Royal College Of Pathologists Of Australasia Research Articles

An update report on the harmonization of adult reference intervals in Australasia.

The Australasian Association of Clinical Biochemists (AACB) has over the past 5 years been actively working to achieve harmonized reference intervals (RIs) for common clinical chemistry analytes using an evidence-based checklist approach where there is sound calibration and metrological traceability. It has now recommended harmonized RIs for 18 common clinical chemistry analytes which are performed in most routine laboratories and these have been endorsed by the Royal College of Pathologists of Australasia (RCPA). In 2017 another group of analytes including urea, albumin and arterial blood gas parameters were considered and suggested harmonized RIs proposed. This report provides an update of those harmonization efforts.

Revalidation

Revalidation of medical practitioners already occurs in many countries, including the UK, Canada and America. However, forensic pathologists in America have expressed dissatisfaction with the use of examinations and the system in the UK is regarded by some as too onerous. The Australia Health Practitioners Agency (AHPRA) is planning to introduce revalidation. In preparation, the Royal College of Pathologists of Australasia (RCPA) formed a steering group to develop Internal Quality Assurance programmes that would meet the needs of revalidation without incurring extra work for practising pathologists. Three areas were considered: pre-analytical, analytical and post-analytical. Within forensic pathology the pre-analytical conditions are mostly dictated and are beyond control. Post-analytical would largely be regarded as court work, but it would be inappropriate to judge pathologists against outcome, as expert evidence must be independent. As forensic pathology is an opinion-based specialty, peer review would be the best method to assess standards. This is already a National Association of Testing Authorities (NATA) requirement. Initial consultation by AHPRA regarding revalidation suggests that peer review will be promoted. Thus, for forensic pathology a system of peer review is proposed.

A Review On International Guidelines For Digital Pathology

Introduction/ Background Pathologists are looking at digital pathology not as much as an efficient telepathology solution but as an instrument to improve the quality and efficiency of their own daily clinical work beyond the use of the conventional microscope. The term digital pathology (DP) should also include interoperability and workflow considerations, and basic technical aspects of whole slide imaging (WSI), messaging, and standards should be also known by pathologists. Aims The aim of this study is reviewing the technical features of WSI systems in existing guidelines available internationally. Methods The following guidelines and technical documents have been evaluated: College of American Pathologists (CAP), 2013: Validation American Telemedicine Association (ATA), 1999: Telepathology Digital Pathology Association (DPA), 2011. First WSI guideline Food and Drug Administration (FDA). Canadian Association of Pathologists (CAP-ACP). Centers for Medicare & Medicaid Services (CMS/ CLIA). Centers for Disease Control and Prevention (CDC/ CLIAC). Society of Toxicologic Pathology (STPath). European Commission (EU-EC). Spanish Society of Anatomic Pathology (SEAP-IAP). The Royal College of Pathologists (RCP). The Royal College of Pathologists of Australasia (RCPA). Results Since February 2015, a draft of Technical Performance Assessment of Digital Pathology Whole Slide Imaging Devices from FDA is available. Regarding display (monitor), a complete description of the display, graphics cards, and control software items to be considered are included (display technology [LED, LCD], color calibration, ambient light sensors,..) although there is no mention to refresh rate). In the College of American Pathologists (CAP) Digital Pathology Resource Guide, references to guidelines or position papers other than CAP guidelines are dispersed in other sections of this document. Hanna et al (2015) reviewed existing guidelines and position statements for digital pathology, with special attention to validation and telepathology. Evans et al (2014) made a comparison between American Telemedicine Association (ATA), Royal College of Pathologists (RCP) and Canadian telepathology guidelines. In summary we could find the following topics in the corresponding guidelines: System architecture was only mentioned in SEAP document. Components of DP system: ATA, DPA, FDA, SEAP, STPath. Badwith/Network: ACP, DPA, SEAP. Interoperability: ATA, ACP, CLIA, DPA, SEAP, STPath. Scanning speed: ACP, DPA, SEAP; Storage: ATA, DPA, RCP, SEAP. Image quality in WSI: ACP, DPA, RCP, SEAP; Image compression and processing: ATA, EU-EC, DPA, SEAP. Conclusions: Some basic technical features of a WSI systems that are of high interest to pathologists are scanning speed (e.g. 1-2 minutes 20x), autoloader capacity (100 slides), image quality (resolution 0.25-0.50 µ/ pixel) rescanning rate (<5%), image compression (<70%), monitor quality (30 inches 4-8 MPx), and viewing experience (refresh rate, network bandwith). In primary diagnosis, we need some new regulations also in European countries. Acknowledgment : This work has been supported by the AIDPATH project, an EU 7FP IAPP Marie Curie action, contract number 612471

