Laboratory Management Curriculum for Cytopathology Subspecialty Training

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Journal of the American Society of Cytopathology (2018) 7,61e78

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REVIEW ARTICLE Laboratory management curriculum for cytopathology subspecialty training

Ritu Nayar, MDa,*,**, Güliz A. Barkan, MDb,*, Cynthia Benedict, MDc,*, Christine Booth, MDd,*, David C. Chhieng, MDe,*, Dina Mody, MDf,*, Momin T. Siddiqui, MDg,*, Laura Z. Tabatabai, MDh,*, Rebecca Johnson, MDi a Northwestern University, Feinberg School of Medicine, Department of Pathology and Northwestern Memorial Hospital, Chicago, Illinois b Loyola University Healthcare System, Department of Pathology, Maywood, Illinois c DCL Pathology, LLC, Indianapolis, Indiana d Cleveland Clinic, Department of Pathology, Cleveland, Ohio e Department of Pathology, University of Washington, School of Medicine, Seattle, Washington f Department of Pathology, Houston Methodist Hospital, Houston, Texas g Department of Pathology, Weill Cornell School of Medicine, New York, New York h Department of Pathology, University of California San Francisco and San Francisco VA Medical Centers, San Francisco, California i American Board of Pathology, Tampa, Florida ** Chair and * Members of The American Board of Pathology’s Cytopathology Test Development Committee.

Received 17 October 2017; received in revised form 7 December 2017; accepted 11 December 2017

KEYWORDS Laboratory management should be an integral part of training in pathology residency and fellowships. Here- Laboratory management; in, we have outlined some basic laboratory management topics a graduating cytopathology fellow should be Cytopathology; familiar with. An overview of regulatory agencies that have oversight over laboratory testing, cytopathology Curriculum; laboratory accreditation, pre-analytic, analytic and post-analytic quality assurance, billing/coding, basic sta- Fellowship training; tistics, verification/validation of testing, physician credentialing, board certification/maintenance of certifica- Pathology tion, and malpractice in cytopathology are addressed. This review is by no means all inclusive, but rather a guide to the basic management related topics to be covered during cytopathology subspecialty training. Ó 2017 The Authors. Published by Elsevier Inc. on behalf of American Society of Cytopathology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

*Corresponding author: Ritu Nayar, MD; Department of Pathology, Northwestern University, Feinberg School of Medicine, 251 East Huron Street, Galter 7-132B, Chicago, IL 60611; Tel.: (312) 926-7002. E-mail address: [email protected] (R. Nayar).

2213-2945/Ó 2017 The Authors. Published by Elsevier Inc. on behalf of American Society of Cytopathology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). https://doi.org/10.1016/j.jasc.2017.12.003

Contents

Introduction ...... 62 Agencies involved in laboratory regulation ...... 62 General aspects and basis of cytopathology laboratory accreditation ...... 62 Specific laboratory pre-analytic, analytic, and post-analytic quality assurance measures in cytopathology laboratories ...... 66 Specimen collection, receipt, and preparation ...... 66 Gynecologic cytology ...... 66 Nongynecologic cytology ...... 66 Diagnostic interpretation ...... 67 Cytology histology correlation ...... 67 Management implications of cytopathology results ...... 67 Federally mandated gynecologic cytology proficiency testing ...... 68 Additional laboratory management essentials for cytopathology fellows ...... 68 Test validation and verification ...... 68 Informatics and telemedicine ...... 69 Statistics ...... 69 Physician/professional regulation ...... 71 Professional practice evaluation (PPE) ...... 71 Certification by the American Board of Pathology (ABP) ...... 71 Maintenance of certification for pathologists ...... 72 Billing and coding with applicable health care laws ...... 73 Stark Law ...... 73 The Sunshine Act ...... 74 Malpractice in cytopathology ...... 75 Conclusion ...... 76 References ...... 76

Introduction and to provide safe health care to every individual who accesses the system. There are a number of historical ex- Laboratory management should be an integral part of training amples in medicine in which lack of standards led to in pathology residency and fellowships. Since 2014, the adverse outcomes. Specific to cytology is the exposé on American Board of Pathology has participated in surveys of “Pap mills” in the Wall Street Journal by investigative new in practice (10 years) pathologists that asked about how journalist Walt Bogdanich that played a major role in the residency and fellowship training correlates with the needs in implementation of the Clinical Laboratory Improvement 2 practice. The feedback has consistently shown that laboratory Amendments of 1988. Federal, state, and local regulatory management, billing and coding, informatics, and molecular agencies often establish rules and regulations for the diagnostics are areas in which training was perceived to be less health-care industry, and their oversight is mandatory. than needed, but important or very important areas for practice. Some other agencies, such as those for accreditation, Similar findings were published in 2007.1 Herein, we have require voluntary participation but are important because outlined some basic laboratory management topics with which they provide rankings or certification of quality and serve a graduating cytopathology fellow should be familiar. An as additional oversight, ensuring that health-care organi- overview of regulatory agencies that have oversight over lab- zations promote and provide quality care (Table 1). oratory testing, cytopathology laboratory accreditation, pre- analytic, analytic and post-analytic quality assurance, billing/ coding, basic statistics, verification/validation of testing, General aspects and basis of cytopathology physician credentialing, board certification/maintenance of laboratory accreditation certification, and malpractice in cytopathology are addressed. This review is by no means all inclusive, but rather a guide to Fundamentally, accreditation is a way to ensure that clinical the basic management related topics to be covered during laboratories meet best practices for proficiency, quality, cytopathology subspecialty training. accuracy, and record keeping. To be accredited, a laboratory must set up and maintain mechanisms that are evaluated regularly by an outside entity. Accreditation signals to pa- Agencies involved in laboratory regulation tients, doctors, and insurers that the laboratory is making every effort to provide them with high-quality, accurate Health care is subject to extensive regulation at both the results and that those results are reasonably translatable federal and the state level in order to ensure compliance across accredited laboratories.3

Table 1 Selected federal agencies and acts related to health care. Agency Acronym Function Centers for Medicare and Medicaid Services CMS CMS is part of the Department of Health and Human Services (HHS) and oversees most of the regulations related directly to the health care system. Centers for Disease Control and Prevention CDC As an active arm of the federal government, CDC is tasked with promoting the public health through surveillance and epidemiologic research. It is programmatically involved in a wide range of public health initiatives from newborn screening to environmental monitoring. The Joint Commission TJC An independent, not-for-profit organization, TJC accredits and certifies health care organizations and programs in the United States. TJC certification is recognized nationwide as a symbol of quality that reflects an organization’s commitment to meeting certain performance standards. Other accrediting organizations include Healthcare Facilities Accreditation Program (HFAP) and Det Norske Veritas Healthcare, Inc (DNV-GL) Occupational Safety and Health Administration OSHA With the Occupational Safety and Health Act of 1970, Congress created OSHA, within the Department of Labor, to assure safe and healthy working conditions for working men and women by setting and enforcing standards and by providing training, outreach, education, and assistance. U.S. Food and Drug Administration FDA Federal regulatory agency responsible for controlling the safety and effectiveness of the country’s drug supply for both humans and animals. The FDA regulates food safety, cosmetics, feed supply for animals, dietary supplements and biologics as well as the national blood supply, medical devices, food additives, and product recalls. Environmental Protection Agency EPA Federal agency created to protect human health and the environment through the writing and enforcing of regulations based on laws passed by Congress. Health Insurance Portability and HIPAA An Act to amend the Internal Revenue Code of 1986 to improve Accountability Act portability and continuity of health insurance coverage in the group and individual markets, to combat waste, fraud, and abuse in health insurance and health care delivery, to promote the use of medical savings accounts, to improve access to long-term care services and coverage, to simplify the administration of health insurance, and for other purposes. Enacted in 1996 and consists of 5 titles.

