The Cytopathology Committee (CC) of the College of

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1 Respirtory Cytology Current Trends Including Endobronchil Ultrsound-Guided Biopsy nd Electromgnetic Nvigtionl Bronchoscopy Anlysis of Dt From 2013 Supplementl Survey of Prticipnts in the College of Americn Pthologists Interlbortory Comprison Progrm in Nongynecologic Cytology Chrles D. Sturgis, MD; Crrie B. Mrshll, MD; Guliz A. Brkn, MD; Christine N. Booth, MD; Dniel F. I. Kurtycz, MD; Rhon J. Souers, MS; Joren B. Keylock, MD; Z. Lur Tbtbi, MD; Donn K. Russell, CT HT(ASCP); Ann T. Morirty, MD; Mry A. Doyle, MS, CT(ASCP); Nicole Thoms, MPH, CT(ASCP); Isil Z. Yildiz-Akts, MD; Brin T. Collins, MD; Rodolfo Luciric, MD; Brbr A. Crothers, DO Context. Nongynecologic cytology (NGC) prctices re expnding in reltionship to historicl gynecologic cytology screening progrms. Bronchopulmonry cytology is experiencing n evolution regrding new procedurl types. The College of Americn Pthologists (CAP) trcks prctice ptterns in NGC by developing questionnires, surveying prticipnts, nd nlyzing respondent dt. Objective. To nlyze responses to 2013 CAP supplementl survey from the Interlbortoy Comprison Progrm on bronchopulmonry NGC. Accepted for publiction April 3, From the Robert J. Tomsich Pthology nd Lbortory Medicine Institute, Clevelnd Clinic, Clevelnd, Ohio (Drs Sturgis nd Booth); the Deprtment of Pthology, University of Colordo Anschutz Medicl Cmpus, Auror (Dr Mrshll); the Deprtment of Pthology, Loyol University Medicl Center, Mywood, Illinois (Dr Brkn); the Wisconsin Stte Lbortory of Hygiene nd the Deprtment of Pthology nd Lbortory Medicine, University of Wisconsin, Mdison (Dr Kurtycz); the Deprtments of Biosttistics (Ms Souers) nd Surveys (Mses Doyle nd Thoms), College of Americn Pthologists, Northfield, Illinois; the Puget Sound Institute of Pthology, Settle, Wshington (Dr Keylock); the Deprtment of Pthology, University of Cliforni Sn Frncisco, Sn Frncisco (Dr Tbtbi); the Deprtment of Pthology, University of Rochester Medicl Center, Rochester, New York (Ms Russell); the Deprtment of Esoteric Testing, AmeriPth, Indinpolis, Indin (Dr Morirty); the Deprtment of Pthology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvni (Dr Yildiz-Akts); the Deprtment of Pthology, Wshington University School of Medicine, St Louis, Missouri (Dr Collins); the Deprtment of Pthology, Bylor College of Medicine, Houston, Texs (Dr Luciric); nd the Deprtment of Pthology, Wlter Reed Ntionl Militry Medicl Center, Bethesd, Mrylnd (Dr Crothers). Dr Yildiz-Akts is now with the Deprtment of Pthology, Greenwich Hospitl, Greenwich, Connecticut. The uthors hve no relevnt finncil interest in the products or compnies described in this rticle. Reprints: Chrles D. Sturgis, MD, Robert J. Tomsich Pthology nd Lbortory Medicine Institute, Clevelnd Clinic, 9500 Euclid Ave L25, Clevelnd, OH (e-mil: sturgic@ccf.org). Design. The NGC 2013 Supplementl Questionnire: Demogrphics in Performnce nd Reporting of Respirtory Cytology ws miled to 2074 lbortories. Results. The survey response rte ws 42% (880 of 2074) with 90% of respondents (788 of 880) indicting tht their lbortories evluted cytology bronchopulmonry specimens. More thn 95% of respondents indicted interpreting bronchil wshings (765 of 787) nd bronchil brushings (757 of 787). A minority of lbortories (43%, 340 of 787) delt with endobronchil ultrsound-guided smples, nd n even smller frction of lbortories (14%, 110 of 787) sw cses from electromgnetic nvigtionl bronchoscopy. Intrprocedurl dequcy ssessments by pthologists (nd less often by cytotechnologists or pthologists-in-trining) were routinely performed in percutneous trnsthorcic spirtion cses (74%, 413 of 560) with less involvement for other cse types. Most lbortories reported tht newly dignosed primry pulmonry denocrcinoms were triged for moleculr testing of epiderml growth fctor receptor nd nplstic lymphom kinse. Conclusions. The prmeters exmined in this 2013 survey provide snpshot of current pulmonry cytopthology prctice nd my be used s benchmrks in the future. (Arch Pthol Lb Med. 2016;140:22 28; doi: / rp cp) The Cytopthology Committee (CC) of the College of Americn Pthologists (CAP) cretes questionnires nd conducts surveys tht re designed to ssess current cytology lbortory prctices. Erly surveys from the CAP CC focused on dequcy nd terminology in cervicovginl cytology nd on gynecologic cytology interprettive ctegories. 1,2 More recently, surveys in nongynecologic cytology (NGC) hve ddressed prctices surrounding exfolitive nongynecologic specimens, including topics such s cell 22 Arch Pthol Lb Med Vol 140, Jnury 2016 Respirtory Cytology Trends: A 2013 CAP Survey Sturgis et l

