Alexis B. Carter

Validating Whole Slide Imaging for Diagnostic Purposes in Pathology: Guideline from the College of American Pathologists Pathology and Laboratory Quality Center

CONTEXT There is increasing interest in using whole slide imaging (WSI) for diagnostic purposes (primary and/or consultation). An important consideration is whether WSI can safely replace conventional light microscopy as the method by which pathologists review histologic sections, cytology slides, and/or hematology slides to render diagnoses. Validation of WSI is crucial to ensure that diagnostic performance based on digitized slides is at least equivalent to that of glass slides and light microscopy. Currently, there are no standard guidelines regarding validation of WSI for diagnostic use. OBJECTIVE To recommend validation requirements for WSI systems to be used for diagnostic purposes. DESIGN The College of American Pathologists Pathology and Laboratory Quality Center convened a nonvendor panel from North America with expertise in digital pathology to develop these validation recommendations. A literature review was performed in which 767 international publications that met search term requirements were identified. Studies outside the scope of this effort and those related solely to technical elements, education, and image analysis were excluded. A total of 27 publications were graded and underwent data extraction for evidence evaluation. Recommendations were derived from the strength of evidence determined from 23 of these published studies, open comment feedback, and expert panel consensus. RESULTS Twelve guideline statements were established to help pathology laboratories validate their own WSI systems intended for clinical use. Validation of the entire WSI system, involving pathologists trained to use the system, should be performed in a manner that emulates the laboratorys actual clinical environment. It is recommended that such a validation study include at least 60 routine cases per application, comparing intraobserver diagnostic concordance between digitized and glass slides viewed at least 2 weeks apart. It is important that the validation process confirm that all material present on a glass slide to be scanned is included in the digital image. CONCLUSIONS Validation should demonstrate that the WSI system under review produces acceptable digital slides for diagnostic interpretation. The intention of validating WSI systems is to permit the clinical use of this technology in a manner that does not compromise patient care.

Intraoperative Testing for Parathyroid Hormone: A Comprehensive Review of the Use of the Assay and the Relevant Literature

OBJECTIVE The rapid intraoperative parathyroid hormone assay is transforming the parathyroidectomy procedure. We present a review of the literature on the use of the assay as an adjunct to surgery. To our knowledge, this is the first review of the literature to encompass and compare all known primary studies of this assay in parathyroidectomy patients. DATA SOURCES Articles were collected by searching MEDLINE databases using relevant terminology. The references of these articles were reviewed for additional studies. Supplementary articles pertinent to the parathyroidectomy procedure, preoperative parathyroid localization studies, and intraoperative parathyroid hormone assay development also were examined. STUDY SELECTION AND DATA EXTRACTION One hundred sixty-five references were analyzed and categorized separately into groups. DATA SYNTHESIS The primary studies of intraoperative data on patients undergoing parathyroidectomy were compared when possible. Studies were analyzed by type of assay used, where performed, turnaround time, and efficiency of use. Reviews of the types of parathyroid surgery and preoperative localization were included for educational purposes.Conclusions.-The intraoperative parathyroid hormone assay is a useful adjunct to preoperative imaging and parathyroid surgery because of its unique ability to detect an occult residuum of hyperfunctioning parathyroid tissue. Use of this assay will obviate the need for frozen section in most routine cases. The test facilitates minimally invasive parathyroidectomy for single parathyroid adenomas, which, in turn, improves cost-effectiveness and cosmetic outcome. Its use in patients with known preoperative multiglandular disease is promising but requires further study.

Use of FTA Gene Guard Filter Paper for the Storage and Transportation of Tumor Cells for Molecular Testing

CONTEXT Efficient methods of storing tumor specimens for molecular testing are needed in the modern surgical pathology laboratory. The FTA Gene Guard system is a novel method for the collection and room temperature storage of blood samples for DNA testing. The method uses index card-sized filter papers that provide an ideal medium on which to store tumor specimens for DNA testing. OBJECTIVE To determine whether FTA filter paper can be used in the surgical pathology laboratory to store tumor cells for DNA testing. DESIGN Cell suspensions were prepared from 60 surgical specimens, and DNA was extracted either immediately or after storage on FTA paper. The DNA extracted by each method was tested by polymerase chain reaction (PCR) for the beta-globin and interferon gamma genes, and the results were compared. Fifteen lymph node specimens stored on FTA paper were then tested for immunoglobulin heavy chain (IgH) gene rearrangement by PCR, and these results were compared with those obtained for immediately extracted DNA. SETTING University medical center. RESULTS The DNA extracted from cells stored on FTA paper performed as well in the PCR as the freshly extracted DNA in nearly all cases (>95%). The results of tests for IgH gene rearrangements showed 100% concordance between the 2 methods of DNA extraction.Conclusion.-Cells from surgical specimens can be stored on FTA paper for extended lengths of time, and DNA can be extracted from these cells for PCR-based testing. FTA filter paper is a reliable medium for the storage and/or transport of tumor cells for PCR-based DNA analysis.

Telepathology for patient care: what am I getting myself into?

The vast advancements in telecommunications and converting medical information to a digital format have increased the number of applications within telemedicine. Telepathology, in simplest terms, is the practice of formally rendering a pathologic diagnosis based upon examination of an image rather than of a glass slide through traditional microscopy. The use of telepathology for clinical patient care has so far been limited to relatively few large academic institutions. Although a number of challenges remain, there is increasing demand for the use of information technology in pathology as a whole owing to the expansion of health care networks and the opportunity to enhance the quality of service delivered to patients. The software used to acquire, display, and manage digital images for clinical patient care may be subject to national and federal regulations just as is any other electronic information system. Despite the barriers, telepathology systems possess the capability to help manage pathology cases on a global scale, improve laboratory workload distribution, increase standardization of practice and enable new classes of ancillary studies to facilitate diagnosis and education even in the most remote parts of the earth.

