Dycvevante) Coser MeO CLEC ENC CY EDITORS The Bethesda System for Reporting Cervical Cytology \ Definitions, Criteria, and Explanatory Notes Second Edition——————— rl ;ellt~CO””™”™~*~‘“‘(‘“(“‘C “‘C‘SC OS The Bethesda System for Reporting Cervical Cytology Definitions, Criteria, and Explanatory Notes Second Edition Editors Diane Solomon, MD itu Nayar, MD Sree me Gyreccioge rector of Sopahaoay Donte ct Cancer Prevention Nerimwostorn Unwersiy SitonaiGarcnrneane”Feirerg cha of Maccne Betronsa, Mervond s With a Foreword by Robert J. Kurman, MD With an introduction by Diane D. Davey, MD and David C. Wilbur, MD With 186 lilustrations Springer 6 Springer Tohye, ia)St Cc tse Resta Unni featole Mb os Semele san Gust ‘Srl Sphsuse(ASEUS, Sant open, aed us So dpe nnn vac {Ro Sgn loon end pai: Hh poe ssa Eo cco rarer cee cee eg of Congres Gunn etn as ace eee ee eer tint ena icin Nl Ste cen ee emu Coma een eve tea Ete nogiane taps" Cota Near noe Sieben sated wr) eeraed oy cei eee a {ng opr ner estore ar th pa can ae ay ep eps) eee eet Some ent SiS Me Bethesda System: ical Perspective 1988, «sal group of individuals wih xpi in yoo. and patient management parcpste in an NCF-sponsoed fn Bethesda, Marylnd, with he pol oF Sevehoping a sytem for ap smear that would commoniate the cology ierpetation jean in clear nd ckvat Fnhion. Belo that ime, aber ilzed a mune "Pap Css” syiem of reporting ress was confusing and ofeniiosynrti, othe “Eysplasi™ ein had por interobserver reproducibility in practice. result ofthis Tis mecing was The 1988 Beesda System (TBS) ne terminology veeted thre fundamental pencples: terminology mast communica clinically relevant the laboratory 1 te patents heakt-cae provide. erinolgy shuld he enor al reasonably reproducible across thologis and Laboratori, ad lio exible enough to be ia wide vary of aoraory stings and geograph stions. erminology must reflect the most current understanding of cer seoplsin new omcnclature was lly et with skepticism by many, ot ‘cause it proposed replacing clasiications tat had been in place several decles but also because ic eliminated the diagnos esepony moderate dysplasia or CIN 2 Tralionaly collar changes of buna lomavins (HPY) Ckilocytoic atypia”) were considered separate “ime cervical cancer precursors, which were sbi into four (Gil. moderate, severe dysplasia, and carcinoma in sit) or thre (CIN 1, 2,3) catepovies,vefzcting what was perceived to be a biologi continuum, ‘TBS proposed a bipartite division, low-grade and high-arade squamous Arepiteil lesions (LSIL and HSIL) (See Fig. Fl on page vi There inal for reducing or consolidating) mop categories of HPV fet, ‘egres of dyspaia, or grades of CIN othe oo ters of LSI and HSIL, as bse onthe principles ofthe Bethesda System ust sate “8 LSILASIL reflected clinical decision threshoks tthe tne LS was ‘often followed, bur HSIL tapered colposcopic evaluation. formation1b. The reduced numberof dignostic categories improved interobserver Sabi and itnerver prods. Rescrch suggested thatthe logy of cervical abnormalities mht ota near and continoous asthe spectrum of morphologic changes would py Of all the changes inueiuced by TBS, probably rome was as problem: tc and controversial asthe nfo “atypical squann clls urd termined spnficans.” or “ASCUS.” ASCUS highligh the inert ten Sion that exists among puhologists who are ot alvays able 0 make blckand white decision on cellular hitlogc specimens and cnc ‘whose rmapement decisions are more cea debetomon--to teal or fot ott. ASCUS, ate reflstion ofthe cytopathologie'inblity 10 ‘make a definitive diagnosis in eran case, ofen lt lncans feting ‘Sompeled to evaluate the patent by colpsscopy, time consing an x petive procedure. Because ASCUS was reported in approximately 25 mi ion Pap est in the United Stes annually this was a major probe, Fur thermore, Because the management of women wi ASCUS rests was luce, the NCI spsored cial ua the ASCUSILSIL Triage tidy (LTS), to determine the best management fer these patents ‘The results of ALTS. provided da forthe development of evidence sed guidelines for managemeat of women wit abnormal estoy F- sults (Using Bethesda terminology) under the auspices ofthe American Society for Colposcopy and Cervical Pathology (ASCP). Aron the ‘major findings of ALTS amd chr suis wat tha the spectra of mor ‘hologe changes that was believed to constitute the pe-invaive phase ‘of eervieal cancer consists of two biologically ferent conditions: a ¥- fa infection caused by HPV that resus in alone grade suamous in ‘apthlia lston nd an HPV-indced cervical cancer pro «high tgrafe squamous intacptelal lesion, These findings conimed the ‘alidiy ofthe parte LSILIHSIL clasifcation in TBS, "ALTS, ited in response tosses eulsed by TBS, has also st ino ‘motion new approach to cervical cancer screening that wiles mole lr testing for HPV to wage women with ASCUS, a its more ses tive and very ikely more costtfestive forthe detection of undeying th grade lesions than repeat cytology Inthe future, cervical cancer scteening may well bepa with HPV testing with cytology axa riage for [HPY.postive samples. This change in sreening will obviously have an ‘enormous impact om cytology On the ane hand the absolute names of ‘erica eytology specimens would dectesse, but onthe oer hand cyt Togic evaluation, ints new role as a method of wags, would hecome even snore imprtant an chalensing. SS Seposercerscincarscie ‘Abbreviations used: CN «cone rrseptla opis: ASC-US = fiypea! squsove cas ot unaetrmined mgeance, ASG = type Snows cet. caretexcun an MoU RM = reget for cop Fetoncr ar manraney. AS ~ supe oars Cee Sic = oat Freepinci ior USt = owgrase sauarnus mesepe! ac Mat ra nner rasp ao Ka tooo yp Sorcbernae smc i= yan Me rouse te“The most recent Bethesda Workshop, held in 2001, wzed the Inter ‘ne 0 widen prisiation in the process of reviewing and revising the ‘ezminology. More than 2000 enmmens were consider Peto the {al meeting. which tought together over 400d ro mor han ‘vo doren countries, The innovative use of the Inert contin with Jmerative Web-based Alas of images that serves & companion 1 this book at woe eytopthology ae/NIHL Tn the intodstion tothe fist TBS Aas, i was state that TBS was esgne to be Meible 20 that it could evolve i response Yo changing sods in cervieal cancer sereeniag a well sto advances in he fed of cervical pathology Its pardoncal hat instead of TBS responding 10 ‘ew developments and changes inthe ld of eric carcinogenesis Pasta Fed he was in many’ aes, Ths, TBS has ps9ed wital oe {in nating resareh i the Biology of cervical cancer. in exploring new approaches and statezes in patent management, and in incorporating new technologies imo cervical cancer seeing. Rober J. Kurman, MD Balimore, Maryland Alias 2003, Acknowledgments 1. For Image Contribution George G. Binkong: 11.12.13, 14 15, 19, 118 ‘Charlot Brahm (courtesy of Cyt9¢ Coporation): 628 Sally-th Buckner 2.10, 2.30 ‘Terence J. Colgan: 212 Ginser, 2.39 Jamie L Covell: 1.11, 117; 22, 29, 2.14, 216, 222, 228, 236 (eign, 237 (efi: 32,47: 417: 5.14, $21, $27, 531, 532: 61 £63.69, 69 (elt) 610, 6.11, 622, 628,6.7,629, 6.32, 633,636, (637, G0, 627.1, 72, 73, 7A, 7S, 26577, 78,79 Teresa M, Darrigh: 8.1, 82,83, 84, 85.86, 87 Diane D. Davey: 2.12; 54, 519, 537 et) Denise VS, DeFrias: $25 Rone Marie Gasca: 5 ‘Micha Heney: 1.6, 1.7, 1.8, 1.10; 2.3 (gh) Ronald D. Luft: $36 ‘Am T, Moriarty: 2.35;33, 35,38 (nse) Ritu Naya: 115,28, 29 (men, 221,231,232, 2.37 (gh, 238 240; 3854.4, 416,420; 52,556,575, 520,529,535, 538, 630, 635 Celeste N. Powers 49 Mark E.Shorman: F1,2.13,227:41.4.5,48,4.11.413.414: 533; 166, 6.18, 6.21, 639: 72 (nse), 7.8 nse) Mary K.Sidavay: 4.12 Diane Solomon: 1.16; 2.1,24,27, 2.1, 2.15, 219,2.20,223,224,, 225, 229, 253, 2.34 M, Mi 42,43, 47, 4.10, 418, 419: 3.1, 54,510, 5:12, 515, $16, 5:17, $8,522,523, 524, 534, 540, 4,69 (right), 6.14, 616, 617, 619, 620, 621, 626,631, 634, 6a ‘Sana 0, Taba: 421 David Will: .12, 113, 114:23 ef), 25,217: 345 46,415: $5, 5.11 5.13,5.26, 528, 50, 5.37 igh, 5.962, 64.65, 612, 6.13, 615,623, 638 Nancy A. Young: 26, 2.18, 223 inser, 226, 2:36 (le)1, Acknowledgment for Image Selection AASCINCI Bethea Task Foe ASC: Rita Nayar, MD (Chait), George G. Binong. MD, Janie L. Covel BSc, CT (ASCP), Aan T, Moriarty, MD. Dennis M. O°Cow te, MD, Marianne U. Pres, MD. Stephen 8. Raab, MD, Mark E Sherman, MD, Sana O. Tatra, MD, Thos C. Weight. MD. Nancy A Young. MD NCH: Diane Solomon, MD (Chin) ‘Consultants: David C. Wilbur, MD and Diane D. Davey, MD Web ste for image seletion: Michael Montgomery, Terapi Systems, Bethesda, MD Brandon K. Winbush:laformaton Tecnology consulta for De parent of Pathology, Nortwestern Universit. Chicago, I Sates Stephen S. Raab, MD 11, Acknowledgment for Manuscript Review ‘The etre woul als ike 1 thank Drs. Dane D. Davey and David C: ‘Wilbur for ther review ofthe manascrip an thr invaable Feedback, Contents Foreword by Robert. Kurman Acknowledgments Contebutors Lis of Abbreviations Introduction by Diane D. Dovey and David C Wir “The 2001 Bethesda System in table format 1 Specimen Adequacy George G. Birdsong, Dione D. Davey, Teresa M. Darragh Poul A. ger and Michael Henry 2 Non-Neoplastic Findings Nancy A Young, Marace Bibbo,Sali-Beth Buckner Terence J. Colgan, and Marianne U. Prey {3 Rndomnetrial Cells: The How and When of Reporting ‘Aum T- Moriarty ond Edun S.Cibas 4: Atypical Squamous Ces ‘Mark E. Sherman Fadi W. Abs-Karim, Jonathan S. Bere, (Celeste. Powers, Mary K. Siwy and Sana 0. Tabbara 5: Epithetiat Abnormalities: Squamous Thomas C. Wri, Rose Mare Gatch, Ronald D, La land Marianne U. Prey © pitheliat Abnormalities: Glandular amie L. Covell David C. Wilbur, Barbra Guides Kenneth R. Le, David C. Cheng, and Dina R. Mad 7: Other Malignant Neoplasms Sana 0. Tabbara and Janie. Covell 4 Anal-Rectal Cytology Teresa M. Darragh, Grorge G, Birdsong, Ronald D. La ‘nd Diane D. Daves 7 o »9 Ancillary Testing ‘Stephon S. Raab and Mark B. Sherman 1: Computer-Asssted Interpretation of Cervical Cytology Marianne U. Prey ‘Faucational Notes and Suggestions Appended to Cxtology Reports Dennis M. O'Connor Index Contributors Fadi W, Aba Korim, MD, Deparaent of Pathology, University Hosp {als of Cleveland and Case Weer Reserve University, Cleveland, OH 44106, USA. Jonathan S. Berek. MD, MiSc, Deparment of Obstetrics & Gynecology. UCLA Wonnen's Reproductive Cancer Program, David Geffen Scot of ‘Medicine ot UCLA. Los Angeles, C4 90095-1740, USA. Mrluce Bio, MD, Department of Pathology Jefferson Medical Col ‘age, Philadelphia, PA 19107, USA George G, Birdsong, MD, Department of Pathology and Laboratory Me Fein, Emory University Schoo of Medicine and Department of Anatomic ogy, Grady Health Ste. Alana, GA 30832 USA leh Backer, SCRASCP), Deparment of Cellular Pathology und Arne Fores lst of Pathology, Washington, D.C. 20806, SA wid C.Chhieng MD, Department of Pathology, Univesity of Alabama Birmingham, Birmingham. AL. 35249-6823, USA und . Ciba, MD, Departmen of Pathology, Bigham and Women’s pital, Harvard Medial School, Boson, MA 02115, USA Ferenc J. Colgan, MD, Deprunent of Laboratory Medicine and Patho- ology University of Toro, Mount Sis Hospital, Toronto, Ontario, ISG 1X Canada ie L. Covell, BS CT (ASCP), Department of Pathology, University of epnia Health System, Charlotewille, VA 22908, USA Teresa M. Darragh. MD, University of California, San Francisco, De animes of Pathology and Ob/GSn, San Francisco, CA 94143-1785, Usa Diane D. Daves, MD, Deparment of Pathology and Laboratory Medi ‘ine, University of Kemtacky Mesieal Cee, Lexington, KY 405360298, USA, Paal A, Elgert, CRASCP) CMIAC, Cpopatology Laboratory, Depart ment of Patiology, Bellevue Hospital Cemer. New York Univeriy Schoo! of Medicine, New York, NY 10016, USA Rose Marie Gatscha, SCTASCP), CFIAC, Cytology Service, Meni ‘Sloun-Ketiring Cancer Cente, New York, NY 10021, USA.Barbara Guidon, SCT (ASCP), The American Society for Clinica Patho ogy. Chicago, I. 60612, USA. Michael Henry, MD, Divison of Laboratory Medicine, Cleveland Cinie Flori, Naples, FL 38119, USA, Kemeih Lee, MD, Deparment of Pathology Brigham & Women’s Hos pill, Harvard Mica Schoo, Bost, MA 02118, USA Ronald D. Luff, MD. MPI, Anatomic Pathology, Quest Diagnostics In ‘somporsed, Teterboro, NI TN, USA Dina 8. Mads, MD, Deparment of Pathology. Baylor Collese of Masi ‘in, Houston, TX 77030, USA. ‘Am T. Moria, MD, AmeePah Indiana Indianapolis, IN 46219, USA Dennis M. O'Connor, MD, Clinical Associates, Louse, KY 40207, Usa Celeste N, Powers MD, PRD, Department of Pathology, Medical College ‘of Virgina, Virginia Commonwealth University. Richmond, VA 23298 1139, USA Marianne U. Prey, MD, Anatomie Pathology. Quest Diagnostics Incr ported, St Loan, MO 63146, USA Siephon S. Raab, MD, Depurent of Pathology. University of Pitsburg Pitsburg, PA 15232, USA ‘Mark E. Sherman, MD, Hrooal and. Reproductive Epidemiology Branch, Division of Epidemiology and Genetics, National Cancer Inst- tute, Roche, MD 20852, USA. Mary K. Siow, MD, Deparinent of Pathology, The George Wasing- tom University Washington, D.C. 20037, USA Sana 0, Tabbars, MD. Deparnent of Pathology, The George Washing to University, Washington, D.C. 20037, USA David C. Wilbur, MD, Deparivent of Pathology, Massachusens General owptal, Harvard Medical Sehoel, Boston, MA 02114, USA Thomas C. Wright, MD, Divisio of ObGyn Pathology. Collegeof Phys ‘ans and Strgeons, Columbia University Presbyterian Medical Cees, New York, NY 10031, USA [Nancy A. Young, MD, Depatent of Pathology, Fox Chase Cancer Cen ter Philadelphia, PA 19111, USA vam List of Abbreviations AASCUS/LSIL Triage sly up hdl cllt tpi gamout cle Anes Society of Coptology ‘Aerie Soviet Fr Colposcopy and Coil Pathegy yp suas cl, cat exldehgh-rde sqm Inept exon ypc sjmous calle undermined sgniicins Batu Inrures Reprosciy jest coil nepal eps omental prepare igh sade ngamoes ncapitisl sion nm ppm ‘rr device ep cectosigieal cnet procere tae mens pera low-grade quae intl eon lignan mind mesodernal oe Nationa Cancer Inti, Bete, MD ative fr inraeiell son or malignancy Squanous nepal ein “The Retest Sytem ‘rusia eleanor gin iit nepia‘oduction “The second don of he Bethesda System las represcmt the joint {ont of ipl invite and ganizations. Neary year Belo the +2001 Betheada Workshop. nine forum props. each consisting oF 640 10 Godiva, insted lengthy pees Jesiged to provide forthe widest “np posible vi an Inemet-based "discussion." Forty-four internation ‘mtarrations with interest in cervical eYiopahology cosponsored the ‘System 2001 Worksop slong with the National Cancer Ini NCD, More than 400 indiels took prin the final working the hind Bethesda workshop, i Api 2001. As a follow-up 1 this fan the publication of te revised 2001 Bethea trminol- 7 eonference moderator Dr. Dine Solomon approsced the Ames- ‘Socity of Cytopatlogy (ASC) zegading the development of a nda Web ste and a updated ein ofthe Bethea "lue book” 'An ASC-NCI taskforce, named by Dr. Diane Davey and David ior (atthe tne the President and President-Elect of the ASC), in the Bethea forum moderators or ther designees and selected ans. Ds Rita Nayar and Diane Solomon joy chaired this ask “The ask force propos working in parle! onthe new eon of tls and an edcstional We ste featringaditinal images beyond ‘number vied inthe ats "This new edition ofthe Bethea System alas expands onthe popular ofthe 1991 ction? The atlas has been divided ino chapters ig t the major Bethosda interpretive categories. Each chapter iso buckgroud discussion, an n-dpih descipion of eytoloc “thera, and explanatory noes, New features include images ofliqid- partons (LBP), sample repos, references. and an index: Cy logic criteria ae described in general forall specimen types in every «with significant differences in LBPs noted following the general “itera when applicable. Note that Bethesda does