2 Volume of Cses in 2012 Tble 1. Volume of Cses Reported by Prticipting in 2012 Min Mx 10th 25th 50th (Medin) cytology cses (gynecologic nd nongynecologic) nongynecologic cses fine-needle spirtion specimens conventionl nd liquid-bsed preprtions ThinPrep preprtions SurePth preprtions b Abbrevitions: Mx, mximum; Min, minimum;, percentile. ThinPrep products mnufctured by Hologic, Mrlborough, Msschusetts. b SurePth products mnufctured by BD Dignostics, TriPth, Burlington, North Crolin. 75th 90th block utiliztion, immunocytochemistry, nd turnround times. 3,4 In erly 2013, subgroup of the CAP CC developed questionnire tht ws sent to prticipnts in the College of Americn Pthologists Interlbortory Comprison Progrm in Nongynecologic Cytology (CAP NGC) to investigte prctice ptterns regrding utiliztion nd reporting of bronchopulmonry cytology. The CAP NGC progrm begn in 1997 with 794 lbortories. At the time of this survey (clendr yer 2013), the CAP NGC progrm hd grown to include 2074 lbortories. The CAP NGC is strictly eductionl, is not grded, nd is not relted to proficiency testing. It consists of qurterly milings of glss slides with ssocited clinicl histories nd ncillry studies s well s supplementl online cses. The purpose of this eductionl ctivity is for prticipnts to consider differentil dignoses bsed upon clinicl histories, morphologic evlutions, nd reviews of ncillry studies to select the most pproprite dignoses from interpretive menus. Becuse of brod subscription to the NCG progrm the udience is good representtion of the prctice of NGC in North Americ. The CAP s NGC 2013 Supplementl Questionnire: Demogrphics in Performnce nd Reporting of Respirtory Cytology ws miled to ll prticipting lbortories nd ws designed to glen informtion regrding lbortory prctices pertining to performnce nd reporting of bronchopulmonry cytology. MATERIALS AND METHODS The NGC 2013 Supplementl Questionnire ws creted by subgroup of CAP CC members nd ws miled to 2074 prticipting lbortories in mid Of the surveyed lbortories, 880 responded (survey response rte of 42%). Not ll lbortories responded to every question. Results re bsed upon subset of 788 respondent lbortories, s 92 lbortories (10.5% of 880) reported tht they did not evlute specimens from the respirtory system. were sked demogrphic questions to identify chrcteristics of their institution nd prctice types, volumes of cses, numbers of pthologists, numbers of cytotechnologists, nd screening duties of cytotechnologists. The supplementl questionnire further queried which respirtory specimen types were performed in ech lbortory (sput, bronchil wshings, bronchil brushings, broncholveolr lvges, percutneous trnsthorcic imge-guided fine-needle spirtions, percutneous trnsthorcic imge-guided core biopsies with touch preprtions, endobronchil ultrsound-guided [EBUS] fine-needle spirtions, bronchil mucosl or trnsbronchil biopsies with touch preprtions, nd electromgnetic nvigtionl bronchoscopies). In ddition, the survey included questions regrding vrious styles of reporting cytology results (seprtely or in combined reports with histologic specimen) nd lso queried which types of clinicins (pulmonologists versus interventionl rdiologists versus surgeons) typiclly cquired nd submitted smples. Dt regrding rpid dequcy evlution were lso requested for the vrious specimen types, including questions clrifying utiliztion of rpid on-site versus offsite versus telepthology ssessments. Questions were lso posed sking who performs rpid dequcy ssessments (cytotechnologist versus pthologists versus pthologists-in-trining). Stin preferences were queried, nd frequencies of immunohistochemicl chrcteriztion nd moleculr trige were included. Informtion regrding turnround times ws lso sought. Sttisticl nlyses of survey responses were performed with SAS 9.2 (SAS Institute, Cry, North Crolin). RESULTS Demogrphic Findings There ws 42% response rte to the survey (880 of 2074 lbortories). Of these 880 respondents, 92 (10.5%) indicted tht they did not evlute cytology specimens from the respirtory trct. (This pproximte 40% response rte held true cross the ctegories of sizes of prctices [numbers of pthologists nd cytotechnologists in groups] nd cross the ctegory of number of cytology cses received). The lrgest cohort of respondents lbortories (48.4%; 367 of 758) reported being ssocited with voluntry nonprofit