Respiratory Cytology--Current Trends Including Endobronchial Ultrasound-Guided Biopsy and Electromagnetic Navigational Bronchoscopy: Analysis of Data From a 2013 Supplemental Survey of Participants in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.
MATERIALS AND METHODS
The "NGC 2013 Supplemental Questionnaire" was created by a subgroup of CAP CC members and was mailed to 2074 participating laboratories in mid 2013. Of the surveyed laboratories, 880 responded (survey response rate of 42%). Not all laboratories responded to every question. Results are based upon a subset of 788 respondent laboratories, as 92 laboratories (10.5% of 880) reported that they did not evaluate specimens from the respiratory system. Laboratories were asked demographic questions to identify characteristics of their institution and practice types, volumes of cases, numbers of pathologists, numbers of cytotechnologists, and screening duties of cytotechnologists. The supplemental questionnaire further queried which respiratory specimen types were performed in each laboratory (sputa, bronchial washings, bronchial brushings, bronchoalveolar lavages, percutaneous transthoracic image-guided fine-needle aspirations, percutaneous transthoracic image-guided core biopsies with touch preparations, endobronchial ultrasound-guided [EBUS] fine-needle aspirations, bronchial mucosal or transbronchial biopsies with touch preparations, and electromagnetic navigational bronchoscopies). In addition, the survey included questions regarding various styles of reporting cytology results (separately or in combined reports with histologic specimen) and also queried which types of clinicians (pulmonologists versus interventional radiologists versus surgeons) typically acquired and submitted samples. Data regarding rapid adequacy evaluation were also requested for the various specimen types, including questions clarifying utilization of rapid on-site versus offsite versus telepathology assessments. Questions were also posed asking who performs rapid adequacy assessments (cytotechnologist versus pathologists versus pathologists-in-training). Stain preferences were queried, and frequencies of immunohistochemical characterization and molecular triage were included. Information regarding turnaround times was also sought. Statistical analyses of survey responses were performed with SAS 9.2 (SAS Institute, Cary, North Carolina).
There was a 42% response rate to the survey (880 of 2074 laboratories). Of these 880 respondents, 92 (10.5%) indicated that they did not evaluate cytology specimens from the respiratory tract. (This approximate 40% response rate held true across the categories of sizes of practices [numbers of pathologists and cytotechnologists in groups] and across the category of number of cytology cases received). The largest cohort of respondents' laboratories (48.4%; 367 of 758) reported being associated with voluntary nonprofit hospitals, followed by proprietary hospitals (14.1%; 107 of 758), regional/local independent laboratories (9.4%; 71 of 758) and city/county/state hospitals (also 9.4%; 71 of 758), university hospitals (7.4%; 56 of 758), Veterans/Army/Air Force/Navy hospitals (5.1%; 39 of 758), national/corporate laboratories (5.0%; 38 of 758), and clinic/group/physician office laboratories (1.2%; 9 of 758). Volumes of cytology cases reported by the laboratories are summarized in Table 1. Most respondent laboratories (63%, 491 of 777) were staffed by 3 to 10 full-time equivalent pathologists with the minority of laboratories having only 1 or 2 pathologists (32%, 245 of 777) or more than 10 pathologists (5%, 41 of 777). Cytotechnologists screened NGC cases in 66% (500 of 758) of the responding laboratories, and in those laboratories where cytotechnologists viewed NGC cases, 92% (460 of 500) reported technical staff involvement in both exfoliative and fine-needle aspiration case types. Cytotechnologist staffing in respondent laboratories is shown in Table 2.
Specimen Types and Reporting
Most laboratories that processed respiratory cytology samples interpreted bronchial washings, bronchial brushings, sputa, bronchoalveolar lavages, percutaneous imageguided fine-needle aspirates, and non-image-guided transbronchial aspirates. Interpretations of touch preparations on transthoracic core biopsies (48.2%, 380 of 788) and bronchial mucosal biopsies (42.3%, 333 of 788) were performed in less than half of laboratories, and EBUS fineneedle aspiration specimens and electromagnetic bronchoscopy cytology preparations were also viewed in less than half of the facilities responding. These data are presented in Table 3. Slightly more than half of respondents (54%, 338 of 622) reported issuing unique surgical pathology and cytology reports when touch preparations of cores were made, and slightly less than half of respondents (46%, 285 of 622) reported issuance of either combined/unified touch preparation and histology reports or a mixture of reporting styles. The survey tool did not question participants regarding their reasons for choice of reporting formats (eg, specialty sign-out of cytopathologists versus histopathologists, billing issues, limitations of laboratory information systems).
