Digital pathology and its role in cytology education.

Digital methods have the potential to greatly expand content availability, accessibility, and quality for pathology education. Use of this technology allows for anywhere/anytime interactions and delivery in a variety of methods to accommodate any learning style. This review introduces basic digital technology, its uses for education, and prospects for the future.

Bethesda 2014: improving on a paradigm shift.

The third iteration of the Bethesda System terminology manual was recently published. This update included changes in the reporting of benign endometrial cells, and guidance for special adequacy situations and for cases in which low grade squamous intraepithelial lesions are accompanied by some cells suggesting that a high grade lesion might also be present. In addition, the manual was increased in size to include more illustrations with special studies and comparisons to histology, a greatly increased reference list, and a new chapter devoted to the modern practice of risk-based management. The third edition of the Bethesda manual is meant to serve as a primary reference for the practice of gynecologic cytology designed to provide a uniform system of reporting Worldwide for clinical, teaching, and research purposes.

Cytologic features of focal papillary thyroid carcinoma arising within follicular adenoma: a masked cytomorphologic analysis of 17 cases.

BACKGROUND/OBJECTIVE: Focal papillary thyroid carcinoma (PTC) arising within a follicular adenoma (PTCFA) represents a clinically significant, but rare, histopathologic subset of papillary carcinomas whose cytologic features have not been well described. This uncommon presentation of PTC may contribute to a subset of thyroid aspirates interpreted as 'atypia of undetermined significance/follicular lesion of undetermined significance' (AUS/FLUS). STUDY DESIGN: Seventeen fine-needle aspiration biopsy (FNAB) cases diagnosed as 'PTCFA' on corresponding surgical excision were identified from the archival records of 2 large academic medical centers. A control group of 40 FNAB comprised of 20 follicular adenomas (FA) and 20 PTC was identified (based on the corresponding surgical pathology diagnosis) for comparison. All 57 FNAB were reviewed in a masked fashion and scored for a series of 31 cytomorphologic features. The intraclass correlation between diagnostic categories and overall agreement between cytopathologists was statistically evaluated. RESULTS: Aspirates of PTCFA were originally diagnosed as 'negative' (n = 3), 'AUS/FLUS' (n = 7), 'suspicious for a follicular neoplasm' (n = 3), 'suspicious for malignancy' (n = 3), and 'malignant' (n = 1). On masked review, the most common cytomorphologic features of PTCFA were a nonmacrofollicular cytoarchitectural pattern (71%), medium-large cell size (74%), and micronucleoli (79%). Intranuclear pseudoinclusions and a papillary architecture were absent in 85 and 88% of the cases, respectively. Relative to the 2 control groups, the PTCFA cases demonstrated overlapping features between FA and PTC for the majority of the 31 examined cytomorphologic features. CONCLUSION: PTCFA represent a rare subset of PTC that is difficult to recognize as PTC by FNAB. Most cases exhibit overlapping features between a benign thyroid nodule and conventional PTC, and they are often interpreted as 'AUS/FLUS'.

The human false-negative rate of rescreening Pap tests. Measured in a two-arm prospective clinical trial.