nt endorse any par ‘cular mhaology Tor specimen cllction ‘Over 1,000 images were evaluated for this als, The majrty went “thrxgh a multistage review process Fit, the relevant forum sroup eval “aed mages fom the previo ats and hundreds of new istrations Submited by the ASC-NCI ask Force and Bethesda frum group men ber. Approximately 30% of images survived tis intial review. cond ‘he impos slated fom the frst round were placed cn a Web ste and Scored independently by the ASC-NCI wsk force members. Only S8% of the imases those sorng above a selected mean threshold in te secon‘ovndwere the nce nthe ts Think ere publican, ap Deinhart te ne 5) were posed ar “knows ona Web tc pen he pate Soman as part of he Bead ners Req Pret {BIRD Hunde of parspane submit thr ase ln, to ‘idea more esis gauge of meine epi. The renin hi togoms of pacpansnerpaion othe Images cin We set "eae lone nh stations in hs as reese! the spectrum of changes sce en bh conventional sears and La 0 renew ager and “47% are fom LBP. Sone nage epee case earls ofan en iy wheres tor, whch were slo ois ince is “bore moro estes maybe nr ne ‘anc way by all clogs We hope tha hi vs ae, Which pre tides exper text and expo cei wil ip nar inplementation of he 201 Bethesda Stem oevcr, ee dpi of inroberve an ineltrsory vray wil alesse? “he 2001 Beda System inde changes hat eb on cline ingt and advances in th unesandig ofthe Hog of eral can ex Thee "ngs replaced by “incon or "eu" eating of theca eyloy report Prints the etna 2001 Confrence sped tt cervcl yloy sk be view pinay a> “renin est hich in some mtnes may sere ss media conel ton by providing an nrpectaton hat cones wa apse" A Patents al denon an nang pan inept ely hr ical eytlogy rout et ako bry. ining, and te aor tyres such 8 Bip nero Tis change in eine pass ht yl tel preset oe corona fan may ‘ocaways lest he al pert dag ‘The gal fhe Bathe Syston hays been o promote eve communica of rev tgs indigs hence he ora slintan opie opin pat cre: New capers aean tes and computed increta hat my be ncrprmed ithe ‘logy repo The most common anil tet wet preset ss ‘angiomas DNA esting, ht prin few sh ‘plicable war mole xs hat may decline fete "The repoting of uaa seine ts aso ben cee the wes terminology emphasizes that o cos seen unsase {ty sigiican bray work mse prone ores td ally ralute the specimen The revel trmtogy fr dec ds lle {othe mention fer perinent indngs eh endo cls a 2 woman age 0 er ldo eran) cn te seston pone seteing umaticen, nm Mn re esd Sytem was develped primal for cervical cytology and bh the terminology aa mophotegc titra reet hin. en “cervical cytology” Ts used in thi edition of the atlas (5 o> cee vaginal eytology”) the vagina not pial sh wih most cervical collection rctbods. However, specimens from Mites sch ste vagina and anal rectal samples may be reported us Sinilrterinolog. An emie new chapter seuss ana-ecal ey Tn includes astruins and spel adequacy eters. Fn heal ofthe American Society of Cytopathology are pleased Jp spt of this ongoing proces, and hope that this updated and ex Fits will prove useful in your eytology practice. Adon in fan ao be found on the Bethesda edocational Web ste Diane D, Davey, MD Lexington, Kencky David C. Wilbur, MD Boston, Massichusets ‘August 2008 SsrnD, Davey DD Karman Te 2001 Bab yew emia or ‘eprint ral ey. AMA 20287 218-3119 ma Sion D The ad yt for Rporing Cran Hoge Dganrs Nex Yor. Sanger 19, Shier onion Masturbate Iecpntonaic ema re ASCU'SLSI ape 04025The 2001 BETHESDA SYSTEM ECIMEN TYPE conventional sear (Pap smear) 3 Higid-bsed preparation -CIMEN ADEQUACY Satisfactory for evaluation (describe presence or absence of ndocer * Vealransformaton zone component and anyother qual indica tors ef. partly obscuring blood, inflammation, et.) imatsfictony fr evaluation. (spec reason) 1 Specimen rejcedinot processed (pe reason) 1 Specimen processed al examined, but unsatisfactory fr evalu tion of epithet abaormalty Beene of speci reason) GENERAL CATEGORIZATION (optional) 2 Negative oF lara Lesion or Maincy Ot: See InerpetatonResl (e endomeria eli woman “_-=#0 years of age) Epil Cet Atmormaiy: Seo Ire Res pec sas ‘is or ‘gina appropriate) INTERPRETATION/RESULT NEGATIVE FOR INTRAEPITHELIAL LESION OR MALIGNANCY (en there ism ela evidence of neoplasia, sate his in the General Categrisiion above andior in the IverpretioReslt section of the reprt-wheter or not there are organism or other nom-noplastic Findings)‘ORGANISMS: > Trichomonas vaginalis > Fungal orgonions morphoogically conssiemt with Candida spp. > Shift in fora sugestive of bacterial vaginosis > Bacteria morphologically comitent with Actiomsces spp. > Cellular changes consistent with heres simplex vins OTHER NON-NEOPLASTIC FINDINGS (Optional to report ot incase > Reactive cellar changes associated with + inflammation Galas typical epic) + radiation + inraterine conracepive device (IUD) > Glandular calls status posthyeretony > Auopty OTHER > Endometrial cll (in a woman =40 sears of age) (Specify if “negative for squamous itrepthelia lesion”) PPITHELIAL CELL ABNORMALITIES. SQUAMOUS CELL, > Apical squamous cls + of undetermined siniicanee (ASC-US) + camot exclude HSH. (ASC-H) > Low-grade squamous insaeptelialfesion (SIL) (encompsising: HEVinid dsplasi/CIN 1) > High-grade squamous iacpithelil lesion (HSL) encompassing: moderate and severe dyplsi, CIS; CIN 2 and ows} + with features suspicious for invasion (if invasion is suspected) > Squamous cll earcinoma Aypical + endocervical els (NOS oF speci in comments) + endometil cells (NOS or specify in comment) + glandular cells (NOS or specify in comment) > Aypics + endocervical els, favorneopisic + andular calls favor neoplastic Endicervical adenocarcinoma in sit Adenocacinom © + endocervical + endomerrial = pot otherwise speci (NOS) MALIGNANT NEOPLASMS: (speci) LLARY TESTING bri description ofthe test mets) an report the result so Tris easily understood by the eliician. IMATED REVIEW ase examined by cmtomated device specify device andres. EDUCATIONAL NOTES AND SUGGESTIONS (optional) Suggestions should be concise and consistent with clineal followup suidelines published by professional organizations references relevant publications maybe included.Chapter 1 Specimen Adequacy George G. Birdsong, Diane D. Davey. Tetesa M. Darrah, Paul A. Elgort. and Michael Henry round of specimen aequicy is considered hy many 1 be the single important quality ssurence component othe Beesda System. Ear ‘esons of Beticul ncaded hee catepois of adequacy Sats y. Unsatisfactory, ana "bordetne™ exc pory inially teed "Less eptimal and hen renamed "Satsatory but hinted by" a 1991. The ‘eshesda System ciminats the borderline category in part case on amon clinicians as the appropri follow-up for such sand also de to te varity n reporting “Satisfactory bu Lim jy” among laboratories! To provide alert indian of equa). ate no designated 6 “Satsfcto” or “Unsaisfctry." eter for determining adequacy were Based on exp opia- ad he few aalale studies in heer, Laboeaoy implemen of some of these exter was sbi to he poor reproducible ‘akon, the increasing use of liquid-based eytlogy necessitated de rier applicable wo these preparations, The 2001 Bethel a eis are tased on published data 1 the excat possible and ae to conventional smers an iqui-Dased specimens Categories Satisfactory Sats fo cthaton deere presence or abene of endcerical Iraormatio ne component anda ater quilters. arly obscuring bv. lamas)Unsatisfactory For anstistictory specimens. indicate wheter oF no the laboratory has ‘ocessed/evaluaed the sie, Suggested wanting [A Rejected Specimen Specimen iejected (not processed) hocause (specimen oh beled, slide broken, et.) 'B, Fully evaluated, unsatisfactory specimen: Specimen processed and examined, But unaifactory for evaluation of epithelial abnormality because of Yobsuring bas ee) Additonal commenivrecommendatons, as approve Explanatory Notes For “Sasi” pesinen,nfaton on tinsormation ron sn lng ad ether aduey qualifier i aso lnclaed. Proving Sianspacinen ike with real eedhack on specie uly pr ints helene tention to specie cll and emsen f imped sapling devi: an cholons. ‘Any specie wih aba cell [api guamous cells f n= "* Bird Be song ecely reviewed his subject! A recent study tat included co: ‘ ‘ossopiecvalution ofall women with abnormal guid-bsed esol {human papillomavirus (HPV) results plus arom sample of tose ‘with negative test ress filed to show at association between absent FECITZ component and missed high-grade lesions.» Filly respective it ‘ee contr staes ve filed to show an asaation between fae ‘gate interpretation of specimens and lack of EC" “The implications ofthe ECYTZ component could change in the fre b De retearee cate trees ees felationship Between the detection of adeccareinoma and the presence 1) Roure 135, Norma squamous metas ce (UB). ove {of endocervial cells on cervical eyology specimens unexplored as of Seong anja woman oaObscuring Factors (Figs. 1.17, 1.18) Specimens with more than 75% of squamous ces cbscued should be ‘termed unsatstacory. assuring tht abnormal cells re Mente (Ff, LID, When SO «075% ofthe call ate obscured ttement descr Ing the specimen as patil) obscured shoul allo the satisfactory rm, The pereetge of cells obscured, nt the side area obscured, shuld he cvaliated although minimal celarity eriteria shoul also be apple, ‘Nica preservation and vinslizaion are of ey importance an changes suchas evtolyis and partial obscuring of etopasn deal mayb ne ‘sarily inerfere wit specimen evaluation, Abundent cytolysis may be mentioned ss quality indian bat most sich specimens do natal. ify as “umsatstacor” unless nearly all male ate devoid ofeytplesm Siar teria apply to LPs In LBP with some obsouring facts ad boxdorlineceloanty (see Figs. 1.8, 19), laboratories shold estate ‘whether minimum numbers of wel-visuaiad squamous cols ae pre entasdescrited above. When puriculr els or aeat of diagnostic in. ers .7, rarer af ctannna wt on a0 te mentonedin te uty etontors aac he rar (7a Ssur glo conaores unastfacary# no sera aya aed. ‘Seang bw eseaury ofa nie wt expect 1 Soecrn acre ad cok ‘eae Srikanth rorom coy evra ear a cra ects cen Bites eae isieen sen ae ee eer eves are obscured, «report comment canbe added. “al-deying of posible siypical els" ig. 1.18), Explanatory Notes ‘Specimens with pail obscuring factors have been shown 0 have fin ferosererrepnduiiiy of aleuacy assessnent™ Although respec Hive cne-contol se il to show tht paral obscuring factor nde Th oa fae-nepative repore”= prospestive sts have nt been done Reporing obscuring factors may be ined because of patent eare ce ual concerns Management Information on adequacy and any implications for patient low-up may be provided sonal in an educational note. The American Society for Colposcopy anf Cervcil Pathology has published management sue Tine for specimen adequacy and quality indicators based onthe 2001 ethesls terminology.”‘Sample Reports sample: Satisfactory for evaluation: endoceveatiansformaton Zone compo: ‘ont presen Anerpretaton Negative fo same 2. Suc fr evan exdcercaltnsfomatin Zoe co ‘nent absenvinsufficient. a Imereti Neg fer niall sono aly Optional Nae Dae cnflising ewig te specs of ncaeinan Torsion sine Semen A opt cel ty 1S men i peel geod (ASCEP Pa Marae Geienes ‘hi hn aod 2018-718 718 rcpt esi or malign. ey. ‘Unsatisfactory for evaluation; Specimen processed and examined bat ‘unsatisfactory for ealuation of epithe abormaity Bocuse of ob curing inflammation, Comment: Trichomonas vaginalis ete. Consider repeat coricaleytlogyPap txt aller treatment of Tr ‘hom Examole Imerpretation: Specimen processed and examine, but unsatisfactory for evasion of epithelial abormaiy because of insufficient squamous ell Parially obscuring bod iene. prion: UUnsatsactiy for evan, Comment: Endomeral cells present consent with day Sof LMP st mens Pio) provided Example: ‘Unsatisfactory fr evaluation; Specimen ejected becatse lide ws ‘sved unable, System 2001 Workshop Group Moderators: D. Davey, MLD., Geoege Binduong, MD. Henry W. Buck, MLD. Darigh, M.D, Pa igor, CT. (ASCP), Michael Henry, M.D, Michell, MD., Suzanne Selvags, M.D. Dey DD, Woods S Set Pea. ype an cnn hoe pce cpa te Calle Aman aa. (Bes intanrany Comparson Prem nevis oy hPa ib a so 0-21 {Gi ow. Pop sa ay: a es 10 cng ake Wha hes meen’ Ae Ge 2087 ar). TAR cen NB Ra re a Aca ad rp of hay he names compet cecal se fa “Cin 9m a Valet P, She Ta I, Te triton of Papin ae Fea ting cote td sen sly. gn Copa Ii 0. Ai MR. ASCP Pe angen ud: Ppt pce sieucy and guy Inher J Lower Gl Tre Ds Boe oN, Ake bo ee Che Pal 221 TTB) “Rand 5, Davey BD, Zl S-Class corel fh wai fey Pgs ce Cacr Caner Cpa) 191 1318 {Ger Caco Cp I Cau cm of mee PREP conic aaa usp wis bp cone HSL. ca Cel 08 as Seas RD. ate OB, Poser he at sly ne ses th man gd ee eye 387 Bh DR. Ko, Shy BE th Ht ety econ ae of ich fed iba sues acini cre Ae Ce 026922923 ‘ieee. De I Mees rasta Ti Prep celular assessment. Dg Chop 20:26 19-21 I Sl I Sumarh Tae La acaba seine funy of he um competi conenton evga ea ied Cn 12 Mah Ld Rav Ey oso iin de 13, Venta A sonra ¥en bet be apa > ‘tal arm andthe compton fer ses ce Cl 8S Mine MP, Cis , Ri Co Te fle of he guy of Papa Aimar th esto cle temas. Cer (Cer Copal: on er th are Pera ha Sie at eta etereen ‘cree te Cyt ineeona 240 = pe ace eres: itn Pane nar endgame Diagn Coys 01:24:79-83 = Sree aaa re ‘pelea rea oa areas ate Jee meer pe Se hats Ge ene Signe nla cmt eet Searels te Seles Seattnckte atic ieee ten ne tran sap Serine nee eae re Eoteminne wa ee stm ae Sere Cnt eri taco Soa es Ties oh a ec rece See enema ie ea Chapter 2 Non-Neoplastic Findings [Nancy A. Young, Marluce Bibbo, Sally-Beth Buckner, "Terence J, Colgan, and Marianne U. Prey for Intraepithelial Lesion there is no cellular evidence of neoplasia. state dhs in the General ‘andor he Imerpretaiow Result section ofthe reper ‘or not there are organisms or other monneoplstic ining) “2 Trichomonas vinais Fungal eraniss morphologically consistent with Candida sp, 6 Shift in fora suggestive of bacterial vaginosis | 2 Bacteria morpboogially coment with Actinomyces SPP. ' Caiular changes consistent with herpes simplex virus Non-Neoplastic Findings 0 report isnot inclusive: 1 Reactive clr changes associated with: > inflammation (inlodes pica esi) > radaion > inrterine contraceptive device (TUD) Glandular cls stats post hysterectomy Awophy ground, previous versions of The Bethesds Systm (TBS), infections and re ve celular changes were reporied under the ext-gorcal beading of ign Cellular Changes” (BCC); bu under the General Categorization "RCC was scart from “Within normal limits” (WNL). Theefore some clinica vewed BCC as something her han WNT. and fl sige vo do more than routine seroening for women wih BCC de. 'gnaton. To emphasize the nezalive” mate of a inerpetton of fe tive changes, the 2001 Bethesda System collapse BEC and WNL ca. pores ime single category: “Negative for Inacptbelol Lesion or Malignancy” (NILM). This er is used both asthe Eonealeategorie. tion andlor asthe nteretton inthe epee “The category of “Infections has been change to “Organisms” bene the presence of some organisms reflects colonization rhe than cial infetion. Ahough not the main focus of cervical screening. roving such information maybe clinically relevant in etn circumstances Ci cians and lboratories should communicate with ane another bout es ‘expectation for reporting organisms. In the absence of speiic comm fication regarding this ste, the onganians Hed sboul! genta Be re onc if enti (Cervical cytology is a seoening test pimanly for detection of a mous cell earinoma ofthe cervix adit precursors. Citea fr reactive llr changes are not always well defined, and consequent the in [rcttion may lack reprodtiliy-* Except for organisms discussed ove, reporting pen-neoplsic findings optional and at the discretion [f the laboratory, However, reasons for continuing 10 reper non ‘neoplastic findings in cervical cytology rept nce: 1. Usliy ava wage oo and as documentation for laboratory seglaions regarding rer for hierarchies review. 