Submitting Provider Types
Bronchial cytology specimens were reported as being most commonly submitted to the respondent laboratories by pulmonologists (85%, 302 of 355), with interventional radiologists and thoracic surgeons submitting the majority of the remainder. These data are presented in Table 4.
Table 5 details the utilization of intraprocedural adequacy assessments in bronchopulmonary cytology. Respondents reported assessment of intraprocedural adequacy in 73.7% (413 of 560) of percutaneous image-guided aspirations, 68.5% (350 of 511) of touch preparations from percutaneous core biopsies, and 59.2% (257 of 434) of EBUS aspirations. Other specimen types were less frequently assessed intraprocedurally. The highest numbers of intraprocedural evaluations were reportedly performed on-site (57.9%, 239 of 413) for percutaneous aspirations with smaller numbers of assessments being performed off-site (in the hospital but not in the procedure room) and with only infrequent use of telepathology for adequacy assessments. When queried about who performed intraprocedural assessments, most respondents (85.5%, 490 of 573) indicated that attending pathologists completed these tasks with laboratory cytotechnologists and pathologists-in-training performing the remainder. The survey questioned whether intraprocedural evaluation results were incorporated into final reports, with 93% (451 of 485) of laboratories reporting incorporation of pathologist-performed adequacy assessments into final reports and with 63% (89 of 141) of laboratories reporting incorporation of cytotechnologist-performed adequacy assessments into final reports. Reasons for having attending pathologists perform adequacy assessments were queried. "Pathologist preference" was given as the most common reason (57%, 245 of 430) for pathologists to perform intraprocedural assessments of adequacy. Other factors influencing who performed adequacy assessments in clinical practice included insufficient cytotechnologist staffing (35%, 150 of 430), clinical colleague insistence upon physician-to-physician communication (30%, 130 of 430), and higher reimbursement for pathologist-performed readings than for cytotechnologist-performed readings (17%, 74 of 430).
For those laboratories evaluating EBUS aspirations, the average number of sites biopsied was variable and ranged on average from 1 site per case (34.4%, 116 of 337) to 2 sites per case (40.9%, 138 of 337) to 3 to 4 sites per case (20.8%, 70 of 337) to 5 or more sites per case (3.9%, 13 of 337). A total of 354 (45% of 788) laboratories responded to the question regarding the average amount of time spent per case in performing adequacy evaluations for EBUS samplings with 28.5% (100 of 351) reporting an average time invested per case of less than or equal to 15 minutes, 15.1% (53 of 351) of respondents reporting an average time invested per case of between 16 and 30 minutes, 22.5% (79 of 351) reporting an average time invested per case of between 31 and 45 minutes, and with 33.9% (119 of 351) reporting an average time invested per case of 46 minutes or more. More than half of respondents (55%, 401 of 725) reported use of modified Giemsa-stained direct smears as the preferred method of preparation for assessments of intraprocedural adequacy. Smaller numbers of laboratories used hematoxylin-eosin-stained preparations (22%, 159 of 725) or rapid Papanicolaou-stained slides (13%, 96 of 725), with other stains (10%, 69 of 725), including but not limited to toluidine blue, accounting for the remainder of responses.
Adequacy Criteria and Statements in Final Reports
A minority of responding laboratories (43%, 307 of 715) indicated that pulmonary cytology results included specific statements of adequacy in all final reports. Most laboratories (57%, 408 of 715) reported that adequacy statements were either not used in final reports or were used inconsistently (in some but not all reports). The survey asked whether specific criteria were used to establish adequacy for final reporting for some of the sample types. The presence of specific cell types seemed valuable for most respondents in reporting bronchoalveolar lavage and EBUS results; however, the "general impression" of the sample was most heavily relied upon to determine adequacy in all categories. Data regarding adequacy criteria are presented in Table 6.