Laboratories in the United States that process clinical 2012, but the cytology-specific initial mandates have not patient samples are regulated by the Centers for Medicare changed. & Medicaid Services (CMS) (Table 1). CMS accredits In addition to CMS, there are several other accredi- nearly all clinical laboratories, usually through the prox- tation organizations for cytopathology laboratories, ies of deemed status inspectors provided by professional including the College of American Pathologists (CAP)6 groups. For services to be covered by Medicare, there and the Joint Commission (TJC),7 both of which are needs to be compliance with the Clinical Laboratory CMS-approved accreditation organizations (ie, provide Improvement Amendments (CLIA) statute. CLIA was “deemed” status), so laboratories accredited by these passed in 1967 but has undergone several amendments. organizations are also CLIA-compliant.8 More recently, CLIA’88 was the result of a two-part exposé in the Wall the International Organization for Standardization has Street Journal in November 1987, with part 2 addressing developed standards for quality management systems; less than optimal practices in cytology laboratories.2 however, it does not audit or certify laboratories and CLIA’88 specifically addressed cytopathology labora- relies on third-party organizations to verify that the tory testing issues; cytology was classified as high- laboratory meets the relevant standards.9 Accreditation complexity testing, and cytology-specific mandates were organizations conduct onsite surveys of laboratories to introduced (Table 2). The final regulations were pub- ensure they meet the necessary requirements. Surveys lished in September 1992 and were implemented January must be conducted at least every 2 years to maintain 1, 1994.5 Additional amendments followed in 1997 and CLIA compliance. Depending on individual state

Table 2 Cytology specific mandates under clinical laboratory improvement amendments of 1988. CLIA’88 mandate Applies to Requirements Details High complexity All cytology tests All general mandates of high CMS in charge of overseeing testing complexity testing laboratories cytology and enforcing the apply to cytology regulations Personnel standards Cytotechnologists (CT) Graduate from CAAHEP accredited Screen and sign out negative Gyn, school of cytotechnology and except reactive/repair/ pass Board of Registry (ASCP) inflammatory exam Screen Non-Gyn/FNA Possess state license (in some Assist in FNA and ROSE states)a General Supervisor (GS) As above plus 3 years or more Prospective Q/C Rescreen (Gyn) and full time experience as CT 5 year retrospective review for HSIL/malignancy Day to day running of laboratory, work with TS for policies, procedures, etc. Technical Supervisor (TS)/ MD or DO with board certification in Participate in sign out of abnormal Medical Director (MD) Anatomic Pathology Gyn including reactive/repair (or combined Anatomic and and all Non-Gyn/FNA cases. Clinical) from the American Evaluate and set workload limits Board of Pathology Other medical director duties Workload limits Cytotechnologists and primary Slide screening limit Z 100 slides/ Every primary screener expected to screening pathologists 8 hour day, prorated/hour maintain records and not exceed (12.5/hr.) maximumb the assigned workload limit Applies to conventional and liquid which are evaluated and based preps. assigned every 6 months by TS FDA Workload recording:

Imaged Gyn slide without manual reviewZ 0.5 slide. Manual reviewZ1.0 þ 0.5 Z 1.5 slide Non-Gyn liquid based Z0.5 slide. Smear Z1 slide General supervisor Same as above Maintains own records and reviews other CTs Technical supervisorb Only if primary screener Ultimately responsible for CTs and GS and other screeners (if pathologist do primary screening) Hierarchical review To the pathologist: GS or TS or designee for Minimum 10% prospective rescreen of slides Gyn: reactive/repair and all Gyn prospective rescreen of negative Gyn to include epithelial cell abnormalities (min 10%) and HSIL/malignancy random and high risk cases All Non-Gyn/FNA cases look backs (retrospective review) Mechanism for resolving major including anal cytology Pathologists review and sign out all discrepancies between Gyn NILM/reactive, epithelial cell Pathologist/CT diagnosisc abnormalities and all Non Gyn/ Document results of rescreens and FNA cases any necessary remedial actions Rescreen function Gyn cytology Done by GS, supervisory level CT or 5 year review of previous NILM in designee. institution ﬁles if a new high TS in lab with one CT or no GS grade or malignancy is detected on Pap test Amended report issued by TS/ Pathologist only if it affects patients current clinical management (continued on next page)

Table 2 (continued) CLIA’88 mandate Applies to Requirements Details Performance CTs for Gyn and Non Gyn/ Done every 6 months by TS in Use individual stats evaluations FNA cytology consultation with GS Prospective and retrospective review misses, Cytotechnologist-pathologist variances, Benchmark data HPV þ rates for ASC-US Performance on PT and peer comparison program(s) Lab statistics Gyn and Non-Gyn/FNA At minimum, maintain by different For Gyn, specimen reporting types of specimens and categories diagnostic categories for For Non-Gyn/FNA, specimen types laboratory. Can do so by and reporting categories individuals Proficiency Any CT or pathologist who Annually for Gyn cytology. Federally To be taken in normal work setting testing (PT) reviews Gyn cytology mandated PT by CLIA '88 with For Non-Gyn/FNA cytology, penalties for failure. participation in peer comparison education programs and Four failures is considered a fail benchmarks encouraged by and reported to CMS accrediting agencies like CAP, No PT requirement for Non Gyn/ ASCP, etc FNA Cytology histology Gyn and Non-Gyn/FNA All high grade (Gyn) and Correlation is mandated; however, correlation cytology malignancy (Gyn and Non-Gyn) timelines and who does it are cases have to be correlated with not. histology and clinical An annual report should be information available. Can be real time or at a later date. Staining Gyn and Non-Gyn/FNA Use permanent stain like Temporary stains such as toludine Papanicolaou for Gyn, blue that fade should not be Papanicolaou and Diff QuikÔ for used Non-Gyn/FNA Slide retention Gyn and Non-Gyn 5 years for exfoliative cytology 5 years because of HSIL/Ca Pap test 10 years for FNA slides look back requirements FNA is a diagnostic test, hence requires longer retention Lab inspections Laboratory Every 2 years or Immediate if CMS, ASCT complaint or compliance issue CAP, TJC, others with CMS reported or adverse media “deemed” status publicity Abbreviations: TS, technical supervisor; GS, general supervisor; CAAHEP, Commission on Accreditation of Allied Health Education Programs; CAP, College of American Pathologists; ASCP, American Society for Clinical Pathology; Non Gyn, non-gynecologic cytology that includes exfoliative and fine-needle aspiration (FNA) specimens and cell blocks; ROSE, rapid on site evaluation; Gyn, gynecologic cytology (Papanicolaou tests). aFor CTs in practice prior to 1992. bIn a lab where the TS performs primary screening function. cMajor discrepancy Z 2 step category difference or if it makes a significant difference in clinical management. Adapted from Smith and Mody.4

requirements, a separate inspection conducted by staff of mock laboratory inspection under the laboratory director's/ the state department of health or similar agency may be supervisor’s oversight to become acquainted with the reg- required. ulatory information required to manage a cytopathology The CAP Checklists provide detailed measures for laboratory. laboratory quality management and quality control.6 Cyto- Table 2 outlines the cytology speciﬁc mandates under pathology fellows should be familiar with the Cytopathol- CLIA’88 that form the basis of the CAP Cytopathology ogy Checklist and the All Common Checklist and perform a Checklist.

Specific laboratory pre-analytic, analytic, and BD FocalPoint GS imaging system also offers location 12 post-analytic quality assurance measures in guided screening with 10 field of view capability. Work- cytopathology laboratories load limits and workload calculations for cytotechnologists and primary screening pathologists, including the US Food and Drug Administration (FDA)eapproved workload Specimen collection, receipt, and preparation calculation for semi-automated screening of gynecologic fi specimens and nongynecologic preparations, are required Fellows should be familiar with speci cs of collection and for compliance.13 transport of cytology specimens and have a good under- Human papillomavirus (HPV) testing may be performed standing of cytology preparatory techniques and know the in house in the molecular or cytopathology laboratory or basics of maintaining optimal technical quality in preparing sent to a referral laboratory. There are various types of high- and staining cytology specimens. All reagents are labeled risk HPV testing options, both DNA- and RNA-based. The for identity, titer, concentration, recommended storage, and relevance of testing only for high-risk viruses in cervical expiration date. The stains and working solutions are dated cancer prevention and the role of genotyping, especially when prepared and initialed by the person preparing the HPV16/18, should be reviewed.14,15 Another area of stain or solution; for commercial solutions the date they are importance in cervical cancer screening and management is received and opened is recorded. All stains and reagents are integration of HPV testing and its results with cytology, as it kept covered when not in use and stored at the proper fi relates to primary screening (HPV only and cotesting), temperature. Chemical safety, re prevention, and biosafety triage, and follow up.16-18 Cervical cancer screening is in hazard policies related to the laboratory specimen prepara- flux in the United States; trainees and practioners need to tion should also be reviewed. Each specimen should be fi keep themselves updated on new testing platforms and submitted with appropriate patient identi cation (a mini- evolving screening and management guidelines. mum of 2 unique identifiers), which should include the patient name, medical record number or date of birth, and, if Nongynecologic cytology applicable, the patient barcode for scanning the specimen Conventional preparations such as smears, touch imprints/ into the laboratory information system. crush preparations, and cytospins, as well as liquid-based methods are utilized for preparation of nongynecologic Gynecologic cytology specimens, including fine-needle aspiration (FNA), body Gynecologic specimens are processed separately from cavity fluid, cerebrospinal fluid, urine, bronchoalveolar nongynecologic specimens. Currently, most gynecologic lavage, bronchial brushing, and pancreaticobiliary brushing. cytology specimens are submitted in liquid based media, Giemsa-based (Diff-QuikÔ), Papanicolaou, and hematoxy- either ThinPrepÔ or SurePathÔ, although conventional lin and eosin staining protocols are used, with the former smears are acceptable for cervical cancer screening. For being utilized most commonly for rapid on site assessment. SurePath, cervical samples are collected using a broom-like Although diagnostic criteria are similar, morphologic device with a detachable head, which is placed in a vial with appearances vary in different preparations and stains. an ethanol-based preservative fluid and sent to the labora- Fellows should familiarize themselves with the differences, tory. The fluid and cells are then centrifuged to isolate the advantages, and limitations of each. An excellent way to cells from the fluid; the cells are re-suspended in a sucrose gain more experience with FNA cytology and core biopsy density gradient, followed by slide transfer using gravity for touch preparations is to use these techniques in the gross adherence. For ThinPrepÔ, the cervical specimen is room, autopsy suite, and during intraoperative consultation, collected using a Cervix BrushÔ, and the brush is rinsed in because this provides an additional real-time means of his- a vial with a methanol-based preservative fluid by the tologicecytologic correlation, especially for organ sites for caregiver. Cells are released by pushing the brush to the which the program may have low volumes in the cytopa- bottom and swirling the brush into the fluid. Subsequently, thology laboratory.18 Coverslipping methods and avoidance the brush is discarded. The specimen is sent to the labora- of artifacts such as “cornflaking” should be observed. There tory, where the cells are then isolated from the fluid by are a number of methods that can be used for preparation of vacuum filtration and are transferred to the slide using air cell blocks from nongynecologic and FNA specimens, pressure for adherence.10 Issues related to lubricant and including thromboplastin, Cellient, histogel, and collodion blood interference with adequacy of ThinPrep testing bag.19 require quality-assurance measures with respect to Pathologist-performed FNA, with or without ultrasound educating providers and use of glacial acetic acid, respec- guidance, is part of fellowship training and requires super- tively. Fellows should familiarize themselves with use of vision from the attending pathologist(s). A TJC mandated automation in cytology preparation and screening, including “time out” procedure for correct identification of the patient basic principles of the ThinPrepÔ imaging system/selection and biopsy site is required at the beginning of these pro- of 22 fields of view and the BD FocalPoint GSÔ imaging cedures. When an FNA biopsy is performed, the first step is system that uses algorithms to determine potential.11 The to verify the patient’s identity using at least 2 identifiers,

