. 2015. termediate category. indeterminate cytology terminology would likely lead to tion be done only in postmenopausal women (table 1) confusion among clinicians and. (Eds). inaccurate. in postmenopausal women. and consensus was achieved that perplasia/carcinoma decreased significantly compared formal TBS nomenclature should be limited to the origi- with the pre-TBS-2001 experience [21]. Exfoliated endometrial cells (conventional preparation) are Bethesda Terminology Changes shown. In cases with ity [2]. unequivocal HSIL. In the 2012 man.1159/000381842 Downloaded by: .international cytopathology community during an open comment period from March to June of 2014 through a widely advertised. Nucleoli are inconspicuous. 1. inappropriate [21]. or HSIL.140. Wilbur DC. Springer. because menopausal status is often un. and cell bor- ogy itself. management. essentially [12]. This process culmi- nated in the refinement of positions and content. Nayar R.). nal LSIL and HSIL categories. Thus. In 2001. small and are similar in size to an intermediate squamous cell nu- cleus. and the suggested ed. ing recommendations also encourage reporting as LSIL ported in women aged ≥45 years. Bethesda 2014: What Has Changed? Fig. TBS-1988 Rationale: Occasionally. ing’ endometrial cells in postmenopausal women to alert however. with LSIL and Few Cells Suggestive of Concurrent their presence is considered abnormal and raises the pos. were openly solicited. to lines all use LSIL and HSIL nomenclature without an in- increase the predictive value of this category. and recent histopathology report- cally ‘benign-appearing’ endometrial cells should be re. 3rd Edition. possibly.7.59:121–132 Nayar/Wilbur DOI: 10. ports classification as either LSIL or HSIL. In preparation practice indicated that. 1). Furthermore. In total. HSIL sibility of endometrial neoplasia (fig. it was necessary to make an interpretation of HSIL. Cytoplasm is scant. Poor reproducibility and overuse of any new ucational note should specify that endometrial evalua. Adding terminology such as ‘LSIL- endometrial assessment only in postmenopausal women H’ would lead to a de facto 3-tiered system. maintaining the 2-tiered agement guidelines. although endometrial investiga. negating the beneficial aspects of the 2-tiered TBS no- During the TBS-2014 update. cannot exclude Evaluation of this TBS-2001 recommendation in clinical HSIL’ or ‘LSIL-H’ have been proposed. which were then incorporated into TBS-2014 (table 1) and into the third edition of the Bethesda atlas [21]. it was decided that. cytologi. Terms such as ‘LSIL. with cytologic features that lie between LSIL and HSIL. after literature review menclature. the ASCCP advised using histologic classification scheme.454 responses were received from individuals in 59 countries and were compiled and reviewed by the chap- ter-based task force working groups. the presence of concurrent LSIL is not clear. suggested that this reporting should be done in women Since the publication of TBS-2001. Reporting of Benign-Appearing Endometrial Cells Is Now Recommended for Women Aged ≥45 Years Rationale: Although exfoliated endometrial cells are a normal finding during menses and the proliferative No New Category Was Created for Squamous Lesions phase of the menstrual cycle. Cells are arranged in 3-dimensional clusters. than LSIL or HSIL.208 .5/12/2017 6:28:51 AM 124 Acta Cytologica 2015. attention to morphologic features usually sup- clinicians to the possibility of an endometrial abnormal. it has been sug- aged ≥40 years to maximize the likelihood of including gested that these intermediate morphologic patterns all postmenopausal women and that clinical correlation might be better designated with a diagnostic term other should be left to the ordering physician’s discretion [4]. or unknown to the laboratory. Of note: cal Cytology. 2. The 2014 Bethesda terminology is summarized ders are indistinct (From: The Bethesda System for Reporting Cervi- in table 1. for the 2014 TBS update. opinions regarding this topic tion increased. Nuclei are There were minimal changes relating to the terminol. 179. Internet-based bulletin board. a specimen is encountered recommended reporting ‘cytologically benign-appear.