Ancillary Testing (Special Stains/Immunochemistry/ Molecular)
Table 7 provides responses to a survey question querying use of various markers for differentiating types of non-small cell carcinoma. Reliance upon immunohistochemical characterization with p63 (91.2%, 547 of 600), cytokeratin 5/6 (CK5/6; 83.8%, 503 of 600), thyroid transcription factor-1 (TTF-1; 93.3%, 571 of 612), and napsin A (52%, 318 of 612) was reported by most respondents. (It should be noted that responses to this category may reflect patterns of sometimes using immunohistochemistry and sometimes not, and the results given are for those instances in which such testing is pursued). The use of cocktail immunohistochemical testing was not queried. Participants were also questioned about preferred specimen types for ancillary testing, with most respondents reporting use of supplemental core biopsy (92%, 523 of 566) and/or cell block materials (56%, 317 of 566) and a minority (18%, 103 of 566) performing ancillary testing on additional dedicated smears, cytospins, or liquid-based cytology preparations. Most laboratories (76%, 532 of 702) indicated that they offered molecular testing for newly diagnosed non-small cell lung carcinomas, with most of those respondents (86%, 455 of 527) indicating that all molecular testing was outsourced to a reference laboratory. Participant laboratories were also queried about practice patterns regarding the triage of newly diagnosed non-small cell lung carcinomas for molecular testing, with a minority of respondents (11.2%, 56 of 502) indicating that all non-small carcinomas were triaged (Table 8). When ancillary molecular testing was requested, most laboratories (64.4%, 277 of 430) reported simultaneous ordering of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tests, with the second most common pattern of triage being ordering of EGFR testing first with reflex testing to ALK if EGFR findings were negative (34.0%, 146 of 430). Median percentages of EGFR and ALK testing in new adenocarcinomas are given in Table 9. (These percentages may be affected by the actual number of cases in which sufficient material was either available for or not available for molecular triage; in addition, the comparatively smaller number of laboratory respondents than for the survey as a whole may also affect these values). Per response data, EBUS and/or transthoracic pulmonary aspirates were performed solely for the purpose of ancillary molecular testing in a minority of laboratories (38%, 230 of 612).
Cytologic-Histologic Correlations and Turnaround Times
Most laboratories (81%, 490 of 608) responded that some or all cases of transthoracic fine-needle aspiration biopsies and EBUS biopsies underwent cytologic-histologic correlation with 73% (346 of 472) of respondent laboratories reporting that these correlations happened at the time of reporting (41% at the time of histologic follow-up reporting and 32% at the time of cytologic interpretation). A minority of respondents (27%, 126 of 472) indicated that cytologichistologic correlations were performed retrospectively through electronic record searches and subsequent review. A minority of laboratories (44%, 205 of 466) reported issuance of amended or "addended" reports in medically relevant cases in which cytologic-histologic discrepancies were discovered. Respondent laboratory information on turnaround times (all means for all specimen types reported at greater than 75% in 48 hours) is given in Table 10.
In an attempt to ascertain information regarding practice patterns in bronchopulmonary cytology, a subgroup of the CAP CC developed the CAP "NGC Supplemental Questionnaire: "Demographics in Performance and Reporting of Respiratory Cytology." This survey was mailed to 2074 participant facilities in the middle of calendar year 2013. Of these laboratories, 42% (880 of 2074) responded. Some laboratories (10.5%, 92 of 880) reported that they did not evaluate pulmonary cytology samples, yielding a subset of 788 respondents providing data for review. The laboratories that responded represented diverse practice types, with the largest cohort of responses coming from laboratories associated with nonprofit hospitals (48.4%, 367 of 758). The median number of pathologists in the respondent laboratories was 4. Of the responding laboratories, 59.1% indicated that their work environments included 1 or more pathologists with added qualification in cytopathology from the American Board of Pathology, indicating that more than 40% of laboratories surveyed issue diagnostic reports on respiratory cytopathology without a board-certified cytopathologist in-house. Only 11.7% of respondents indicated employing cytopathologists who practiced cytopathology only. The mean number of cytology cases (gynecologic and NGC combined) was 30 934 (median, 4000).