Reporting unit size and measurement uncertainty: current Australian practice in clinical chemistry and haematology

In this study we aimed to compare the reporting unit size used by Australian laboratories for routine chemistry and haematology tests to the unit size used by learned authorities and in standard laboratory textbooks and to the justified unit size based on measurement uncertainty (MU) estimates from quality assurance program data. MU was determined from Royal College of Pathologists of Australasia (RCPA) - Australasian Association of Clinical Biochemists (AACB) and RCPA Haematology Quality Assurance Program survey reports. The reporting unit size implicitly suggested in authoritative textbooks, the RCPA Manual, and the General Serum Chemistry program itself was noted. We also used published data on Australian laboratory practices.The best performing laboratories could justify their chemistry unit size for 55% of analytes while comparable figures for the 50% and 90% laboratories were 14% and 8%, respectively. Reporting unit size was justifiable for all laboratories for red cell count, >50% for haemoglobin but only the top 10% for haematocrit. Few, if any, could justify their mean cell volume (MCV) and mean cell haemoglobin concentration (MCHC) reporting unit sizes.The reporting unit size used by many laboratories is not justified by present analytical performance. Using MU estimates to determine the reporting interval for quantitative laboratory results ensures reporting practices match local analytical performance and recognises the inherent error of the measurement process.

Standardised reporting protocol for endoscopic resection for Barrett oesophagus associated neoplasia: expert consensus recommendations

Endoscopic resection (ER) is considered the therapy of choice for intraepithelial neoplasia associated with visible lesions and T1a adenocarcinoma. Pathologists are bound to encounter specimens collected via these techniques more frequently in their practice. A standardised protocol for handling, grossing, and assessing ER specimens should be adopted to ensure that all prognostic information and characteristics influencing treatment are included in reports (see Supplementary Video Abstract, http://links.lww.com/PAT/A22). The entire specimen should be appropriately oriented, processed and assessed. An ER specimen will commonly show intraepithelial neoplasia or invasive carcinoma. There are essential features that should be recorded if invasive carcinoma is found as they dictate further management and follow-up. These features are the margin status, depth of invasion, degree of differentiation and presence or absence of lymphovascular invasion. Important features such as duplication of muscularis mucosae should be recognised to avoid misinterpretation of depth of invasion. Key diagnostic and prognostic elements that are essential for optimal clinical decisions have been included in the reporting format proposed by the Structured Pathology Reporting committee of the Royal College of Pathologists of Australasia (RCPA).

Quality standards for DNA sequence variation databases to improve clinical management under development in Australia

Despite the routine nature of comparing sequence variations identified during clinical testing to database records, few databases meet quality requirements for clinical diagnostics. To address this issue, The Royal College of Pathologists of Australasia (RCPA) in collaboration with the Human Genetics Society of Australasia (HGSA), and the Human Variome Project (HVP) is developing standards for DNA sequence variation databases intended for use in the Australian clinical environment. The outputs of this project will be promoted to other health systems and accreditation bodies by the Human Variome Project to support the development of similar frameworks in other jurisdictions.

Lab tests online Australasia

Lab Tests Online Australasia is a patient-centred website providing information on pathology testing (http://www.labtestsonline. org.au/). There is also an app that can be downloaded. While the primary purpose of this website is to provide information to patients, caregivers, and their families, it is also used by general practitioners, nurses and medical students to gain up to date information on diagnostic testing. It is a peer-reviewed, noncommercial entity providing information on tests, sample collection and clinical associations. The site is managed by the Australasian Association of Clinical Biochemists (AACB) with support from the Royal College of Pathologists of Australasia (RCPA) and a funding grant from the Quality Use of Pathology Program (Commonwealth Department of Health and Ageing). The site is accredited by HONcode, which is an ethical standard aimed at offering quality health information. As part of this accreditation the site is fully reviewed every 3 years to ensure content is current and correct. For immunology, this is currently performed by Dr Daman Langguth who has been instrumental in updating and modifying content for the Australian market.