hospitls, followed by proprietry hospitls (14.1%; 107 of 758), regionl/locl independent lbortories (9.4%; 71 of 758) nd city/county/stte hospitls (lso 9.4%; 71 of 758), university hospitls (7.4%; 56 of 758), Veterns/Army/Air Force/Nvy hospitls (5.1%; 39 of 758), ntionl/corporte lbortories (5.0%; 38 of 758), nd clinic/group/physicin office lbortories (1.2%; 9 of 758). Volumes of cytology cses reported by the lbortories re summrized in Tble 1. Most respondent lbortories (63%, 491 of 777) were stffed by 3 to 10 full-time equivlent pthologists with the minority of lbortories hving only 1 or 2 pthologists (32%, 245 of 777) or more thn 10 pthologists (5%, 41 of 777). Cytotechnologists screened NGC cses in 66% (500 of 758) of the responding lbortories, nd in those lbortories where cytotechnologists viewed NGC cses, 92% (460 of 500) reported technicl stff involvement in both exfolitive nd fine-needle spirtion cse types. Cytotechnologist stffing in respondent lbortories is shown in Tble 2. Specimen Types nd Reporting Most lbortories tht processed respirtory cytology smples interpreted bronchil wshings, bronchil brushings, sput, broncholveolr lvges, percutneous imgeguided fine-needle spirtes, nd non imge-guided trnsbronchil spirtes. Interprettions of touch preprtions on Arch Pthol Lb Med Vol 140, Jnury 2016 Respirtory Cytology Trends: A 2013 CAP Survey Sturgis et l 23

3 Cytotechnologists in Lbortory Tble 2. Distribution of Cytotechnologist Stffing in Responding Full Time (n ¼ 734) Percentge Prt Time (n ¼ 642) Percentge trnsthorcic core biopsies (48.2%, 380 of 788) nd Intrprocedurl Evlutions bronchil mucosl biopsies (42.3%, 333 of 788) were Tble 5 detils the utiliztion of intrprocedurl dequcy performed in less thn hlf of lbortories, nd EBUS fineneedle spirtion specimens nd electromgnetic bronchos- reported ssessment of intrprocedurl dequcy in 73.7% ssessments in bronchopulmonry cytology. Respondents copy cytology preprtions were lso viewed in less thn (413 of 560) of percutneous imge-guided spirtions, hlf of the fcilities responding. These dt re presented in 68.5% (350 of 511) of touch preprtions from percutneous Tble 3. Slightly more thn hlf of respondents (54%, 338 of 622) reported issuing unique surgicl pthology nd cytology reports when touch preprtions of cores were mde, nd slightly less thn hlf of respondents (46%, 285 of 622) reported issunce of either combined/unified touch core biopsies, nd 59.2% (257 of 434) of EBUS spirtions. Other specimen types were less frequently ssessed intrprocedurlly. The highest numbers of intrprocedurl evlutions were reportedly performed on-site (57.9%, 239 of 413) for percutneous spirtions with smller numbers preprtion nd histology reports or mixture of reporting of ssessments being performed off-site (in the hospitl but styles. The survey tool did not question prticipnts not in the procedure room) nd with only infrequent use of regrding their resons for choice of reporting formts (eg, telepthology for dequcy ssessments. When queried specilty sign-out of cytopthologists versus histopthologists, billing issues, limittions of lbortory informtion bout who performed intrprocedurl ssessments, most respondents (85.5%, 490 of 573) indicted tht ttending pthologists completed these tsks with lbortory cytotechnologists nd pthologists-in-trining performing the systems). Submitting Provider Types reminder. The survey questioned whether intrprocedurl evlution results were incorported into finl reports, with Bronchil cytology specimens were reported s being 93% (451 of 485) of lbortories reporting incorportion of most commonly submitted to the respondent lbortories pthologist-performed dequcy ssessments into finl by pulmonologists (85%, 302 of 355), with interventionl reports nd with 63% (89 of 141) of lbortories reporting rdiologists nd thorcic surgeons submitting the mjority incorportion of cytotechnologist-performed dequcy ssessments into finl reports. Resons for hving ttending of the reminder. These dt re presented in Tble 4. pthologists perform dequcy ssessments were queried. Pthologist preference ws given s the most common Tble 3. Bronchopulmonry Cytology Specimen reson (57%, 245 of 430) for pthologists to perform Types Interpreted by Respondent intrprocedurl ssessments of dequcy. Other fctors influencing who performed dequcy ssessments in clinicl Specimen Types Interpreted (n ¼ 787) prctice included insufficient cytotechnologist stffing (35%, Percentge 150 of 430), clinicl collegue insistence upon physicin-tophysicin communiction (30%, 130 of 