2. Fostering a discipline in applying eytomorpologic enters. during screening and sign-ut, Documentation of morphologic findings to explain differenes ini terprction on review." Feciltation of cinical-eytologie comlation. For example, the ext Jogi finding of hyperkeratosis and parkeraois may eorlae with the colposeopia’s ausestnet ofthe cine cern. 5. Documentation of eactive cellar change athe report sp tends in a series of cervical cytology specimens from one woman, Stutis Ihave repo sigh inerese inthe incidence of squamous intacp ihe eson (SIL) in cases inerpeted as reactive compre to those ierpreted as within normal Hints" Repating now-ncoplatic find: ‘ngs may facitat faire ste to eniyspctic monpologe find. ings that beer eorelate with ‘Note sat heist of non-neoplastic Findings a Bees 2001 i not com- prchensive Ih aiion, the iterpretive categories do ot necessity com "spond to regulatory Feqirements fr hierarchical sopervisory review! the parameters of government regulon, sp 10 the laboratory ndings that gger sch esto for intraepithelial Lesion lalignancy (NILM) for which no pis abnormality is idenitid are reported “Negative for inacpthelial lesion or maignaney” (NILM). If no findings are reported, NILM shoul til be incladed a an in ‘or asthe General Caeporiation to avon ambiguity. isms vaginalis (Figs. 2.1-2.3) aps oval, or round cyanopillc organism ranging in size fom 15 30 um (Fg. 2.1, spl, vesicular an ecenriclly locate ie cyoplai granules are ten evident Hl ate usally ot seen ‘may be sen in association with vaginalis (Fg. 2.2). lean eytoplsni eosinophilic granules ar often beter visualize. ls may be presered and Keni in hgud-bved preparations (LBP) (Fg. 23.Fungal Organisms Morphologically Consistent with Candida species. (Figs. 2.4-2.6) Criteria ‘Buding yeasts 7 um): pseudobyphie ae eosinophilic wo gry-brown fon the Papanicolaou stun, Pscudohypha, formed by elongated budklng, show constitons along their length (Fig. 2.4) Fragmented leukocyte nucle and rotea formation of squamous eiths- Tia els “speared” by hyphae maybe son, Liquic-Bazed Preparations “Spearng”of epithelial cells is more common in LBP and canbe scen low power even if the poeodhypae ae not promincot ish Kebab ‘ec (Fig 23) ‘Nove: Candid (Trulopsis) glabrata consis of smal, uiform, round bung yeast forms surtounded by cla alos on Papanicolaou sain Un like ott Candida species i doesnot form psuayphae in vivo on cule Fig. 26)Shift in Flora Suggestive of Bacterial Vaginosis (Figs. 2.7-2.8) Criteria. Friny background of smal coccobuili is evident (Fig. 2.7) Individual gusmous ces may bo coveted ya ayer of Baer tt ob- Sure the cll membrane, forming Soll clue cll (Fg. 28), ‘There isu conspicuous sbrence of lactobail (Fg. 2.9), Liquid-Based Preparations Squamous cells are covered with cccabocls however, the background Fs clean Fig 28) ‘eure 27. Sn fon suggestive of bacteral vag (CF). Note he (cake ty beep du otha coveoeaoh Snr Compare socsomaan Figs 27 ans 28Bacteria Morphologically Consistent with Actinomyces (Figs. 2.10, 2.11) Criteria Tangle clumps of lamentous organs often with acute angle brah ing, re recognizable as "coton ball” hier a low power Fig 2. 10) Filaments sometimes hve a radial dstibtion or have an inceulr ‘wooly ody” appearance (ig, 2.11, Masses of leukocytes adherent t© microcolonies of the organism, with swollen laments lbs” tthe periphery. may be ened An acute inflammatory response with polymxphionuca leukocytes is ‘often presen Cellular Changes Consistent with Herpes. Simplex Virus (Fig. 2.12) rteria Nate have a “pround-lass” appearance duet intranuclear viral parti les and enhancement of th nuclear envelope caused by peripheral ‘margination of enon, Dense coxinoilicitanuclea inclusions surrounded by a hal o “one are variably presen. Large mukinuclewed epic cells with molded mole are characteris ti but may nt always be present: mononcleate cells withthe melee features deserted above maybe the only finding. Explanatory Notes ‘Occasionally degenerated fragments of eytopas or macrophages can be mistaken for trchomonads, particularly in lgud-based. preperation Therefore at ast one of he following good nuclear deal, esinophilic «tplasmic granules, or Nagela—should be present to make an inter ection of Trichomonas, When Leproeri sen, one shuld Seach for the possible presence of tichomonais “Lactobils spp conse 4 major component of the nocmal vaginal fora ace Fig. 29). Predominance of coccabacll represents a shift in ‘znal lr fom lactobcilo polymicobial process involving ev ral types of obligate and facultative anaerobic acter, incline ha nt limited o Gardnreta vaginalis and Mobilinens spp" THs sh a ‘ors, wih or without accompanying cl cells smo sulin fr the I Fene 210 actora rerpniogeay const wth Actos ees darps of tarertovm care. an acne arity resp Sats er Sons rr Posty Peet PP) Fume 2.1, Batra morproigcalycandset with Acnomyens (CP Tym tarnisus tas we snr fonghsdnay and on ener Mah maBe [Pune 2.2. Cor changes consistent wis herpes singin vu [Cer Note he eoenopnc ntaracear pele Ter “yound-jsn”apposrance ot nie Gute courant al ries enc to pepe margration of tvarnin RBP oer oor om linia gross bce vaginosis ease specimens chine fm day single st sent neces repre ot he ee or of te Gericand vagina! However he presence of cscobcil and nence of acolo corel wth grim stained seas of vail ct ninth proper lineal contest provide supportive evident ch, ical igniter ano” Batra vaginas ee se. ine wth ple nammatiry ese, at; posepea sy esp intetos, and sora Pap tes = The presence of Actnones species nevi etolgy i asscated ih natin corracepve device UD) wsage- Detection of ne Ice era ey pcm gh ln so ‘eli infcon cr paler lian ths psi fs pel a -nomycotic abscess! Piaens Because fe contoveny rating theses and ed inal igo Comal vay oe pe ‘ls detction method uch calireczyninkedimanessy, Sed Tolymense chan reaton PCR), inept ol Cham ‘not included in TBS."7!* = a Non-Neoplastic Findings Cellular Changes ition jive celular changes that ave Reng i nature, ssc ith i fadaton, an TUD, o ther nonspecific cases. Cellular Changes Associated with mmation (Includes Typical Repair) ‘2A3-2.22) enlargement (one and one-lf otwo times the sea of nema Antermetiate quits cll mile or mre) (Figs 213, , ical cells may sow preaer nuclear enlargement (Figs. 2.17. 218). 51 binuceution or mulkinsleaton may he observed lear oui are smo, ou, and ior, lei may appear vesicular and hypochromtie (igs. 213. 2.14. yperehomasia may be present. but the chromatin structure and dis tibuioo remain uniformly finely grams. en single or mute ucleol may be present sn ray show polychromasia, vacuolation, or perinclear halos but without peripheral thickening Fig. 2.14). ike changes may be seen in squankus metaplastic cll (Fig. 215), eyoplasmie processes (spider cel) may also he sen Fig 2.1) Intypical epi, any ofthe above cellar changes may be seen; how “eer, cls occur in lt, monolayer shets with distinct cytoplasmic out Tine i contrast the syria appeaanceof some hih-rae lesons ‘and cancer), searing nulear polarity, and types mitotic igures. Sn. il cells with nuclear changes are not way seen (Figs. 217-220. Liguic-Based Preparations (Figs. 2:21, 2.22) Reparative groups ate more rounded, with less sreasng (Fig, 2.22 Nucleoii maybe more prominent2 ‘a << 1s] ume 2.13 Roscoe eases cle (CP. Mi nia erlogement 2s. sqamous mataponic cue (OP); Metapast cots ave ‘tou ary alpicart cremaen noma (Raped wi nen rare cele, aA ruses ror fom Koran Feo), Buntorrs Pay othe Forse Sota Tact testa rina ay Jonson vey aes out Ean, epinge-rng New Yor S580) round ric can bo St » S1petS Enero rman syn hehe". oeae {9 Feu pect squares cts 0) Rete sen of 2 {tc eran re’ Snare oe ray etn Cen une 2.22. Repor(L8.22yeu-id worn. Charges se emt to sy sng on Sat ut tearing ay bene ape of ene Se. anoter feature seen nvopar Compre ts gures 219 wat 230, Cettular Associated with ation (Fig. 223) Griteria (ell ize is markedly increased witout substan increas in them ‘ear © cyoplasmi rat, Biase cel shapes may occu Enlarged uci may show degenerative changes including mca plo, erinling or staging o the chromatin, and miclar vacuolation, [Nac may vary inne, with ome call groups ving bot enlarged nd eel sized uc: binuclestion or mulmaceuion is common, Milt cca hyperchromasia ma) e poset ‘Prominent single or mutple nclen may be seen fcoeisting epi is presen, {Cyeplsmic vacvolization andor cytoplasmic polyehromatic suning ray be eon. ‘sr competed raaaton tera B wooo ear Ce wh ariod r= Sa soit vcs per epee, ‘Seaton lurpor come se,Reactive Cellular Changes Associated with intrauterine Contraceptive Device (Figs. 2.24, 2.25) Criteria ‘Glandular cells may be resent singly oF in casters, sully of § 4 15 cells, ami clean Background (Fig. 224), ‘The amount of cytoplasm varies, and Tequently large vacsoles ma ds Place the micleus,ceaing a sgnetsing appearance (Fig: 22), ‘Oceavonal single epithelial ells with increas nuclear size nd igh nu leafetopsmic ratio may he present Fig. 225), Nuclear degencration requnty i evident, Nacleoli may be prominent (Caletcations nxembling psimmoms bie are vaibly present Glandular Cells Status Posthysterectomy (Fig. 2.26) Criteria ‘enign-appering endocervical-ype ganar cells that cannot der tiated rom those sample fom the endoccrin Gobet cell. mucinous maps nay be seen, Round to cuboidal ells may resemble endometial-ype cel fours 2.24. Peace cular cargos associ wth itaterne con Sogn devon (UD) (Snot al une perce cons Wes ‘epee vocules ae mae Te (Pome 2.25. Paacive cour cunges associated wth UD (CP) Epted Sa aig arora my ene rae a {us anno son (tw however te marpraoge sosceuny rafts uy preert win squoous resents wacne 2 Gert Pecanen cruciet m soutes cole wa a ign NG ra int fetch. Foure 2.26. cancer cols stats postytarectomy (CP). Vagal snsar irra Sigel eran tin pnt fy mqAtrophy with oF Without inflammation (Hon. 2292.5) Criteria Flat, monolayer sheets of pura cells with preserved esp Tarts (Fig. 2.28). Dispersed parabasa-ype cells may predominate (Generalized nilear eblrpemen, opt thst ive times the aca of an inermedist cll cles, may occur with a slight increase in nu leafeytoplasmic rato. Intermediate cells tend to be normochromatic, but purabassl-ype cell may have mid hyperchromasia and end to have tne elongated na le Chromatin is wifonnly distribute, Aublysis may result in naked nace ‘An abundant inlarmatoryexudat and basophilic granular background ‘that resembles tumor dates may be preset (Fg. 229). Globular collections of basopiic amorphous material (bv labs reflect clther degenerated pasha clls oe impssted mucus, Degenerted orangeopilc or eosinophilic parabasl eels with clear pyknosis resembling “parakeraotie™ ell maybe present (Fig. 231). istioyts varying in size and shipe, and containing multiple, round to pitlioid nuclei and foany or dense cyoplam, may be seen (Fig 230, Liquid-Based Preparations Ligui-hased preparations have less mickar enlargement than conver tional smears due to immadiae fixation, Naked cli from autolysis may be reduced in umber Granular background materia tends to clump rather than be dispersed ‘elding a “cleane” background Fig. 231), however, the clumps ney lng” to te ells and make it ica o visualize individual cel hg. 232). {o)Feune 2.20. aos (ny, Nee a, moringe seet t perabn [Gbrum ain peenaved mclear poy, Aopte cole may have (ir ht nerOther Non-Neoplastic Findings Not Specifically Listed in 2001 Bethesda Terminology Tubal Metaplasia (Figs. 2.33-2.35) Criteria CColumnar endocervical eels tha may oscur in smal go4ps oF peo stated often crowded groups (Fig. 234). "Nac ae rund w oval and may be enlarged, pleomorphic, an ten yperehomatic (Chromatin is evenly distributed and nucleoli ae usually 01 seen | Nuclear wo eylplasmic rato canbe high ‘The cytoplasm may show discrete vacules or goblet cell change (Fig 235), Presence of iis andlor termi hars i characteristic, but single its ‘coll insolation are not suicent for the designation “poune 2.4, Ts retplaca (CP). Note terial ar ana tt ce ed * we rears 2.90. Tubatacten (OP, Ter ee ecerar nssoe 1 Powe 2.33, Tul metptaca (atoey, HEE) eee =Berstotic Cellular Changes («typical Parakeratosis") (Figs. 2°36, 2.555 Cuiterta Mickie aericll souanom coy with dese ormgrptiic eosinophilic evoplanms Co may Senta, in aes o in whads cl tape may ‘ound, oval, polygonal, or spindle sped ‘Nuclei ae small and dense (prhnatig” Iriel carr cell change re pesca, cont atypicel sq "ous cell (ASC) interpretation Keratotic Cellular Changes (“Hyperkeratosis”) (Fig. 2.38) Criteria Aowclats but otberise unre mature polygonal sqpaneus cel hen seca wih mare xasmous eh with herby gern Empty spaces or “ghost ruc" may fe soon, ee SS ee SoasiasseoeeLymphocytic (Follicular) Cervicitis. (igs. 23,2540)” nterta Polymorpows population of lymphocytes wth oe without ingle oy macrophages af gen in lr or steaming atin mac Fg. 2) Liquid Based Preparations “Lymphoid sts may appear in clases and more sated single cells ean te sce inthe hackaround (Fig. 240), Explanatory Notes Reactive changes are include inthe 2001 Bethe stem under NLM Recognizing such changes is imputant for defining the boundary bres ILM and epithelial abnormalities, In general, round miccerconturs and even chromatin dsinbutin favora nomncoplsic proces However, cxuberant reactive changes in mature squamous cell may raise the di ferential of "low-grade squamous intapithcia esie™ (LSIL) or even ner if reparative features ae present (ce following paragraph on Pair and an imerpetaton of “atypical squamous cells of undterined sizifeanee"(ASC-US) or “atypical squamous cells canot exclude high rae SIL” (ASC-H) may be considered. Reactive maces enlargement {in squamous metaplastic ells may mimic “high rae SIL” (HSI), Squamous metplsic cells in LBPs, in pac, often Jemmsate on increased ncteareyoplasmic (NC) ratio Jv to oaning up of ells which may ase the differen of an HSI In ation, ovetapping ne lo in a inucleste cell may give the impression of hypereluomania ce Fig. 421), An N.C ratio of ess han SO, smooth mca conrad ven gistrbuton of chromatin al avec benign squamous metaplasia, © higher NC rt in conjunction with hypetchrmasia andor mtler con ‘our itegulrties such notching o grooving shod prompt conser ‘tion of HSIL or an ASC-H designation,” Note that with degcacaticn, ‘nucle may bécome wrinkled and hypercromtic and thetefore dificult ‘ocliferentate fom HSIL: in such cases, a interpretation of ASCH may appropiate sce Fig. 412) Irene 2.39. Lyrerocyte Hoioun canis (OP). Abunsart rehots (Shlain a tage oay mosropnage nena conta Fume 2-40. Lyrehooyc Hoan conics (LB). Note porous opuaton othe ene and tric coay macropnones cols eyReraniv changes Cynic pi") ay inal mate gus, ‘uo tpn umna ptm, The ceed cet an pomin nclchartos of enrages Iresencs of ure stir kaon Hoveter Ia eicpaeiee ree cel pica ceria monolayer sss wi te aed cone ition inpaing a steaming lok to he etapa ae toner na pony esi cals witha chnges ood ag toss egulaiesinchmutin dtbuton oration ns gs uc are presen. socal asp pai th changer tla fe atid as “apie sandr elt or “atl games cl Ace rationed Changes, consitng. degenerated lod bizar cl ems nd ella de generly sole ini oe flowing dry. However. in om pate, conic raion npr -panrane” an skera a deve fr rch angen ta have been wid acon Inthe pt inexto cnn ciety tn her css nina dec Changer cms ere mx seal Ind in Bethesda ein Gheto ko cones dete by ae inl parently fo tlrifeaton ol. Atbough ome cyt my shone ce ch fem dite smog ti, So mona Imre ascot Be st soe 0 pe ess “he Bah sso snd inepeaon of ich Ke chins eyed on tecnica acter shratons preset Mla pe Beas it ad phonic