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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.

The Cytopathology Committee (CC) of the College of American Pathologists (CAP) creates questionnaires and conducts surveys that are designed to assess current cytology laboratory practices. Early surveys from the CAP CC focused on adequacy and terminology in cervicovaginal cytology and on gynecologic cytology interpretative categories. (1,2) More recently, surveys in nongynecologic cytology (NGC) have addressed practices surrounding exfoliative nongynecologic specimens, including topics such as cell block utilization, immunocytochemistry, and turnaround times. (3,4) In early 2013, a subgroup of the CAP CC developed a questionnaire that was sent to participants in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology (CAP NGC) to investigate practice patterns regarding utilization and reporting of bronchopulmonary cytology. The CAP NGC program began in 1997 with 794 laboratories. At the time of this survey (calendar year 2013), the CAP NGC program had grown to include 2074 laboratories. The CAP NGC is strictly educational, is not graded, and is not related to proficiency testing. It consists of quarterly mailings of glass slides with associated clinical histories and ancillary studies as well as supplemental online cases. The purpose of this educational activity is for participants to consider differential diagnoses based upon clinical histories, morphologic evaluations, and reviews of ancillary studies to select the most appropriate diagnoses from interpretive menus. Because of broad subscription to the NCG program the audience is a good representation of the practice of NGC in North America. The CAP's "NGC 2013 Supplemental Questionnaire: Demographics in Performance and Reporting of Respiratory Cytology" was mailed to all participating laboratories and was designed to glean information regarding laboratory practices pertaining to performance and reporting of bronchopulmonary 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).

RESULTS

Demographic Findings

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.

Intraprocedural Evaluations

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.

COMMENT

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.

References

(1.) Davey DD, Nielsen ML, Rosenstock W, Kline TS. Terminology and specimen adequacy in cervicovaginal cytology: the College of American Pathologists Interlaboratory Comparison Program Experience. Arch Pathol Lab Med. 1992; 116(9):903-907.

(2.) Davey DD, Nielsen ML, Naryshkin S, Robb JA, Cohen T, Kline TS. Atypical squamous cells of undetermined significance: current laboratory practices of participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. Arch Pathol Lab Med. 1996; 120(5):440-444.

(3.) Moriarty AT, Nayar R, Auger M, et al. Nongynecologic cytology practice patterns: a survey of participants in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology. Arch Pathol Lab Med. 2014; 138(7):885-889.

(4.) Fischer AH, Schwartz MR, Moriarty AT, et al. Immunohistochemistry practices of cytopathology laboratories: a survey of participants in the College of American Pathologists Nongynecologic Cytopathology Education Program. Arch Pathol Lab Med. 2014; 138(9):1167-1172.

(5.) Pilotti S, Rilke F, Gribaudi G, Ravasi GL. Sputum cytology for the diagnosis of carcinoma of the lung. Acta Cytol. 1982; 26(5):649-654.

(6.) Mehta AC, Marty JJ, Lee FY. Sputum cytology. Clin Chest Med. 1993; 14(1): 69-85.

(7.) Kern WH. The diagnostic accuracy of sputum and urine cytology. Acta Cytol. 1988; 32(5):651-654.

(8.) Perlman EJ, Erozan YS, Howdon A. The role of the saccomano technique in sputum cytopathologic diagnosis of lung cancer. Am J Clin Pathol. 1989; 91(1): 57-60.

(9.) Jay SJ, Wehr K, Nicholson DP, Smith AL. Diagnostic sensitivity and specificity of pulmonary cytology: comparison of techniques used in conjunction with flexible fiberoptic bronchoscopy. Acta Cytol. 1980; 24(4):304-312.

(10.) Saita S, Tanzillo A, Riscica C, Maresca A, Potenza E, D'Arrigo M. Bronchial brushing and biopsy: a comparative evaluation in diagnosing visible bronchial lesions. Eur J Cardiothorac Surg. 1990; 4(5):270-272.

(11.) Deppen SA, Davis WT, Green EA, et al. Cost-effectiveness of initial diagnostic strategies for pulmonary nodules presenting to thoracic surgeons [published online ahead of print July 31, 2014]. Ann Thorac Surg. doi:10.1016/j. athoracsur.2014.05.025.

(12.) Adams J, Wu HH. The utility of fine needle aspiration in the diagnosis of primary and metastatic tumors to the lung: a retrospective examination of 1,032 cases. Acta Cytol. 2012; 56(6):590-595.