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Secondly, the procedure site must be properly changes, indications for using these tests, and testing marked to identify the area of the patient’s body that is to be methodologies used in various tumors originating from the aspirated, and before the procedure starts, a third step or lung, thyroid, colon, gastroesophageal junction, skin (mel- "time out" is initiated by the physician conducting the anoma), and so on, should be part of the cytopathology procedure to give all members of the clinical team an op- training curriculum. portunity to perform a final verification of the correct patient, correct procedure, correct side, correct site, correct Cytology histology correlation patient position, and availability of any special equipment The cytopathology laboratory should have a program for that is needed for the procedure. The "time out" can be correlating histologic cases that are associated with cyto- documented either as a note in the patient’s medical record, logic specimens. There is no standard method for this or by incorporating it as part of the FNA report.20 The quality assurance activity, although ideally all cytology re- fellow should learn to observe, practice, and document this ports with corresponding surgical pathology follow-up “time out” process. In programs where pathologists do not should be reviewed and discordant cases undergo review perform FNA, training with a radiologist can be offered; of the cytology and histology slides.27 In some laboratories, certification and/or continuing education courses conducted the term “error” is avoided because of negative connota- by professional organizations such as the CAP and Amer- tions; alternative terms, such as discrepancy or variance, can ican Society of Cytopathology are also available. be used. It is well established that colposcopy and biopsy Fellows should be familiar with the requirements for are not gold standards, and follow-up is warranted if biopsy sample adequacy techniques for preparation of good FNA following a high grade/malignant cytology is negative. smears, collection methods/preservation of cytologic speci- Findings from the cytologicehistologic review should be mens for molecular testing, and other relevant ancillary documented and classified as sampling or interpretation testing such as thyroglobulin, parathyroid hormone, flow variances. The majority of cytologicehistologic variances cytometry, and cytogenetics. are due to sampling, either on cytology or on histology. Interpretation variances can further be subclassified as mi- Diagnostic interpretation nor and major, and at least major variances should be shared with the involved cytotechnologist and/or pathologist. Dis- Cytopathology specimens typically undergo screening by crepancies may also be due to locator problems, where a cytotechnologists before final sign-out by a pathologist. The lesion may not have been identified due to the observer not screening process involves locating and marking cells of visualizing the area of interest. The course of action will diagnostic interest. Gynecologic cytology slides that are vary based on the nature/timing of detection of the variance. identified as negative for intraepithelial lesion or malig- Amended reports are only warranted if current patient care nancy (NILM) can be signed out by a cytotechnologist. Any is impacted.28 Follow-up letters may be issued to clinicians, case with reactive/reparative changes or epithelial cell ab- especially in major cervical cytologyehistology sampling normality requires triage to a pathologist for final interpre- variances. This is an excellent educational opportunity, and tation. Nongynecologic, anal cytology, and FNA cases can cytopathology fellows should be involved in reviewing also be screened by the cytotechnologist, but must be signed these cases to appreciate its significance for laboratory out by a pathologist. quality assurance and patient management. Criteria for diagnostic interpretation of gynecologic, nongynecologic, and FNA are an essential part of the core Management implications of cytopathology results fellowship curriculum. There are a number of well- established standardized cytology reporting systems used Fellows should understand the clinical implications of in clinical practice. Examples include the Bethesda systems cytopathology interpretations for screening and diagnostic for cervical cytology and thyroid cytology, and more recent tests. Several professional organizations have screening ones such as the Papanicolaou Society of Cytopathology and/or management guidelines tailored to specific cytopa- guidelines for pancreatobiliary cytology, the Paris system thology/surgical pathology testing methods and/or for urinary cytology, the Milan system for salivary gland interpretations. Examples include screening and manage- cytology, and the Lower Anogenital Tract Standardized ment guidelines for cervical cancer from the American Terminology for reporting HPV-associated squamous le- Society for Colposcopy and Cervical Pathology and for sions of the lower anogenital tract. Trainees should be thyroid FNA from the American Thyroid Association.16,29 familiar with these reporting systems and their implications Knowledge of recent, relevant developments in compan- for patient management.21-26 ion diagnostics for targeted therapies and prognostic and Results of ancillary studies such as immunohistochem- therapeutic ancillary studies is an important part and parcel of istry, flow cytometry, and molecular testing, when available, clinical practice. Familiarity with preventive measures such should be reviewed and correlated with morphology for as HPV vaccinesdtheir composition, delivery indications, final interpretation of cases, and such results should be role in prevention of cervical cancer, and impact on the

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Federally mandated gynecologic cytology proficiency testing Additional laboratory management essentials for cytopathology fellows Under CLIA’88 guidelines, each laboratory involved in gynecologic cytology must enroll in an approved profi- Test validation and verification ciency testing program, and individual cytotechnologists and pathologists involved in screening and/or evaluating Clinical laboratory tests are classified into waived and nongynecologic cytology are required to pass a CMS-approved waived tests by CLIA’88. Before any non-waived test is gynecologic proficiency test annually.31 The test set must implemented for clinical use, vigorous validation or verifi- contain at least 1 slide from each of the following 4 cation is required. The process of validation/verification Bethesda interpretation categories: unsatisfactory, NILM, requires the clinical laboratories to conduct and carefully low-grade squamous intraepithelial lesion (LSIL), and high- document designed experiments/studies to evaluate the new grade squamous intraepithelial lesion (HSIL)/cancer. Each assay and its performance characteristics to ensure reliable, cytotechnologist receives a 10-slide test to screen in the reproducible, and accurate results for the intended application. same manner as they do patient specimens, and write their For tests approved by the FDA, CLIA requires interpretation on their score sheet. Physicians who perform verificationda laboratory must demonstrate its ability to any primary screening (screen slides that have not been pre- obtain performance specifications, including accuracy, pre- screened by a cytotechnologist) must be tested in the same cision, reference range, and reportable range (Table 3), manner as a cytotechnologist. Physicians who examine established by the manufacturer during the FDA trial. For slides after they are pre-screened by a cytotechnologist may tests that have not been cleared or approved by the FDA, or choose a set of test slides that have been previously screened those tests developed in-house (laboratory-developed test and dotted by cytotechnologists or they may examine a set [LDT]) and FDA-cleared/approved tests modified by the of slides that have not been previously screened and dotted. laboratory, CLIA requires validationda laboratory must If the physician chooses to examine a pre-screened set, the provide objective evidence through a defined process that a cytotechnologist’s diagnosis will accompany the test set. A test performs as intended.34,35 In addition to the 4 perfor- passing score for all test takers is 90%, although the scoring mance specifications that are required for FDA cleared/ grid differs for cytotechnologists and pathologists. Primary approved tests, the laboratory is expected to determine an- screening pathologists are graded using a pathologists’ alytic sensitivity, analytic specificity including interference, grid.31 Initially, individuals are required to take a 10-slide and any additional relevant performance characteristics test; and if they pass they do not need to be tested again (specimen stability, linearity, etc) (Table 3). until the following year. If the individual fails the first 10- For laboratory tests in which the outcome variable is slide test, they must take a 10-slide retest within 45 days binary (eg, high-risk HPV status), the most commonly used after notification of test failure. If the individual fails the measures of performance include sensitivity, specificity, second 10-slide retest, they must obtain documented, positive (PPV) and negative predictive values (NPV); all of remedial training in the area of test failure, which will be which can be estimated by constructing a 2 2 contingency noted on the test results letter. All Papanicolaou tests table and determining the number of true positive (TP), true screened by the individual subsequent to the notification of negative (TN), false positive (FP), and false negative (FN) second failure must be re-examined, and the individual must from the validation data set. It is important to recognize that successfully pass a 20-slide test. If the individual fails the PPV and NPV vary depending on the prevalence of the third, 20-slide, test, they must cease examining gynecologic disease being tested, whereas, sensitivity and specificity do cytology immediately upon notification of failure, and not. By plotting the TP rate (the sensitivity) against the FP obtain at least 35 hours of documented, formally structured, rate (equivalent to 1 e [specificity]), one can obtain the continuing education in gynecologic cytology, and suc- receiver operator characteristic (ROC) curve. Each point on cessfully participate in another 20-slide proficiency test. the ROC curve represents a sensitivity/specificity pair that This final cycle can continue until the individual success- corresponds to a particular cutoff point for a particular assay. fully participates in another 20-slide test. This measure was By calculating the area under each ROC curve (AUC), one finally implemented nationwide in 2005. Since 2008, the can compare the ability of two or more tests to discriminate failure rate has been at 2% to 3% for cytotechnologists and between the two outcomes; the larger the area under the pathologists who are secondary screeners and 8% to 12% curve, the better the discriminatory ability of the test. for primary screening pathologists.32 Cytopathology fellows Cohen’s kappa statistic can be used to determine the degree and residents are exempt from proficiency testing during of agreement between two tests that yield categorical or training and in the year in which they receive board ordinal data that can be compiled in N N tables. Kappa