Greater than 90% of laboratories reported interpreting specimens submitted in the categories of sputa, bronchial brushings, and bronchial washings. Examination of sputum is the least invasive respiratory cytology method for obtaining a cytologic diagnosis for patients suspected of harboring a lung carcinoma. Sputum cytology is known to be highly specific for the diagnosis of malignancy with peer-reviewed literature indicating that specificities for sputum diagnoses can exceed 95%. (5-8) Sputum cytology studies are, however, not as highly sensitive as they are specific, with the literature ranging widely from between 37% to 75% for confirmation of malignancy. (5-8) By the time sputum cytology findings are documented as positive, many patients with lung cancer are no longer candidates for surgery secondary to high-stage disease; hence, sputum cytology is not an effective screening test for the early detection of pulmonary malignancy. In addition, positive sputum cytology results for malignancy do not allow for specific localization of a neoplastic process in regard to laterality or specific sublocation. Traditional exfoliative bronchial cytology preparations, such as bronchial brushings, bronchial washings, and bronchoalveolar lavages, have the capacity to increase diagnostic sensitivity to around 85%. (9,10) Some lesions (especially those in the peripheral lung parenchyma) cannot be effectively sampled by sputum cytology or traditional bronchoscopic means. Historically, many such patients were subjected to image-guided percutaneous transthoracic biopsy, a method that has proved more cost-effective than either video-assisted thoracoscopic surgery or F-fluorodeoxy-glucose positron emission tomography. (11)
Most survey respondents (66.3%, 522 of 787) reported interpreting transthoracic aspirates. Fine-needle aspiration biopsy of lung tumors has also been shown to provide sufficient material to allow for subclassification of non-small cell carcinomas into squamous and nonsquamous categories in 89% of cases. (12) Endobronchial ultrasound-guided fine-needle aspiration is a minimally invasive modality for evaluating the mediastinum and staging patients with lung carcinoma. Expanding use of this technology is noted in the literature with positive and negative predictive values (in samples submitted by experienced operators) reported at 95% and 100%, respectively. (13,14) A minority of laboratories in the survey (43.2%, 340 of 787) reported interpreting EBUS samples. Electromagnetic navigational bronchoscopy (ENB) is a new technology that incorporates image-guided localization and allows the operator to steer a bronchoscope to a peripheral lung lesion with catheters used to collect samples from small peripheral lung lesions. When performed by experienced operators, ENB aspirations have been shown to have high diagnostic yields ranging from 77% to 94% with sampling possible in small airways at the fourth order of branching and beyond, including subpleural lesions. (15-17) Electromagnetic navigational bronchoscopy aspirates were interpreted by only 14% (110 of 787) of respondent laboratories.
Intraprocedural rapid evaluations to assess adequacy and quality of samples were reported most frequently in transthoracic fine-needle aspiration specimens (73.7%, 413 of 560). Most laboratories also reported using intraprocedural evaluations for touch preparations of transthoracic cores and for EBUS aspirates. Traditional bronchoscopic samples such as brushes and washes were less likely to be rapidly evaluated for quality/adequacy. Intraprocedural evaluations have been shown to add value in pulmonary cytology with communication between pulmonologists and pathologists, as well as between radiologists and pathologists, allowing for triage of samples to appropriate ancillary testing and optimized utilization of small-volume samples. (15,18,19) While some peer-reviewed literature does exist on criteria for adequacy in pulmonary cytology (such as criteria for specimen adequacy in EBUS), the greatest number of respondents to the survey indicated that "general impressions" of samples were used more often than cell counting or the presence of specific cell types. (13,20,21)
A recent study from the CAP Interlaboratory Comparison Program confirmed a significant trend toward subcategorization of non-small cell carcinomas by cytomorphology alone, suggesting that participants are cognizant of the impact that more specific cytomorphologic interpretations have in directing molecular triage and patient therapies. (22) More than half of survey respondents reported routinely using p63, CK5/6, TTF-1, and napsin A immunohistochemistry on pulmonary cytology samples to differentiate between types of non-small cell carcinoma. A growing volume of literature confirms that ancillary testing, such as immunocytochemistry, polymerase chain reaction, fluorescence in situ hybridization, and next-generation sequencing, can be performed on pulmonary cytology samples. (23-28) More than half of laboratories (52.2%, 262 of 502) reported utilization of molecular testing on a subset of carcinomas diagnosed by thoracic cytology, with most laboratories (86.3%, 455 of 527) indicating that molecular testing was outsourced to a reference laboratory and with the most common pattern of requested testing being simultaneous ordering of EGFR and ALK tests (64.4%, 277 of 430). The largest percentage of laboratories (45.5%, 221 of 486) responded that molecular diagnostic results were reported separately from main cytology reports. This practice may be influenced by hopes of preserving quick turnaround times and/or incompatibility of computer interfaces from reference laboratories. Respondent laboratory information on turnaround times showed the quickest result reporting for conventional bronchoscopy samples with 86.9% (590 of 679) of laboratories reporting a 2-day or less turnaround time for bronchial brushings, and the slowest turnaround times for transthoracic aspirations with cell blocks with 78.5% (482 of 614) of laboratories reporting finalized results within 2 days.