430), nd higher Bronchil wshings Bronchil brushings Sput reimbursement for pthologist-performed redings thn for Broncholveolr lvges cytotechnologist-performed redings (17%, 74 of 430). Percutneous/trnsthorcic For those lbortories evluting EBUS spirtions, the imge-guided fine-needle verge number of sites biopsied ws vrible nd rnged spirtes on verge from 1 site per cse (34.4%, 116 of 337) to 2 sites Non imge-guided trnsbronchil/trnstrchel per cse (40.9%, 138 of 337) to 3 to 4 sites per cse (20.8%, spirtes of 337) to 5 or more sites per cse (3.9%, 13 of 337). A Percutneous/trnsthorcic core totl of 354 (45% of 788) lbortories responded to the biopsies with touch question regrding the verge mount of time spent per preprtions cse in performing dequcy evlutions for EBUS smplings with 28.5% (100 of 351) reporting n verge time Endobronchil ultrsoundguided fine-needle spirtes Bronchil mucosl or invested per cse of less thn or equl to 15 minutes, 15.1% trnsbronchil biopsy with (53 of 351) of respondents reporting n verge time touch preprtions invested per cse of between 16 nd 30 minutes, 22.5% (79 Electromgnetic nvigtionl bronchoscopy Multiple responses llowed of 351) reporting n verge time invested per cse of between 31 nd 45 minutes, nd with 33.9% (119 of 351) reporting n verge time invested per cse of 46 minutes or 24 Arch Pthol Lb Med Vol 140, Jnury 2016 Respirtory Cytology Trends: A 2013 CAP Survey Sturgis et l

4 Tble 4. Submission of Respirtory Cytology Specimens per Clinicin Type Providers Who Submit Pulmonry Smples nd Their Estimted Frequencies (n ¼ 355) Percentge Men Frequency Submitted by Provider, Pulmonologists Interventionl rdiologists Crdiothorcic surgeons Generl surgeons Other Multiple responses llowed. more. More thn hlf of respondents (55%, 401 of 725) reported use of modified Giems stined direct smers s the preferred method of preprtion for ssessments of intrprocedurl dequcy. Smller numbers of lbortories used hemtoxylin-eosin stined preprtions (22%, 159 of 725) or rpid Ppnicolou stined slides (13%, 96 of 725), with other stins (10%, 69 of 725), including but not limited to toluidine blue, ccounting for the reminder of responses. Adequcy Criteri nd Sttements in Finl Reports A minority of responding lbortories (43%, 307 of 715) indicted tht pulmonry cytology results included specific sttements of dequcy in ll finl reports. Most lbortories (57%, 408 of 715) reported tht dequcy sttements were either not used in finl reports or were used inconsistently (in some but not ll reports). The survey sked whether specific criteri were used to estblish dequcy for finl reporting for some of the smple types. The presence of specific cell types seemed vluble for most respondents in reporting broncholveolr lvge nd EBUS results; however, the generl impression of the smple ws most hevily relied upon to determine dequcy in ll ctegories. Dt regrding dequcy criteri re presented in Tble 6. Ancillry Testing (Specil Stins/Immunochemistry/ Moleculr) Tble 7 provides responses to survey question querying use of vrious mrkers for differentiting types of non smll cell crcinom. Relince upon immunohistochemicl chrcteriztion with p63 (91.2%, 547 of 600), cytokertin 5/6 (CK5/6; 83.8%, 503 of 600), thyroid trnscription fctor-1 (TTF-1; 93.3%, 571 of 612), nd npsin A (52%, 318 of 612) ws reported by most respondents. (It should be noted tht responses to this ctegory my reflect ptterns of sometimes using immunohistochemistry nd sometimes not, nd the results given re for those instnces in which such testing is pursued). The use of cocktil immunohistochemicl testing ws not queried. Prticipnts were lso questioned bout preferred specimen types for ncillry testing, with most respondents reporting use of supplementl core biopsy (92%, 523 of 566) nd/or cell block mterils (56%, 317 of 566) nd minority (18%, 103 of 566) performing ncillry testing on dditionl dedicted smers, cytospins, or liquidbsed cytology preprtions. Most lbortories (76%, 532 of 702) indicted tht they offered moleculr testing for newly dignosed non smll cell lung crcinoms, with most of those respondents (86%, 455 of 527) indicting tht ll moleculr testing ws outsourced to reference lbortory. Prticipnt lbortories were lso queried bout prctice ptterns regrding the trige of newly dignosed non smll cell lung crcinoms for moleculr testing, with minority of respondents (11.2%, 56 of 502) indicting tht ll non smll crcinoms were triged (Tble 8). When ncillry moleculr testing ws requested, most lbortories (64.4%, 277 of 430) reported simultneous