BACKGROUND: Routine quality control rescreening often is used to calculate the false-negative rate (FNR) of gynecologic cytology. Theoretic analysis suggests that this is not appropriate, due to the high FNR of rescreening and the inability to actually measure it. The authors sought to determine the FNR of manual rescreening in a large, prospective, two-arm clinical trial using an analytic instrument in the evaluation. METHODS: The results of the Autopap System Clinical Trial, encompassing 25,124 analyzed slides, were reviewed. The false-negative and false-positive rates at various thresholds were determined for routine primary screening, routine rescreening, Autopap primary screening, and Autopap rescreening by using a simple, standard methodology. RESULTS: The FNR of routine manual rescreening at the level of atypical squamous cells of undetermined significance (ASCUS) was 73%, more than 3 times the FNR of primary screening; 11 cases were detected. The FNR of Autopap rescreening was 34%; 80 cases were detected. Routine manual rescreening decreased the laboratory FNR by less than 1%; Autopap rescreening reduced the overall laboratory FNR by 5.7%. At the same time, the false-positive rate for Autopap screening was significantly less than that of routine manual screening at the ASCUS level (4.7% vs. 5.6%; P < 0.0001). Rescreening with the Autopap system remained more sensitive than manual rescreening at the low grade squamous intraepithelial lesions threshold (FNR of 58.8% vs. 100%, respectively), although the number of cases rescreened was low. CONCLUSIONS: Routine manual rescreening cannot be used to calculate the FNR of primary screening. Routine rescreening is an extremely ineffective method to detect error and thereby decrease a laboratory's FNR. The Autopap system is a much more effective way of detecting errors within a laboratory and reduces the laboratory's FNR by greater than 25%.

Detection of high grade squamous intraepithelial lesions and tumors using the AutoPap System: results of a primary screening clinical trial.

BACKGROUND: The AutoPap System for the initial screening and quality control of conventional cervical cytology slides previously has shown superior performance for the detection of abnormal slides of low grade squamous intraepithelial lesions and above. This report presents data regarding the important category of high grade squamous intraepithelial lesions and above (HSIL+). METHODS: All slides were run through a Current Practice (CP) arm of manual screening with 10% random quality control followed by an AutoPap (AP) arm of device initial screening with approximately 25% of slides receiving no further review; 75% received a manual rescreen with AP ranking and QC rescreening of 15% of the top ranking negative manual screen slides was performed. Detection performance for truth-determined HSIL+ cases was compared between the two study arms. Available follow-up biopsy results were correlated for cases determined to be HSIL+. RESULTS: Of 25,124 analyzed slides, 70 slides had truth-determination at the HSIL+ level (67 HSILs, 1 adenocarcinoma in situ, and 2 invasive tumors). The AP arm identified 68 of 70 cases (including both invasive tumors). Neither false-negative HSIL+ was found in the 25% "No Further Review" population. The CP arm identified 65 of 70 cases (missing both invasive tumors). The results showed statistical equivalence between the two arms (P = 0.0129). Biopsy follow-up was available in 27 of 70 HSIL+ cases identified by AP and showed abnormality at some level in 100% of cases. CONCLUSIONS: The AP arm was statistically equivalent and showed numeric superiority to the CP arm for the category of HSIL+. Follow-up data confirmed the true-positive nature of these findings. These results are significant because any overall improvement in the performance of an initial screening device must be paralleled by at least equivalence in the clinically important subset category of HSIL+. Cancer (Cancer Cytopathol)

AutoPap system detection of infections and benign cellular changes: results from primary screener clinical trials.

Primary screening devices for cervical cytology must show performance data for the detection of infectious organisms and benign cellular changes (BCC) for cytologists who routinely report these findings. The data on infection and BCC from the AutoPap primary screening clinical trials are presented herein. The presence of infectious organisms (candida, trichomonas, shift in bacterial flora, herpes, actinomyces) and BCC were noted in each of the clinical trial arms (current practice, CP; AutoPap-assisted practice, AP). For the purposes of these analyses, a report of infection or BCC from either arm was considered to be "truth." In 25,124 slides analyzed, there were 2,925 cases of infection identified. Of these, CP identified 2,141, and AP identified 1,985. The overall detection results are statistically equivalent. Of 17 cases of actinomyces, CP detected 8, while AP detected 12. Of 1,282 cases of candida, CP detected 983, and AP detected 865. Of 1,375 cases of shift of bacterial flora, CP detected 897, and AP detected 869. Of 14 cases of herpes, CP detected 9, and AP detected 11. Of 343 cases of trichomonas, CP detected 293, and AP detected 275. There were 5,156 cases of BCC identified in the trial. CP detected 3,431, and AP detected 3,276. The detection rates for BCC are statistically equivalent. The results show that the AutoPap-assisted practice for the primary screening of conventional cervical cytology slides is equivalent to the current practice for the detection of cervical infections and benign cellular changes.