inflammation.140. Table 1.. liquid-based preparation vs.) ‰ Unsatisfactory for evaluation .7. e. state this in the General Categorization above and/or in the Interpretation/Result section of the report--whether or not there are organisms or other non-neoplastic findings) Non-Neoplastic Findings (optional to report) ‰ Non-neoplastic cellular variations o Squamous metaplasia o Keratotic changes o Tubal metaplasia o Atrophy o Pregnancy-associated changes ‰ Reactive cellular changes associated with: ¾ Inflammation (includes typical repair) o Lymphocytic (follicular) cervicitis ¾ Radiation ¾ Intrauterine contraceptive device (IUD) ‰ Glandular cells status post hysterectomy Organisms ‰ Trichomonas vaginalis ‰ Fungal organisms morphologically consistent with Candida spp. ‰ Shift in flora suggestive of bacterial vaginosis ‰ Bacteria morphologically consistent with Actinomyces spp. other SPECIMEN ADEQUACY ‰ Satisfactory for evaluation (describe presence or absence of endocervical/transformation zone component and any other quality indicators.g. partially obscuring blood.59:121–132 125 DOI: 10.5/12/2017 6:28:51 AM The Pap Test and Bethesda 2014 Acta Cytologica 2015. endometrial cells in a woman •45 years of age) ‰ Epithelial Cell Abnormality: See Interpretation/Result (specify ‘squamous’ or ‘glandular’ as appropriate) INTERPRETATION/RESULT NEGATIVE FOR INTRAEPITHELIAL LESION OR MALIGNANCY (When there is no cellular evidence of neoplasia. ‰ Cellular changes consistent with herpes simplex virus ‰ Cellular changes consistent with cytomegalovirus OTHER ¾ Endometrial cells (in a woman •45 years of age) (Specify if “negative for squamous intraepithelial lesion”) 179. (specify reason) ‰ Specimen rejected/not processed (specify reason) ‰ Specimen processed and examined. The 2014 Bethesda System SPECIMEN TYPE: Indicate conventional smear (Pap smear) vs.208 . but unsatisfactory for evaluation of epithelial abnormality because of (specify reason) GENERAL CATEGORIZATION (optional) ‰ Negative for Intraepithelial Lesion or Malignancy ‰ Other: See Interpretation/Result (e.1159/000381842 Downloaded by: . ..g. etc. .

1159/000381842 Downloaded by: .140. specify device and result. however. a com. For occasional cases in which it is not possible to cat. COMPUTER-ASSISTED INTERPRETATION OF CERVICAL CYTOLOGY If case examined by an automated device. CIS. Alternatively. sibility of HSIL. EDUCATIONAL NOTES AND COMMENTS APPENDED TO CYTOLOGY REPORTS (optional) Suggestions should be concise and consistent with clinical follow-up guidelines published by professional organizations (references to relevant publications may be included). follow-up guidelines for these ment explaining the nature of the uncertainty may be ap. favor neoplastic • glandular cells. an interpretation of ASC cannot in patients (such as young women) who have samples for rule out HSIL (ASC-H) may be made in addition to an which the guidelines differ between LSIL and ASC-H. the LSIL interpretation.7. interpretations are for colposcopy and biopsy.208 . CIN 2 and CIN 3) • with features suspicious for invasion (if invasion is suspected) ¾ Squamous cell carcinoma GLANDULAR CELL ¾ Atypical • endocervical cells (NOS or specify in comments) • endometrial cells (NOS or specify in comments) • glandular cells (NOS or specify in comments) ¾ Atypical • endocervical cells. Table 1 (continued) EPITHELIAL CELL ABNORMALITIES SQUAMOUS CELL ¾ Atypical squamous cells • of undetermined significance (ASC-US) • cannot exclude HSIL (ASC-H) ¾ Low-grade squamous intraepithelial lesion (LSIL) (encompassing: HPV/mild dysplasia/CIN 1) ¾ High-grade squamous intraepithelial lesion (HSIL) (encompassing: moderate and severe dysplasia. propriate. This would indicate that definite addition of the ASC-H interpretation should lead to col- 179. favor neoplastic ¾ Endocervical adenocarcinoma in situ ¾ Adenocarcinoma • endocervical • endometrial • extrauterine • not otherwise specified (NOS) OTHER MALIGNANT NEOPLASMS: (specify) ADJUNCTIVE TESTING Provide a brief description of the test method(s) and report the result so that it is easily understood by the clinician.59:121–132 Nayar/Wilbur DOI: 10. In general.5/12/2017 6:28:51 AM 126 Acta Cytologica 2015. LSIL is present as well as some cells that suggest the pos- egorize an SIL as either low-grade or high-grade.