The 2013 CAP "NGC Supplemental Questionnaire: Demographics in Performance and Reporting of Respiratory Cytology" was a valuable tool for assessing recent trends in the real-world practice of clinical bronchopulmonary cytology. The information acquired from the survey provides insights into the demographics of laboratories and test types that are performed and also addresses the frequency with which intraprocedural evaluations are performed. The average "attendance time" by a cytology professional and/ or technical staff for an EBUS case was reported to range from 31 to 45 minutes. Helping to ensure specimen adequacy and directing appropriate triage of small samples for the best available ancillary tests takes time. As newer technologies such as EBUS and ENB are introduced in clinical spheres, laboratories will need to be adept at processing and interpreting these samples. The first study of real-time ENB using overlaid digital computed tomographic images was published in 20 06.27 The current study shows that 14% (110 of 787) of participating laboratories now interpret samples procured through the small catheters of this sampling technique. The results of the current survey give valuable information about clinical practice patterns and will allow for comparison of practice trends in the future.
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Charles D. Sturgis, MD; Carrie B. Marshall, MD; Guliz A. Barkan, MD; Christine N. Booth, MD; Daniel F. I. Kurtycz, MD; Rhona J. Souers, MS; Joren B. Keylock, MD; Z. Laura Tabatabai, MD; Donna K. Russell, CT HT(ASCP); Ann T. Moriarty, MD; Mary A. Doyle, MS, CT(ASCP); Nicole Thomas, MPH, CT(ASCP); Isil Z. Yildiz-Aktas, MD; Brian T. Collins, MD; Rodolfo Laucirica, MD; Barbara A. Crothers, DO
Accepted for publication April 3, 2015.
From the Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio (Drs Sturgis and Booth); the Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora (Dr Marshall); the Department of Pathology, Loyola University Medical Center, Maywood, Illinois (Dr Barkan); the Wisconsin State Laboratory of Hygiene and the Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison (Dr Kurtycz); the Departments of Biostatistics (Ms Souers) and Surveys (Mses Doyle and Thomas), College of American Pathologists, Northfield, Illinois; the Puget Sound Institute of Pathology, Seattle, Washington (Dr Keylock); the Department of Pathology, University of California San Francisco, San Francisco (Dr Tabatabai); the Department of Pathology, University of Rochester Medical Center, Rochester, New York (Ms Russell); the Department of Esoteric Testing, AmeriPath, Indianapolis, Indiana (Dr Moriarty); the Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (Dr Yildiz-Aktas); the Department of Pathology, Washington University School of Medicine, St Louis, Missouri (Dr Collins); the Department of Pathology, Baylor College of Medicine, Houston, Texas (Dr Laucirica); and the Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland (Dr Crothers). Dr Yildiz-Aktas is now with the Department of Pathology, Greenwich Hospital, Greenwich, Connecticut.
The authors have no relevant financial interest in the products or companies described in this article.
Reprints: Charles D. Sturgis, MD, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 9500 Euclid Ave L25, Cleveland, OH 44195 (e-mail: firstname.lastname@example.org).