Fine-needle aspiration of the macrofollicular and microfollicular subtypes of the follicular variant of papillary carcinoma of the thyroid.

BACKGROUND: The follicular variant of papillary carcinoma of the thyroid (FVPCT) is being increasingly diagnosed on excised thyroid nodules. However, the fine-needle aspiration (FNA) and intraoperative diagnosis is often that of a follicular neoplasm, especially in papillary carcinomas with a pure or predominantly follicular pattern. The authors undertook this study in an attempt to refine the cytologic criteria for the diagnosis of FVPCT. METHODS: The authors reviewed 16 cases with cytologic diagnoses of FVPCT (9 cases), suspicious for FVPCT (6 cases), or cellular adenomatoid nodule (1 case) based on aspirates stained with Papanicolaou stain or a Giemsa-type stain (Diff-Quik). All cases had been confirmed histologically as pure or predominantly (>80%) FVPCT in 13 cases and as follicular adenoma in 3 cases. Cytologic features evaluated included cellularity, cell arrangement, nuclear features, cytoplasm, and colloid. RESULTS: Twelve of 13 cases of FVPCT were correctly diagnosed cytologically. Features that proved useful in the diagnosis of FVPCT were the concomitant and conspicuous presence of ovoid or pear-shaped nuclei with hypochromasia and nuclear grooves. Soft features included nuclear overlap and eccentric, small nucleoli. Cytoplasmic features were not useful in making this diagnosis. Based on cell arrangement and colloid, it was possible to predict microfollicular and macrofollicular variants. The microfollicular subtype showed rosettes or microfollicles and scant, thick colloid in casts and blobs. The macrofollicular subtype had predominantly sheets or spherules with abundant, thick background colloid. Nuclear pseudoinclusions and psammoma bodies were absent and multinucleated giant cells rarely found. Pitfalls leading to a "false-positive" FVPCT diagnosis included oncocytic adenoma (in 2 cases) and atypical adenoma (in 1 case). A cytologic diagnosis of cellular adenomatoid nodule was made in one case of macrofollicular FVPCT. CONCLUSIONS: The authors present improved cytologic criteria for the diagnosis of pure FVPCT on smears stained with Papanicolaou stain or Diff-Quik, and they elaborate on the clues and pitfalls associated with this diagnosis. The cytologic features of the macrofollicular and microfollicular subtypes of FVPCT are also described.

Leiomyosarcoma of the maxillary sinus: CT and MRI findings.

This report describes the CT and MRI appearances of a leiomyosarcoma of the maxillary sinus. CT showed frank bony destruction, no calcification and a low attenuation area within the mass. MRI showed intermediate intensity on T1 weighted images, intermediate to slightly high signal intensity on T2 weighted images and moderate inhomogeneous enhancement. Precise identification of the extent of the tumour, especially of orbital invasion, is of utmost importance because local recurrence is common after the resection of leiomyosarcomas.

The cost-effectiveness of fine-needle aspiration cytology and 14-gauge core needle biopsy compared with open surgical biopsy in the diagnosis of breast carcinoma.