both text and illustrations. (3) sample reports. The content.140.208 . Nayar R. and (4) selected key references. (Eds).000 images were evaluated for the third edition of the Bethesda atlas. in- cluding basic cell biology.1159/000381842 Downloaded by: . educational notes. Wilbur DC. ratio and nuclear hyperchromasia are worrisome for high-grade ations observed on both conventional smears and liquid. Final selections were made after a multistage review process: first by the dedicated chapter Fig. because classification into either LSIL or HSIL is possible in most instances after a careful overall evaluation of the cellular morphology (fig. a. second.59:121–132 127 DOI: 10. c Similar cells are observed in a follow- up cervical biopsy (HE stain) (From: The Bethesda System for Re- ventional preparations. HSIL is shown (liquid-based preparation. and the re. intraepithelial lesion cells elsewhere on the slide. illustrate a spectrum of morphologic vari. b These single cells (liquid-based Task Force. the final interpre- computer-assisted screening. and tables have been added to com. More than 1. the presence of a nucleolus. Even if these cells are maining chapters are dedicated to other malignant neo. 40% are from con. 2015. by a subgroup of the Bethesda 2014 ter of pregnancy was interpreted as negative for intraepithelial le- sion or malignancy (NILM). Note that TBS does not endorse any particular methodology or manufacturer(s) for speci- men collection. ThinPrep). Cervical Cytology.5/12/2017 6:28:51 AM The Pap Test and Bethesda 2014 Acta Cytologica 2015. including all 186 images from the second edition. The cytomorpho- logic criteria are described in general terms. reflecting continued experience and changes in practice. followed by any significant differences related to specific preparation types where relevant. explanatory notes covering difficult morphologic patterns. Third Edition of the Bethesda Atlas Providing an updated atlas with retention of the popu- lar features of the 2004 edition and additional images and content. diagnostic HSIL cells are present. The 370 atlas illustrations. Intermediate interpretations should comprise only a small minority of cases in any laboratory. Nayar R. cytologic criteria. computer-assisted screening.poscopic evaluation. an entity. mimics of epithelial lesions. 3rd Edition. Some images represent classic examples of Springer. 2. (2) description of definitions. complemented by preparation.). observed in the background of a majority of low-grade squamous plasms. 58% of the images are new. have been increased by approximately 66% compared with the sec- ond edition [5]. and a tation should be HSIL (From: The Bethesda System for Reporting new chapter on cervical cancer risk assessment [21]. Wilbur DC. b pare and contrast criteria. and 60% are from liquid-based porting Cervical Cytology. Among the 12 chapters. In this the major Bethesda interpretive categories. 2015. was the main motivation for the 2014 update [21]. anal cytology. and a c current clinical management guidelines for reporting in the 6 interpretation category-based chapters. whereas others were selected to illustrate inter- pretive dilemmas or ‘borderline’ morphologic features 179. squamous intraepithelial lesion. (Eds). ThinPrep) with an increased nuclear to cytoplasmic robust legends.). This sample from a young woman in the late second trimes- group and. Features suggesting the true stro- based cytologic preparations. 2). mal decidual nature of the cells include the smudgy chromatin and and 42% are from the second edition. 3rd Edition. reporting of adjunctive testing. and the format includes: (1) background and introduction. adjunctive HPV or other testing. preparations. Each chapter has been extensively updated. 6 correspond to Fig. specimen.7. 3. Spring- er.