Table 1. Volume of Cases Reported by Participating Laboratories in 2012 Volume of Cases in No. of 10th 25th 2012 Laboratories Min Max Pctl Pctl No. of cytology cases (gynecologic 759 1 1 443 292 317 876 and nongynecologic) No. of 761 0 57 210 242 500 nongynecologic cases No. of fine-needle 752 0 38 010 33 100 aspiration specimens No. of conventional and liquid-based 526 0 90 154 0 55 preparations No. of ThinPrep 525 0 46 328 0 128 preparations (51) No. of SurePath 270 0 47 145 0 0 preparations (15) Volume of Cases in 50th Pctl 75th 90th 2012 (Median) Pctl Pctl No. of cytology cases (gynecologic 4327 14 043 43 875 and nongynecologic) No. of 1000 2114 5187 nongynecologic cases No. of fine-needle 274 725 1533 aspiration specimens No. of conventional and liquid-based 300 800 1978 preparations No. of ThinPrep 710 2118 5237 preparations (51) No. of SurePath 0 200 2107 preparations (15) Abbreviations: Max, maximum; Min, minimum; Pctl, percentile. (a) ThinPrep products manufactured by Hologic, Marlborough, Massachusetts. (b) SurePath products manufactured by BD Diagnostics, TriPath, Burlington, North Carolina. Table 2. Distribution of Cytotechnologist Staffing in Responding Laboratories No. of Full Time Cytotechnologists (n = 734) in Laboratory No. of Laboratories Percentage 0 263 35.8 1 158 21.5 2 102 13.9 3 73 9.9 4-5 63 8.6 6-10 45 6.1 >10 30 4.1 No. of Part Time Cytotechnologists (n = 642) in Laboratory No. of Laboratories Percentage 0 389 60.6 1 139 21.7 2 57 8.9 3 22 3.4 4-5 19 3.0 6-10 13 2.0 >10 3 0.5 Table 3. Bronchopulmonary Cytology Specimen Types Interpreted by Respondent Laboratories Specimen Types Interpreted No. of (n = 787) (a) Laboratories Percentage Bronchial washings 765 97.2 Bronchial brushings 757 96.2 Sputa 749 95.2 Bronchoalveolar lavages 690 87.7 Percutaneous/transthoracic image-guided fine-needle aspirates 522 66.3 Non-image-guided transbronchial/transtracheal aspirates 424 53.9 Percutaneous/transthoracic core biopsies with touch preparations 380 48.2 Endobronchial ultrasound- guided fine-needle aspirates 340 43.2 Bronchial mucosal or transbronchial biopsy with touch preparations 333 42.3 Electromagnetic navigational bronchoscopy 110 14.0 (a) Multiple responses allowed. Table 4. Submission of Respiratory Cytology Specimens per Clinician Type Providers Who Submit No. of Percentage Mean Pulmonary Samples Laboratories Frequency and Their Estimated Submitted Frequencies by Provider, (n = 355) (a) Percentile Pulmonologists 302 85.1 71.3 Interventional 95 26.8 16.4 radiologists Cardiothoracic surgeons 64 18.0 8.1 General surgeons 34 9.6 2.7 Other 19 5.4 1.5 (a) Multiple responses allowed. Table 5. Performance of Intraprocedural Adequacy by Case Type and Location Which Pulmonary Cytology No. of Intraprocedural Specimen Types Are Performed With Laboratories Adequacy Not Intraprocedural Adequacy Assessments? Performed, % Sputum 633 93.6 Bronchial brushing 622 81.3 Bronchial washing 627 91.7 Bronchoalveolar lavage 597 92.8 Bronchial biopsy touch preparations 497 62.0 Nonimaged transbronchial FNA 490 64.5 EBUS FNA 434 40.7 EBUS FNA with ENB 320 72.5 Percutaneous imaged FNA 560 26.2 Percutaneous core biopsy 511 31.5 touch preparations Which Pulmonary Cytology Adequacy Adequacy Specimen Types Are Performed With Assessed Assessed Intraprocedural Adequacy Assessments? On-site, % Off-site, % Sputum 0.2 6.2 Bronchial brushing 10.6 7.9 Bronchial washing 1.6 6.7 Bronchoalveolar lavage 1.3 5.9 Bronchial biopsy touch preparations 29.8 7.8 Nonimaged transbronchial FNA 26.9 8.0 EBUS FNA 46.3 11.8 EBUS FNA with ENB 21.6 5.6 Percutaneous imaged FNA 57.9 15.2 Percutaneous core biopsy 