BACKGROUND: Judicious utilization of fine-needle aspiration cytology (FNAC) and 14-gauge core needle biopsy (CB) theoretically should result in greater accuracy in breast carcinoma diagnosis and fewer unnecessary open surgical biopsies (OSBs), thus lowering health care costs. METHODS: In 1995 in Rochester, New York, the ratio of open surgical breast biopsies per each verified breast carcinoma (OSB/Ca) in a freestanding breast clinic (EWBC) was compared with the OSB/Ca ratio of all physicians in the remainder of the city. The EWBC differs from all other diagnostic facilities in Rochester in that it routinely performs FNAC and CB. RESULTS: The EWBC recommended 462 OSBs resulting in 310 verified carcinomas, for a OSB/Ca ratio of 1.5. The physicians in the remainder of the city recommended 2036 OSBs resulting in 513 verified carcinomas, for a OSB/Ca ratio of 4.0. If the EWBC OSB/Ca ratio had been identical to the remainder of the city, the number of extra OSBs recommended by the clinic would have been 778, resulting in an additional cost of $1,712,082. When the added cost of the 2594 FNACs ($256,285) and 403 CBs ($252,278) performed by the clinic was subtracted from the $1,712,082, the freestanding breast clinic cost savings was $1,203,519. The lymph node metastasis rate of 19% for the breast carcinomas diagnosed in clinic patients was identical to that of the women with breast carcinoma in the remainder of the city. CONCLUSIONS: Utilization of FNAC and CB allows radiologists to lower their OSB/Ca ratio without sacrificing early detection. In this study, these less expensive procedures result in lowered medical costs for the health care system.

Automation in cytology: a survey conducted by the New Technology Task Force, Papanicolaou Society of Cytopathology.

Despite the overwhelming interest in the development of several computer based technologies in the last several years, the role of automation in cytology has remained controversial. The potential of these technologies in the reduction of false negative results in pap smears is well recognized. However, there is still remarkable confusion as how to incorporate automation in the routine practice of cytology. This prompted the New Technology Task Force of the George Papanicolaou Society of Cytopathology to design a survey to seek the opinion of those engaged in cervicovaginal cytology screening regarding the value of automation in cytology. In 1996, a ten question survey was sent to 1800 cytopathology laboratories throughout the nation. The response rate was 23% (416/1800). The responders represented laboratories varying from those with less than 5,000 pap smears to those with over 100,000 cases per year. The majority of the responders did not believe that automation is essential for cervicovaginal cytology. This was evidenced by the fact that only 12% of the laboratories were engaged in automated cytology and predominantly used it for quality control measures. The inability of small laboratories to absorb the extra expense involved in the integration of automated cytology in their practice, particularly in the current era of managed care was a major concern. There was also concern about the potential for compromise of patient care by the drive for corporate profits and the dissemination of wrong information to the public and physicians. Suggestions most frequently proposed included appropriate patient and physician education about the merits and pitfalls of the pap smear, and also endorsing an affordable universal fee for pap smears. Rescreening for all pap smears, reassessing the benefits of automation in cytology and development of the standards were other proposals. Partnership with larger cytology laboratories, creation of "cytology consortiums" with shared resources to provide regionalized automated rescreening services were also strongly suggested. This survey clearly indicates the need for further evaluation of automation in cytopathology and a focused attention to various issues surrounding cervicovaginal cytology screening.