5. perchromatic HSIL cell with a high nuclear to cytoplasmic ratio are although indicative of a reparative reaction. Wilbur DC.). 3). 2015. cervical cytology preparations (fig. Confirmation with immunostains non-neoplastic mimics of classic epithelial abnormalities can be helpful. and nuclear grooves.7. (Eds). These are images of lobular breast carcinoma (liquid-based quacy on HPV testing. This HSIL (liquid-based preparation. such as assessing cellularity in spec- imens obtained from postradiation patients. 6. Chapter 1: Adequacy c d Evaluation of specimen adequacy is considered by many to be the single most important quality assurance component of the Bethesda system. (Eds). blood). including gross cystic disease fluid protein 15 (c) and estrogen receptor immunocytochemistry (d) (From: The are included.59:121–132 Nayar/Wilbur DOI: 10. Data and clinical ex- perience regarding specimen adequacy since 2001 were reviewed. 3–6). Nuclei ex. preparation.). a Note the syncytial arrangement hibit pleomorphism of size and shape. Lobular breast cancer presenting in an atrophic background pattern can be challenging. In this Fig. Springer. leading to the inclusion of additional guidance for special situations. These changes. and the effects of ade- Fig. 2015. a b that may not be interpreted in the same way by all cytolo- gists. Springer. Springer. Nayar R. cells are arranged in a 2-dimensional sheet with abundant edly hypochromatic. 4. Unique to this edition is the substantially larger number of composite images for a side-by-side illustra- tion of mimics and cytologic-histologic correlations (fig. may be classified as shown (From: The Bethesda System for Reporting Cervical Cytolo- ASC-US because of the nuclear pleomorphism noted. lubricant. 3rd Edition. interfering substances (e. 3rd Edition. a reactive process is the generally fine granularity of the chromatin pattern (From: The Bethesda System for Reporting Cervical Cytol- ogy. but a diligent search may reveal more classic cytoplasm showing a ‘pulled-out’ or streaming effect.208 . a b Fig. A brief summary of the atlas chapter updates and their rationale is provided below. ThinPrep) is mark- image. 2015. Wilbur of the morphologic variations that can be encountered in DC. Most nuclei have prominent nucleoli. cells elsewhere on the same slide. Small clusters of Chapter 2: Non-Neoplastic Changes cells (a) and individual cells (b) with mucin vacuoles contrast with An expanded variety of ‘normal’ findings as well as a background of parabasal cells.).g.140. Nayar R. Nayar R. b Abnormal. Wilbur DC. SurePath).5/12/2017 6:28:51 AM 128 Acta Cytologica 2015. providing a more complete representation Bethesda System for Reporting Cervical Cytology.1159/000381842 Downloaded by: . naked nuclei and a single. 3rd Edition. ASC-US atypical repair (conventional preparation). 179. and some cells have multi. (Eds). In favor of gy. hy- ple nuclei.