Table 3 Definition of performance specifications as related to validation and verification. Performance specifications Definitions Accuracy The closeness to the “true” value the new method can achieve by comparing the results of the new method with known values from the reference sources, another certified laboratory’s results, or with results from the current method. Precision (reproducibility) The ability of the new method to duplicate the same results “between runs” (ie, will the test have the same result for the sample on different runs on different days?) and also “within run”. Reportable range The highest and lowest test values that can be analyzed while maintaining accuracy. For tests depending on a cutoff value to determine positive results, testing positive specimens near the cutoff can serve as the cutoff validation. Reference range Normal values provided by the manufacturer or published from textbooks or scientific articles and can be verified by running known normal patient samples provided that the laboratory has a similar patient population. Analytic sensitivity The lowest concentration of the analyte that the test can reliably detect as positive in the given matrix. Analytic specificity The ability to detect only the analyte that it is designed to identify or quantify in the presence of interfering or cross-reactive substances. scores range from 1 to 0, with 1 indicating perfect agreement practice, allowing cytologists to remotely evaluate cyto- and 0 indicating no agreement. For tests that yield contin- logic preparations without being locally tethered to a uous data, paired t test and linear regression are often used conventional light microscope. One challenge of WSI for comparing the levels of performance between two assays. unique to cytology is the difficultyinfocusingoncytology Neither CLIA nor CAP specify requirements for valida- material as a result of obscuring material or presence of 3- tion or verification with regard to number of samples, dimensional cell groups; one solution is to perform z- criteria of acceptability, statistical analysis, and so forth. stacking of multiple images in different vertical (focal) Therefore, laboratory directors are responsible for deter- planes. Telecytology has been increasingly utilized for mining these specifics. In general, validation for a LDT or rapid onsite evaluation at remote locations and can be modified FDA cleared/approved test generally entails larger performed using static images, real-time video streaming studies with more samples than are required to verify a FDA with or without the use of robotic microscopy, or WSI. If a cleared/approved test.35 There are a few exceptions; for laboratoryisinvolvedinadequacyassessmentofFNAsat example, CAP specifies the minimum number of samples an offsite location, then telecytology may be utilized by the required for the validation of HER2, ER, and PR tests as pathologists for assessing adequacy of the specimen. The well as the minimum concordance acceptability threshold laboratory must perform a validation study for the tele- for ER/PR in breast carcinoma tissue. cytology system utilized and train each cytotechnologist and pathologist who participates in this process.37,38 A billing process with adequate documentation should also Informatics and telemedicine be established. Fellows should also familiarize themselves with principles of microscopy, including Köhler illumi- The laboratory information system (LIS) is a critical tool in nation, photomicroscopy, and scanning of slides. The latter fl work ow management, specimen tracking, patient infor- are increasingly used for archiving and documenting in- mation archiving, accurate and timely delivery of cytology formation about cases. reports to providers, as well as facilitation of quality management and regulatory compliance for clinical practice. The LIS consists of both hardware and software compo- Statistics nents. LIS software comprises a database management system that manages a central, relational database and LIS Practicing pathologists routinely use statistics when signing hardware includes computers such as servers and worksta- out cases, interpreting ancillary test results, reviewing the tions as well as peripheral devices such as printers, barcode literature, and conducting research. For example, when readers, and so on. An interface connects the LIS with in- signing out a case, a differential diagnosis is considered, after struments, such as imaging systems or HPV testing taking into consideration the clinical history, morphology, instruments, and other information systems such as the and results of applicable ancillary studies. Statistics under- electronic medical record system.36 line the composition and ranking of such a list. Statistics are Increasingly, digital imaging, including the use of static also frequently utilized in research to design a study, analyze images, real-time video streaming, and whole slide imag- results, and evaluate validity of the study. The following is ing (WSI), is incorporated into clinical cytopathology not intended to be an extensive review of statistics but to

Table 4 Examples of types of analysis and the corresponding statistical tests. Types of analysis Parametric tests Non-parametric tests Estimate the degree of association between Pearson correlation coefﬁcient39 Spearman correlation coefﬁcient40 2 quantitative variables Compare means between 2 distinct/independent groups 2-sample t-test Mann-Whitney test41 Compare means between 3 or more distinct/independent ANOVA Kruskal-Wallis test42 groups Compare 2 quantitative measurements taken from the Matched-pair t-test Wilcoxon test43 same individual

provide a study framework for achieving a working under- distributed. On the contrary, nonparametric statistical pro- standing of statistics applicable to cytopathology (Table 4). cedures do not rely on the assumptions about the shape of In the process of designing the study, one would generate distribution of the underlying population and are widely a question or a hypothesis, which is followed by devising a used for studies with nominal and/or ordinal variables, such method for testing the hypothesis as well as estimating the as comparing the nuclear grades of ER-positive and ER- minimal sample size (ie, statistical power analysis) that will negative breast carcinomas. have the power, usually 80%, to reject the null hypothesis. A contingency table or cross tabulation47 shows the Hypothesis testing starts with proposing a null hypothesis observed frequencies of data elements classified according (there is no difference, there are no effects, etc.). The to two variables with rows representing one variable and P value,orlevel of significance, is the probability of falsely the columns indicating the other variable; it is used for rejecting that null hypothesis or the type I error rate (a). examining relationships between categorical (nominal or P values should almost always be 2-sided. In contrast, type ordinal) variables. The c2 test48 is the most common test II error rate (b) is the probability of falsely accepting the for evaluating the null hypothesis that 2 categorical vari- null hypothesis; the power to reject the null hypothesis is ables are independent by determining whether there is any defined as 1 minus b. significant difference between the expected and observed It is important to be familiar with variables (ie, things frequencies in one or more categories. Fisher’s exact test49 that can be measured, manipulated, and analyzed) when should be used instead of the c2 test when the expected conducting research. Variables can be classified as nominal, numbers are small; the usual rule of thumb for deciding ordinal, interval, and ratio according to the type of mea- whether the former is more suitable is when the expected surement scale. Descriptive statistics are used to quantita- values in any of the cells of a contingency table are less tively describe or summarize variables and include mean, than five. median, range, standard deviation, confidence interval, and Concordances and reproducibility analyses are shape of the distribution. Typically, one would be interested commonly used in pathology studies and include several to know how well the distribution of a variable can be methods such as percent agreement, intraclass correlation approximated by the normal distribution (ie, symmetrical coefficient, and kappa statistics. Intraclass correlation co- distribution). The confidence interval is a type of interval efficient50 deals with continuous variables and is suitable for estimate of a variable or parameter, whereas the confidence comparing two methodologies of instruments for measuring level refers to the frequency/probability that the observed quantitative data in question and when the question of how interval contains the true variable if the experiment is closely these methods or instruments agree arises, whereas repeated. The confidence level is the complement of the the kappa statistic51 is suitable for assessing the degree of level of significancedfor example, a 95% confidence in- agreement between two raters for categorical (nominal) terval equates a significance level of 0.05. ratings. When comparing ordinal ratings, one may wish to When analyzing continuous (interval or ratio) data, the use weighted kappa, namely, assigning less weight to most frequently used statistical tests are Student t test,44 agreement as categories are further apart (eg, when evalu- which is used to determine whether two sets of data are ating cervical Papanicolaou tests, a disagreement of NILM significantly different from each other; ANOVA,oranalysis versus ASC-US could still be considered as partial agree- of variance,45 which is used for comparing 3 or more sets of ment, but a disagreement of NILM versus HSIL would be data for statistical significance; and linear regression,46 counted as no agreement). which is used for modeling the relationship between a Regression analysis52 is used to determine which inde- dependent variable and one or more independent variables pendent variables are related to the dependent variable and and is represented by Pearson correlation coefficient.39 to explore the forms of these relationships. It is often used These parametric statistical procedures rely on the for predicting and forecasting the outcome of a categorical assumption that the underlying populations from which the variable of interest. The simplest form is simple linear samples derived are normally, or at least symmetrically, regression,53 which involves one independent variable (x)