ASCUS and AGUS criteria. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: The conference participants addressed the following issues: (1) reporting of equivocal diagnoses, (2) strategies to minimize the use of such diagnoses, (3) morphologic criteria, and (4) management of women with equivocal diagnoses. CONSENSUS POSITION: Equivocal diagnoses should be minimized, to the extent possible, by emphasizing cytologist education and training, improved specimen collection and quality assurance monitoring of individual and laboratory diagnosis rates. Cases fulfilling criteria for other diagnostic entities should not be included in the equivocal category. Regardless of the term utilized, an equivocal diagnosis should be qualified in some manner to indicate that the diagnosis defines a patient at increased risk of a lesion, particularly for those cases which raise concern about a possible high grade lesion. Qualification of an equivocal diagnosis can also be accomplished by appending laboratory statistics of the likelihood of various clinical outcomes or recommendations for patient follow-up. In contrast to favoring a reactive process versus squamous intraepithelial lesion (SIL), a more rationale approach to qualification of atypical squamous cells of undetermined significance may be to separate cases equivocal for low grade SIL from those suspicious for high grade SIL. With regard to glandular lesions, the conference participants expressed unanimous support for the separation of adenocarcinoma in situ (AIS) from atypical endocervical cells of undetermined significance when sufficient criteria are present. However, the diagnosis of a precursor lesion to AIS, endocervical glandular dysplasia, was controversial. The majority of conference participants discourage the use of such terms as mild glandular dysplasia and low grade glandular dysplasia for cytologic diagnoses. ONGOING ISSUES: Conference participants agreed that a term reflecting diagnostic uncertainty is necessary to communicate findings that are equivocal. However, participants could not agree on the wording of such a term. Opinions differed as to: (1) use of atypical, abnormal or morphologic changes to describe cell changes, (2) whether the diagnosis should indicate a squamous or glandular origin of the cells in question when this determination can be made, and (3) the value of defining morphologic criteria for such a diagnosis. The debate over terminology, as well as morphologic criteria, is ongoing, and the readership is invited to communicate opinions to Acta Cytologica. Management of women with equivocal diagnoses varies widely from locale to locale and may differ based on how the equivocal diagnosis is qualified. Findings insufficient for the diagnosis of a high grade lesion may warrant more aggressive follow-up than cases equivocal for a low grade lesion. Where sensitivity of detection of lesions is of paramount importance, follow-up will generally consist of more frequent cytology screening or colposcopy and biopsy. However, in some countries it is considered unethical to have a high percentage of false positive diagnoses, which result in overtreatment and an unnecessary burden for women participating in cervical screening. Future studies may provide a morphologic, or perhaps molecular, basis for distinguishing true precursors of neoplasia from minor lesions of no significant clinical import; this would allow a more coherent and rational approach to diagnosis and management of women with equivocal cytologic findings.

Cell preparation methods and criteria for sample adequacy. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Cell Preparation Methods Standardized fixation and optimal staining Sampling of cervix, sampling error, homogenization of sample, subsampling Assessment of liquid-based preparations: efficacy and economic impact Training and transitional procedures before full implementation of new technologies Criteria for Sample Adequacy Clinician responsibility for collecting and providing representative sample to laboratory Collection instruments, number of slides Cellular content of samples: evidence of transformation zone (TZ) sampling, number of squamous cells present, obscuring factors Screening issues CONSENSUS POSITION The conventional cervical smear remains the standard method of cervical cancer screening but has limitations in individual test sensitivity and specificity. Sample takers should: (1) receive appropriate training in sample collection, (2) be held responsible for providing the laboratory with appropriate samples, and (3) have their performance monitored. The instruments used for sampling should collect cells from both the ectocervix and endocervix; optimally, TZ sampling, represented by the presence of endocervical or squamous metaplastic cells, should be identifiable in samples other than atrophic specimens. The adequacy of a specimen (as judged microscopically) does not guarantee that it is representative of the cervix. Each cytology report should include a comment on cellular content/adequacy of the specimen. Liquid-based preparations may overcome many of the inherent problems with the conventional cervical smear. ONGOING ISSUES: We need further data on the cost-effectiveness of making two slides from cervical specimens and/or using two samplers rather than a single one. Do we have enough information to make recommendations as to the appropriate type of sampler to be used in particular situations, such as routine screening? What is the best method of screening for/detecting endocervical glandular neoplasia? How are such terms as unsatisfactory and inadequate defined in cervical cytology classifications other than the Bethesda System? What number and types of epithelial cells should be present (visualized) in a cervical smear or liquid-based preparation for it to be considered adequate? Do we need to have evidence of TZ sampling in specimens taken during the follow-up period after treatment of squamous intraepithelial lesion or after detection of endocervical glandular neoplasia? What criteria for obscuring factors, such as blood and inflammation, should be used in assessing adequacy? Cost-benefit analyses of utilizing liquid-based preparations are needed. Should we inform women about the technical details of the test methods available or chosen by the laboratory? Are women in a position to decide which method is the most appropriate to assess their cervical scrape sample? We need to obtain more information about the properties of proprietary liquid fixative/transport media with respect to inactivation of viral pathogens, tuberculosis and other bacterial pathogens and suitability for immunobiologic and molecular tests, etc. We need to obtain more information on the use of stoichiometric stains and the limitations of Papanicolaou stain for image analysis systems. The use of liquid-based preparations for nongynecologic cytopathology and ancillary tests must be considered, including criteria for adequacy. We need to obtain more information on the time required for and best methods of training experienced cytotechnologists to become competent at assessing liquid-based cervical preparations.