Data set for pathology reporting of cutaneous invasive melanoma: recommendations from the international collaboration on cancer reporting (ICCR).

An accurate and complete pathology report is critical for the optimal management of cutaneous melanoma patients. Protocols for the pathologic reporting of melanoma have been independently developed by the Royal College of Pathologists of Australasia (RCPA), Royal College of Pathologists (United Kingdom) (RCPath), and College of American Pathologists (CAP). In this study, data sets, checklists, and structured reporting protocols for pathologic examination and reporting of cutaneous melanoma were analyzed by an international panel of melanoma pathologists and clinicians with the aim of developing a common, internationally agreed upon, evidence-based data set. The International Collaboration on Cancer Reporting cutaneous melanoma expert review panel analyzed the existing RCPA, RCPath, and CAP data sets to develop a protocol containing “required” (mandatory/core) and “recommended” (nonmandatory/noncore) elements. Required elements were defined as those that had agreed evidentiary support at National Health and Medical Research Council level III-2 level of evidence or above and that were unanimously agreed upon by the review panel to be essential for the clinical management, staging, or assessment of the prognosis of melanoma or fundamental for pathologic diagnosis. Recommended elements were those considered to be clinically important and recommended for good practice but with lesser degrees of supportive evidence. Sixteen core/required data elements for cutaneous melanoma pathology reports were defined (with an additional 4 core/required elements for specimens received with lymph nodes). Eighteen additional data elements with a lesser level of evidentiary support were included in the recommended data set. Consensus response values (permitted responses) were formulated for each data item. Development and agreement of this evidence-based protocol at an international level was accomplished in a timely and efficient manner, and the processes described herein may facilitate the development of protocols for other tumor types. Widespread utilization of an internationally agreed upon, structured pathology data set for melanoma will lead not only to improved patient management but is a prerequisite for research and for international benchmarking in health care.

Performance monitoring and transfusion QAP performance levels

This presentation will endeavour to provide an understanding of Performance Monitoring in Quality Assurance of Transfusion as measured by a project undertaken by the Royal College of Pathologists of Australasia (RCPA) Quality Assurance Program (QAP) in 2012. In 2001 the Commonwealth Department of Health and Ageing (DoHA) sought proposals to undertake an evaluation of Australian pathology laboratory accreditation arrangements. Recommendations from the report were that (1) the DoHA and the Health Insurance Commission seek the cooperation of the RCPA QAP to establish explicit external quality assurance performance criteria and a mechanism for the RCPA QAP to identify relatively poorly performing laboratories; (2) RCPA QAP and other external quality assurance providers regularly submit to the National Association of Testing Authorities (NATA) reports identifying laboratories that are poorly performing according to these agreed performance criteria. The review process included establishment of a methodology/scoring system; a retrospective data analysis; establishment of criteria for acceptable performance based on the retrospective data analysis and reasonable expectations for completing a corrective action. Information and results from QAP surveys was used to assess individual participant data against established criteria to provide laboratories of an objective measure of their performance relative to their peers whilst meeting the needs of the performance review process.

Point of care (POCT) testing for human immunodeficiency virus (HIV) infection in Australia: in context