Downloaded for Anonymous User (n/a) at SAN FRANCISCO VA MEDICAL CENTER from ClinicalKey.com by Elsevier on January 14, 2020. For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved. Laboratory management curriculum for cytopathology training 71 and a linear relationship between x and the dependent problems involving a privileged provider are identified variable (y); the null hypothesis is that no linear relationship (either through the OPPE process or by any other means, exists between x and y. Multiple linear regression involves such as complaints or significant alteration from accepted multiple independent variables (x1, x2, ., xp). Logistics practice). The FPPE process should be clearly defined and regression54 relates a binary outcome to one or more in- documented with evaluation criteria and a monitoring plan. dependent variables or predictors. The process should be performed in predetermined dura- Survival analysis55 refers to statistical methods for tions and have measures for acceptable performance. analyzing longitudinal data on the occurrence of dichotomous The PPE is based on evaluation of the 6 events (yes/no) such as death, development of tumor recur- competenciesdpatient care, medical knowledge, practice- rence, and so forth. It can be used for randomized clinical trial based learning and improvement, interpersonal and or cohort study design, both prospective and retrospective. communication skills, professionalism, and systems-based Some of the tools include Kaplan-Meier curves56 for practicedthat were originally defined in 1999 by the describing the survival times of members of a group, log-rank Accreditation Council for Graduate Medical Education test57 for comparing the survival times of two or more groups, (ACGME) and the American Board of Medical Specialties and Cox proportional hazards regression for describing the (ABMS) for outcome-based evaluation of residency training effect of categorical or quantitative variables on survival. The programs. The methodology and the timing of the evalua- reader is referred to additional resources.58-61 tion are mostly left up to the individual organizations, although many perform OPPE every 6 months. It is the Physician/professional regulation organized medical staff of the health care organization that ultimately must approve the number and type of metrics monitored for any individual practitioner or group of similar In order to practice pathology, having successfully finished practitioners. In addition, although TJC recommends that an medical school and postgraduate training in pathology is the OPPE/FPPE program be organized into these 6 compe- basic requirement. If practicing in the United States, a tencies, it is not required that all 6 areas be monitored for a physician must also have a valid medical license in the state given practitioner.63,64 of the practice (or any state if practicing for the federal government), have the required credentials for the privileges they will need for credentialing by the hospital medical staff fi office, and ideally be board-certified by the American Board Certi cation by the American Board of Pathology of Pathology. Table 5 defines and explains these steps. (ABP)

In June 1935, the American Medical Association (AMA) Professional practice evaluation (PPE) Section on Pathology and Physiology and the American Society for Clinical Pathology (ASCP) appointed commit- Throughout the education and certification process, a phy- tees that together considered the feasibility and desirability sician’s skills and knowledge are assessed. For decades, of establishing a national certifying board. In May 1936, physician evaluation by hospital medical staff offices the ASCP and the AMA Section on Pathology and Physi- occurred every 2 years with a subjective and often mini- ology accepted the proposed bylaws, authorized the malistic approach to renewal of privileging and credential- nomination of 4 members each to the ABP, which was ing. In 2007, TJC announced a new requirement for incorporated in Michigan. Approval of the ABP was hospitals to evaluate their providers objectively and regu- granted by the Advisory Board for Medical Specialties larly.62 This TJC mandate included two forms of evaluation: (ABMS) and the AMA Council on Medical Education and Ongoing Professional Practice Evaluation (OPPE) and Hospitals. On July 19, 1936, the ABP met for the first time Focused Professional Practice Evaluation (FPPE). OPPE in Chicago. The mission of the ABP, as a member of the was intended to be a means of performance evaluation ABMS, is to promote the field of pathology and the conducted on an ongoing basis, and must occur more continuing competency of practicing pathologists. The frequently than every 12 months. The aim was to monitor ABP does not confer a legal qualification or license to competency, identify areas for improvement, and use practice pathology, does not delineate who may or may not objective data in decisions for continuation of privileges. engage in the practice of pathology or obtain hospital OPPE information is factored into the decision to maintain, privileges, nor does it define the scope of specialty practice. revise, or revoke existing privileges at the time of renewal. After successful completion of ACGME or RCPSC- FPPE involves more specific and time-limited monitoring of accredited training, obtaining a full and unrestricted medi- performance and is used specifically in the following situ- cal license, and passing a rigorous examination, a pathol- ations: (1) when a provider is granted privileges for the first ogist can become a diplomate of the ABP. The ABP time, (2) when additional/new privileges are requested for nominates pathologists to serve in 4 positions on the an already privileged provider, and (3) when performance ACGME Residency Review Committee, and thus

Table 5 Glossary of terminology for credentialing, licensing, privileging, and board certification. Terminology Definition Examples/explanatory notes Credentials The physicians’ postgraduate training and A physician with residency training in Anatomic and background should be appropriate for the services Clinical Pathology has acquired the credentials to he/she will perform. perform the duties of a pathologist practicing in either Anatomic or Clinical Pathology. Of note, a physician does not need to be board certified to practice, but he/she does need to be licensed in the state they practice. Credentialing The process used to evaluate and verify a physician’s Credentialing is performed by the medical staff office qualifications and competence to practice of the specific institution at which the physician medicine at a specific institution or hospital. will be practicing. It usually requires a multitude of forms to be filled out by the physician to include demographic information, training, previous work, licensure information, continued medical education to upkeep the licensure, and legal issues regarding licensing, physician’s practice, etc. Privileges The services and procedures that are within the Privileges can be highly specific (e.g., ultrasound- physician’s scope of practice. guided fine-needle aspiration) or can be more general (e.g., performing fine-needle aspiration). If they are highly specific, they can be grouped by common or like procedures into “privilege bundles”. Privileging The process in which a hospital determines the Usually for privileging, the referees determined by services and procedures that a physician is allowed the physician are queried for the competency of to perform in the hospital. This usually occurs after the physician for the required privileges. In the hospital has verified the physician’s addition, verification of training is completed from credentials. information provided by the postgraduate program from which the physician graduated. Licensing Medical licensing is the procedure that the state In the United States, in order to practice medicine a medical boards in the U.S. uses to license and physician must have a valid license in the state discipline allopathic and osteopathic physicians. they are practicing. The federal government does In some jurisdictions, other health care not grant licenses. This usually requires professionals, other than physicians (e.g., verification of graduation from medical school and physician’s assistants) can also be licensed by the postgraduate training among others. Individual state medical board. states may have different regulations to confer a medical license. Board Certification The American Board of Pathology (ABP) certifies The ABP certifies physicians in Anatomic and Clinical physicians who have successfully completed ACGME Pathology, Anatomic Pathology, Clinical or Royal College of Physicians and Surgeons of Pathology, and 11 subspecialties. Certification Canada (RCPSC) accredited postgraduate training requirements can be found in the ABP Booklet of in pathology and have successfully passed the Information at www.abpath.org. examination administered by the American Board of Pathology.

participates in the review of pathology training programs pathology. The program requires ongoing assessment of the and assists in setting training program requirements.65 6 competencies adopted by the ACGME and the ABMS to ensure that all aspects of practice are evaluated and Maintenance of certification for pathologists outcomes are measured. As of January 1, 2006, all primary and subspecialty certificates issued by the ABP are time- Maintenance of certification (MOC), or continuing certifi- limited, and diplomates are required to participate in the cation, assists physicians in maintaining standards necessary MOC program to maintain their certification. Continuing for them to provide quality care throughout their careers. In certification status is contingent upon meeting all addition, it assures the public that the physician is requirements and deadlines of the program during each committed to lifelong learning and competency in 2-year MOC cycle.66,67