Computerized screening devices and performance assessment: development of a policy towards automation. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: The extension of automation to the diagnostic assessment of clinical materials raises issues of professional responsibility, on the part of both the medical professional and designer of the device. The International Academy of Cytology (IAC) and other professional cytology societies should develop a policy towards automation in the diagnostic assessment of clinical cytologic materials. CONSENSUS POSITION: The following summarizes the discussion of the initial position statement at the International Expert Conference on Diagnostic Cytology Towards the 21st Century, Hawaii, June 1997. 1. The professional in charge of a clinical cytopathology laboratory continues to bear the ultimate medical responsibility for diagnostic decisions made at the facility, whether automated devices are involved or not. 2. The introduction of automated procedures into clinical cytology should under no circumstances lead to a lowering of standards of performance. A prime objective of any guidelines should be to ensure that an automated procedure, in principle, does not expose any patient to new risks, nor should it increase already-existing, inherent risks. 3. Automated devices should provide capabilities for the medical professional to conduct periodic tests of the appropriate performance of the device. 4. Supervisory personnel should continue visual quality control screening of a certain percentage of slides dismissed at primary screening as within normal limits (WNL), even when automated procedures are employed in the laboratory. 5. Specifications for the design of primary screening devices for the detection of cervical cancer issued by the IAC in 1984 were reaffirmed. 6. The setting of numeric performance criteria is the proper charge of regulatory agencies, which also have the power of enforcement. 7. Human expert verification of results represents the "gold standard" at this time. Performance characteristics of computerized cytology devices should be determined by adherence to defined and well-considered protocols. Manufacturers should not claim a new standard of care; this is the responsibility of the medical community and professional groups. 8. Cytology professionals should support the development of procedures that bring about an improvement in diagnostic decision making. Advances in technology should be adopted if they can help solve problems in clinical cytology. The introduction of automated procedures into diagnostic decision making should take place strictly under the supervision and with the active participation and critical evaluation by the professional cytology community. ONGOING ISSUES: Guidelines should be developed for the communication of technical information about the performance of automated screening devices by the IAC to governmental agencies and national societies. Also, guidelines are necessary for the official communication of IAC concerns to industry, medicolegal entities and the media. Procedures and guidelines for the evaluation of studies pertaining to the performance of automated devices, performance metrics and definitions for evaluation criteria should be established.

Human papillomavirus. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Cervical squamous cell carcinomas, adenocarcinomas and their precursors are caused by the human papillomavirus (HPV). Although HPV appears to be essential to the transformation of these epithelial cells, it is not sufficient, and a variety of cofactors and molecular events must take place between when an HPV infection occurs and a cervical cancer or its precursor develops. This review examines the data supporting these contentions, briefly outlines the molecular events that occur, considers the epidemiology and natural history of the disease, and details the implications of using HPV detection and typing in both clinical management and population-based screening programs. CONSENSUS POSITION: 1. Based on the available molecular, clinical and epidemiologic data, a subset of HPVs are unequivocally the etiologic agents for cervical cancers and their precursors. 2. Different mucosotropic HPVs have varying neoplastic potential. However, the great majority of cervical HPVs have oncogenic potential. Since oncogenic HPV-induced epithelial transformation to a high grade lesion or cancer is rare relative to the rate of infection, the term high risk is discouraged. 3. HPV's interaction with host cells has two principal biologic consequences: a) All anogenital HPVs induce low grade squamous lesions, which are the morphologic correlate of a productive infection. b) Rarely, HPVs induce a proliferative epithelial phenotype that pathologists recognize as a high grade lesion and that is the proximate cytohistologic precursor of invasive cervical carcinoma. 4. HPV biology and issues of practical clinical management should be reflected in the classification systems used for cytologic and histologic diagnosis. ONGOING ISSUES: The molecular identification of HPVs (HPV testing) potentially may be very useful for primary screening or secondary triage of patients with certain lesions. However, the technology available to the practicing clinician is still evolving. Optimization of type spectrum, sensitivity, specificity and ease of use is under development. Data regarding these factors as well as a clear cost benefit analysis are sparse or pending in several large trials. Until such data are available, caution in clinical implementation of HPV testing is warranted.