This update in- cludes many more images of glandular lesions and differ- Chapter 3: Endometrial Cells ential diagnostic considerations. Springer. Chapter 6: Glandular Epithelial Cell Abnormalities The Pap test was not designed to screen for glandular lesions of the cervix. On the basis of our understanding collect anal cytology specimens. past 2 decades. ThinPrep) (From: The Bethesda System for Reporting Cer- sampling devices and the increase in endocervical adeno- vical Cytology. 7. This edition low-grade changes represent productive. 6). hence. 179. cytologists currently encounter more challenging presentations of glandular lesions and their mimics in cervical cytology specimens.1159/000381842 Downloaded by: . variable inter. because of improvement in Fig.5/12/2017 6:28:51 AM The Pap Test and Bethesda 2014 Acta Cytologica 2015. ing’ endometrial cells has been increased to women aged ≥45 years (the rationale for this is presented above). Tables illustrating dif- The age for reporting of ‘cytologically benign appear. these HSIL. liquid-based prep- aration. Sampling devices used to precancerous lesion.59:121–132 129 DOI: 10. in conjunction with high-resolution anoscopy and biop- ing of the natural history of HPV-related infections – sy – in a role similar to that of the Pap test. that nevertheless may be observed in cervical cytologic categorization as ASC-US and ASC-H.140. common primaries arising in the uterine corpus or aden- imen. carcinoma relative to squamous cell carcinoma over the 2015. A new category was not created for squamous lesions with LSIL that also contain a few cells suggestive of con- current HSIL. largely transient further elaborates on new epidemiologic literature and HPV infection. and these abnormalities are more difficult to sample and interpret compared to their squa- mous counterparts. ferences in criteria are included for quick reference. not individual cells. These may create interpretation chal- reporting for ASC mirrors that observed for LSIL and lenges and result in diagnostic pitfalls. especially in high-risk groups. In- pretation. Wilbur DC. However. 3. ASC-H are reviewed and guidance provided to enable laboratories to use this reporting category along with Chapter 8: Anal Cytology HPV test results to monitor quality and consistency Although anal cancer is relatively uncommon in the among practitioners and laboratories (fig.7. ASC nomas. Most often. It must be emphasized that the ASC category was tumors are special variants of cervical carcinoma or un- developed to designate the interpretation of an entire spec. criteria for adequacy. this chapter has been substantially ex- panded to include problematic patterns and mimics that may lead to locator and/or interpretation errors of non- neoplastic changes as HSIL/ASC-H and vice versa (fig. Thus. the rationale for which is described above. mary squamous carcinomas and endocervical adenocarci- ported abnormal cervical cytology interpretation. Common patterns interpreted as ASC-US and creased numbers of such cases are now illustrated. rates have been increasing over the last several decades. Anal Chapter 5: Squamous Epithelial Cell Abnormalities cytology was first included in the 2001 Bethesda atlas and The dichotomous reporting terminology for LSIL and has gained acceptance as a tool for anal cancer screening HSIL is maintained and reflects our current understand.208 . (Eds). 5). of HPV biology and the behavior of pre-invasive. and high-grade morphology represents a defines high-risk populations. exfoliated cells or through direct sampling of tumors.). other than the usual variants of pri- The category of ASC is by far the most commonly re. The dichotomous preparations (fig. Pinworm eggs are shown (anal cytology. because atypia in individual exa that appear in the cervical cytology specimens either as cells remains a highly subjective and. the focus of cervical cancer screening is primarily aimed at detection and treatment of HSIL. 4). 3rd Edition. that infrequently involve the uterine cervix but continues to be defined as the general category with sub. HPV- associated squamous lesions. general population. Nayar R. Chapter 7: Other Malignant Neoplasms New published literature since TBS-2001 has described Chapter 4: Atypical Squamous Cells malignant neoplasms.