ordering of epiderml growth fctor receptor (EGFR) nd nplstic lymphom kinse (ALK) tests, with the second most common pttern of trige being ordering of EGFR testing first with reflex testing to ALK if EGFR findings were negtive (34.0%, 146 of 430). Medin percentges of EGFR nd ALK testing in new denocrcinoms re given in Tble 9. (These percentges my be ffected by the ctul number of cses in which sufficient mteril ws either vilble for or not vilble for moleculr trige; in ddition, the comprtively smller number of lbortory respondents thn for the survey s whole my lso ffect these vlues). Per response dt, EBUS nd/or trnsthorcic pulmonry spirtes were performed solely for the purpose of ncillry moleculr testing in minority of lbortories (38%, 230 of 612). Cytologic-Histologic Correltions nd Turnround Times Most lbortories (81%, 490 of 608) responded tht some or ll cses of trnsthorcic fine-needle spirtion biopsies nd EBUS biopsies underwent cytologic-histologic correltion with 73% (346 of 472) of respondent lbortories reporting tht these correltions hppened t the time of Tble 5. Which Pulmonry Cytology Specimen Types Are Performed With Intrprocedurl Adequcy Assessments? Performnce of Intrprocedurl Adequcy by Cse Type nd Loction Intrprocedurl Adequcy Not Performed, % Adequcy Assessed On-site, % Adequcy Assessed Off-site, % Adequcy Assessed by Telepthology, % Sputum Bronchil brushing Bronchil wshing Broncholveolr lvge Bronchil biopsy touch preprtions Nonimged trnsbronchil FNA EBUS FNA EBUS FNA with ENB Percutneous imged FNA Percutneous core biopsy touch preprtions Abbrevitions: EBUS, endobronchil ultrsound; ENB, electromgnetic nvigtionl bronchoscopy; FNA, fine-needle spirtion. Arch Pthol Lb Med Vol 140, Jnury 2016 Respirtory Cytology Trends: A 2013 CAP Survey Sturgis et l 25

5 Tble 6. Criteri to Estblish Adequcy in Certin Smple Types Criteri Used to Estblish Pulmonry Specimen Adequcy No. % No. % No. % Specific Cell Type(s) Specific Cell Number(s) Generl Impression Broncholveolr lvges (n ¼ 587) Fine-needle spirtions (n ¼ 634) EBUS fine-needle spirtions (n ¼ 355) Abbrevition: EBUS, endobronchil ultrsound. Multiple responses llowed. reporting (41% t the time of histologic follow-up reporting nd 32% t the time of cytologic interprettion). A minority of respondents (27%, 126 of 472) indicted tht cytologichistologic correltions were performed retrospectively through electronic record serches nd subsequent review. A minority of lbortories (44%, 205 of 466) reported issunce of mended or ddended reports in mediclly relevnt cses in which cytologic-histologic discrepncies were discovered. Respondent lbortory informtion on turnround times (ll mens for ll specimen types reported t greter thn 75% in 48 hours) is given in Tble 10. COMMENT In n ttempt to scertin informtion regrding prctice ptterns in bronchopulmonry cytology, subgroup of the CAP CC developed the CAP NGC Supplementl Questionnire: Demogrphics in Performnce nd Reporting of Respirtory Cytology. This survey ws miled to 2074 prticipnt fcilities in the middle of clendr yer Of these lbortories, 42% (880 of 2074) responded. Some lbortories (10.5%, 92 of 880) reported tht they did not evlute pulmonry cytology smples, yielding subset of 788 respondents providing dt for review. The lbortories tht responded represented diverse prctice types, with the lrgest cohort of responses coming from lbortories ssocited with nonprofit hospitls (48.4%, 367 of 758). The medin number of pthologists in the respondent lbortories ws 4. Of the responding lbortories, 59.1% indicted tht their work environments included 1 or more pthologists with dded qulifiction in cytopthology from Tble 7. Testing Preferences for Differentiting Types of Non Smll Cell Crcinom Ancillry Tests for Differentiting Squmous Crcinom From Adenocrcinom Percentge Squmous crcinom mrkers (n ¼ 600) p Cytokertin 5/ Cytokertin 34 b E p SOX Other Adenocrcinom mrkers (n ¼ 612) Thyroid trnscription fctor Npsin A Mucicrmine Crcinoembryonic ntigen Alcin blue Other Multiple responses llowed. the Americn Bord of Pthology, indicting tht more thn 40% of lbortories surveyed issue dignostic reports on respirtory cytopthology without bord-certified cytopthologist in-house. Only 11.7% of respondents indicted employing cytopthologists who prcticed cytopthology only. The men number of cytology cses (gynecologic nd NGC combined) ws (medin, 4000). Greter thn 90% of lbortories reported interpreting specimens submitted in the ctegories of sput, bronchil brushings, nd bronchil wshings. Exmintion of sputum is the lest invsive respirtory cytology method for obtining cytologic dignosis for ptients suspected of hrboring lung crcinom. Sputum cytology is known to be highly specific for the dignosis of mlignncy with peerreviewed literture indicting tht specificities for sputum dignoses cn exceed 95%. 