Computerized training and proficiency testing. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Computerized technologies probably will revolutionize the field of gynecologic cytology in the next century. Such technologies will be useful in both training and evaluating proficiency. However, manual screening/review of gynecologic cytology preparations is the current "gold standard" for both training and assessment of proficiency. CONSENSUS POSITION: Training programs for cytotechnologists and pathologists should provide instruction and experience in new technologies, but their introduction may depend on the availability of equipment and staff. Advantages of digital images for training include standardization of teaching sets and interactive capabilities, allowing educational feedback. Computerized support/assistance devices aid in complete screening of the slide during training and provide feedback to cytologists on screening techniques. Liquid-based cytopreparatory instruments facilitate multiple glass slides for teaching or testing. Proficiency testing (PT) in cytology has similar quality assurance goals as in other areas of the laboratory, but the subjective nature of cytologic analysis poses many challenges for implementation. There is consensus that all cytology practitioners would like to know the proficiency of the laboratory. However, the majority question the value and validity of any large-scale formal testing programs. Locator and diagnostic skills are both critical in cytology, but assessment of each skill may occur in different ways using computerized technologies. Any type of assessment should provide educational feedback to participants. Psychometric issues in PT include the consideration of different types of validity, including face, content, construct and criterion related. The reliability or consistency of the testing event is also critical. A valid and reliable correlation between work performance and performance on a PT needs to be established. The goal is to ensure that PT will identify submarginal practitioners and that persons successful on PT are in fact competent. Any cytology PT program should also be considered in the context of other laboratory quality assurance tools and the entire cervical cancer screening program. Regulatory agencies should evaluate entire laboratory performance, while each laboratory director should assume primary responsibility for evaluating and documenting the competency and daily performance of each practicing cytologist. Professional scientific organizations should take the lead in recommending methods and standards of performance assessment. ONGOING ISSUES: A reliable method of correlating daily competency with results on PT is not yet established. Methods may evolve ever time using new technologies. The use of computerized techniques and images for assessment will require careful deliberation by experts as well as validation by practicing cytologists. Variables include diagnostic categories for testing, numbers of challenges per testing event, types of slide preparations and characteristics of the digital images. Availability of equipment and staff will affect the introduction of new technologies in different regions.

The AutoPap system for primary screening in cervical cytology. Comparing the results of a prospective, intended-use study with routine manual practice.

OBJECTIVE: To evaluate the effectiveness of the AutoPap System in detecting abnormal and normal cervical smears when used in a primary screening/quality control mode, as compared with currently established laboratory practices. STUDY DESIGN: Slides were obtained prospectively and were initially processed in the routine fashion with cytotechnologist screening followed by 10% random quality control rescreening. Slides were then processed on the AutoPap System and allocated into the following groups: (1) approximately 25% of the lowest-ranking slides were placed in the laboratory's archives as within normal limits; (2) the remaining approximately 75% of slides were subjected to manual screening. Approximately 15% of the highest-ranking slides in this group underwent quality control rescreening. For each slide needing manual screening, the cytotechnologist was supplied with a report giving the ranking score of that slide. All discrepant slides for either adequacy or diagnosis were subjected to a truth-determination process. The results obtained from the two arms of the protocol were then compared. RESULTS: The AutoPap System-assisted arm of the study was superior to the current practice arm for the identification of abnormal slides at the level of atypical squamous cells of undetermined significance and above (ASCUS+), low grade squamous intraepithelial lesion (LSIL) and higher LSIL+. AutoPap System-assisted practice was equivalent to current practice for the identification of unsatisfactory and satisfactory but limited by slides. All results showed statistical significance. In addition, AutoPap System-assisted practice in the study indicated improved specificity of diagnosis. CONCLUSION: AutoPap System-assisted practice shows superior sensitivity and specificity when compared to current practice. Its clinical use as a primary screening device should improve the overall practice of cervical cytology as well as provide potential enhancement in overall laboratory productivity.