kien omega oii Spun paket) anaes eace cela chang. ow fet sngl also cell ses emo lenis fell Sine ose sat octet cel ani nese rc Bis and cromia ype peaks or pleat aepucinlcellirnaliy. Such iting snl exept s a ical uous cls (ASC) ora «squamous inept son (I). Cependng onthe degre of cellar normaly Wei se Figs. 43, ain s8 523,528 Anvceas bat acre uenaable mee, squmons cel ype Teron) a nocopeti change nave conaination ofspecimen wih vulvar metral may als nace anatet squamous cells ‘of the cervical eytlogy specnen. When extive gprs cen ‘an underying nplasi nonneopastc procera be preset? Thich, plagues of pleomorphic anucleatetqunons cells it inepla omy ‘may rarely be the ony clue wo an undersing suemous ce carcino {Lymphocyte cervicis (oil ceric) isan uncommon form of| ‘hronic cerita esl inthe formation of mature Iymphod fl ‘les inthe subepthliam of the urine ceri ‘Sample Reports Esamle Specimen Adequacy Satisfactory for evaluation; endocervcalransarmatio zene compe et present Imerpretation: Negative for nraepthelia lesion oe malignancy Exam 2: Specimen Adequacy Satisfactory for evaluation: endocerviesransormation zone compo- ne present patlly obscuring inflammation presen Inception Negative fo intraepithelial ce malignancy. Trichomonas vaginalis Seite, Reactive siuamous eels associated with inflammation, ‘Example 3: Specimen Adequacy Satisfactory for evaluation; endocericlAransfonmation zone compo nent aba Ibuerpretation: [Neptive for inaepihelil lesion or malignancy. Reactive clllar changes associated with radio, Example 4 ‘Specimen Adequacy Satsatory fr evaluation; endocervialransfomtion zone compo nent camot be assessed because of severe arp. AImerpretation: Negtive for inmepithoi lesion or malignancy. Fungal exganisms morphology consistent with Candide species |A. Young, MD. Marice Bibto. MLD. Sally-Beth Buckner, $erT (ASCTY, Terence Colgan, M.D, Dorey Rosenthal, M.D. award ikinson. M.D. “1, Ciln 1), Wena SL, Se PE, ea. Repti charges and ce fae itl patne Pops th Pt Jab Med 201280138 2 Secon nth geen somali Pais ay eh pea patio 32-37 “None Re ee dg thi He ths Sons Dap Cpe 91-0708, 4. anthocy Coopricn Pog a ContiapadCxay AP) 182 Dy 0 eM Foe Wh, a ry cg Pip tonto i Coley of ncn Puhongss cin Compson oem in CorvcvegealCygy foe seen) Ach atl Lat Med 198 {inane {Young NA Back he ine Pap x: in he en Be 01, Cot aha 4, Ss BX Resrencg eolpey:Recening of 37 ev ae force hp pase ou spl es nl inom Cale af oc aig Qs 312 oe a Rr MI Rent get on ia fr ‘ra fo mre a HPAL Gases giance ts Ce 201818 10, coco G.Fancos J ike. Mimtopeeisfeaton of evga ‘hn Fico mc Aes C09 HDT 11, Gasmin Saty WT apn mec ine ed eter Cet mao Ingen ne eal we ol at An se cl TLS 13, ML. Roe Papen rte gre pi in 14, Dantes GG Van BulckB, Cain 3, a Relationship of tater agin andegret in me ie aes faeeenaesteee ses ee ae ees $24 Chums rach sly sine ae eae J Pea ken omnis 21, Gonos SL. Tinted DE Cp anos enc ici Io coungn ts Cu 91) 3, 22 Sch Te Mg AB Vga iw 23 Bw C Clare npc tpl snes: Dag Cops 24201 taser Compan Prin in Cerca Como (PA) a arnt Seay fpr et a of Sn Pt ge tem ns ol Te Mpc BaP Upon ‘ego, bal metaplasia an ih anal amen ne log sea an deminer ee Ra ma ‘itanson BA Des DVS, Goon Ro Serie env ype ‘sen eral sean eC ote 9.2 28, it Mc Wie SL, La aus: nga any. Wied Ter ‘avo dos, No 1, dE. Cag Teor Cg P88 Chapter 3 endometrial Cells: The How and ‘When of Reporting ‘Ann T. Moriany and Edmund S. Cibas 2 Endometrial cells (na woman 240 years of age) (Specify negative for squamous inracpheil lesion") ckground ated endomeral eels ae commonly scom in specimens obtained the proliferative phase of the mensral ele. However, endome- lls hve Been considered potential harbinger of endretial ale ia when seen in cervcal¥agialeytology preparation of post al women or outside of the proliferative pase of the menstrual Inthe 1991 Bethesda System, “cpoloically benign appearing” en- ‘cells in postmenopausal women were reported as an “Epithe- ell abmormaly” Thi perspective was based upon retrospective r= formed inthe 19705 on the significance of endometrial els in cervical smears. In the largest ofthese ery ste, follow ‘showed that women ver 40 years of age occasionally demonstrated rial abnormaies, wheseas women under 40 didnot have e tral ptology 7 A more recent stay suggests that most women ‘pdometial carcinoma present with being symptoms, whereas ‘ater studies note thal the presence of endomeuia els Was the oly ab ‘onal ing ia a snl proportion of asymptomatic women in who endometrial adenocarcinoma was detected. ‘An individ womans sk factors for endometrial carinoms, lia al symptoms, mons history. hormone therapy. and menopausal st tus are often uncear, inaccurate, of unknown 10 the laboratory. Ther rein the 2001 Bethesda Syste, the presence of exited endometrial fells i poe in all women 40 or older the general ctepwization, ifed. is “Other.” Atpiclendometial cll should sil he reported wn ‘dere general category of "Epthla cel sbecrmaly, 1 should also be emphasized that cervical eyagy i primarily serecning tes for squamous inacptbetl lesions and agus el car ‘toma Is uncial forthe dteton of endometrial esi al sh ot be used to evaluate causes of suapcted endometrial sbaormaiie Exfoliated Endometrial Cells (Figs. 3.1-3.4) Criteria Exfoited cells eceurin bal-ike clusters an rarely as single cells (Fig. 3,32) [Nace re small, round, and apposite the ara of & normal interne ite cell nucleus Nuclear chromatin pater is often difficult to discern because of thse limensional rounding of the cll haste [Nacleol ae inconspicuous, Copia is sant, basophil, and occasionally vacvoited (Cel border ae ill ene During the fist al ofthe menstrual cl, double-conture casters of ‘endometrial cells (exo patern) my be sen Fig. 83), Liguid-Baeod Preparations Cell groups may appear “above the plane” of samous epithelial cells, ‘especially in graent-used mths, Cells appear in ight thre-dimensonal later ose clusters and singly Single cells may be more evident nthe cleaner hackground Nuclei may be bean shaped: nucleo and chromatin detail may beware apparent (Fg, 32), Inraeytoplasic vacuoles are moce common and easily visible Single cell necrosis (apoptoni) is easily scen fn the endometrial eet groups of ligid-based preparations (Fi. 8.) Background sppess cleaner, especially im mensial smears (Fig. 33) ‘compared conventional preparations, “Cin ocean $Strove oot nce: Nhe ae neonepcsoun. Ofopasm Sears wean yo eres, eee Sty t(etre plc sean Lh mera specmere: Flow pes he [ta Sermeca rtransoner Roproarsty Proj! (EM) age foe fasacion) r ott oras cy. Seage co recon arta) ca be tn Pe Explanatory Notes In the 2001 Bethesda System (TBS, aly exfoliated ntact endometrial {lls should te cepted in women 4 years oF ole, Exfolated groups [rendomeral els may he of ei anor toa oigin; however, tnorhelogi distinction ofthese two el types snot sully posible. ka Tigurused preparations, exfoitd endometrial cells maybe slghly Inger with more obvious nucle and enkanced chromatin detail, com: fd to conventional sincary.These fetes maybe worrisome w those Titania withthe sppeuranceof endometrial cells in iguid-tased pea ‘Nbraed endometrial cells or lower werine segment (LU) fragment baie stoma els and hsocytes, whon sen in the absence of exo ited dometial cc are not asocated with ineeased sk of en theta cancer and therefore o not generally wasran eporing”* THUS may be seen sa result of vigorous endocevial sampling and is ‘uracteristcally composed of biphasic tas fragments with densely focked spinile cell vascular spaces, and simple cr branching tubular lands embeded within the strom (Fg. 33). Glandular and stromal fells rom inadvertenly sampled endometrium during the proliferative 1 Pme 2.8, Lower sore segment (US) ragrents (CP) tne ‘ects creme Sonora of thy packed Serded ate, LS eprserta Sass roomate cy annaS27, open oy vie mnt ‘timers! yi, stoops hae ron fa rece micas Sa Src gna yc senna CR itty necator re ences may have aban rious, beaded “esp stoma” encom nay ry for ound to spe shaped and ave small oval mle scant cytoplasm (Fig. 36), Hinheytes are fen associated with and te indisinguishable rom. speeial stromal cli Bosh demon Pie single els with moderate, vocunated ytopanm and bea-sbaped fo round ncte (Fg. 3.7). Toe cluster of naked nace sowing smooth cea contours, mol Jeu, tn crenlyisuibted.ronlar chromatin bave heen report in Fae recivingtamosife therapy and also in atrophic smears. Ii os Pram tnat the Incidence of such "sal cells” increases with QE f= eiics of tamoxien therapy but thatthe cllsvnaed moc are more Meiy detected inthe background of etrgenized squamous cells ds to Pantkifen °' The naked nuclei may be of prahasal or reserve cll [i and should ot te mistaken fr endometrial cells (Fiz. 38) Ham optional educations concn recommended for we when re [pong exited endometrial cells a woman who s 40 years ole. Meay comment shuld stress that exfoliated emfometa cells ae wtally dated tron a benign process a that ony small proprio of women * FRoume 3.8, Noted nic soon here in ote cuore at mene Rng and ancsr ciromotin The Mer lower Faro stow a aa ee a aa wi oan crema BP). bon Tene pe seep gromen ey Sos ksit his finding ave endometrial sbaermalitics the date ofthe lst ‘mens period (LMP) s provided andthe apse wk aed in the fet half ofthe eel, the laboratory may wha to append a comncn, indicating thatthe finding of endometrial sels errelaen with the ten Stussy (se sample report 3), nis upto the laboratory to have policy specifying the circumstances under which endometial cellstha re not cytolosialy apie ee refed or pubolgists review. ‘Sample Reports 1 General Categorization: Otter: See Interpretation Resi, Inverprettion eval Endomcrial cells present in a woman 240 years of eg (cent), Negative for squamous inespithcil lesion 2 Endometrial el are resent ina woman =40 years of ape cen). Negative for squamos ita pteil lesion, 3. flutionl Noi) (options) ‘A: For all repens with endometrial cells in wamen 40 years older Endomeiral cells ser age 40. particularly ot of phase or ater ‘menopause may be associated with Benign endometrium, hore ‘aleations and less commons, endometrauterine dbmormatien Glnica correlation 1s recommended. B, Additonal not o consider when a woman's LMP is povided and ‘endometrial cells ar seen inthe fi al ofthe mewtral eye, Endometrial els correlate withthe menstraal histor provided Bethesda System 2001 Workshop Forum Group Moderators: ‘Bamand Citas, M.D, Gary W. Gil, CT (ASCP), Meg MeLaclin, MD, ‘nn T, Moriany. MD, Ellen Shes, MLD, Theresa M. Soma, .D. (CT. (ASCP), Rosemary E, Zana, MD. — "rs SoS ema sroerea oa Bn te nnmncncn Semen epi s ge aes ee eet tee ea es ee sana 7 Chg Sci Bs, yay Di eno el Ps ee renee te ceca orcas in era Seca Scien Soidiaitencuat cera sean eee eres ae Be ee na ca tsChapter 4 Atypical Squamous Cells ‘Mark E. Sherman, Fadi W. Abdul-Karim, Jonathan S. Berek, Celeste N, Powers, Mary K. Sidawy, and Sana O, Tabbara 3 Aaypical squamous calls (ASC) Sot undetermined significance (ASC-US) © cannot exclude HSI (ASC-H) ground foreruner of the new category “Aypial squamous cell” (ASC) the more broadly define interpretation of aypical squamous els of ned significance A national sey of reporting practices in laboratories daring 196 found that the lassifiston of atypical a ells of undetermined significance accounted for a mean of 52% ‘a inedian of 4.5 ofall ervca eytlogy reports These data i= that many laboratories inthe United Sates were male to meet he ‘of maintaining «reporting raquney for apical squamous cells ‘of udeternined significance under." These findings prompted he de Yelopment of th new eategory. ASC, which has a nartower definition “and tsp dichotomous system of qualifier TASC docs not represent single biologic entity subsumes changes ‘hat are unrelated to oncogene human poplomavires (HPV) infection te pops an wel as ings tht suggest the possible presence of un- lying cervical intranet neoplaia (CIN) and rarely earinoms, In Sercering programs represenaive of the US. population, approximately 150% of women with ASC are infected with high rskloncopenic types of Inuman papillonavituses (HPV)* The remaining noninfected women are tot at increased cancer risk, Numerous n-neoplstiecodins tht ae tinted wo HPV infections may produce cytologic mimics clasfed 3sASC ning nano, ayn, apy with desncraion and ‘ser tfc, ln many instances. th process hat aed athe ASC ‘erretation remain undefined, cen follwing dagnomie won, Duta demonstrate that spl lining the ASC catepny Y cis fing every specimen as “negate for rapt seals (S1LM) or "squaousiaepithetil lesen (SIL) sng igh money sone i not feasible: mislasifistion may lad to os of baloney iy and ponive proictive value” Acconlingy. he 2001 Bethola ye tem mintined an equivocal etegory (ASC) ar sinpiled te gus {0 eal reflet he ini of paolo securely a eps uci thes specimens The two mex common qua fy ical squamous cols in the 1991 Btheads chsifaon, aver rose and "Not otherwise specifi” have been cline in he new Bets, Spitem' All inerretations of ASC shoul be quill ss “OF enfcee mined sgiticance"(ASC-US) ot “cannot exclude HSIL” (ASC ASCCUS refers to changrs ht ate eter suggestive of LSIL a SIL of indeterminate grade, Although most ASC-US interpretations are sg. ‘ve of LSIL, the quer "undermined significances pcfee he ‘aus approximately 10% to 206 of women with ASC-US prove ta hive an undying CIN 2 or CIN 3+ ASC-US is expected to comprise mone than SO of ASC interpretations in moa boretorcs ASCH Is de ination reserved forthe minority of ASC cases (expected represent less than 10%) in which the eytloge changes ae suggestive of HSIL ny equivocal specimens specify worrisome for HSI shouldbe “nguibed from the bk of ASC using the designation ASCH. Casse slaved as ASC-H ae sociated with higher postive predictive value for detecting a endkrying CIN 2 or CIN 5 than ASCSLS, but a lens redistive of CIN 2 or worse than definive iterectatons of HSIL* Atypical Squamous Cells Definition ASC refers t"eyologic changes suggestive of SIL, which ae qualita tively or quanitaively insist fora definitive interpretation | Cyto. logic findings tht are suggestive of benign reactive changes shold be ‘areully reviewed and judiciously clasifed as “negative fo inne pita lesion or malignancy” whenever possi ‘he iteretton of ASC requires tht the cel in question demon ‘sate thee event features: (1) squamous differentiation, 2) increased tc yi end (minal ce yee Sea Sa yeaa ee Se ra erat nee Sais ae ee es eee a a ee ae Bee ares pa a ee oe SR iipslpprertechay em SS ee ee eae oer ers | Squamous Cells of Undetermined icance (ASC-US) (Figs. 4.1—4.7) i ae approximately toad nt tf 0 tee tines he we of betula normal name urna ol appoinaly $8 ian esas ratio of nuclear to cytoplasmic area (NAC). ral ccs hypeomaaan relrtymomatinS- tomo ser shape Tick sbnomalticsasocaed with dene orngeopil etplsn CCaypical pushers Fp 43) Liquid-Based Preparations “The appearance of ASC-US in smears and guid: based cytology ssi ir in smears, cells may appear larger and later (Figs. 4.1, 42,47){baw 4. AS0-US Promega woman, ts th carl (erston (Reprod win permatin arm furan Reo Baasos Fei the avn Sot Tot Fours Eaton Snes ale nN ne SSS i arcs ert awit Be 5 pt ee Fan S720, prepress Explanatory Notes Me normal-appearng intermedi cells tat ae present on a sie pro- ‘ide an appropriate source of comparing for asensing wheter nuclear five and appearance mest citer for ASC-US, Typical ASC-US cells fave the size and shape of superticial or intermediate squamous cells Round or ovoid els hat are approximately one hid the sizeof super fill cols and therefore resemble large metaplastic oe small interne te ces may also be clsiied ax ASC-US. These cells sggest SIL intrmesise gre (i.e. ponsible CIN | of CIN 2) "The descriptive ter “porkeratoris™ and “dsskerstosis” have been used inconsistently, by some