5 8 Sputum cytology studies re, however, not s highly sensitive s they re specific, with the literture rnging widely from between 37% to 75% for confirmtion of mlignncy. 5 8 By the time sputum cytology findings re documented s positive, mny ptients with lung cncer re no longer cndidtes for surgery secondry to high-stge disese; hence, sputum cytology is not n effective screening test for the erly detection of pulmonry mlignncy. In ddition, positive sputum cytology results for mlignncy do not llow for specific locliztion of neoplstic process in regrd to lterlity or specific subloction. Trditionl exfolitive bronchil cytology preprtions, such s bronchil brushings, bronchil wshings, nd broncholveolr lvges, hve the cpcity to increse dignostic sensitivity to round 85%. 9,10 Some lesions (especilly those in the peripherl lung prenchym) cnnot be effectively smpled by sputum cytology or trditionl bronchoscopic mens. Historiclly, mny such ptients were subjected to imge-guided percutneous trnsthorcic biopsy, method tht hs proved more cost-effective thn either video-ssisted thorcoscopic surgery or F-fluorodeoxyglucose positron emission tomogrphy. 11 Most survey respondents (66.3%, 522 of 787) reported interpreting trnsthorcic spirtes. Fine-needle spirtion biopsy of lung tumors hs lso been shown to provide sufficient mteril to llow for subclssifiction of non smll cell crcinoms into squmous nd nonsqumous ctegories in 89% of cses. 12 Endobronchil ultrsound-guided fineneedle spirtion is minimlly invsive modlity for evluting the medistinum nd stging ptients with lung crcinom. Expnding use of this technology is noted in the literture with positive nd negtive predictive vlues (in smples submitted by experienced opertors) reported t 95% nd 100%, respectively. 13,14 A minority of lbortories in the survey (43.2%, 340 of 787) reported interpreting EBUS smples. Electromgnetic nvigtionl bronchoscopy (ENB) is new technology tht incorportes imge-guided locliztion nd llows the opertor to steer bronchoscope to peripherl lung lesion with ctheters used to collect 26 Arch Pthol Lb Med Vol 140, Jnury 2016 Respirtory Cytology Trends: A 2013 CAP Survey Sturgis et l

6 Tble 8. Moleculr Trige Ptterns for Newly Dignosed Non Smll Cell Crcinoms Which of the Following Sttements Best Chrcterizes the Prctice Pttern in Regrd to Moleculr Testing for Newly Dignosed Non Smll Cell Lung Crcinoms? (Totl 502) Percentge A subset of crcinom undergo moleculr testing All denocrcinoms of lung undergo moleculr testing All non smll cell lung crcinoms undergo moleculr testing Moleculr testing is not regulrly performed Tble 9. Reported Percentges of Newly Dignosed Adenocrcinoms Undergoing Testing Newly Dignosed Primry Pulmonry Adenocrcinoms Triged to Moleculr Testing for Specific Muttions 10th 25th Medin 75th 90th KRAS EGFR ALK Abbrevitions: ALK, nplstic lymphom kinse; EGFR, epiderml growth fctor receptor; KRAS, Kirsten rt srcom virl oncogene homolog. smples from smll peripherl lung lesions. When performed by experienced opertors, ENB spirtions hve been shown to hve high dignostic yields rnging from 77% to 94% with smpling possible in smll irwys t the fourth order of brnching nd beyond, including subpleurl lesions Electromgnetic nvigtionl bronchoscopy spirtes were interpreted by only 14% (110 of 787) of respondent lbortories. Intrprocedurl rpid evlutions to ssess dequcy nd qulity of smples were reported most frequently in trnsthorcic fine-needle spirtion specimens (73.7%, 413 of 560). Most lbortories lso reported using intrprocedurl evlutions for touch preprtions of trnsthorcic cores nd for EBUS spirtes. Trditionl bronchoscopic smples such s brushes nd wshes were less likely to be rpidly evluted for qulity/dequcy. Intrprocedurl evlutions hve been shown to dd vlue in pulmonry cytology with communiction between pulmonologists nd pthologists, s well s between rdiologists nd pthologists, llowing for trige of smples to pproprite ncillry testing nd optimized utiliztion of smll-volume smples. 15,18,19 While some peer-reviewed literture does exist on criteri for dequcy in pulmonry cytology (such s criteri for specimen dequcy in EBUS), the gretest number of respondents to the survey indicted tht generl impressions of smples were used more often thn cell counting or the presence of specific cell types. 