The laboratory diagnosis of HIV infection is most often made by the detection of antibodies to the virus. Conventional serologi-cal tests for detection HIV antibodies are usually referred to as ‘screening or standard’ tests (the initial test) or ‘confirmatory, supplemental or reference tests’. Screening tests identify samples that contain antibodies to HIV but are usually not used to provide a presumptive diagnosis for a patient whose sample is found to be initially reactive. Only after confirmatory or reference tests have been performed can an individual conclusively be identified as being seropositive and having established HIV infection. Screening and confirmatory tests are performed in a testing strategy which has been scientifically validated for a particular population demographic to provide the most sensitive and specific result for the individual tested. For many years, point of care (PoCT, rapid or short incubation) tests for HIV have been successfully used in many developed and developing countries. In 2012, the US Food and Drug Administration (FDA) announced the approval of a home test or over-the-counter HIV PoCT that would enable individuals to perform self-testing. In many countries the use of rapid tests has overcome resource constraints where laboratory infrastructure and sample transportation logistics are limited, in remote settings and in populations where the return rate for receiving a confirmed result is poor. Recent research suggests that much HIV transmission occurs from people who have themselves only recently have become infected. Many approaches have been tried to increase the demand for testing and improve rates of testing amongst people at risk of acquiring HIV. There is a strong case of for the introduction of PoCT for HIV in Australia including the desire to improve the rates of testing for populations at risk of infection. Reducing barriers around testing through improving access and consumer experiences suggests that more convenient testing could increase the rates of testing and stimulate the demand for HIV testing in target groups. In Australia, all in vitro diagnostic devices (IVD) are regulated according to a public health risk stratification. Currently all HIV and HCV screening tests are classified in the highest category (Class 4) and undergo a high degree of scrutiny before they are approved for registration on the Australian Register of Therapeutic Goods (ARTG) and approved for sale. This ensures that tests that are available in the Australian market are of a high standard. At the time this abstract was prepared there were two PoCT tests approved on the ARTG; however, one test was approved for use as a screening test and could only be used in laboratory settings. In 2011, the National HIV Testing Policy underwent significant review and established a framework for the introduction of PoCT in Australia proposing standards around training, settings and quality assurance. This presentation will outline the current situation of point of care tests for HIV in Australia and highlight some issues around their introduction and regulation in the broad non-laboratory based context. Data will be presented on the performance of participants in the Royal College of Pathologists of Australasia (RCPA) external quality assurance program (QAP) for HIV PoCT, highlighting issues with quality in regional laboratories where PoCT are widely used.

Yeast susceptibility testing

<h3>Background</h3> Invasive yeast infections are an important clinical problem. The incidence of a non-<i>albicans Candida</i> species has been increasing and several non-<i>albicans</i> species have reduced susceptibility to azole agents. Significant work has been undertaken to improve antifungal susceptibility testing and susceptibility results help predict those isolates more likely to respond to therapy. Encouraging moves are being made to align Clinical and Laboratory Standards Institute (CLSI) and EUCAST interpretative criteria. <h3>Methods</h3> The new CLSI interpretation criteria for fluconazole, caspofungin and voriconazole will be discussed. <h3>Results</h3> The impact of the new CLSI criteria on the interpretation of more than 1400 New Zealand yeast isolates will be presented. Recent susceptibility results from the Royal College of Patholo-gists of Australasia (RCPA) Microbiology Quality Assurance Program (QAP) will also be discussed. <h3>Conclusion</h3> Although more data are required for some agents and organism pairings the use of molecular methods, pharmacodynam-ic information, epidemiological cut-off values, and clinical data will continue to improve the interpretation of yeast susceptibility results.

RCPA/HGSA Resources for quality assurance in genomics

The scope and technology of genetic testing is ever increasing and consequently the provision of external quality assessment (EQA) needs to reflect this. The Royal College of Pathologists of Australasia (RCPA)/Human Genetics Society of Australia (HGSA) Quality Assurance Program (QAP) provides assessments locally within Australasia where there is a sizable local demand. For rare disorders there are rarely enough local providers to enable effective comparisons and EQA for these is provided in collaboration with larger schemes, namely the European Molecular Network and the Cystic Fibrosis Network. A major challenge is how to provide EQA for the multitude of tests likely to appear shortly using next generation (massively parallel) sequencing; associated with this is assessment of the use of the range of bioinformatics interpretational tools which go hand in hand with this technology. Discussions are underway to consider integrating the EQA for molecular genetics and other programs with significant molecular components.