As of 2017, the ABP’s MOC program consists of 4 parts: Papanicolaou test is defined as a screening (routine) test. A Papanicolaou test is considered a screening (high-risk) Part I e Professionalism and Professional Standing: The test when the patient has a history of early onset of sexual diplomates must hold a valid, unrestricted medical li- activity (<16 years old), a history of 5 or more sexual cense, meet the ABP’s professionalism expectations, partners, a history of HIV infection, or is the daughter of a and abide by the AMA’s or the American Osteopathic woman who used diethylstilbestrol during pregnancy. Association’s Code of Ethics. Conditions that define a diagnostic Papanicolaou test Part II e Lifelong Learning and Self-Assessment: The include significant complaints, signs or symptoms in the diplomates must meet the ABP’s learning and self- female reproductive system, prior history of vaginal, cervi- assessment requirements. cal, or uterine cancer, or current abnormal findings of the Part III e Assessment of Knowledge, Judgment, and vagina, cervix, uterus, or ovaries. Of note, only the referring Skills: The diplomates must assess their pathology spe- physician can classify a Papanicolaou test as either cific knowledge, judgment, and skills by passing a secure screening (routine), screening (high-risk) or diagnostic. examination once every 10 years. When the cytology laboratory realizes that the referring Part IV e Improvement in Medical Practice: The diplo- physician may have ordered the Papanicolaou test incor- mates must engage in specialty relevant performance- rectly, the lab should contact the referring physician and in-practice assessment and improvement activities. amend the order only after obtaining authorization to do so. The reasons that these definitions are important is that billing for the test depends upon its classification. Only Billing and coding with applicable health care diagnostic Papanicolaou tests are given a CPT code, laws whereas routine and high-risk screening Pap tests are given HCPCS codes for billing purposes. In order for laboratories to receive payment from CMS and With regard to FNAs performed by a clinician in which TriCare, they must maintain a CLIA certificate, adhere to the pathologist performs a rapid on-site evaluation, each CLIA’88 regulations, and be reaccredited by the CAP or the decision that a pathologist makes that results either in the TJC every 2 years. When a laboratory submits a claim to bill continuation or conclusion of the procedures is termed an for a laboratory test, the claim must include the date and “evaluation episode”. Each evaluation episode must be location of the service, a procedure code, and an International carefully documented during the FNA procedure, as one or Classification of Diseases, 10th revision, Clinical Modifica- more needle passes may be part of a single evaluation tion (ICD10-CM) code, which is used for medical necessity episode. The first evaluation episode of an FNA performed justification. There are two types of procedure codes for the by a clinician with slides reviewed by a pathologist is coded service(s) being billed. One common terminology used in the as 88172, and each additional evaluation episode is coded as United States is the current procedural terminology (CPT), 88177. Of note, these codes are only used when the clinician which is owned and maintained by the AMA. Each laboratory is performing the FNA. Pathologist-performed FNAs without (“technical”) and physician (“professional”) service provided image guidance are coded as 10021 and those performed with by the cytopathology laboratory has an associated 5-digit CPT image guidance are coded as 10022. For pathologist- code, and these codes are published annually by the AMA, performed FNAs, only a single 88172 should be billed, with new codes added and old codes deleted. Occasionally, regardless of how many passes or evaluation episodes are guidance or clarification is provided on certain codes during performed. The initial evaluation episode for touch prepara- the year, in between annual updates. For the most current code tion rapid on-site evaluations of core-needle biopsies per- listing, please see the most recent edition of the AMA CPT formed by a clinician is coded as 88333, with each additional Professional code book. evaluation episode being coded as 88334. The code for FNA Table 6 lists representative relevant CPT codes in interpretation and report is 88173, and this should not be cytopathology. billed if the specimen received is completely acellular. Another coding system that is maintained by CMS are Additional rules relevant to billing in cytology are the fact the Healthcare Common Procedure Coding System that codes 88108 (concentration technique) and 88112 (se- (HCPCS) codes, which are used to describe supplies, drugs, lective cell enhancement) cannot be billed together on the and other services that are not included in CPT codes. The same part. In addition, 88112 (selective cell enhancement) only HCPCS codes that are applicable to cytology are those and 88173 (FNA interpretation and report) cannot be billed for routine and high-risk screening Papanicolaou tests, together. Additional information on billing and coding prac- which are summarized in Table 7. A Papanicolaou test is tices in cytopathology can be found in relevant textbooks. classified as either screening (routine), screening (high- risk),ordiagnostic for CMS purposes. When a woman has Stark Law no current abnormal signs or symptoms within the female reproductive system, no prior abnormal Papanicolaou tests, The Stark Law68 addresses physician self-referral for CMS and no high-risk factors for cervical or vaginal cancer, the patients. From section 1877 of the Social Security Act, it is

Table 6 Representative relevant CPT codes in cytopathology. Code Description 88164 Technical component for diagnostic Papanicolaou smears 88142 Technical component for diagnostic liquid-based Papanicolaou tests 88141 Professional component for diagnostic Papanicolaou tests (both smears and liquid-based tests) 10021 FNA performed by a pathologist without image guidance 10022 FNA performed by a pathologist with image guidance 76942 Use of ultrasound for needle placement 88172 FNA adequacy assessment first episode by a pathologist 88177 FNA adequacy assessment each additional episode by a pathologist 88333 Touch prep evaluation initial episode by a pathologist 88334 Touch prep evaluation each additional episode by a pathologist 88173 FNA interpretation and report 88120 UroVysion FISH interpretation by pathologist with manual review 88121 UroVysion FISH interpretation by pathologist with computer-assisted technology 88104 Direct smear. 88108 Concentration technique (cytospin) 88112 Selective cell enhancement for non-gynecologic specimens (ie, ThinPrep SurePath) 88305 Level IV e Surgical pathology gross and microscopic examination (cell block and some core biopsies); certain core biopsies may be coded as 88307 (Level V) 88312 Special stains for microorganisms 88313 Other histochemical stains (ie, mucin) 88342 Immunohistochemical stains first stain (qualitative) 88341 Immunohistochemical stains each additional stain (qualitative) 88360 Immunohistochemical stains (quantitative) 88321 Review of outside slides Abbreviations: FISH, fluorescence in situ hybridization; FNA, fine-needle aspiration. named after Congressman Pete Stark who sponsored the practice of medicine, particularly in relation to physician first version of the bill. The law states that a physician may participation in managed care networks and the accompa- not refer patients to an entity for a designated health service nying complexity of payment arrangements. Phase III of the (DHS) if the physician or his or her immediate family Stark law, which excludes some of the banned DHS and member has a financial relationship with the DHS, unless an repeals the prohibitions based on compensation arrange- exception applies. The goal of the law is to prevent physi- ments in Stark II, was published on March 26, 2008. cian self-referrals and limit overutilization of services that drives up health-care costs. Stark I, effective January 1, The Sunshine Act 1992, prohibits physician self-referral for clinical laboratory services for Medicare patients. Stark II expanded the regu- The Physician Payments Sunshine Act69 is a health care lations under Stark I to include both Medicare and Medicaid reform law that was a component of the Affordable Care patients and introduced further restrictions regarding Act signed into law in 2010. As a part of this Act, medical self-referral for additional DHS beyond clinical laboratory product manufacturers and global purchasing organizations services. The law specifically states that if an entity provides (GPOs) are required to report any payments or other a DHS by an inhibited referral, the entity may not submit a transfers of value given to physicians (doctors of medicine, claim to Medicare for that service. Likewise, no Medicare osteopathy, dentistry, optometry, podiatry, and chiropractic payments will be made for DHS claims under a prohibited medicine) or teaching hospitals to the CMS. The medical physician referral. When Stark II passed, concerns were product manufacturers include companies that manufacture raised with regard to the intrusion of this legislation into the pharmaceuticals, medical devices, and biologics. The

Table 7 Representative HCPCS procedure codes for screening (routine and high-risk) Papanicolaou tests. Code Description P3000 Technical component for screening Papanicolaou smears P3001 Professional component for screening Papanicolaou smears G0123 Technical component for liquid-based screening Papanicolaou tests G0124 Professional component for liquid-based screening Papanicolaou tests