13,20,21 A recent study from the CAP Interlbortory Comprison Progrm confirmed significnt trend towrd subctegoriztion of non smll cell crcinoms by cytomorphology lone, suggesting tht prticipnts re cogniznt of the impct tht more specific cytomorphologic interprettions hve in directing moleculr trige nd ptient therpies. 22 More thn hlf of survey respondents reported routinely using p63, CK5/6, TTF-1, nd npsin A immunohistochemistry on pulmonry cytology smples to differentite between types of non smll cell crcinom. A growing volume of literture confirms tht ncillry testing, such s immunocytochemistry, polymerse chin rection, fluorescence in situ hybridiztion, nd next-genertion sequencing, cn be performed on pulmonry cytology smples More thn hlf of lbortories (52.2%, 262 of 502) reported utiliztion of moleculr testing on subset of crcinoms dignosed by thorcic cytology, with most lbortories (86.3%, 455 of 527) indicting tht moleculr testing ws outsourced to reference lbortory nd with the most common pttern of requested testing being simultneous ordering of EGFR nd ALK tests (64.4%, 277 of 430). The lrgest percentge of lbortories (45.5%, 221 of 486) responded tht moleculr dignostic results were reported seprtely from min cytology reports. This prctice my be influenced by hopes of preserving quick turnround times nd/or incomptibility of computer interfces from reference lbortories. Respondent lbortory informtion on turnround times showed the quickest result reporting for conventionl bronchoscopy smples with 86.9% (590 of 679) of lbortories reporting 2-dy or less turnround time for bronchil brushings, nd the slowest turnround times for trnsthorcic spirtions with cell blocks with 78.5% (482 of 614) of lbortories reporting finlized results within 2 dys. The 2013 CAP NGC Supplementl Questionnire: Demogrphics in Performnce nd Reporting of Respirtory Cytology ws vluble tool for ssessing recent trends in the rel-world prctice of clinicl bronchopulmonry Tble 10. Men Turnround Times (TATs) for Vrious Pulmonry Cytology Specimen Types Men TAT (Working Dys) From Specimen Receipt in Lbortory to Issunce of Finl Report Specimen Type 0 48 Hours, % Hours, % Hours, %.96 Hours, % Broncholveolr lvge Bronchil brushing/wshing Trnsthorcic FNA/cell block EBUS FNA Trnsthorcic core biopsy Abbrevitions: EBUS, endobronchil ultrsound; FNA, fine-needle spirtion; %, percentge. Arch Pthol Lb Med Vol 140, Jnury 2016 Respirtory Cytology Trends: A 2013 CAP Survey Sturgis et l 27

7 cytology. The informtion cquired from the survey provides insights into the demogrphics of lbortories nd test types tht re performed nd lso ddresses the frequency with which intrprocedurl evlutions re performed. The verge ttendnce time by cytology professionl nd/ or technicl stff for n EBUS cse ws reported to rnge from 31 to 45 minutes. Helping to ensure specimen dequcy nd directing pproprite trige of smll smples for the best vilble ncillry tests tkes time. As newer technologies such s EBUS nd ENB re introduced in clinicl spheres, lbortories will need to be dept t processing nd interpreting these smples. The first study of rel-time ENB using overlid digitl computed tomogrphic imges ws published in The current study shows tht 14% (110 of 787) of prticipting lbortories now interpret smples procured through the smll ctheters of this smpling technique. The results of the current survey give vluble informtion bout clinicl prctice ptterns nd will llow for comprison of prctice trends in the future. References 1. Dvey DD, Nielsen ML, Rosenstock W, Kline TS. Terminology nd specimen dequcy in cervicovginl cytology: the College of Americn Pthologists Interlbortory Comprison Progrm Experience. Arch Pthol Lb Med. 1992;116(9): Dvey DD, Nielsen ML, Nryshkin S, Robb JA, Cohen T, Kline TS. Atypicl squmous cells of undetermined significnce: current lbortory prctices of prticipnts in the College of Americn Pthologists Interlbortory Comprison Progrm in Cervicovginl Cytology. Arch Pthol Lb Med. 1996;120(5): Morirty AT, Nyr R, Auger M, et l. Nongynecologic cytology prctice ptterns: survey of prticipnts in the College of Americn Pthologists Interlbortory Comprison Progrm in Nongynecologic Cytopthology. Arch Pthol Lb Med. 2014;138(7): Fischer AH, Schwrtz MR, Morirty AT, et l. Immunohistochemistry prctices of cytopthology lbortories: survey of prticipnts in the College of Americn Pthologists Nongynecologic Cytopthology Eduction Progrm. Arch Pthol Lb Med. 2014;138(9): Pilotti S, Rilke F, Gribudi G, Rvsi GL. Sputum cytology for the dignosis of crcinom of the lung. Act Cytol. 