posted as ‘unknowns’ on a website that was open to the ed the so-called ‘location-guided screening’ devices that international cytopathology community. The group will also explore new atlas. The results of this exercise will be used systems and updates recommendations. It is the responsi.1159/000381842 Downloaded by: . could not be provided in the print atlas. options will be provided. ibility study (BIRST-II) and accompanying histograms based information. there are changes to the rules regarding patient access to test reports. Dr.g. These have includ. and mimickers of squamous lesions benefits and harms of screening. will provide a realistic normalities – essentially providing a prescreened slide. A variety of search when included in the cytology report. some may question the significance of a new edition Chapter 12: Risk Assessment in Cervical Cancer of the Bethesda atlas. Given all the recent press about new methods of cervi- thology reports. In the second edition of the Bethesda will be posted on this site. For further information on the not communicate directly with the patient unless specifi. as of 2014. project in 2003 [6]. it must be remembered that it still has significant atlas. These changes may have fur- ther implications for the use of recommendations in pa. 2012 management guidelines for abnormal cervical can- cer screening tests and cancer precursors [12]. this website will contain each other. The use of written recommendations and/or many other examples of presentations and entities that comments in cervical cytology reports is optional. subsequent publication.7. page on the American Society of Cytopathology website. ‘equal management for equal risk’.140.5/12/2017 6:28:51 AM 130 Acta Cytologica 2015. Before exaggerating the demise of the This new chapter is an important addition to the third Pap test. cal cancer screening and the lack of sensitivity of the Pap test. formed the basis of the are included (fig. Chapter 11: Educational Notes and Comments Bethesda 2014 Web Atlas One of the guiding principles of TBS has always been An accompanying Bethesda website resource is being to improve communication from the laboratory provider developed under the direction of Dr. Bethesda web atlas. Additional images of car. Cytopathology website [23] and will be discussed in a ing’ devices in addition to those covered previously. Chapter 9: Adjunctive Testing Reporting of the results from ancillary studies has Bethesda Interobserver Reproducibility Study evolved since the second edition. In the United States. p16) are included. along with balancing cinoma. and this chapter updates (BIRST-II) reporting schemes. evidence. it was recommended that such comments be direct. 22]. because it is key to understanding how the results of utility worldwide. 85 images from the third atlas were ing have occurred in the past decade. gree of interobserver and interlaboratory variability in cervical cytology and histology interpretation will always Chapter 10: Computer-Assisted Interpretation remain a reality [6. and. its varia- for the current HPV testing schemes and adjunctive im. Daniel Kurtycz and to the physician caring for the patient. Because of its greater specificity com- various screening and triage test combinations relate to pared with HPV testing. which is currently ongoing. Data concerning use and reporting Although knowledge of normal morphology. and the results of the reproduc- ed carefully and relay clear. Conclusions tion has been encouraged. tions. current.208 . and a relevant discussion is now included.59:121–132 Nayar/Wilbur DOI: 10. the Pap test will have importance 179. 7). concise. In addition. some de- munocytochemistry procedures (e. Paul Staats and with the help of a Bethesda Website bility of both laboratorians and clinicians to stay current Task Force (see Appendix). The concept of correlation data are reviewed. In an effort to build on the infor- Several new US Food and Drug Administration ap. effort. Data from this identify areas at highest risk for containing potential ab. standardization of reports to fa- cilitate widespread electronic health record implementa. avenues for delivery of the content that has been assembled ed to the clinician and that the laboratorian/laboratory during this update process. mation gathered from our experience with the BIRST provals in the field of automated cervical cytology screen. which now posted during spring of 2015 on the American Society of include the reporting items for ‘location-guided screen. organisms. In addition to all of the images with recent developments and communicate these to from the third edition of the atlas. they must be word.and the role of cytohistologic/high-resolution anoscopy the patient’s risk for cervical cancer [20]. gauge of interpretive reproducibility across a wide (and The third edition provides an overview of the currently defined) demographic. and epithelial abnormalities is essential. please visit the educational resources cally instructed to do so.