(13.) Karunamurthy A, Cai G, Dacic S, Khalbuss WE, Pantanowitz L, Monaco SE. Evaluation of endobronchial ultrasound guided fine needle aspirations (EBUS FNA): correlation with adequacy and histologic follow up. Cancer Cytopathol. 2014; 122(1):23-32.

(14.) VanderLaan PA, Wang HH, Majid A, Folch E. Endobronchial ultrasound guided transbronchial needle aspiration (EBUS TBNA): an overview and update for the cytopathologist. Cancer Cytopathol. 2014; 122(8):561-567.

(15.) Loo FL, Halligan AM, Port JL, Hoda RS. The emerging technique of electromagnetic navigation bronchoscopy guided fine needle aspiration of peripheral lung lesions: promising results in 50 lesions. Cancer Cytopathol. 2014; 122(3):191-199.

(16.) Mahajan AK, Patel S, Hogarth DK, Wightman R. Electromagnetic navigation bronchoscopy: an effective and safe approach to diagnose peripheral lung lesions unreachable by conventional bronchoscopy in high risk patients. J Bronchology Intervent Pulmonol. 2011; 18(2)133-137.

(17.) Odronic SI, Gildea TR, Chute DJ. Eletromagnetic navigation bronchoscopy guided fine needle aspiration for the diagnosis of lung lesions. Diagn Cytopathol. 2014; 42(12):1045-1050.

(18.) Yarmus L, Akulian J, Gilbert C, et al. Optimizing endobronchial ultrasound for molecular analysis: how many passes are needed? Ann Am Thorac Soc. 2013; 10(6):636-643.

(19.) Mondoni M, Carlucci P, Di Marco F, et al. Rapid on site evaluation improves needle aspiration sensitivity in the diagnosis of central lung cancers: a randomized trial. Respiration. 2013; 86(1):52-58.

(20.) Nayak A, Sugrue C, Koenig S, Wasserman PG, Hoda S, Morgenstern NJ. Endobronchial ultrasound guided transbronchial needle aspirate (EBUS TBNA): a proposal for onsite adequacy criteria. Diagn Cytopathol. 2012; 40(2):128-137.

(21.) Alsharif M, Andrade RS, Groth SS, Stelow EB, Pambuccian SE. Endobronchail ultrasound-guided transbronchial fine-needle aspiration: the University of Minnesota experience, with emphasis on usefulness, adequacy assessment, and diagnostic difficulties. Am J Clin Pathol. 2008; 130(3):434-443.

(22.) Yildiz-Aktas IZ, Sturgis CD, Barkan GA, et al. Primary pulmonary nonsmall cell carcinomas: the College of American Pathologists Interlaboratory Comparison Program confirms a significant trend toward subcategorization based upon fine-needle aspiration cytomorphology alone. Arch Pathol Lab Med. 2014; 138(1):65-70.

(23.) Mitushkina NV, Iyevleva AG, Poltoratskiy AN, et al. Detection of EGFR mutation and EML4-ALK rearrangements in lung adenocarcinomas using archived cytological slides. Cancer Cytopathol. 2013; 121(7):370-376.

(24.) Marshall D, Laberge JM, Firetag B, Miller T, Kerlan RK. The changing face of percutaneous image guided biopsy: molecular profiling and genomics in current practice. J Vasc Interv Radiol. 2013; 24(8):1094-2103.

(25.) Karnes HE, Duncavage EJ, Bernadt CT. Targeted next generation sequencing using fine needle aspirates from adenocarcinomas of the lung. Cancer Cytopathol. 2014; 122(2):104-113.

(26.) Heymann JJ, Bulman WA, Maxfield RA, et al. Molecular testing guidelines for lung adenocarcinoma: utility of cell blocks and concordance between fine needle aspiration cytology and histology samples. Cytojournal. 2014; 11:12. doi: 10,4103/1742-6413.132989.

(27.) Schwarz Y, Greif J, Becker HD, Ernst A, Mehta A. Real time electromagnetic navigation bronchoscopy to peripheral lung lesions using overlaid CT images: the first human study. Chest. 2006; 129(4).988-994.

(28.) Reynolds JP, Tubbs RR, Minca EC, et al. EGFR mutation genotyping of liquid based cytology samples obtained via fine needle aspiration (FNA) at endobronchial ultrasound of non small cell lung cancer (NSCLC). Lung Cancer. 2014; 86:158-163.

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: sturgic@ccf.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.
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Author:Sturgis, Charles D.; Marshall, Carrie B.; Barkan, Guliz A.; Booth, Christine N.; Kurtycz, Daniel F.I
Publication:Archives of Pathology & Laboratory Medicine
Article Type:Survey
Date:Jan 1, 2016
Words:5780
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