to indicate benign process and by eters foincicateanstypical nding. Because these terms are not well defined. they are not prt of the formal Bethesda lexicon: the ters are inched Parentetically for clinton, Minne polygonal quamous cell with tense orangeaplili or coxnopilc exept and small pyknotic nk (Charest) should be eased as NILM if the nucle appear hommal see Figs 2.36, 2.37), Howes, ifthe mick ae enlarged, hy Pchromai. er iegula in Contour, or ifthe cell oceur in thee tlincsional clase, an inlerpretation of ASC-US, ASC-H,o SIL shouldbe considered depending on the deze of the abnormality (atic Barakeratonis")" ee Figs $3,417,599, $50,994) Rely te ie, Lneton between SIL and! decid cl, wophobinste o other ually ‘encountered elements may alo prompt at intereaton of ASC US Determining wheter to classify a specinen a NILM oe ASCAUS ry ‘be dificuin the presence of inflame or degenonine chang, tying with nuclear enlargement, and ober atts, The patent's age tnd history shold be considered nd previous specimens sho Be viewed miroscopielly if deemed rolevast to Imeepreting the. corse Specimen. Generally, when cureateytologic findings favor teactve ‘rocess over SIL and the patient isa isiry of muliple prior nective specimens, th interpretation of NILM should be favored Casifiation of specimens showing mild diffe clear enlargement should take ito account the presence of inflarmation nfo gen adequacy of fiation, patent ae, history. and eter factor In genra, the presence of cells with ple sean nace and even chromatin ds bution favors an interpretation of NLM over ASC. Most specimen ela sii as ASC demonstrate 2 numerically minor sabpopston of yp al cells that are ether isolated or occ in sinallshects ov arupings ‘ASC may alo bean appropriate designation forsee pecmecs eco ‘ain abnormal-appearing naked ale without associated eytoplan, ‘Criteria fr ASC-US may cfr subly among labora, reflecting ferences in sans and tehniqus for side preparation, Atypical Squamous Cells, Cannot Exclude HSIL (ASC-H) (Figs. 4.8-.16) ‘ASCH cll are usually sparse. The following pattems maybe sca ‘Small Cells with High N/C Ratios: “Atypical mature) Metaplasia® (Figs. 4.8-4.13) Criteria Cel sally occur ingly o in sal agents Fes thn 10 cells; cece siomlly, in ctnvetonal smear, cells may “scan in muees Pg 43), Cells are the sizeof metaplsi cells with nucle that are about Ts 0 2 times larger than moval Ratio melear to cytoplasmic (IC) area may approximate that o HSIL In considering «posible interpretation of ASCH or HSIL- nucle anor lites such shypercromasia, brmatin regulary. al abonmal lea shapes wih focal iegulrty favor an interpctaton of HSL ey Peme 4.9 LM versus ASC-US versus ASE-H (CP) 27-yorols Sstran ay 8 of renal oye, wt etary of pr sara yoo. Ex a are ta ore tape oon crt Srerges nie rh ven artes woruore oa (ose between (St ors SO," [Rune 4:10, 490-1 (CP) Cote wan recast cytoplasm showing Vector sie; hope, sre rao sor fe ejopente oe [a Peure 4:32, 50-4 erm HEL (LEP. 27-yeo-08 woman. On oft (aired arat cnte wr vara WG rtoo nd Soma cme pays rier rl eroguary. On te rue arigh-pewor wow of x hat cto win snaroes ans neauer te aegererted ce Faw > crowded Sheet Pattern” (Figs. 443, 414, 4.15) Caitoria A mirobipsy of crowded cells containing nce that may show loss. of | polarity o are dificult visualize, Dense esoplasm, polygonal cell shape, and fagments with harp inst ‘eges generally favor squamous over alandular (endocervical) ie Liquié-Bosed Preparations ASCH cells may appear quite small with nuclei that are only to to se lime the sizeof the netrophil mill (Fg. 1).Explanatory Notes ‘omal meupaic guano cls within mecinen may ary com erly nel ie and shape miler in und nul o eto tho States pesto om ars ave foun! ht inimaie cas suamous cls ave a ean celular ae aout 318 yn opt ‘ormatie metaplastic cel, which hive # mean area of 640 gn Th, mean acer area of etapa cel seat 0 0 a en ina och higher ato near cytoplasm ses than fund nr ‘al interme call Rese cs which ae ecetered als en sali ran elle, 125-175 jm’), even though ey pos Ses mil compare insist tne of metic xe ‘When cls wa etal apesrnce demons eave mi ucla engeen eau. even chromatin itt, hy perchomusi, SIL i's concer becaun the ato of acer toe Plasmic ae mayb ino that oud nent HSI, The ane Sze and cer appearance of ronal maple tana es on = slide provide sana fo jag wheter ale of cons wart iervetation of ASCH. Defining the rage appear Imeplsic ells inthe spesinen unr review i ita, case tis ‘ates wih be yo epaion ceo elise) a ter fers ‘ASCH may abo presenta atypical mare) metaplasia in beh smears and iui prepuration, abo is fining mse cry tom in the later Not hat degenerated mucin the bees of bons fe SL, ar fen ero perc ute relics eh to imal the entre nuclear ote. paring winked sppearance. ad te eho is madsy. ASC cll are well spre Wen mal ap a ae Kesh mec of HS more key. The “roe sit puter” may rest CIN 2 CIN 3 pictry imolvng endocervical plan) ate or neplcencer els tr aropy withers artifact ce ge $1314 S30) These ees se wmetines csi ayes land Cll (AGO), leading ‘n nexpecely song asin batven the ater cater ade tection of CIN Dene cytoplasm, polygonal il sap, and amen ‘ith tape edpes general favor squanous oe lanl ier ovate. Excessively igo roping wih sampling devices ay op feat an avid cae of tick cl amen a Licmitcacion of prominent male mae pa of ep han Sthowent, nl maybe found In esos Of SIL, especialy "scied with inept ened vos Ge Fg 52% re ttl snag tomcat) wth contours and mick favors reparative oes, Dt miler romero cokowon ay eit an nection of ASC fo a oat ion. ‘opie secinens te small ize ahd igh roof macaw Pani aca peal of sop cll tay rae concms stout HSL aly wher rack hyprchoma and sadgng associ with tion ae och (rigs 417,18), Appcaton of pale rede suficent atron 4 al ive asieaton peat same lod an isms maybe present ott ren un crc, ber nk cfr pcos Would ‘ meoplxm Siar ngs may prom at neretaon of ASC lowing rato ry orca Typ eign ted rr rpertinte mata and tpi erg mrad wih Emmi and miles genera ce ig. 2.23), bah inept not ASCH ic appropiate when csr dsincion rom HSI or a Einoms imps Comparton with the mere he ia fom avai ay ee Deferred sional clk and acrphags may lo poses fit mini ho SL tng gone iret 3110, 420), Simla soe aloes wering an ners deve ty sed are smal igh coll witha exemel Ripa of cr fo Steplamic area at tsenble SIL” Ax cpt of ASCH oF TAGC nay be aprotic of th change stern 50 Fis 204,22763) TnL ASC cells may appear git sl wih ut ha ae nly woo hee tines the size of netophl mile. In some stan. i Teemiaing ve cveraping mile om sings ier mks ay pov dicucs. sug ths can wally be resolved by fusing op ic down thigh per Cig 421) CBPs may ao comin ellen he Sire range of mua elisha poses pret rund pale mike Sich mnths appear 0 ean the ayo he eas Tome isco the oeplon of high NAC rao repesents an aft tuling fom yetg ofthe cel oqamoss metaplastic ender {Smt seman enn ha sm era he a Cylon volume. As monte, compro of make fees {heels question vith mont appearing metas r endocervical cells ieume 421, NLM vores ASC-H (LBP), On Cl Wi nee Gopier ‘rs fds iat eupaotwtrer ruc seguro Srasoaeas easy ‘Ro up and own may sy eres Management ‘The new consensus management pudenes tailored to the 2001 Bethea System clasifiaton recommend diferent follow-up for women with ASC-US as ppned to those with ASC-H.!® Oncogene (high-ssk) HPV DDNA testing isthe prfered management for ASC-US when it cat be revformed concurenily with cytology: repeat ctoogie testing and in ‘mediate colposcopy also represent aceptble management tn conta ‘he recommended managenent for ASC-H i colposcopy: Manager ‘of women with ASCH following colposcopy that docs ot ein hs tologicdgnoss of CIN 2 ora me severe lesion should be individual ized based oneview ofall pathologic and linia! finding, In con ‘taistntion wo definitive inepretations of HSIL- inure weston ito spss i tale Cat view fee ee teaing Nomen with ASCH who dos not ve hsopelly dg eS. son the ASCUSLSIL rage ts (ALT) fn hei enuf ASCH were nox wha ig i oer DRA deco sn ety kof weing CIN 2 or one come 0 ASUS (10-158 tk of CIN 2 wore). i slo wren forth coven! sea ad Sond pepe Use trun te emcgei tengo tangs wom nih ASUS ae cours So isp esng vas cetctny, ncaa frac Fic of HIV ict teens women it ASUS Meola ith ag” ela cg tins Mould ber given compan cations, Wes tarp {in spoon op czenl cnon pee CP) lot fling 2 rol mp of A, the Ci of ib erly Uc ™ Liat of CN 3 mpc Nock DUET men long tg eet of ASCs rome iy mec ey toy voce fhe ota side Pie. boots nes ogee lop of Sant ASCat scary wh feb cen or nde Bess cncpcs don roi eng tcl rte. Reports Tpitheisl Cell Abnormal Appia squamous cells-undetermined significance (ASUS) “Comment: Suggest igh-isk HPV eng if linically waranad reflex wsting ‘ot ordered or if conventional prepartion) on Specimen set for reflex HPV testing pr clinician request Fpitholil Cell Abnormally: Atypical squamous cell-cannot exclde a high-grade squamous in ‘maith sion (ASC), Comment: Suggest elposcop/binsy as incall indicated For examples of reporting ASC-US in conjnction with MPV testing see Chapter 9 on Ancillary Tesi.Bethesda System 2001 Workshop Forum Group Moderators: “Mark E, Sherman, M.D. Fadi W. Abgl-Karim, M.D, Jonathan Berek M.D. Patricia Bray, Mi. Rober Gay. C-T. (ASCP), Celeste Power M.D. PhD. Mary K. Siwy. MD, and Sana 0, Tabbors, MD. References 1, Soloman Dey D Karan Rt The 204 Bethea $n rang ‘epeingfcreeey JAW 20022731 10 2. Nina! Cae ste Way. 101 Behe Spe fr epering esi ‘alkagnl ie Sapp 181 ete Wate JANE No Ey Compare gn Ca Ct Pa shi ic rr hl eel ya The ALTS Grow: Ress fs rnd trian the management of yogi ‘erwin pl wes amide {07 mpl quot cals of sds tes dese Sages {i hcuy oe ipnesinn ecaCor Cop 9628 a 1. Quo Sung Seo NIN =a Apc gems mew racy, eae and gon eres be Tay Fap te. one 1 Seman SE, Slonon D Ssh M fr he ALTS Gp Qiioe the ASCUS SH Tage Soy JC Pind 0-16. 3 ‘Shr MHL Sunn rte ALS Gp rb pei fe ‘el iui ab halos ier estrus In ASCE SI ge Soy ANA 32881505 10, Pata SF Bein plete rato umes aia ei ei In Wie Lito M Keser CM Kes Pas. Renta Dh Cn ‘Prd on agen Ces, AB Cag Tu of Cogs ET Atmos Mt, Wasa, Sie. Hogi can a params aps ering Say Ae Chl SA ses 12 on ME, Zp Ounce Nada Et ping he sti te? site Cyt plas embasngetcevsal amp AC 19137 's ings Meo Lume igh ae uum opel k= —— sy nt ee et of SS ais Reece kan ence eee en ae ee ee ce Be moe ete tan tt en, a wt a a 201 Comers is ma fee pots vd. scotty ae om mm "Spams Colo Unmet Gnd Sumo are Apia ae Togs Siny (ALTS)1 Nat Cater far D017. ‘Sermen ME. Wang Taner Rc Haupt ene cv cy ‘eta spn Ses ete Apc Sqatmen els of Undcrie Sin- Iecsr eSwmsarcta Lv ogS pt Forays dame br Cancer Eel Barer Pre 208125723‘Chapter 5 Epithelial Cell Abnormalities Squamous “Thomas C. Wright, Rose Marie Gatscha, Ronald D. Lal ‘and Marianne U. Prey Cell Abnormalities: cell ‘Squamous IntracptelialLesion (SIL) 7 Vow gre squamous inaepiieli lesion (LSHL) © Hlah-grade wusmous inracpthlia sin (SIL) + with features suspicious for invasion (if masini suspected) 3 Squamous cell arcinoms ind intact ein (SIL) encompass the spectrum of nonin ive cervical squamous epithelial abnxmliies associated with aman p= rns (HPV), which ange fom the cer chanes tat are assei- vith anit HPV ines shoo cellular changes presenting grade precsrs to invasive squamous canoe. In The Deeds Sys- {TBS), the spectrum i vided iw low grade (LSIL) and high-grade egies Low-grade sons encompass the celular changes vari iy teed “HPV cytopabic ete” (koto) and mill dysplasia or sel cpt meeps (CIN) 1. High-grade sions encompass oder dpa severe dysplasia and acinoma inst or CIN 2,3, THPY sociated squamous cell changes or eytoputic effects wer first described s perinuclear lering with peripheral condensation ofthe toplism'? These features, tered “Liloytoss” were intally com fered to represent proces separate from “tue” dysplasia. However, Iounting evidence over the past 20 years has established HPV asthe ‘main causa aco nthe pathogenesis of virally all cervical cancer p= ‘arses and angers” HPV-DNA Is detected by molecular techniques in the vst majority of SILS apd cancers. The majority (>98%) of invasiveerica cancers and their precuroes contin HPV apps refed 4 3s high-sisk” HPVs the most common being HBV 164 iphisk HPVs ne sociated wih both Kw and high grad SI, but ae served wil si nifleany greater frequency inthe hsh-prads pup’ Concepuly, MPV-ssociatedabnormalies canbe divided into an siem infections tha generally regres over the comc af Ito yeu on) HPV persisience thats associated with an increased ik of developing 8 cancer precursor or invasive cancer” There has ben a sh i th ‘United States in recent yeas wih regard 10 the management of biopsy confirmed CIN 1 based on the recognition that most CIN I especially young women, represents sesimitd HPV infection. The cre! sr hans of cervical cancer seoening is fcised on detection and wears ‘of biopy-confimed high-grade disease, regardless ofthe distinction be tween CIN 2 and CIN 3," ‘At the 1988 Bethesda workshop, the spectrum of SIL was subi imu two categories ase on 1) he desi to use morphologic eae zores ‘hat eat to the biology and clinical management of HPV-ssciaed le sions. and (2) the acknowledged low inter and intraobserver repro Aucblty wih conventional twee- and fourgrade elasiieation ys tems I has teem argued that 4 twotered apsem provides fess information wo clinicians than a thre deed CIN terminology" Homer, te eyolgiedsincion of CIN 2 and CIN 3 is poorly repucble, e ‘combining the eyilogic comets of biopy-confmed CIN 2 and CIN 3 into a single HSIL category was shown, inthe ASCUS LSIL Triage Sualy (ALTS),to have impeoved reproducibility (M. Scifinan, personal ‘ommusication. ‘Anoter concer voiced about the two-tiered asiision thatthe Aividing tne eeween low-grade and high-grade precursors should ese ‘between CIN 2 and CIN 3 becase the nara Hisry of teed Cl 2s cloner to that of CIN I than it isto CIN 3." i some European co tries CIN 1 and CIN 2 are grouped together for teutment purposes" However as. screening tes ceria etology mus emphasiee Semi iy. Given the variability i the interpretation an biologie behavior of “eyologe CIN, sting the eytlopie threshold for low-grade and high-prae esons between CIN T and CIN 2 fs considered appropiate ‘This cut point aso demonstrate the bes interabservereprodutiy s ings dichotomous postive/neatve esl, axed om daa from ALTS (ML ‘Schitnan, personal commumiation. Even with ony two calepoie of SIL, there san overall 104% to 186% Interpatholgist discrepancy fate between SIL and HSIL interpretations ‘0% cervical tology slides Cytology my alo be discrepant with hie: tology: 184% 10254 of women with LSIL cytology are found whine hi tologle CIN 2 or CIN 3 upon further evaluation ncellchangeanccated wih MPV infection ncompss ikl dys Gi” and "CIN 1” Sever studs have demonstd ha the rcxpbo- ra for dsinguishing “hye frm mid dysplasia or CIN ay song investigators na! ak clea significance In alton, tah Sins shar similar HPV pes. and tc bilgi vio and cli mar Sexment ar slr, ths sopping common designation of LSI ts cur ingly ain shes ; lope sees re ws cofsd coh wth ams” or nip fiat yee oem ic se are with uy suman nat” ellen ey om dear enrgement mre than he tmes the of orl inte Sia mt rls na sgh increned mer xpi ato. abi depes of mcr hypuchomania re scoped by Yar oe eles miner nd sae etn ed enconton necormon i 52 {Chroma sternite drs arcasy guise ie chromatin my sper smd or dey opae ps 8.152) sess we pony et or crepes {Concur of mer nemine fen shy eer my’ he 5 Calshne ds asi oies. Fence cvaton chy) costing of shy delineated che piel sve ant yep node ined 0+ Piso chuncersc fan bat wnt ried for enter fon of SIL tp 1: akematvy, he etna may appear Sense fd rngepie eine. Catt win tops pri caviation c ene rangi mes ‘he show new seats to be diagnose of LSI (gs 3.3 34,32) perimeter talon