Downloaded for Anonymous User (n/a) at SAN FRANCISCO VA MEDICAL CENTER from ClinicalKey.com by Elsevier on January 14, 2020. For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved. Laboratory management curriculum for cytopathology training 75 manufacturers and GPOs began to collect data on August 1, underlining medicolegal issues, making this type of litigation 2013, and were required to report the data electronically to part of tort law. A person who alleges a pathologist showed CMS by March 31, 2014. They must report the following negligent medical malpractice must prove four elements: (1) data elements to CMS: (1) physician name, (2) business a duty of care was owed by the pathologist; (2) there is a address, (3) National Provider Identification (NPI) number, breach of the applicable standard of care; (3) the person (4) state license and license number, (5) physician specialty, suffered a compensable injury; and (4) the injury was in fact (6) payment amount, (7) payment date, (8) payment form, and proximately caused by the substandard conduct. The (9) payment nature, and (10) name of related covered drugs burden of proving these elements is on the plaintiff (ie, pa- and devices. tient) in a malpractice lawsuit. The standard of care,defined Of note, there is no reporting requirement for physicians as the level of care delivered by a reasonably competent as a part of this act, and therefore no penalty for physicians pathologist in similar circumstances, is determined based on under this law. the testimony of expert witnesses who are responsible for (1) defining a standard of care, (2) determining whether the standard of care was breached, and (3) determining whether Malpractice in cytopathology any injury or harm was caused by the breach. To qualify as an expert witness, a pathologist must have sufficient knowledge, The Doctors Company, a physician-owned professional lia- education, training, and/or experience relevant to the specific bility insurance company in Napa, California, is one of the issue presented before the court. nation’s largest insurers of physician and surgeon liability. Pathologists are strongly advised to notify their risk Their records showed that pathology is a low-claim frequency management office or malpractice insurer at the first indi- specialty, and the “average” pathologist had a claim every 12 cation of any potential medicolegal concerns with a case, years. Types of pathology claims include false-negative although a pathologist’s formal involvement in a malprac- diagnosis of cancer, false-positive diagnosis of cancer, and tice lawsuit begins only with the service of a summons, systems error. Many are frivolous and companion claims that which includes a statement of the plaintiff’s complaint. do not pay indemnity, and the pathologist is not the focus.70 Discovery takes place after a lawsuit has been filed and Although not all medical errors result in litigation, a survey of before the trial begins; it refers to the exchange of infor- legal claims is one method of identifying errors that generate mation concerning the lawsuit between plaintiff and adverse outcomes. Kornstein, in a review on medicolegal defendant. One frequently used method of discovery is aspects of pathology, identified records of 171 pathology deposition, which consists of testimony of a witness taken legal cases from 1988 through 2005. Nearly half involved under oath before a court reporter. A claim is a demand for surgical pathology; among the remainder, cytology cases payment. A verdict is an award by a jury. A settlement,in slightly outnumbered those pertaining to clinical pathology.71 this context, is an agreement between the disputing parties Among the 48 cases related to cytology, 37 involved false- to resolve a civil case through a negotiated solution. negative cervical cytology; less common were cases related Good practices prevent errors! These include but are not to FNA of the breast, FNA of the thyroid, and FNA/exfoli- limited to the following: (1) Comprehensive quality assur- ative lung cytology. Gynecologic cytology has ranked among ance plan for the laboratory to limit pre-analytic, analytic, the top three causes of pathology litigation, although it has and post-analytic errors. (2) Appropriate use and integration decreased in frequency in the past several years, likely due to of validated ancillary studies (special stains, flow cytometry, utilization of liquid based preparations, HPV testing, auto- immunohistochemistry, molecular testing). (3) Adequate mation, use of standardized Bethesda reporting terminology, consultation in difficult, unusual cases and review of high and management guidelines that are synchronized with grade and malignant diagnosis by a second pathologist. (4) reporting terminology. Additionally, practices now have Complete, clear and concise reporting with use of more subspecialty-boarded pathologists, and there are newer, standardized terminology, appropriate use of addendums more stringent requirements for continuing medical education and amendments, and inclusion of the differential diagnosis and maintenance of certification. In FNA cytology, use of in difficult or unusual cases. (5) Notification and docu- techniques such as EBUS and EUS pose new challenges and mentation of critical diagnosis. (6) Continuing education of pitfalls, and these, as well as interpretation of stains and pathologists, and/or clinical colleagues.72-74 molecular tests that are now linked to specific therapies, are Medical professional liability insurance, also known as likely to become relatively more frequent in litigation related malpractice insurance, protects physicians from wrongful to cytopathology. practice resulting in bodily injury, medical expenses, and In addition to being sued for alleged misdiagnosis, cyto- the cost of defending lawsuits related to such claims when pathologists may be named in lawsuits not because the providing professional medical services. Two types of cytology report is the immediate issue, but because all coverage exist, occurrence policies and claims-made pol- potentially liable parties must be named before the statute of icies. Occurrence policies cover the insured for incidents limitations (the time period in which a lawsuit must be filed) that occurred during the policy period, regardless of when runs out. Negligence is the predominant theory of liability the claim was made. The date of the incident determines the

Downloaded for Anonymous User (n/a) at SAN FRANCISCO VA MEDICAL CENTER from ClinicalKey.com by Elsevier on January 14, 2020. For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved. 76 R. Nayar et al. coverage, even if the claim is made many years later and 2. Bogdanich W, Lax laboratories. The Pap test misses much cervical that particular insurance policy has expired. Claims-made cancer through labs’ errors. Cut-rate ‘Pap mills’ process slides policies cover the insured for incidents that occurred and with incentives to rush. Misplaced sense of security? Wall Street Jour- nal; 1987:1. were reported during the policy term, and do not cover 3. Unger P. Laboratory accreditation. Available at: http://www. claims made prior to the first date of coverage or claims labmanager.com/business-management/2014/11/laboratory-accreditation#. made after the date of policy expiration. The date of WlwHEIWcE5s. Accessed January 14, 2018. reporting the incident triggers coverage for this type of 4. Smith DA, Mody DR. Quality improvement and lab management. In: policy. Upon cancellation of a claims-made policy, an Mody D, Thrall M, Krishnamurthy S, eds. Diagnostic Pathology. Cytopathology. 2nd ed. Elsiever; 2018:722e727. Part V, section 1. extended reporting endorsement (also known as tail 5. US Department of Health and Human Services, Centers for Medicare endorsement or tail coverage) is usually purchased so there and Medicaid Services. Clinical laboratory improvement amendments is no lapse in coverage. This tail endorsement provides of 1988; final rule. Fed Regist. 1992;57:7182 [42CFR493.1485]. coverage for incidents that occur during a claims-made 6. CAP Accreditation Program. All Common Checklist and Cytopathol- fi policy period but are reported after the policy has expired. ogy Checklist. North eld, IL: College of American Pathologists. Available at: http://www.cap.org/web/home/lab/accreditation. If the covered physician is changing practices and the new Accessed December 5, 2017. employer agrees to pay for medical liability insurance, the 7. The Joint Commission. Facts About Laboratory Accreditation. Avail- new employment agreement should address who is able at: https://www.jointcommission.org/accreditation/accreditation_ responsible for the purchase of the tail endorsementdthe main.aspx. Accessed December 5, 2017. physician, the prior employer, or the new employer. 8. The Partners in Laboratory Oversight. Guidance for coordination of CLIA activities among CMS central office, CMS regional offices, state The limits of coverage available vary depending on the agencies (including states with licensure requirements), accreditation or- insurance company, state of medical practice, practitioner ganizations and states with CMS approved state laboratory programs. specialty, and practice demographics. Limits of liability are the Available at: https://www.cms.gov/Regulations-and-Guidance/ dollar amounts of coverage for each claim and the aggregate Legislation/CLIA/Downloads/090606-RevPartners-Lab-Oversight.pdf. limit for the policy term, which is usually 1 year. A policy that Accessed November 20, 2017. 9. Liberty Management Group Ltd. ISO 9001: 2015 certification - Chi- provides $1,000,000/$3,000,000 means that for the term of the cago. Available at: https://www.iso-certification.us/index.html. policy, the amount of coverage for each claim is $1,000,000, Accessed November 20, 2017. and coverage for the combined number of claims is 10. Hoda RS, Loukeris K, Abdul-Karim FW. Gynecologic cytology on $3,000,000. Patient compensation funds are available in some conventional and liquid-based preparations: a comprehensive review e states and provide coverage in addition to the primary policy. of similarities and differences. Diagn Cytopathol. 2013;41:257 278. 11. ThinPrepÔ Imaging System. Available at: http://www.hologic.com/ Policiesalsomaybewrittentoexcludecertainproceduresor products/clinical-diagnostics/instrument-systems/thinprep-imaging- medical practice at certain geographic locations. Medical system. Accessed October 11, 2017. professional liability insurance may be purchased for an indi- 12. Parker EM, Foti JA, Wilbur DC. Focal Point slide classification algo- vidual physician, physician group, or corporate/partnership. If rithms show robust performance in classification of high-grade lesions other health-care professionals, such as pathologists’ assistants on SurePath liquid-based cervical cytology slides. Diagn Cytopathol. 2004;30:107e110. or nurse practitioners, are working under the direct supervision 13. Moriarty AT. Cytology workload calculationdhas anything really a physician, vicarious liability coverage is often added to the changed? Cancer Cytopathol. 2014;119:77e79. policy. Locum tenens coverage is often written as an 14. Davey DD, Goulart R, Nayar R, Cytopathology Education and Tech- endorsement to the employing physician’s policy.75 nology Consortium. 2013 statement on human papillomavirus DNA test utilization. Cancer Cytopathol. 2014;122:83e86. 15. Medical Laboratory Observer. The five FDA-approved HPV assays. Conclusion Available at: https://www.mlo-online.com/the-five-fda-approved- hpv-assays.php. Accessed November 20, 2017. Our trainees should be exposed to laboratory management 16. Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and Amer- throughout the course of their residency and fellowship ican Society for Clinical Pathology screening guidelines for the pre- training. Some pathology professional organizations provide vention and early detection of cervical cancer. Am J Clin Pathol. training courses and modules related to laboratory accredi- 2012;137:516e542. tation and management. We hope that this summary docu- 17. Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus ment will provide guidance on topics that should be guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121:829e846. addressed during cytopathology training, such that upon 18. Shidham V, Gupta D, Galindo LM, et al. Intraoperative scrape graduation, cytopathologists are prepared to handle the cytology: comparison with frozen sections, using receiver oper- spectrum of clinical, administrative, and accreditation ating characteristic (ROC) curve. Diagn CytoPathol. 2000;23: requirements in their practice. 134e139. 19. Rollins SD, Russell DK. Cell blocks: getting the most from the least invasive method. Available at: http://www.captodayonline.com/ References cytopathology-cell-blocks-getting-least-invasive-. Accessed November 20, 2017. 1. Kass ME, Crawford JM, Bennett B, et al. Adequacy of pathology resi- 20. Siddiqui MT. Pathologist performed fine needle aspirations & imple- dent training for employment: a survey report from the future of pa- mentation of JCAHO universal protocol and "time out. Cytojournal. thology task group. Arch Pathol Lab Med. 2007;131:545e555. 2007;4:19.