MD. New York. Criteria. New York. cytotechnologists. and Ex. hensive group of illustrations that contains.140. American Society of Cy- Appendix topathology in 2013–14). and in low-resource environments. Arch Pathol Lab Med 2004. will also make the corre- sponding electronic version (ebook) available online. Solomon D (eds): The Bethesda pathol 2007. Staats.techriver. ed 3. Russell. PhD. fort over the past quarter of a century [3–5.111:15–25. TJ. 11 Wright TC Jr. methods and character- 1988 Bethesda System for reporting cervical/ server Reproducibility Study (BIRST): a web. PhD. 1224–1229. and Diane Solomon. Atlas. regular Pap testing will remain the screening iel F. (Advisor).as a diagnostic triage tool after a positive HPV screening song. we thank As in previous editions. MD (Cochairs). Waxman. Dr. of Cytopathology: Bethesda System Website tological abnormalities. Sidawy. Dina R. Henry. the 2014 Bethesda Task Force members.net/ (accessed De. a robust content of K.7. the new atlas contains a greater discussion The 2014 Bethesda Website Task Force: Daniel F. David C. American Society of Cytopathology. 21]. MD There was no funding support for The Bethesda 2014 Atlas Up- (Chair). and tions. 6 Sherman ME. PhD. 931–934. mund S. MD and Paul N. MD. in Nayar R. Wilkinson EJ: 2001 consensus guidelines for System for Reporting Cervical/Vaginal Cyto. MD. and will be accepted by the editors/authors. Cibas. Ed- test. single-volume resource that will MPH. ment of women with abnormal cervical can- porting the results of cervical cytology. Criteria. Kurtycz. Styler PE. Wilbur 5 Solomon D. Davey D. Wilbur. Moriarty.5/12/2017 6:28:51 AM The Pap Test and Bethesda 2014 Acta Cytologica 2015. Overall. Paul N. 287: planatory Notes for Terminology and Speci. Members: Deborah Chute.59:121–132 131 DOI: 10. Mody DR: Bethesda 2001 im. Sana O. istics of trial participants. American Pathologists Interlaboratory DC (eds): The Bethesda System for Reporting tem for Reporting Cervical Cytology: Defini. MD. 179. look-alikes and equivocal presentations. The publisher. MD. Diane D. David Chelmow. Springer. 2002–2003). Robert Kurman for their pioneering have committed to making the third edition affordable vision in initiating and organizing the implementation of The and. An increased number of recommended report formats and a compre- Acknowledgments hensive reference list have also been included. paperbound mono. MD. Powers. Palefsky. Ritu Nayar. Dan- bursed. Abdul-Karim. Triage Study: design. including practitioners Bethesda System. The 2014 Bethesda System Task Force: David C. MD. 1994. Acta Cytol 2000. vid C. practices of participants in the College of 2007. widely accessible to all.1159/000381842 Downloaded by: . Khalbuss. JAMA 1989. Donna K. Wilber DC. MD. CT(ASCP). includes all current rec. Bird- References 1 Solomon D: Foreword. the current editors and authors Dr. for classifying cervical cytology. in addition to Maria Freidlander. MD. graph. An updated and enhanced Bethesda at. I. MD date Project. 2120–2129. MPA. Ann T. cember 17. Davey. MEd. MD. of HPV biology and pathogenesis. HT(ASCP). MD (Cochair). MEd. las will continue to serve its current purpose – that of being Russell. Tabbara. Ritu Nayar. Wilbur. Mody. Kurtycz. Nayar R (eds): The Bethesda Sys. Disclosure Statement Dr. MD. Wilbur (Past President.262: based assessment of the Bethesda 2001 System 726–742. 7 National Cancer Institute. 9 Schiffman M. et al: The 8 Davey DD. Springer New York. Darragh. Colgan 2006 consensus guidelines for the manage- Bethesda System 2001: terminology for re. MD. 2004. Mary K. I. 2015. second edition. Compared with the MD. and has a more compre. Springer. MD (Advisors). Joel M. In locales where HPV testing is not available or reim. Massad LS. Nicolas Wentzensen. Mark Schiffman. Teresa M. Twiggs LB. Cancer Cyto. MD.197:346–355. 2014). Stoler. Comparison Program in Cervicovaginal Cy- Cervical Cytology: Definitions. MD. Cox JT.287:2114–2119. Members: Fadi W. JAMA plementation and reporting rates: 2003 cer screening tests. Massad LS.208 . MD. Dasgupta A. Chhieng. 128: Explanatory Notes. ed 2. Neal MH. tology. men Adequacy. Criteria. Schiffman M. 3 Kurman RJ. CT(ASCP). portable. the con- tributors of the first and second editions of the Bethesda atlas. MD. MD. CT(ASCP). an inexpensive. Solomon D: The Bethesda Interob. hence. MD. 10 Wright TC Jr.44: vaginal cytologic diagnoses. http://nih. this makes the third edition a greatly enhanced resource. Celeste N. Donna the prior version’s classic examples. and the edition clinical colleagues who have volunteered to contribute to this ef- will remain a graphically high-quality. Kurman R. Nayar (Immediate Past President. MD. Am J Obstet Gynecol 2002. No honoraria or royalties all of the other dedicated cytopathologists. American Society the management of women with cervical cy- logic Diagnoses: Definitions. MD. and Explanatory Notes. be widely available internationally. Springer. Michael R. MD. Mark H. et al: 4 Solomon D. Sara Monaco. Alan G. Adrianza ME: ASCUS-LSIL 2 National Cancer Institute Workshop: The Nayar R. MD and Da- ommendations for management. Staats. On behalf of the American Society of Cytopathology. Diane Solomon and Dr. Walid E. JAMA 2002. George G. method of choice. Dunton CJ. MD.