A feasibility study of the AutoPap system location-guided screening.

OBJECTIVE: To study the feasibility of AutoPap System location-guided screening and to evaluate the accuracy of the AutoPap System in selecting locations of potentially abnormal cellular material, the accuracy of triaging slides using the selected locations and the improvement in laboratory accuracy and workload reduction resulting from a combination of location-guided rescreening and AutoPap System primary screening. STUDY DESIGN: For the study, 683 conventionally prepared cervical cytologic smears (263 WNL, 184 atypical squamous cells of undetermined significance/atypical glandular cells of undetermined significance, 173 low grade squamous intraepithelial lesions, 55 high grade squamous intraepithelial lesions and 8 cancer slides) were acquired from nine laboratories. The study slides were independently screened to establish study reference diagnoses. The slides were processed on the AutoPap System and screened by cytotechnologists who were guided by the field of view (FOV) locations provided by the AutoPap System. The location-guided information was used either for initial manual screening (location-guided screening or after initial manual screening of the entire slide (location-guided rescreening). The results were compared to the study reference diagnoses. Sensitivity and workload reduction figures were estimated for different slide populations. RESULTS: The accuracy of location-guided slide triage was high and did not vary significantly over different slide populations. Also, for > 80% of the abnormal slides, the AutoPap System-selected FOV slide locations did contain the most diagnostic cells, which were used to assign an accurate diagnosis to the slide. By combining location-guided rescreening with AutoPap primary screening, the estimated overall location-guided screening false negative fraction (FNF) for LSIL+ slides was approximately 40 times lower than the cytotechnologist-only FNFs, and this improvement was achieved-even at a no review rate of 70%. CONCLUSION: The feasibility study results showed that the AutoPap System location-guided screening process can triage slides accurately and enhance the overall accuracy of slide diagnosis. The combination of location-guided rescreening and AutoPap primary screening could improve the accuracy and workload of the laboratory.

Atypical squamous cells of undetermined significance. Stratification of the risk of association with, or progression to, squamous intraepithelial lesions based on morphologic subcategorization.

OBJECTIVE: To analyze follow-up data on atypical squamous cells of undetermined significance (ASCUS) based on morphologic characteristics. STUDY DESIGN: Five years of follow-up was obtained on a cohort of 437 consecutive patients from 1986 who had initial diagnoses of ASCUS, with a further categorization of type based on the maturity of the atypical cells. All such categorizations were made on the basis of specific cytologic criteria. Follow-up cytology and/or biopsy was available on 366 patients. RESULTS: During the follow-up period, 40 patients (13.5%) with ASCUS were diagnosed as having a squamous intraepithelial lesion (SIL); 15 (5%) were interpreted as high grade. When stratified by type of ASCUS based on cellular maturity, the following association/progression rates were noted: mature ASCUS, 10%; metaplastic ASCUS, 24%; and immature metaplastic ASCUS, 42%. In metaplastic and immature metaplastic ASCUS cases, high grade SIL accounted for 42% and 60% of those subsequently diagnosed with a squamous intraepithelial lesion, respectively, versus 30% for mature ASCUS. CONCLUSION: With well-defined and consistent criteria for the diagnosis of the variety of "squamous atypias," a stratification of risk of progression to or association with SIL can be made. When features of metaplasia and immature metaplasia are noted in the cells of ASCUS, patients were observed to be at increasingly greater risk for the detection of SIL; those cases were proportionately more likely to be high grade.