21. Nayar R, Wilbur DC, eds. The Bethesda System for Reporting Cervi- 43. Wilcoxon signed-rank test. Available at: https://en.wikipedia.org/ cal Cytology. 3rd ed. New York: Springer; 2015. wiki/Wilcoxon_signed-rank_test. Accessed November 30, 2017. 22. Cibas ES, Ali SZ, eds. The Bethesda System for Reporting Thyroid 44. Student’s t-test. Available at: https://en.wikipedia.org/wiki/Student’s_ Cytopathology. 2nd ed. New York: Springer; 2018. t-test#Independent_two-sample_t-test. Accessed November 30, 2017. 23. Pitman MB, Layfield L, eds. The Papanicolaou Society of Cytopathol- 45. Analysis of variance. Available at: https://en.wikipedia.org/wiki/ ogy System for Reporting Pancreaticobiliary Cytology. New York: Analysis_of_variance. Accessed November 30, 2017. Springer; 2015. 46. Linear regression. Available at: https://en.wikipedia.org/wiki/Linear_ 24. Rosenthal DL, Wojcik EM, Kurtycz DFI, eds. The Paris System for regression. Accessed November 30, 2017. Reporting Urinary Cytology. New York: Springer; 2016. 47. Contingency table. Available at: https://en.wikipedia.org/wiki/ 25. Rossi DE, Faquin WC, Baloch Z, et al. The Milan System for Report- Contingency_table. Accessed November 30, 2017. ing Salivary Gland Cytopathology: analysis and suggestions of initial 48. Chi-squared test. Available at: https://en.wikipedia.org/wiki/Chi- survey. Cancer Cytopathol. 2017;125:757e766. squared_test. Accessed November 30, 2017. 26. Darragh TM, Colgan TJ, Cox JT, et al. The lower anogenital squamous 49. Fisher’s exact test. Available at: https://en.wikipedia.org/wiki/Fisher terminology standardization project for HPV-associated lesions: back- %27s_exact_test. Accessed November 30, 2017. ground and consensus recommendations from the College of American 50. Intraclass correlation. Available at: https://en.wikipedia.org/wiki/ Pathologists and the American Society for Colposcopy and Cervical Pa- Intraclass_correlation. Accessed November 30, 2017. thology. Arch Pathol Lab Med. 2012;136:1266e1297. 51. Cohen’s kappa. Available at: https://en.wikipedia.org/wiki/Cohen% 27. Crothers BA, Jones BA, Cahill LA, et al. Quality improvement oppor- 27s_kappa. Accessed November 30, 2017. tunities in gynecologic cytologic-histologic correlations: findings 52. Regression analysis. Available at: https://en.wikipedia.org/wiki/ from the College of American Pathologists Gynecologic Cytopathol- Regression_analysis. Accessed November 30, 2017. ogy Quality Consensus Conference Working Group 4. Arch Pathol 53. Simple linear regression. Available at: https://en.wikipedia.org/wiki/ Lab Med. 2013;137:199e213. Simple_linear_regression. Accessed January 14, 2018. 28. Davey DD. Amended reports: when, if ever? Diagn Cytopathol. 1997; 54. Logistic regression. Available at: https://en.wikipedia.org/wiki/ 17:399e400. Logistic_regression. Accessed November 30, 2017. 29. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid 55. Survival analysis. Available at: https://en.wikipedia.org/wiki/ Association management guidelines for adult patients with thyroid Survival_analysis. Accessed November 30, 2017. nodules and differentiated thyroid cancer: The American Thyroid As- 56. Kaplan-Meier estimator. Available at: https://en.wikipedia.org/wiki/ sociation Guidelines Task Force on Thyroid Nodules and Differenti- Kaplan%E2%80%93Meier_estimator. Accessed November 30, 2017. ated Thyroid Cancer. Thyroid. 2016;26:1e133. 57. Log rank test. Available at: https://en.wikipedia.org/wiki/Log-rank_ 30. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for hu- test. Accessed November 30, 2017. man papillomavirus vaccination d updated recommendations of the 58. Baumgardner KR. A review of key research design and statistical Advisory Committee on Immunization Practices. MMWR Morb Mor- analysis issues. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. tal Wkly Rep. 2016;65:1405e1408. 1997;84:550e556. 31. Cytology proficiency testing. Available at: https://www.cms.gov/ 59. Ludbrook J. Statistics in biomedical laboratory and clinical science: Regulations-and-Guidance/Legislation/CLIA/CytologyProficiency applications, issues and pitfalls. Med Princ Pract. 2008;17:1e13. Testing.html. Accessed October 11, 2017. 60. Szczech LA, Coladonato JA, Owen Jr WF. Key concepts in biostatis- 32. Cytology proficiency test results e initial test 2005 to 2015. Available tics: using statistics to answer the question "is there a difference?". at: https://www.cms.gov/Regulations-and-Guidance/Legislation/ Semin Dial. 2002;15:347e351. CLIA/Downloads/CYTO-PT-RESULTS-2005-to-2015.pdf. Accessed 61. Wissing DR, Timm D. Statistics for the non-statistician: part I. South December 5, 2017. Med J. 2012;105:126e130. 33. Informational supplement. Available at: https://www.cms.gov/ 62. The Joint Commission. What is the intent of the requirement for Regulations-and-Guidance/Legislation/CLIA/Downloads/Informational_ Ongoing Professional Practice Evaluation?. Available at: https:// Supplement.pdf. Accessed October 11, 2017. www.jointcommission.org/standards_information/jcfaqdetails.aspx? 34. Savaloja L, Birdsong G. Validating and verifying molecular tests in cyto- StandardsFaqIdZ1431&ProgramIdZ46.AccessedJuly13,2017. pathology. CAP Today 2011. Available at: http://www.captodayonline. 63. Hunt JL. Assessing physician competency: an update on the joint com/Archives/0511/0511_cyto_validating.html. Accessed October 10, commission requirement for ongoing and focused professional prac- 2017. tice evaluation. Adv Anat Pathol. 2012;19:388e400. 35. Halling KC, Schrijver I, Persons DL. Test verification and validation 64. Makary MA, Wick E, Freischlag JA. PPE, OPPE, and FPPE: complying for molecular diagnostic assays. Arch Pathol Lab Med. 2012;136: with the new alphabet soup of credentialing. Arch Surg. 2011;146: 11e13. 642e644. 36. Hanna MG, Pantanowitz L. The role of informatics in patient-centered 65. The American Board of Pathology. About the ABPdour history. care and personalized medicine. Cancer. 2017;125:494e501. Available at: http://www.abpath.org/index.php/our-organization/ 37. Monaco SE, Pantanowitz L. Telecytology value and validation: devel- about-the-abp. Accessed July 13, 2017. oping a validation and competency tool for telecytology. Diagn Cyto- 66. The American Board of Pathology. Maintenance of Certification pathol. 2015;43:1e2. (MOC) booklet of information. Available at: http://www.abpath.org/ 38. Collins BT. Telepathology in cytopathology: challenges and opportu- images/booklets/MOC_BOI. Accessed July 13, 2017. nities. Acta Cytol. 2013;57:221e232. 67. Johnson RL. The American Board of Pathology’s Maintenance of Cer- 39. Pearson correlation coefficient. Available at: https://en.wikipedia.org/ tification program update. Arch Pathol Lab Med. 2014;138:512e517. wiki/Pearson_correlation_coefficient. Accessed November 30, 2017. 68. Stark Lawdinformation on penalties, legal practices, latest news and 40. Spearman’s rank correlation coefficient. Available at: https://en.wikipedia. advice. Available at: www.starklaw.org. Accessed July 5, 2017. org/wiki/Spearman%27s_rank_correlation_coefficient. Accessed 69. Agrawal S, Brennan N, Budetti P. The Sunshine Acteeffects on phy- November 30, 2017. sicians. N Eng J Med. 2013;368:2054e2057. 41. Mann-Whitney-U test. Available at: https://en.wikipedia.org/wiki/ 70. Troxel DB. Trends in pathology malpractice claims. Am J Surg Mann%E2%80%93Whitney_U_test. Accessed November 30, 2017. Pathol. 2012;36:e1ee5. 42. Kruskal-Wallis one-way analysis of variance. Available at: https://en. 71. Kornstein MJ. The medicolegal aspect of error in pathology a search wikipedia.org/wiki/Kruskal%E2%80%93Wallis_one-way_analysis_of_ of jury verdicts and settlements. Arch Pathol Lab Med. 2007;131: variance. Accessed November 30, 2017. 615e618.

72. Troxel DB. Medicolegal aspects of error in pathology. Arch Pathol 74. Allen TC. Medicolegal issues in pathology. Arch Pathol Lab Med. Lab Med. 2006;130:617e619. 2008;132:186e191. 73. Troxel D B. Medicolegal issues in surgical pathology. In: Weidner N, 75. Proassurance. Physician Medical Liability Professional Insurance - a Cote R, Suster S, et al., eds. Medicolegal Issues in Surgical Pathol- Practitioner’s Primer. Rockville, MD: Physician Insurers Association ogy. Saunders Elsevier; 2009:131e137. of America (PIAA); 2013.