2014. Colgan TJ. cytopathology. J Low Genit 1297. 2010.1159/000381842 Downloaded by: . for Reporting Thyroid Cytopathology. Pitman MB.16:205–242. tions. Lower Anogenital Squamous Terminology 22 Stoler MH. http://www. Springer. Colgan TJ. Lyon. 285: 16 Darragh TM. 13 Ali SZ. et al: The Pathologists and the American Society for 1500–1505. et al: mendations from the College of American Gynecol 2007. necol Pathol 2013. Cibas ES (eds): The Bethesda System Lower Anogenital Squamous Terminology 20 Castle PE. pp 172– Tract Dis 2013. New Standardization Project for HPV-Associated Schiffman M: Risk assessment to guide the York. Huh WK. J Am Soc Cyto.org/cytopathology-educa- recommendations from the College of lial tumours. Genit Tract Dis 2012. Young RH (eds): Tumours of updated consensus guidelines for the man. ogy. Criteria. Arch Pathol Lab Med 2012. thology education and resources. Pancreaticobiliary tract cytology: journey to. mendations from the College of American ASCUS-LSIL Triage Study. 136: 1266– Tumours of Female Reproductive Organs. and Explanatory Notes.7. et al: 2012 American Pathologists and the American Herrington CS. tion-2/ (accessed December 18.e1–e6. ed 3. Lower Anogenital Squamous Terminology Colposcopy and Cervical Pathology. Pathologists and the American Society for 21 Nayar R. Solomon D.3:II–III. Springer. chapt 7.5/12/2017 6:28:51 AM 132 Acta Cytologica 2015. et al: The 198. IARC Press. 2014). ed ing tests and cancer precursors.197:356. Int J Gy. Colgan TJ. Wojcik E: The quest for stan. 18 Darragh TM. 2015.140. Sideri M. et al: Epithe.17(5 suppl 1):S1–S27. DeMay RM. Wilbur DC (eds): The Bethesda Sys- ward ‘Bethesda’ style guidelines from the Pa. Einstein MH.59:121–132 Nayar/Wilbur DOI: 10. in Kurman RJ. Am J Obstet 14 Layfield LJ. Colgan TJ.11:18. Lesions: background and consensus recom. Cox JT. 179. Cyto. Jeronimo J.12 Massad LS. Lesions: background and consensus recom. 17 Darragh TM. Carcangiu ML. Cox JT. Society for Colposcopy and Cervical Pathol. Bergeron C. J Low tem for Reporting Cervical Cytology: Defini- panicolaou Society of Cytopathology. journal 2014.32:76–115. the Uterine Cervix: WHO Classification of agement of abnormal cervical cancer screen.208 . Cox JT. ed Lesions: background and consensus 19 Stoler M. prevention of cervical cancer. 15 Rosenthal D. Schiffman M: Interobserver vari- dardization of urine cytology reporting – the Standardization Project for HPV-Associated ability of cervical cytologic and histologic in- evolution of the Paris system. et al: The New York. terpretations: realistic estimates from the pathol 2014. JAMA 2001. 4. 23 American Society of Cytopathology: Cytopa- Standardization Project for HPV-Associat. Colposcopy and Cervical Pathology.