hc aoe af rc abormalis 3 tot quai forthe meron of SU. (5. Liguic-tased Preparations larg mit! may ot sow significa nuclear hyperchromssia Fi. 55), [Angulte chasers ofayprealdysplsi els maybe more clearly vist- ue they shouldbe classified based on the degree of male abnor rmaliy Fg. 59)Explanatory Notes ‘An terpetation of LSI shouldbe bated om sit rteria avo over interpretation and unnecessry treatment of women for ponspeie or ‘hologi changes. For example, cytoplaunic perinuclear halos Withous sccompanying atypical nuclear fetus should ote coder Lt. (fig. $7), Tem sich as “Lollocytoss” “holoeyatic apa” and "condylomatous atypia” ae ot incl in TBS terminaogy, Socal 'ypial parakerstovis” showing nuclear abnormalives shou be cate sgotized a SIL (Fg. 58). Specimens with borer changes that fl shor ofa definitive SIL imeypretation may he estgorzed ss “Atypical sguamowscells-of undetermined signiticnes”(ASC-US) Figs. 36,10, sup, 1 ours 63, Low grace square hiraephe len (SL) Conve ova preparation O9-Nusow enargerert ara hypatcvemsas oo Stages te nla woeaione re G} Bovense rises Re roducbity Proje Se) nape (se aft recto | Faure 5.2. LS (cased preparation LBP). A S2-yerols woman, "5, rovine cone sycogy secure Nee he overage ooh See SShucand nacew cleonain wehae'ned sfopasn end maucta, Rune 5.3. LAL (LBP. 20ye0r type of tops, which be can ether ley and dete oe Imciaplstic, with rounded call Borders. Over cell ize is salle « ¢ - > = 7 3 Peame 9.27, grade canct be determina CP) Raine screen $LPSrsea2as worn Mot oftnoce col uly mt LS, tare oe fap cement cer tron vows aIm HSIL as compared with LSI In ascasiona eases whet itis nt pos sible to grade an SIL as clay low or high: an itergetation of rae canot he determine maybe appr (See Figs 5.2%, $27) ‘designation of “atypical squamous cells cannot exclade HSIL (ASC: ‘sgproprate for specimens wih sme features of HSIL but a fll hy ‘of deinve interpretation of SIL (ase Figs 410-418) Keratinizing Lesions (Figs. 8.23, 6.24) Although most HSILS are characterized by cell wth «high nicks ‘yteplasmic ratio, some high-grade lesions are composed of cll, yh ‘more abundant, but abworally Keratinze, cytoplasm (sce Fign, S $524,528), These eels may be shed singly in the-dimensional hs? ters and have enlarge hyperchromtic mal often wih dense core a that obscures otber nuclear features. In aditon these cells at fen que pleomorphic with marked aration of nuclear size (anisokayenis) sd ‘ella ape, including elongate, spindle, cade at tape eel In contnst to invasive squamous carcino, clo and tumur dates fare generally absent. Such lesions have heen variously termed atypia ‘ondylom""Keatnizing dsplsi” and “pleomorphic dysplasia tines, thes keratnized lesions maybe indinguishable fom fave carcinoma, especially i samples witha relatively scant numberof ‘oxmal cells In thes stances, an explanatory note ay he appended > indicate hat the sifferetal diagnosis inelods an invasive squamous éarcinoma, or the interpretation of HSIL with eatres spins for ‘son can be used (Fg. 5.28). SIL with Gland Involvement (Figs. 6:20-6:23) When SIL esilly HSIL exe ino the endocervical glans, te s users may be misled feng lar in origin. Cs hth sions squamous in nate cle ceall Ios ells showing spin, tor whoring (Fie 5.14) wih tring ofthe nace at the periphery cluster, giving a smoot, rounded rer (Figs. 5.29, 530). However, HSI. in glands may demensate peripheral plating of els nd aka pt ‘sociated with inrauterine device (UD) ws (se Figs 2.25, 68) an "sola els of endocervical or endometrial on ‘Stroam of HSIL Cells, Usually Within Mucus (Fig. 5:24, 6.25) FHSIL in mucus stands can resemble hstocytesuperfcalendome ‘ria stromal cells or depencrated endocevicil els sin mirolandulsc hyperplasia (Fig. 5.84, 535). The low-power pater of small ells in = steak of mucus warns evaluation at higher power. This pate is pe rally ot observed in liguid-bsed preparations which frame mucus HSIL with Features Suspicious for Invasion (Figs. 5.28, 5.32) ln care cases of HSL, nesive earinoma ficult to excl. This si "tation may oseue when thee ae hihly pleomorphic HSI cells with ker stinized cytoplasm present at are not accompanied by the characte. ie background feuturesof invasion (necrosis or tumor dates se Fi 528). Conversely, there may he fetes sugzesng tumor Gabor (blo seers or granular rosnaceous debris inthe background} but malignant cells are no identified, Occasionally, HSIL. extending nto lands may be asocnted with foal epithelial cl necrosis and mi nell, without invasion: in such ete, the acti is seen ac. ‘ted with the cell group with an otherwise clean Backpround snd sot ‘mixed wih roken-down Blood and inflammation as ustll seen in at invasive tomor dates ™ (Fig. 3.32), 7 ate stocring tuna can mm reaoryon ane Beer ctivetrishe cots Aan power, Hc canbe fesaly (Qasr (ove abo Fi 535,170,420 Sager erateenca cols scene srbamPa pata ona wih Scene ser et hw er specote eh mere 9 ‘rua nen Geen spay For ance Po a er Eira ayn, een st wemen whng ord careagoptves nd ay FSi tte mmgreaton Folow'se was NLMManagement of HSiIL Most women with cytologic res of HSH, will have biopsy-confirey CIN 2 oF CIN 3 ieniied a the time of calponcopy Melos 2001 ASCCP consensts guidelines recommend ta if biopsies CCN in ot ied at colposcopy in «woman wit 4 etalon sc Pretation of HSIL, all cytologic and histologic material shuld be viewed If the eytologie interpretation of HSI supe on review ‘sgnost xcisional procedure shoul he performed." ‘Squamous Gell Carcinoma (Figs. 5.36-5.41) Detinition ‘Armaligant invasive tumor showing iferetaton toward suas cel ‘The Bethesds System doesnot sulvde squats cll arinoms ow, ve, for desrptive purposes, nonkeratnising and kertniring cuss mas are hee discussed separately Poin 6:37. sess ol ccna (CF) in het at he Ponto athe cae, ror danoce port Sn ory rec sive seen nts Bod ears 8:98, Sao ot sarcoma Marr nt cht re ‘Bande’ Ween mayb arcu Atenton staid be Quen to Bosna or Sotiee onmtate cats inthe backgrunKeratinizing Squamous Gell Carcinoma (Figs. 5.36-5.39) Criteria Relatively few cellsmay be prsen: often as slated single cells and kes “commonly in aggregates. Marke aration in cellular sve and shape is typical with caudate an spin cells that frequently contain dense orangeoplic ytopasn cle alo vary markedly in size, noclear membranes may be iregus in configuration, and numerous dense opaque nucle are ofen press (Chromatin pattem, when since, scouslygranla and ieee’ “istrbated with parachromatin clearing Macronuceolimay be scen but ae less common than in nonkeratnizine Squamous eel earcnoms. Associated Keratotic changes hyperkeratosis” “pleomorphic prs ‘atsis") may be present but are not sufiient forthe interpretation ureinoma in the absence of mica ahora ‘A tumor diatesis maybe present, but i usualy Fess than tat sce in onkeratiniing Squamous el carcinomas Liquid- Based Preparations LLBPs ar often characterized by lower tumor celui. Rounding up of indvidual coll and cell groups may impart hn es urs to squamous tumors, leading oa misinirretation of aceno noma (Fig. 3.38). Diatess i usually identifiable, but can he sub companed to coven tional smears: necrotic material often collects athe periphery of the cell groups. refered to “singing dates,” as opposed to Being dis ‘whuted in tbe backsound a i conventional smear" (Fi. 5.9) Nonkeratinizing Squamous Cell Carcinoma (Figs. 5.40, 5.41) Criteria ‘Cells occur singly or in syncytial aggregates with poorly defined cell order (Cells ae frequent some hat smaller han those of many HSIL, bat di play mow ofthe features of HSIL Niele demonsate markedly iteaular dstibaton of coors clumps ‘hromatin ‘A tumor dathess consisting of nero debris and ok bod i often present Hib tele ry be more ste LBs an often to ote Stine psrcrary cot gruen = pater Petras boon referred to ae Someta dar Potew op was squamous al carcroma Fours 6.40. Squamous col cana oferta (CF. Tes cys Src me concern tram cue fh pronrt cio oe treeIn ato, large cell vaviane ums (Fig. 541) may show: Prominent macromilel Basophliccstplasm Explanatory Notes Invasive squamous cll carcinoma isthe gant nop cas he mut commen mal ss afte wen cen Previn itn ve ve usc ‘noma into keratnzing, nonkeatiniing. and snl cell ypex. However these are offen nr earl distinet ens: ertinnzng and nokta ing ps may cnet oth sae se, ess commonly en ait of ‘wonkeratizng squamous cell carcinoma isa "arge cel Yara in which theism be seen singly andin yy and dsp a mode nut of yeni an rine mice Fg 5) amor dates ad invasive features may’ be more dificult discern in liguidbased preparations resulting in some cancers fn igi te prop " being interpreted Historically, “sal ell carcinoma” comprised a heterogeneous 04 peoples, including poorly iferentited squamous cel carcinoid well as tumors demonsating aeuteendocrin features (Vien ofthe ell "ot cel” ype). Crretclasiiations init the we of the all cell carcinoma” o nom squamous mors with evidence of Ipeurvendecrivedilferenttnn, Sock tame thr couerpars i he Tong, ar cstegorizedseprsely nthe World Health Organization casi fiotion (See Chaper 7, Other Malignant Neoplasms) ‘Sample Reports same ‘Satsfcior for evaluation; endocericalAransformaton zone present Inverpretation: {Low grae squamous inapitlial lesion (LSI). ‘Note: ure fllw-op ax cieally warated. (Wright TC Jr, e al 2001 Consensus Gnelines for the management of women wih cer ‘eal extlopicaldbnonnatie, JAMA 2002:287°2120-2128,) Example 2: ‘Satsfctory for evahation. Incerpretaton High-grade squamous intpithelial sion (HSIL) Note: Suggest caloscopie examination (with endocervical assessment) “sclinialy indicate (Wright TC e ol 2001 Consensus Gide Ties forthe management of women with ersealevoogial ab normalities JAMA 2002:287:2120-2129.) Satisfactory fo evalation, ndoveriealeasformaton zone not Wen ed. Interpretation {low grade squamous inraepthelil lesion arising in an tropic back- ‘oun. [Note Saggest colposcopy/bipsy oF repeat Pap test 1 week after in Trvaginl estrogen therapy. (Wright TC Jr, eta. 2007 Consens Guidelines forthe management of wowen with cervical cytological tamormaites JAMA 2002;287.2120-2129‘Thomas C. Wrigh, MD. Richird DeMay, M.D. Rose Mare Gatch CX. (ASCP), Lydia Howell, MD. MPH, Ronald D. Lull, Mb MPL, Voller Schelde, MD, Len Twigs MD. References sca phos aly At Cha 9a 990 2. Klute CX Umi at lomo et ce sg poe Sahota mp oS sh sis crac in Pa 2038360388 4. oct Pe be a aig sant fessor me in sel cc Ee a 5: Cel Mar A Bay 8 it Cpr na pt ‘ie ain i mi «106% herman iy Ra ity af i pp sagen ae oa i ten Mee Sp ays gee i {ct ihe pti ee espe en Seas insta Cancer Ren 200:6027-4102 ce 1 Sede AF ate Sa Pet nn etn ice seaport as Fan Ee 9: Belt 1, Caan Th face en ‘ie ion ne ues Zn CHD TE so Wiper cox Mada! Cosa Ct re man ‘Soro inet ep mee See on Banham gate pic ey rt aT Sennen lee i, Siac Shee rere ear ee ae ay isda ae pig ctoneret Orel las 4 Syn katana Na hapa eee ea stn nts hag ios sa am 1s NGL Hh. ot a pte fl pia opin cu or eet inp ra at Sapna ceeeee Ee Senor epee ee eect Fo aS Bart RD, Ks a man lori of fee eine pees eer ihr GO, Karan 8, Res etal. Canein teil apa of Bee neacoepseceanon io nes Bee roroenkaee Bess tosses ee ecto ee eee Peete araaes re arene meee Tr Pe 2087200208 a eco eeceoat acess ne reo {ats aise! by te ets Som ag Congr! A420 essen eit rent 26 Cc Hem Je int mop mihi nave Pee ieee tana eer ee coeerny mea peo ce Riper deere tore ant eae ee Sion cats pt Dag Osan SOA Soe eee eee re Seteceaern ances Eo aesiere eee 1, Sa) Re ong TA Kaman Rea Hil Tn of mae ena a a eee!Chapter 6 Epithelial Abnormalities: Glandular Jamie L. Covell, David C, Wilbur, Barbara Guides, Kenneth R. Lee, David C. Chhieng, and Dina R. Mody Cell Abnormalities 8 Aypical > endocervical ells (NOS or speci in comments) © doar els (NOS or specify in comments) landelr cells (NOS or spel i comments) 2 Apical > endocervical els, vor neoplastic > sland clls, favor neoplastic 1 Endocervssl adenocarcinoma in sts 5 Adenocarcinoma > endocervical > endemeria © ot oterwive specified (NOS) Background “The 2001 Bethesds System teeminology hs incorporate changes to he Ieponting of slandularabnormalies to ater reflect curent knowledge Gnd understanding of glandular neoplasia in cervical eytlogy improve ‘Sommnication among Ioratoies and clinicians. and thereby facilitate Spyropriate management of pints. As nied previously. cervical €)- tology is peimarily a sorening fst fr squamous intraepithelial lesions nd squamous cell cucinoma; semsivity for glandular sions is ited by problems ith bot sampling and interpretation?[Endocrvcal aoracioma in sit ix consid 4 be the sland nna of cervical inating (CIN) 3 and the prem 'o imasive endoerial adenocacinon Similar human puploms in, (GHPY) types have Been desaa in mod nase endocervical an. may be Completely obscured (sce Fig. 6.27). Close and cael srainy een, fal to comectly categorize tone clases as glandular n oii, Wolted normal ell re roe frequently sen, Because ofthe xe open chro natn ptr seen nq bases preparations, mice are mre promi nent However tumor dese may be less aperet, consisting. ofa {Pcztes of proteinaceous and iaflammatory debris often found clinging fete surface of nial cello al clusters ina ptem tat has been referred to as “clinging dates” (se Fig 6.30) "The possibly of coexisting glandular and squamous Jesion inthe cervix shuld always be considered when aking an inerpretaion of r= (Gccrvcal AIS (rig. 633)" In some sis, up to hal of AIS lesions Inne + coexting squamous intapihea lesion, usually of high gad. ‘Often the cytplismic features andthe cll rangement different the two neoplastic processes. Endometrial Adenocarcinoma (Figs. 6.34-6.38) cnteria Cll typically oecur singly or in sal, ight eases. Tn well-iferetated tumors, le ay be only sigh enlarged com ped to non-ncoplaic endometrial calls, becoming larger with in- ‘rsing grade ofthe tor: Variation in nuclear size and loss of nsclear platy ae evident ‘Noclei diply moderate hyperchromasia regular chromatin distbuton, ‘nd prschromatn clearing, particularly in high-grade tumors ‘Sul o prominent nile represent; nucleo become larger within cessing grade of tamer. ‘Cyoplasn sypially sca, ysnopbilie, and often vacvlaed: nay Toplasmic neirphis are common. A finely ranlar of “watery” tumor dates s variably present Liquid: Based Preparation ‘Thre-dimensonal groups and casters oF papillary configuration. ‘Nice ted vo be ltper with more open cern, "Tumor datess ray be fess prominent, al seen as finely rane de Tis clinging the peripety of cls of abnormal calls 35 coas slat debris(1 Poume 037, rcnoma. enti LSP). 