Evaluating laboratory approaches to the identification of lupus anticoagulants: A diagnostic challenge from the RCPA Haematology QAP

Laboratory identification of lupus anticoagulants (LA), an important component of the clinical diagnosis of the autoimmune disorder antiphospholipid syndrome (APS), is challenged by the heterogeneity of tests available, the diagnostic and laboratory approach undertaken, and the heterogeneity of the autoantibodies present. : To assess the laboratory approach for investigation of LA, as well as the utility of various tests and test approaches, given a difficult clinical scenario in which LA might or might not be present. Ninety-three participants in the Royal College of Pathologists of Australasia (RCPA) Haematology Quality Assurance Program (QAP) were sent 4 mL of a complex but strongly positive LA sample blinded to the nature of the abnormality. Seventy-three (79%) participants returned results and in most cases diagnostic interpretations. The laboratory approach to LA investigation of this sample was quite varied: 34.7% of participants concluded the sample was LA negative, with 91.7% of these performing dilute Russell viper venom time (dRVVT) testing without mixing, whereas 43.5% of participants identified a strong LA, with 96.7% of these having performed mixing studies. Most laboratories reporting negative LA instead identified the false presence of specific factor inhibitors against a variety of factors, including II, V and VIII. For this difficult challenge, performance of non-mixing dRVVT was associated with a high false negative LA rate.

Meet the chief examiner microbiology 2012

The Chief Examiner coordinates the MBI and two examinations, reviews, laboratory accreditation, attends the Royal College of Pathologists of Australasia (RCPA) Board of Censors meetings (2 per year), the Microbiology Advisory Meeting (~1 per year) and the RACP/RCPA Joint Specialist Advisory Committee for advanced training in Infectious diseases and Microbiology (IDJSAC) with two face to face meetings and one teleconference annually. There are a team of accredited and trained microbiology consultants who support the chief examiner and who assist with setting and marking of the microbiology examinations each year. The Chief Examiner is also supported by the RCPA management staff. The microbiology curriculum and assessment processes are continually being modernised and update to reflect modern assessment practises. Educational resources for supervisors and trainees are now available on the RCPA website and access to this and the variety of material available will be demonstrated.

Monitoring laboratory performance: assessment criteria

The Royal College of Pathologists of Australasia (RCPA) Immunology Quality Assurance Program (QAP) is developing a system to monitor laboratory performance, to be introduced in 2013. Each of the Immunochemistry, Allergy, Autoimmune and Immunophe-notyping Working Parties have produced assessment criteria on which the system will be based.

Standardisation of pathology terminology: how e-health records should work

Attempts to progress e-health in pathology in Australia have been hindered by a lack of standardisation in key requesting and reporting parameters, such as request codes, test panels, test names, units and reference intervals. Leverage off electronic health records (e.g., development and use of decision support systems) is difficult without agreement in these areas. The Royal College of Pathologists of Australasia (RCPA) led ‘Pathology Units and Terminology Standardisation’ (PUTS) project is showing leadership in these areas by bringing together pathologists, scientists and IT professionals to make recommendations on best practice. Working groups have been established to review request codes, recommended units, and reporting codes for seven pathology disciplines. Each group will also consider the terminology most applicable to that discipline (e.g., SNOMED-CT, LOINC, both, or possibly other) and where necessary highlight tests for which results should not be combined across pathology providers. Work on the ambitious Personally Controlled Electronic Health record program continues, with initial operation scheduled for mid 2012. Although participation will not initially be mandatory for patients or providers, Pathology reporting will be included. The pathology industry needs to be actively engaged in this rapidly changing landscape for optimal outcomes.

Performance monitoring in gynaecological cytopathology

Following the establishment of the Cytopathology Performance Review Committee this year, criteria for monitoring laboratory performance have been developed and a pilot phase will be undertaken in 2012. Criteria are based on both results from routine gynaecological Quality Assurance Program (QAP) surveys and Performance Measure data. The pilot phase will help determine the effectiveness of these criteria in assisting the National Association of Testing Authorities (NATA) to identify laboratories that may require early review. Criteria for the pilot are: one Performance Measure outside the National Standard set by NPAAC; non-submission of results for Performance Measures; one major error in a conventional gynaecological (GYN) survey; three unacceptable responses in any GYN survey in any 12 month period; non-submission of results for any GYN survey. Results will be reviewed within a rolling 12 month cycle. When a laboratory’s results have fallen outside these established criteria, the laboratory’s results will be forwarded to the Cytopathology Peer Review Committee for review. If results are assessed as unacceptable, notification letters will be sent to the laboratory in accordance with the framework developed by the Royal College of Pathologists of Australasia (RCPA) QAP. It is hoped the outcomes of the pilot phase of the Cytopathology Performance Monitoring Project will assist in evaluating criteria for unacceptable performance in Cytopathology. As the project progresses results will be monitored by the Cytopathology PRC and these criteria may be reviewed.