1982;26(5): Meht AC, Mrty JJ, Lee FY. Sputum cytology. Clin Chest Med. 1993;14(1): Kern WH. The dignostic ccurcy of sputum nd urine cytology. Act Cytol. 1988;32(5): Perlmn EJ, Erozn YS, Howdon A. The role of the sccomno technique in sputum cytopthologic dignosis of lung cncer. Am J Clin Pthol. 1989;91(1): Jy SJ, Wehr K, Nicholson DP, Smith AL. Dignostic sensitivity nd specificity of pulmonry cytology: comprison of techniques used in conjunction with flexible fiberoptic bronchoscopy. Act Cytol. 1980;24(4): Sit S, Tnzillo A, Riscic C, Mresc A, Potenz E, D Arrigo M. Bronchil brushing nd biopsy: comprtive evlution in dignosing visible bronchil lesions. Eur J Crdiothorc Surg. 1990;4(5): Deppen SA, Dvis WT, Green EA, et l. Cost-effectiveness of initil dignostic strtegies for pulmonry nodules presenting to thorcic surgeons [published online hed of print July 31, 2014]. Ann Thorc Surg. doi: /j. thorcsur Adms J, Wu HH. The utility of fine needle spirtion in the dignosis of primry nd metsttic tumors to the lung: retrospective exmintion of 1,032 cses. Act Cytol. 2012;56(6): Krunmurthy A, Ci G, Dcic S, Khlbuss WE, Pntnowitz L, Monco SE. Evlution of endobronchil ultrsound guided fine needle spirtions (EBUS FNA): correltion with dequcy nd histologic follow up. Cncer Cytopthol. 2014;122(1): VnderLn PA, Wng HH, Mjid A, Folch E. Endobronchil ultrsound guided trnsbronchil needle spirtion (EBUS TBNA): n overview nd updte for the cytopthologist. Cncer Cytopthol. 2014;122(8): Loo FL, Hllign AM, Port JL, Hod RS. The emerging technique of electromgnetic nvigtion bronchoscopy guided fine needle spirtion of peripherl lung lesions: promising results in 50 lesions. Cncer Cytopthol. 2014;122(3): Mhjn AK, Ptel S, Hogrth DK, Wightmn R. Electromgnetic nvigtion bronchoscopy: n effective nd sfe pproch to dignose peripherl lung lesions unrechble by conventionl bronchoscopy in high risk ptients. J Bronchology Intervent Pulmonol. 2011;18(2) Odronic SI, Gilde TR, Chute DJ. Eletromgnetic nvigtion bronchoscopy guided fine needle spirtion for the dignosis of lung lesions. Dign Cytopthol. 2014;42(12): Yrmus L, Akulin J, Gilbert C, et l. Optimizing endobronchil ultrsound for moleculr nlysis: how mny psses re needed? Ann Am Thorc Soc. 2013; 10(6): Mondoni M, Crlucci P, Di Mrco F, et l. Rpid on site evlution improves needle spirtion sensitivity in the dignosis of centrl lung cncers: rndomized tril. Respirtion. 2013;86(1): Nyk A, Sugrue C, Koenig S, Wssermn PG, Hod S, Morgenstern NJ. Endobronchil ultrsound guided trnsbronchil needle spirte (EBUS TBNA): proposl for onsite dequcy criteri. Dign Cytopthol. 2012;40(2): Alshrif M, Andrde RS, Groth SS, Stelow EB, Pmbuccin SE. Endobronchil ultrsound-guided trnsbronchil fine-needle spirtion: the University of Minnesot experience, with emphsis on usefulness, dequcy ssessment, nd dignostic difficulties. Am J Clin Pthol. 2008;130(3): Yildiz-Akts IZ, Sturgis CD, Brkn GA, et l. Primry pulmonry nonsmll cell crcinoms: the College of Americn Pthologists Interlbortory Comprison Progrm confirms significnt trend towrd subctegoriztion bsed upon fine-needle spirtion cytomorphology lone. Arch Pthol Lb Med. 2014; 138(1): Mitushkin NV, Iyevlev AG, Poltortskiy AN, et l. Detection of EGFR muttion nd EML4-ALK rerrngements in lung denocrcinoms using rchived cytologicl slides. Cncer Cytopthol. 2013;121(7): Mrshll D, Lberge JM, Firetg B, Miller T, Kerln RK. The chnging fce of percutneous imge guided biopsy: moleculr profiling nd genomics in current prctice. J Vsc Interv Rdiol. 2013;24(8): Krnes HE, Duncvge EJ, Berndt CT. Trgeted next genertion sequencing using fine needle spirtes from denocrcinoms of the lung. Cncer Cytopthol. 2014;122(2): Heymnn JJ, Bulmn WA, Mxfield RA, et l. Moleculr testing guidelines for lung denocrcinom: utility of cell blocks nd concordnce between fine needle spirtion cytology nd histology smples. Cytojournl. 2014;11:12. doi: 10,4103/ Schwrz Y, Greif J, Becker HD, Ernst A, Meht A. Rel time electromgnetic nvigtion bronchoscopy to peripherl lung lesions using overlid CT imges: the first humn study. Chest. 2006;129(4) Reynolds JP, Tubbs RR, Minc EC, et l. EGFR muttion genotyping of liquid bsed cytology smples obtined vi fine needle spirtion (FNA) t endobronchil ultrsound of non smll cell lung cncer (NSCLC). Lung Cncer. 2014;86: Arch Pthol Lb Med Vol 140, Jnury 2016 Respirtory Cytology Trends: A 2013 CAP Survey Sturgis et l

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