7-year woman ‘Gatpnrerpa toca Te ren popes aayExplanatory Notes “The cytologic findings in endometial adenocarcinoma re largely de pendent upon the grade of the tumor, Grade 1 tumors tend 10 shes fet moral cols with minimal eytologi ya an would typically be in terpced Ss aypical endometial ells (See Fig. 6.10) Cytologic de tection of endometial ademcatcinoma, especialy wel-diflerentated tumors i cervical spsimens i Tiited by the small number of well fprevervd abnormal cel and the sully of thei celllar alterations. In Bint wo endocervical adenocarcinomas fat are ety sampled he ‘ection ofendomatial carcinomas in cervical estology depends on eX foliated cells being preset i the collected specimen. Thus there are gen- aly fewer abnormal cells preset as compared o endocervical cancers {see Figs 6:34.67), Inadtion, the malignant eels fom endometial farinonas generally have a sale cell and oclear size, null are tens prominent and tor dithesi if presenti "watery" a move i ficult appreciate" Fig, 6.35) High-pradeendometal serous c ‘noms mephologcally resemble theif ovarian counterpart with papi Tar fragments lrg cll ize, and prominent mule (see Fig. 6238). Extrauterine Adenocarcinoma (Figs. 6.40-6.42) When cells diagnostic of adenocarcinoma cecurinasocation witha clean uackgrund or wth morphology unusual for tumors ofthe teas o ce ‘mentralerinencopasshould be considered, Sources inthe female gen ital wat iclad the ovary and, less commons the fallopian tube" A though noe specific, the presence of papillary clusters and psarimoms tdi suggests an ovaran eacinoma (Fig. 640), Because thy are lols and trvel from distant ses, the malignant cells may show ‘legeneative changes. The lack of tumor dates sa clue to the no vial origin of the mlignant cells, When dathess x preset, it ws Sly ssociated with metastasis othe aervs or vagina. = Other tumors ‘netstat ote cervix ower reconsidered ia Chapter 7. Other Ma Tgnant Neoplasms,‘Sample Reports Satisfactory for evaluation; endocervicaArafomation zone presen Imerpretaton Atypical endometrial clls present not aherwise spite. Example 2: Satisfactory for evaluation; endocervialAransformation zone preci Inception [Api enocervical cells pest, ay Hikely derived fom tubs tls same: ‘Saisfactory for evaluation; endocericatransfonmation zone present Ierpretaton Atypical lander cells presen, favor neopatic [Neer Suggest colposcopy (with endocervical sapling) and edome: til sampling (iF >38 years ld oe shnormal bleeding) clinically indicated. (Wright TC Jr, Cox JT. Massa ES, Tweet LB, Wikio Son ES. 200] Consensus Guidelines for he maerent of women vit cerialetloical abnormalities. JAMA 2072287 2120-2120) Sathfactory for elution Ierpretation Endocervicladenacarcinoms in wit Examples: Satisfactory for ealuation. -Adenocarenoma, favor endometrial orgin. Bethesda System 2001 Workshop Forum Group Moderators: David Wilbur, M.D. David Chhieng, M.D. J, Thomas Cox, M.D, Jamie Covel, BS, C.T (ASCP), Barbara Guides, 8.C:T (ASCP), Kenneth Lee, MD., Dina Mody, M.D, References Sa Se aig ee tae Soa ieee eo a eta cat Reece ee Aa mares Po Tat eT ott as Voc Geen Ca Pub Fee cage tom ere eee en tee ales ath spe be ce rem Sec ene eran ee Fe ee CIN non MU, Ki SR nfo es of he oer pie enae cope nora son anton se oreeerctegamos Fe a parte of exe ancora wi he Ti Fe cope ei a ses. Rao NO Ren onl penn Bp Ed New Ys NEG ig Scie cere oe Sis ene taal oma ie ee en pet eter es M, Bousfield IL. The cyslogic diagnosis of wlenocarei- ‘oka et ne A Compan gas ahtenme‘nea i on he omy of eee Ay mi atenitdgee eee SS Chapter 7 Other Malignant Neoplasms ‘Sana ©. Tabbara and Jamie L. Covel Background ‘Malignant neoplasms ther than squamus and adenocarcinoma, ine Gocny involve te rine cervix ut ueverteless may be sem in cer Erevtologe reparations Mos ofen thse tor re uncommon pi mais arising in the erin cops crane hat appear inthe evil Preparation ether as exfoliated cello via direct sampling of tumors that Frvoive the cervix or vagina by direct extension, Secondary oe metastatic tumors to the urine cervix acur rarely, ening Wo the mature ofthe fate daiage and low vascuanity ofthe uterine cervix In general. ‘einiiveclsacotion ofthe tuners described in his chapter may tbe posible on eto preparations alone because of Kimited sampling al ytomorpholopie overlap with ether ents. However. fait with thew ees susefol when an sal tor morphology i encountered Uncommon Primary Tumors of the Cervix and Uterine Corpus (Figs. 7.1-7.4) Carcinomas ‘Spindle Squamous Ceol Carcinoma (Fig. 7.1) Spindle squamous cel carcinoma 3 post dierette vain of sa ous cll excinomsa characeized by pleomephic, nd non-Aeraini- ing cells with igh mii acy. The dflerenal icles sarcoma and Iignant canons with spindle el features mumacyoshemsy Fr ‘tokerain may he hep demonstra an epithelial iin. Poorly Diterentiated Squamous Carcinoma with ‘Smail Cole Poors ifeveniated squanou carcinoma with mal els morpholosilly resembles high-grade suumous inspite son and may also be Confused with sal cell undifferentiated earinom® (see below). The cells‘tare arargea ina own cofeave sunt Tre opeloge tates ae ‘not Spc: are co be compute wih sara: spree Cl carara ' heidi cae, ea neces rar Soer omen Soe have mote cytoplasm. greater eyopannic densi; beter defini of et Tres and es crn fat dsl cell wnifrettd carcino” ‘Smat! Cot Unatrorentiated Carcinoma (“Oat Cell”) (Fig. 72) ‘Small nciferetata carcinoma newendoctne acinomae I) ompees sl minority of all ceva eariaomas.® Asin eer bay Sie ths tamor i igly aggressive and is weaed diferent from other Ccinomas. Tetfoe, is import to recognize this tomer a dint from poly diferenned squamous carcinoma with small es, Sl ell tiie carcinoma ts composed of small, relatively uni cells trina eyanopiiccytoplam, Characeristically, the cells ae seen inal) and in props wih lear molling, wih “rush aif” being 2 Frege finding. The ck ae hyperctrematic wih gral 0 ile’ ‘thomatin an inconspicvous mele Background tumor dates is com thon. Although the eologic Teutues of smal cll unfree ex oma ofthe ceri a similar to those described in the lang ane by Sites inthe crix thee tumor are stongly asacated with human pllomavins (HPV) 1, a feature mo dented in eer primary sites The ferential inches poorly iferenisted squamous earcinoma With somal cel, poorly differentiated adenocarcinoma, low-grade ender Stromal sarcoma, a fmpbiom, The inerpretation of sal ell nile ited arin sould be fexeve for tumors compored of sal calls in which squamous or glandolr differentiation saben or minimal The reence of abnormal Keratiniced cols would far an iferpeaion of Doory diferente squamous cel carcinoma f esi material fro a Tigi sed pecen avalible, mmunceytochenseal staining fo ew roemocrne nukes [neon specific enolase (NSE), symplopysin, chro ‘mogranin| may be wat to demonstrate neuroendocrine fetes, Carcinoid Tumors Carcinoid tumor (neuroendocrine careinoms, gre ) i are primary tumor ofthe cervix The sl els wih high ncteareyoplasmic rato ‘esemble small cell uillerstated carcinoma bullock nuclear mol ing Adenocarcinonas of he cervix may also demonsrate “carcinoid ike” fetes Malignant Mixed Mesodermal Tumor (MMMT) or Careinosarcoma (Figs. 7-3, 7:4) Malignant mixed mesodermal tumor (MMMT) i an uncommon (<35 ‘of malignant nsoplsms ofthe uterine comps) and highly agaressve careume 7.4, Maric mixed masoderma uner QAMRT (CP) ence Sarton perme mes, conse gr Gres, arc cinosurcoma tha arises inthe endometrom but may extend ss fans ‘hg man nto the cevisl o: By definition, the tumor sips eine ‘cinpood of malignant pthc apd meseneyma ecmmponens The igen epithelial component morphologically most often resembles et (luntrild adenocarcinoma, Mesenciymal Gacomatos) elements re Say atom, Horblaste, or leomyosarcomatous occasional eter ra ements nay ince thabsdomsosarsona,chondrosircoma, oF 0 een a Recent clncopahologic snmnohistochemical and ols ter dies have provided srong evince that MMMTS ar Best ‘Gawd s variants of carcinoma” st ay natgnnt cells from the endometrium or dest sampling of ett an MMINIT tothe cervi/vagina may yield malignant cells exer eylogy sample The presence ofboth malinantepitelia ie al comato cmponcis (i. 7) sugges the possi i MIM. However, degeneration o imited sampling of poorly dit io od malignant cells may Be interpretive ciicuhies 1° The viniceaial diagnosis includes enlometial adenocarcinoma and pure Sarcomas (Fig. 7.5) Primary sarcomas of the female genital tract re rae; these can rigiate rae gion, servi, ters fallopian tubes, or varies Dut ox cn soa tint werine cons Saco ray be pore or mixed with redial components and usally present with degenerated, spare, oF ned mer cls nthe cervical mpl? re cepa nude ekmyrstcoma,cpdometra stromal scons ee satan, and brsaroma, Mest pure sarcomas present with vetted pcomoryi, multinucleated, andor bizare cells and maar be force sobypet (Fi. 75) If present, characteristic cytologic cam sop o strap cells may sbggest the specific type of Other Primary Tumors: Primary cervical germ cel tors have been describe, ieing choo Fi ike tn, and erator Lexkemisymphons and Tiga melamore aly ca be primary i he ceriSecondary or Metastatic Tumors Extrauterine Carcinomas (Figs. 7.6-7.8) Extrauterine carcinomas may spe to the ceri, of he present in acer ‘ca cel sample in one of three was, Ditet extension from & prin tumor nthe pelvis. such as endometriam, blr, ad rectum, isthe most mmo sours of cervical involvement by secondary carcinoma Ly atic andor hematogenous metastases 10 the cervt ane les reg, ith the mos common primary sts being the gstontesinal wast (Figs 76-78, the ovary andthe breast Last exfoliated eel from an vary tumor (se Figs 6.40-6.42) o from malignant ascites may pase trough ‘he fallopian tubes, endometrial cavity, and endocervical sand end sp ‘nthe ceria sample ‘The majority of patens with metastatic tumors ina cervical sample have prior history’ of a malignancy that lead to the correct interpre tion" Very rue, cervical involsement i the fist manifestation of ‘ee. The metastasis my be recognized by its unique cyolorte features fr because the ells appear feign tothe preparation 2" able 7), ‘The majority of metastatic tumors ae characterized by acean backsoud area seers ra Soiaave Secon Asya euce tarmattoe ee ooh eres eae eree Scams neers loans Tams 7.4. Morpotg features of elected exrautorns carenomas, Prima ‘Cte tere vay an he rz ts a i en ae Sinai spo ct ee Perea zepe Se RE (a Tea arate aaa censors ree, See rne eee re a mg a eo nena landing dgar-anaped Aude, and scattered goblet Cele containing Gatercod See Sant ae are ere Be ‘hss of rasan ots tom muanons cot cations mes fren be corer Gov cate rent thea ee Seu, i Sour errr rtf: conpaon wets ‘or absence of tun dthesis (ae Fig. 641). However when there ‘Rt extension of taror to the ceuvagin, the asia Hs V8 ‘Nom and destuction can progoce a tumor dass. Tratsitinal cell a= ‘noma may invose the vagina hy inaeptielial spread and ach csc Stay ponemtally be confused wth squamous intepiatia lesions ‘Motignant Melanoma (Fig. 7:8) Five person 1 10% of malignant melanoma in females arses in the gen falter nthe vulva oe vagina. Primary cervical melanoma is exceed inal oe bt metastatic melanoma relatively more common. The tettoteYesture are tose comnon to melanoma from other sits, Cells tically isolated nd round, valor pingled in shape, wit age fist and prominent maces. Inanuclearpsewoinlusions and e0- ‘lnm melanin pigment may be sen. The diferent dagnisincales any poly differentiated malignant neoplasms (primary o metalic) reune 7.0, Maran leno (CP). Dispersed noel oasis Wetec hte Smaserate emeant of opopaem round ck egsar "525. teenoranen, Soest camped remanded cea ‘seman nia vstisme pmort concert wa msern Fear nt cae ve omermmanceytocemical stains fee S100 proc, HMMS, ad Melanin, A ay be useful ‘Malignant tympnoma ‘Matigant ymphoma may uncommonly involve the cervix in the contexs of dseminated disease of asa primary site The ymphome cele ‘isperseandoften show nuclear abnormalities inclding mle men brane regularities and care uneven chromatin, An abnormal sop Population is generally more monotonous ax compaed to reactive chic inflammatory processes: however. the specific mrpholosy depends on ‘he type of fymphoma. The ileental goss nce hence Oymphocytic) eric (se Figs 2.39, 2.40) and smal ell unifeen Unt carcinoma. Ifa igus specimen is avaiable immunocyo. ‘temisry may be helpful in identifying 4 monoclonal Ipod popu References el oe bi ind tes fut tame Yc purse Res Plans po 2: Fe YS ME The ici eS Saat RA Fae Pomeroy al Tis nin Sf Nps ‘ra in WR Mates asin oo xp ene Cop iyoten Ce SSE Sage Ramu Reman Cn tri hee ‘ee Bo Pee eFC Tt SE Ses Seger TA Pl FR. Sq lca wi coe soma Sem pet a Chip ah a cn Ca Son Manin aD Sn ce fied ann of ‘eri mpg tl nce ye ‘evi Rot ibe eee Yee ence a ft 10, Sle MI Mil SE, Geel ls cal Sal sundae fae ese 0 ha ing ny a nce crae eer tease Canta MU, Ted, Wis D. Cervical ely i carinmarcoma imal Peer ere eae ade, LN. eta. Abnormal cervical cytology Helin 4 te de Seo romarr ie cence. Seg tant arn vaetinodas ere eee eee ete Mis NU Sealy RE, tat ago an mi as veChapter 8 Anal-Rectal Cytology ‘Teresa M. Darragh, George G. Birdsong, Ronald D. Loft, ‘and Diane D. Davey Background “These of ana ctl tology in he evaluation of human papillomas (HPV) yl esos is lave new tok: its useless sill being Investigated, demonstrate, art dss” hasbeen utilized inthe ‘valaton of HPW-rclated disease ofthe anal canal. pariculary in bil Fisk" populations sch as those who engage nara nercoure and hose ‘vith Human immunodeficiency vin (HIV) disene+ The 1991 Bethesda System dino include ser organ sites; however, thee are parallels be {veer cervial¥aginal and nsb-realsceenng. and Bethesds Sytem texminology has bsen Wed fo porting anal-reval estology. ‘Sampling “The target of sampling includes the entire anal cana the Kerainized and ronkeratnized portions nd the sna asformation zone the erm "al ‘eval was proposed to highligh the aed to sample above the distal por ‘om ofthe al ena ‘Cyologic samples are commonly collected without diet visualization ofthe anal canal although some clinicians repo using a small anoscope to intodoce dhe collection dovice. No specific iterature exis epading the appropiate sampling device for aol cytology. Bath Dacron fiber Swabs and eytbruses ave Been sted for sampling’ The Dacron sab is recommended over citon stab because it releases it cellular hu ‘estore readily and it has pase sickMandle that may be moeeap- Prope for se wth iui sed sapling. Based on experienc af one bf the ators (T- Darragh) the Dacron swabs beter tolerated by the p- tint than is the cyto ‘Both comentinal sears and ligui-hased cytologic preparations are used Some investgstor have reported that igi samples inrease cell Yield and lo reduce compromising facts sch as obscuring feel ma {eta airdrying, apd mechanical riftsAdequacy (Figs. 8.1-8.4) ‘There isa paucity of Irate repanting what consis an adequate snal-ecal sample, andthe lower ims for aqua cellar ft tology specimens have not been defined. Genoa he cea adequate anal sample aproaces that of acral samp: Ace mimi adequacy clarity is approsimately 2000 to 3060 nace Suan el fr convetoal ser, bse on expe opin er dbase anal sample, thsi approximately equivalent or? coe ste squamous cells per high-power field (hp) for ThinPueps tith as ‘uncer of 20 mm) and 3 to 6 noleated squamous cll for Surety (witha aiameter of 13 mm). depending on the opel pranccr foe smroscope being sed. Typical celular elements found on these preperation inl anace ‘Me squams, miclated squamous cells squamous melanie eel, ost rectal columar cells Fig 8.1)- Presence of an transformation sone con onents (rectal colurmar eas and ssamous etapa ceils) std be reported as an indicator of sampling shove the hertinied potion ot the canal Fig. 82) Lack of cel preservation and conumination with bacterial ate ial may compromise evaluation (Fig. 8.3). A sample compos predone inant of anvcleatesquames or moty obscured by fecal mater sun satisfactory for evaluation (Fig 8.) roams 22, Satefacory scien, cegnive fr hercpthet! son MM) (sctomses reps cB) Suir Wan great tr races, wer presrved squemaus cols and andra ory foun. Norma cia sot cle BP) nt wih corn Ruta be mace on an anarecta etogyfopert aa 8 Massa ofInterpretation (Figs. 8-5-8.7) Squamous inacpthti lesions, sqapus el carcino anfectous organisa can sient in thee specimens. Terminology, stead tuielne forthe evaluation fanal-etal specimens souk pall hone for ceria! esol. “The eytomorphlogc rita wse forthe evution of HPV cated anal esons are analogous 1 those for cervial¥aginal tology (Figs. {85-87} Degenoratve cellular changes and mous lesions with rom ent orngsophilic cytoplasmic kertnization are common (Fig. 8.7) in ‘alectal specimens Apical squamous osteo undetmined sgnfcarce ASC ‘SS Ter, nica smanre” squamous cal at do ot oe he caer ‘Ss arto oreeeamnoin rents meen{4 Pew 8.6. LSI LP. Crt for iteration ct SL are tne sae Setar conse wecinans (see Cuapor 3) te Goioada resronaore he proaccotty Pont (SP) mage fe ti radar} ome 6.7 St (LP) Both HON. ae prosert th re Note