53.8 14.3 touch preparations Which Pulmonary Cytology Adequacy Specimen Types Are Performed With Assessed by Intraprocedural Adequacy Assessments? Telepathology, % Sputum 0.0 Bronchial brushing 0.2 Bronchial washing 0.0 Bronchoalveolar lavage 0.0 Bronchial biopsy touch preparations 0.4 Nonimaged transbronchial FNA 0.6 EBUS FNA 1.2 EBUS FNA with ENB 0.3 Percutaneous imaged FNA 0.7 Percutaneous core biopsy 0.4 touch preparations Abbreviations: EBUS, endobronchial ultrasound;ENB, electromagnetic navigational bronchoscopy; FNA, fine-needle aspiration. Table 6. Criteria to Establish Adequacy in Certain Sample Types Specific Specific Cell Cell Type(s) Number(s) Criteria Used to Establish No. % No. % Pulmonary Specimen Adequacy (a) Bronchoalveolar lavages (n = 587) 347 59.1 152 25.9 Fine-needle aspirations (n = 634) 302 47.6 226 35.6 EBUS fine-needle aspirations (n = 355) 187 52.7 117 33.0 General Impression Criteria Used to Establish No. % Pulmonary Specimen Adequacy (a) Bronchoalveolar lavages (n = 587) 363 61.8 Fine-needle aspirations (n = 634) 461 72.7 EBUS fine-needle aspirations (n = 355) 255 71.8 Abbreviation: EBUS, endobronchial ultrasound. (a) Multiple responses allowed. Table 7. Testing Preferences for Differentiating Types of Non-Small Cell Carcinoma Ancillary Tests No. of Percentage for Differentiating Laboratories Squamous Carcinoma From Adenocarcinomaa Squamous carcinoma markers (n = 600) p63 547 91.2 Cytokeratin 5/6 503 83.8 Cytokeratin 34 b E-12 122 20.3 p40 47 7.8 SOX-2 6 1.0 Other 35 5.8 Adenocarcinoma markers (n = 612) Thyroid transcription factor-1 571 93.3 Napsin A 318 52.0 Mucicarmine 262 42.8 Carcinoembryonic antigen 213 34.8 Alcian blue 91 14.9 Other 84 13.7 (a) Multiple responses allowed. Table 8. Molecular Triage Patterns for Newly Diagnosed Non-Small Cell Carcinomas Which of the Following Statements Best No. of Percentage Characterizes the Practice Pattern in Laboratories Regard to Molecular Testing for Newly (Total 502) Diagnosed Non-Small Cell Lung Carcinomas? A subset of carcinoma undergo molecular 262 52.2 testing All adenocarcinomas of lung undergo 136 27.1 molecular testing All non-small cell lung carcinomas 56 11.2 undergo molecular testing Molecular testing is not regularly 48 9.6 performed Table 9. Reported Percentages of Newly Diagnosed Adenocarcinomas Undergoing Testing Newly Diagnosed Primary No. of 10th 25th Pulmonary Adenocarcinomas Laboratories Percentile Percentile Triaged to Molecular Testing for Specific Mutations KRAS 321 0 5 EGFR 378 10 50 ALK 363 10 25 Newly Diagnosed Primary 75th 90th Pulmonary Adenocarcinomas Median Percentile Percentile Triaged to Molecular Testing for Specific Mutations KRAS 25 80 100 EGFR 90 100 100 ALK 80 100 100 Abbreviations: ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; KRAS, Kirsten rat sarcoma viral oncogene homolog. Table 10. Mean Turnaround Times (TATs) for Various Pulmonary Cytology Specimen Types Mean TAT (Working Days) From Specimen Receipt in Laboratory to Issuance of Final Report Specimen Type No. of 0-48 Hours, % 49-72 Hours, % Laboratories Bronchoalveolar 642 87.7 10.7 lavage Bronchial 679 86.9 11.5 brushing/washing Transthoracic 614 78.5 19.2 FNA/cell block EBUS FNA 375 79.7 17.6 Transthoracic 605 79.3 17.4 core biopsy Mean TAT (Working Days) From Specimen Receipt in Laboratory to Issuance of Final Report Specimen Type 73-96 Hours, % >96 Hours, % Bronchoalveolar 1.1 0.5 lavage Bronchial 1.2 0.4 brushing/washing Transthoracic 1.6 0.7 FNA/cell block EBUS FNA 2.4 0.3 Transthoracic 2.5 0.8 core biopsy Abbreviations: EBUS, endobronchial ultrasound; FNA, fine-needle aspiration; %, percentage.