Performance monitoring in anatomical pathology

In 2012, the Royal College of Pathologists of Australasia (RCPA) Anatomical Pathology Quality Assurance Program (QAP) will introduce a pilot for performance monitoring in the General and Breast Diagnostic Modules. The Anatomical Pathology Performance Review Committee has developed a set of criteria for Diagnostic Pathology assessment. If any of the following criteria apply, a participant will be considered to be outside criteria for satisfactory performance: <h3>Participation</h3> 1 x survey non-participation. <h3>Performance of test</h3> ≥ 3 x in the bottom 10% survey rank, over 3 years; thereafter, if in bottom 10% rank subsequently. Average survey rank ≤10%, over 3 years; thereafter, if average survey rank is < the average survey rank on the previous survey; thereafter reset scoring if > 10% 3 x consecutively. If average discordant sum is ≥1.50 AND number of surveys completed is ≥2 (in rolling 12 month period); thereafter, if ≥1.50 AND ≥2 surveys completed AND survey contains discordant result. ≥5 non-concordant results per survey. <h3>Notification</h3> RCPA QAP response to notifiable unsatisfactory performance will initially take the form of letter to participants; subsequent deviations from the outlined criteria may result in copies of notifications forwarded also to National Association of Testing Authorities (NATA).

An audit of detailed margin assessment in breast conserving surgery specimens supports the routine use of shaved radial margins

Aim The status of excision margins is a well recognised predictive factor for likelihood of recurrence following breast conserving surgery (BCS). Radial margins may be examined by perpendicular sections or shaving. The aim of this audit was to determine what, if any, additional information shave margins provide. Methods Three hundred consecutive BCS specimens were reviewed, with shave margins having been performed in 209. Histological involvement of radial and shave margins for invasive carcinoma, ductal carcinoma in situ and pleomorphic lobular carcinoma in situ was recorded, as were findings in any further re-excision specimens. Results In 13% of cases shave margins only were positive, and 57% of these cases had residual invasive or in situ disease in re-excision specimens. In 8% of cases where both the radial and shave margins were involved, the positive shave margin was different to the radial and would have led to a more extensive re-excision. Therefore shave margins gave additional information to clinicians and impacted on surgical management in 21% of cases. Conclusions Shave margins from BCS specimens appear to identify margin involvement in an increased proportion of patients who would otherwise be left with residual disease. We suggest that these findings support the routine use of shave margins despite current Royal College of Pathologists of Australasia (RCPA) recommendations.

Laboratory aspects of PNH

A flow cytometric assay demonstrating the loss of GPI-linked proteins on at least two haemopoietic lineages is now the only appropriate laboratory test to diagnose paroxysmal nocturnal haemoglobinuria (PNH). The Ham’s test (1939), sugar water test (1966) and sucrose haemolysis test are no longer considered appropriate. Guidelines have recently been released by the Australasian Flow Cytometry Group and the Clinical Laboratory Standards Institute and a proficiency testing module has been commenced by the Royal College of Pathologists of Australasia (RCPA) Hae-matology Quality Assurance Program (QAP). In the 2011 QAP survey, 21 of 30laboratories used FLAER as a marker. Laboratories should report results in a format that is clear and satisfies the requirements of drug regulatory authorities. It is recommended that lineage gating of granulocytes using either CD15/SS or CD33/SS shouldbe followedbythe useofCD24/FLAER for granulocytes and CD14/FLAER for monocytes. CD59 (clone MEM43) antibodies should be used to identify Type I, II or III red cells. Anti-glycophor-yin-A (CD235a) may be used to identify red cells but needs to be titrated to avoid formation of aggregates. Careful planning can ensure that all necessary leukocyte markers can be included in a single tube for diagnosis of PNH and the detection ofsmall numbers of PNH cells in aplastic anaemia.