ecpepcims leans fose tat Wer re ore Bethesda System 2001 Forum Group Moderators: Diane D. Davey. MED, George G. Birdsong. M.D. Henry Buck, MLD, ‘Teresa M. Daragh, MD, Paul Elgort, C1 (ASCP). Michact Henry, MD, Heather Michell, MD. Suzanne Sevag, M.D. References 1 Py 2M, Hay EA Hope CJ tA ly» eg elo ‘alsin ntl oes ADS tam Re 97S 2. Seater A Caner Fae Dt a onion etc ogy ley 4, Satta aon eek eta Gens al lg 0 make ‘Sop gan ilo ap rach moras. Cpa 19891822 «GSS Ud prs tm ‘5 Mond Hie Ne Soa et a Rak tr sma nl gy Seome heel women. Concedes Maar Py 19BA173-7 (6 Daruh Ilo Scopes Bk oa Compara ef comely ‘Smarts Ton open om hl ci cs Ca OAT. 1. Shaman ME, Fru i Rosa AE ca Chloe dpm ol ‘it nan gman ma Ta Be Po! HSChapter 9 Ancillary Testing Stephen S, Ran and Mark E. Sherman Ancillary Testing refi describe the assay performed and repor he reat clears Background “The 2001 Bethesda System neither promates nor discourages the we of| ancillary esting conjunction with cervical eytlogy however, he work ‘op forum group members recognized the need develop guidlines for ‘porting results of human ppillomavius (HPV) esting an ther ays that might be implemented inthe frre" Following the Bethea 2001 worktop the American Society or Col poscopy and Cervical Pathology develope consensus management guide Tins that suggest testing for oncogeichigh-sk types of HPV DNA to determine the management of “Agpicl samo cells of undermined Significance” (ASC-US) when the text can te performed using an aretdy ‘ailable sample This recommendation was based on fells fom ALT and the large ste demonstrating thot HPV testing was ts sensitive x colpecipy in ening women with an anderying cer Cal intraepithelial neoplasia (CIN) 2 or CIN 3, burs the number of refels by nearly SO. and data demonsuating the optimal cos effetvenes ofthis approach The U.S. Food and Drug Administration has approved HPV ancillary testing for management of ASC, ad in March 2005, approval was extended to clade primary srceing in conjunction ‘vith cytology among women 30 yeas Of age and older. Using the spe- tific example of HPV wesing, recommendation for reporting ancillary ‘ests in conjunction wit cervical eytlogy are summarized belowDescription of Test Method and Result The est method) should be biel described (eg. yb apr, ply merase chain reaction pst hybridization, es) ad the fess ete ina mamer undestapdable wth clinician: For HPV testing the spec Iypes detected hy the assy shoul be rept esting shouldbe rest tw oncopenichighisk types when posible Example: HPV hybi cape ssay-Postve fo highrisk types of HPV “The HPV assay was perfor unas the [Asay nae] (Mansfacterer ‘name. City State]. The Assay nae high-k panel tests fr HPV {apes [Mat HPV types). A positive test ites the presence of one ‘or more HPV type in the panel Example 2: Insta hybeiiation aay for HPV high-isk type is mea, “The assay [Asse name Manga ane, iy, Sate shades pres foe HPV types list HPV pes. Reporting of Molecular and Cytologic Results Its preferable for eytlogy ad anil teat ret oe reported con utenlt faite communication and record keeping. I ato, cor ‘elton of merplogie nd ancillary test els ca be vas tol for pathology education and ongoing quality assurance. However, nota clin Teal practice settings allow foe ategrated reporting of cytology and mo lecular resus If concurrent reporting iso feasible, shen the ep for each type of result sould refer othe pending or previous report of the ‘ter tex when posible, Educational Notes and Suggestions “There are various mols fr repotinganilay tes data that may oF may ot incorporate nanazerca suggestions based on tho combination of tology and ancillary tex rel, Laboratories and clinicians sbould con muna their expectations regarding reporting of ancillary text results and inclusion of clinical management suggestions (See also Chap Educational Notes and Suggestions Appended 19 Cytology Reports) Rel: rence wo pablished gidoins for asing asa results may Be wef in _uidng patient anagernem when appropiate, ‘Sample Reports Examples of reporting ae provide below: Thuenreation: ASC-US with detection of oncogenic HPV DNA. ates Interpretation: ASC-US with detection of high sk oncogenic HPV DNA. ‘oe: The ASCCP consensus guidelines recommen that women with "ASC-US who ae HPV postive undergo colposcopic examination (Wright TC eal JAMA 2002:287:2120-2129), Inierpretation: ASC-US with detection of igh-sk oncogenic HPV DNA. Nove: These findings are asecsted with a 18%-25% risk of under ing CIN 2 or higher grade lesion (Cas JP eal. Am J Ob Gy 2008, 188:1405-1812), Example 4. Aca definitive interpretation sates bo he stoma. Tncerpretation: LSI ‘Nove: The preliminary cytologic finding are ASC-US. High-iskonco- enic HPV DNA has ben detected In combination these ress ae ‘most consistent with a interpretation of LSI Bethesda System 2001 Workshop Forum Group Moderators: Stephen S. Raab, MID. Karen A. Allen, CT. (ASCP), Chistne Ber set, MD. PhD, Diane Harpe, M.D. Walter Kinney, M.D, Alexan- tle Menels MID, Mark E. Sherman, MD,2 Bagh Cie oust malt igs Wik 301 mangement BRR repels “mild cytologic atypia. Obsier Gynecol 2099:52 1-827. ‘aE Ss SS ee {ese bopy. Am J Ober Gece 33 81608-1412 =r Chapter 10 Computer-Assisted Interpretation of Cervical Cytology Marianne U. Prey Automated Review ‘ease is examined by entomated device, specify device and res, Background acy atcmpis to objectively quan, microscopic images began with simple cell and nuclear measurements Inthe 1960s, computes allowed for autration ofthis process and also permited analysts of rameroas ‘cr cella estes, Liston of computing power hampered sini ‘ont advancement i te fli until the 1980, when teccogical de- ‘client in computer rdware and artificial inellzence rekindled in ‘erat in atomating cervical eytlogy screening! Different compuler-anoratd slide scanning instruments are now used in various way nthe laboratory, Some isaments are designed pr ‘dean independent assesment ofthe specimen: others are designed 10 imceactively asist manual micoscapy (ex. By locating potentially a onal areas for ssiew). The follwing are general reporting eecom: Inendations for spoimens else by an automated deve. These re ‘ommendations afe not itended to be alkinclsive: ational relevant information maybe inl in the pot, depending on the speci type of device employe. Reporting the Results of Computer-Assisted Review ‘The preferred report format is wince a spoiic Held designated for reporting appropri information concerning the us of, and esl rom,the imtomated device: F his is not posible eg. becae of aborstry Information system consumo lol reptiag convention), the ar nate screening information en be lade ts a comment radeon ‘Some data resting rom auomated review may mit be ited ford ‘eet patent care ut may be used for ara Iaboratory quality sr lance sch data should no be include inthe repo.) ‘The following information should he provide inthe report Type of instrumentation used. 2. Whether or not the specimen was succesfully processed by the vice (eegadless of heres 3. Aditoal information depends upon wheter tres manual een inpheviw ofthe specimen 4 Atomated Device Evaluation Without Manual ScrvningReview Ir the automated sreening roves an intepetaton ofthe pe: men ht replaces manual sremingireview, then thi rest an ny, adequacy data derived fom the compu assesment mist he stated ia tere AS With any automated Ihoraory instrument, the ress gone aed by the instrument must be reviewed and verified hy abo toran with appropiate taining and authorization, even ithe ab Sence of maa sreningreview, A record of who performed his dita verification must ie intsined as an interval aba record ‘according to regulations ised pursuant the Clinical Laboratory Improvement Amendments of 1988 In gona, the nan ofthe i vidual performing such veriction sould ot be ind i he cervical eyology repr, 0 a ovoid giving the false impression that the individ examined the specimen. However, if al labo ratory policy regiesinelosion of the nam the rport shoul indi «ate thatthe individual didnot examine the ld. The name of the ‘medial director may be inloed as pat othe Laboratory ident {tion per lec ent and where ried by wate regulations. by. Automated Serening Combined with Marval ScrecingReview a specimen is manually send oe reviewed following auto- mato screening. then resl erived fom th two msthods must be compared. This comparion mus be performed fr bth the ae ‘quacy evaluation and the interpretation f sich determinations ae ‘provided by the devie. Any discrepancy aut be reconciled ere Suing the report. The nme of anyone who examines a cervecy- ‘ology slide and renders an opinion forthe inl report should be documented in the report with the role ofthe person cea ste, ————— Sample Reports ‘ample Nenu fornia son malian, sto ssisnonk: ‘Test Method: Liquid based cervical eytolony Source Corie Specimen Adequicy: ‘Satisfactory for evaluation endocervical tansermaton vote comme preset Inverpretation Negative for inact lesion or rlignancy ‘Awtomated Examination: Process suecesily, manual sccening ot required [Device namel [Mana afer a CHG SLAST fanmade: “est Meth Tiguibsed cervical eytlogy Source: Cervix Spevimen Adegsscy: Satisfactory forevaluation, endocervical’ rrsfomaton zone component presen General Category Epithelial cell abnormality See Interpretation ncerpretation High-grade squamous inracpthelia Je ‘ion (HSL) Fungal organisms momhoogialy on ‘sen with Candida species Atomated Examination: Processing failed, manual screening ered [Device name] (Manufoe turer name, City, Stat) Educational Nove Suggest urtereliicl investigation OR Suge colposcopy and endocervical as ‘essen! (ASCCP guidelines: JAMA 2002:2872120-2129) € totecinologie crascr) Pathologist Doctor, MD.‘Example. Epithelial ell abnormality, with ecessful tomate stsen ‘dma sessing: Tex Mea Conventional Pap sear ‘Source: Cervix oi Specimen Adequcy: Saco fer vation endocervical General Category: Epithelial cell ‘ecomty 7 See ners Inert Appa quran cells of undetermined ‘nies (ASC-US) ‘Automated Scaming: Specimen proceed ssc by tomate locate devise [Device nome] Maafacarer name, Cis, Sate Educational Not Suggest highrisk HPV testing ay inc ‘ally indicated (ASCCP_ gunn JAMA 2002287:2120-2125) Cyotechnologint crease) Pathologist Doctor, M.D, Bethesda System 2001 Workshop Forum Group Moderators: Marianne U. Prey, M.D., Michael Facik, C7, (ASCP), Albrecht Reith, M.D. Max Robinowitz, M.D, Mary Rubin, NP, Phi. Sue Zaleski SCT (ASCP), References 1 oD: Cy an ptr a as Lip Chapter 11 Educational Notes and Suggestions Appended to Cytology Reports Dennis M. O'Connor Educational Notes and Suggestions (optional) ‘Suggestions should be concise and conssont with elnca follow-up fuidelinesublshedb professional organiatons (references 0 relevant ubiicaions may be inhaled, Background Communication between lkoratres and clinical prondos is 2 key ele ‘ment of effective cervical caer sceening. Labotaiies and elnicans ‘hare the respoasibilty of remaining cure i dst field a comma ‘ating significant changes in thei respective disciplines 1o one ane Conmanicaton may take many form fom informal conversations to fr ‘al grin rounds, ural arcs, or prsemttions at meetings. One e- Fecive means of writen communication sto append edcatioal notes or sggestons to the cytology report. The mods) of communication are [eft the discretion ofthe laboratory and should he ated on the in ‘il practice song an the content of the information 1 be convey ‘Writen comment regarding the validity and significance ofa yto logic repr are the responsibility ofthe pathologist and shouldbe directed tothe heatheare provider who requested the test. Generally. the labora tory should fan fom diet communication of rests othe patient ur les specifically requested by the provider andor patent Educational Notes and Suggestions cational noes provide addtional information regarding the signi cance or predictive value ofthe eteogie findings an may bo based onreferences w the mec irate o the aber’ experince, Ap- ening educational noes oF suggestions to the report son, bat "edhe comments shouldbe eaflly worded, conc, ee nd ev once-hased when posible, For example, ection nts ht highlight the imitations of cervical " the American College ‘of Otstevcis and Gynecologists (ACOG). the National Comprehensive ‘Cancer Nework (NCCN)° and the American Cancer Society (ACS)! ‘Apyendng sugzestos (preveuly refered 36 “ecormeatons”) 19 the cology repr aso atonal If used, the format my vary depending ‘on th preferences ofthe laertory a its eliniins. The allowing xan es hai sme cicumtanes in which sogestions cou be el 1. To improve the quality of epet specimen following receipt of at unsatisfactory specimen. 2 To ieniy patents with cytologic findings that may require fer ‘Wage aad management. 4. To imfiate when Tother procedures would be hep 10 elaifyam- biguous mombolgic findings. ‘Occasionally, clafcton or amplification ofa paricularly comple re Dortmay require specific dealed suggestions. These points are bet dis ‘ins dtetly withthe prover hore writen comment re incl inthe report I his dane, sentence recording that the dscesion tok Place is aivsable ("The ignioace of tis report and possible man fagement options were discussed with Dr. or Nurse vat time on ite"). IK ect conta wih the provider ‘annot be accomplished, general satemens sachs “Supzet flop 45 clinically indicated" of "Funhor diagnostic patent folow-ap proce dre are suggested as clinically indicated” should be used, because the pathologist may be unaware of ether pertinent clinica information. OD EE’ ‘Sample Reports sample: Specimen Adequacy Satisfactory for evaluation, endocervical lls present Ierprettion ‘Negtive for inept lesion oF maligna. dncational Noe (Cervical cytology isa screening test primarily for squamous cancers Sind precursors and has aoc ase-ogaive apd false postive tex, New technologies such sliqid-bned preparations may de ‘Crease but vill not eliminate all false-negative fests. Regular r= pling and follow-up of unexplained elincl signs and symptoms ae Fecommended to minimize false negative ress ‘Example 2: Tnerpretaion: Specinen process and examined, but unsatisfactory for evasion of cpithlia somali due to excessive alrdrying atic Sugeeston: CCarefl tntion wo rapid conventional slide fixation or the use of & Tuuid-based preparation s suggested to improve specimen suai. sample &: Interpretation ‘Aypletl slandular cells, favor neoplastic. Educational Noe “Ava signficat percentage of pos with his ierpreaion have un- ‘dying high-grade squamous oe glandular intoepithelial abnor ‘males forer diagnostic follow-up procedures are suggested 3s linicaly indicate, {Optional ation of appropiate eerence or references, fr exams Wright TC eto, 2001 Consens guidelines for the management of ‘emneul eytologcal abnormalities, AMA 2002:287:2120-228) Bethesda System 2001 Workshop Forum Group Moderators DDeonis O'Connor, M.D. Marshall Austin, M.D., PLD. List Flowers MD. Bhir Holladay, PhD. C.T, (ASCP), Deanis McCoy, LD., Pal Kiieger MD. Gaile Medley, MD., Jick Nash, M.D., Mark Sit 1D.‘Eccpnce wt nid pin, nf Oe ae SONS 2 Wa TC he Cou Mss LS cf 0 ASCCRspnseed Coen Cane 201 Cnsensnain fr Se mnspees of cel usa ah bonmaes Me Saws Pape pines) a iy incon. J Loner Can Tt 2 44 The ACOG Paci latin Cel Car Sting” Ns, ag 2003, 5: Page EE RCCN pacts rca cane eng Venn 0 9123p npn gt guest 46 Sato, Rowe Cb, Somer Be a Aran Cans Sty gle ‘eee cary deta 9 cea eps acne CA Caner Chr RDS Index at age mes in es aera mage ‘mac so 124 181-48 sac yt. aatomeoene eerste tea rotor eee, S128 eee econ ene interes “high- pascal Se -H, 0..68, anole eer Soon seni gn gon “me Cine cy =n goon pee “si ma 7172 ortaa weyers eens ccereaconnonpmry i seca iy gy a ans cl an “Senet ga S78 ‘eqn 8 Dowie Se? 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