The history of pathology informatics: A global perspective

Pathology informatics has evolved to varying levels around the world. The history of pathology informatics in different countries is a tale with many dimensions. At first glance, it is the familiar story of individuals solving problems that arise in their clinical practice to enhance efficiency, better manage (e.g., digitize) laboratory information, as well as exploit emerging information technologies. Under the surface, however, lie powerful resource, regulatory, and societal forces that helped shape our discipline into what it is today. In this monograph, for the first time in the history of our discipline, we collectively perform a global review of the field of pathology informatics. In doing so, we illustrate how general far-reaching trends such as the advent of computers, the Internet and digital imaging have affected pathology informatics in the world at large. Major drivers in the field included the need for pathologists to comply with national standards for health information technology and telepathology applications to meet the scarcity of pathology services and trained people in certain countries. Following trials by a multitude of investigators, not all of them successful, it is apparent that innovation alone did not assure the success of many informatics tools and solutions. Common, ongoing barriers to the widespread adoption of informatics devices include poor information technology infrastructure in undeveloped areas, the cost of technology, and regulatory issues. This review offers a deeper understanding of how pathology informatics historically developed and provides insights into what the promising future might hold.

Standards and Guidelines for Validating Next-Generation Sequencing Bioinformatics Pipelines: A Joint Recommendation of the Association for Molecular Pathology and the College of American Pathologists

Bioinformatics pipelines are an integral component of next-generation sequencing (NGS). Processing raw sequence data to detect genomic alterations has significant impact on disease management and patient care. Because of the lack of published guidance, there is currently a high degree of variability in how members of the global molecular genetics and pathology community establish and validate bioinformatics pipelines. Improperly developed, validated, and/or monitored pipelines may generate inaccurate results that may have negative consequences for patient care. To address this unmet need, the Association of Molecular Pathology, with organizational representation from the College of American Pathologists and the American Medical Informatics Association, has developed a set of 17 best practice consensus recommendations for the validation of clinical NGS bioinformatics pipelines. Recommendations include practical guidance for laboratories regarding NGS bioinformatics pipeline design, development, and operation, with additional emphasis on the role of a properly trained and qualified molecular professional to achieve optimal NGS testing quality.

Digital Pathology: Data-Intensive Frontier in Medical Imaging

Pathology is a medical subspecialty that practices the diagnosis of disease. Microscopic examination of tissue reveals information enabling the pathologist to render accurate diagnoses and to guide therapy. The basic process by which anatomic pathologists render diagnoses has remained relatively unchanged over the last century, yet advances in information technology now offer significant opportunities in image-based diagnostic and research applications. Pathology has lagged behind other healthcare practices such as radiology where digital adoption is widespread. As devices that generate whole slide images become more practical and affordable, practices will increasingly adopt this technology and eventually produce an explosion of data that will quickly eclipse the already vast quantities of radiology imaging data. These advances are accompanied by significant challenges for data management and storage, but they also introduce new opportunities to improve patient care by streamlining and standardizing diagnostic approaches and uncovering disease mechanisms. Computer-based image analysis is already available in commercial diagnostic systems, but further advances in image analysis algorithms are warranted in order to fully realize the benefits of digital pathology in medical discovery and patient care. In coming decades, pathology image analysis will extend beyond the streamlining of diagnostic workflows and minimizing interobserver variability and will begin to provide diagnostic assistance, identify therapeutic targets, and predict patient outcomes and therapeutic responses.

Privacy and security of patient data in the pathology laboratory

Data protection and security are critical components of routine pathology practice because laboratories are legally required to securely store and transmit electronic patient data. With increasing connectivity of information systems, laboratory work-stations, and instruments themselves to the Internet, the demand to continuously protect and secure laboratory information can become a daunting task. This review addresses informatics security issues in the pathology laboratory related to passwords, biometric devices, data encryption, internet security, virtual private networks, firewalls, anti-viral software, and emergency security situations, as well as the potential impact that newer technologies such as mobile devices have on the privacy and security of electronic protected health information (ePHI). In the United States, the Health Insurance Portability and Accountability Act (HIPAA) govern the privacy and protection of medical information and health records. The HIPAA security standards final rule mandate administrative, physical, and technical safeguards to ensure the confidentiality, integrity, and security of ePHI. Importantly, security failures often lead to privacy breaches, invoking the HIPAA privacy rule as well. Therefore, this review also highlights key aspects of HIPAA and its impact on the pathology laboratory in the United States.

Intraoperative Parathyroid Hormone Testing Survey of Testing Program Characteristics

OBJECTIVE To examine the number and testing characteristics of laboratories that offer intraoperative testing of intact parathyroid hormone (PTH). DESIGN Laboratories (n = 355) that participated in 2001 in PTH proficiency testing with the College of American Pathologists Special Ligand Survey were surveyed about intraoperative PTH testing. RESULTS Of the 320 laboratories that responded to the survey, 92 performed intraoperative PTH testing. Testing practices were divided nearly equally among laboratories that performed intraoperative PTH testing for all parathyroidectomies (40%), most but not all cases (31%), and less than half of cases (30%). Testing frequency usually was low, with about two thirds of laboratories reporting 5 or fewer cases per month. A surprising finding was that, although intraoperative PTH testing originally became widely practiced as a point-of-care test, 71% of laboratories performed testing in a central laboratory, 6% in satellite laboratories, and only 23% in operating suites. A survey of methods showed that 33% used the manual QuiCk-Intraoperative test, 47% used the automated Immulite Turbo intact PTH assay, and 20% used other methods. CONCLUSIONS Intraoperative testing of intact PTH, although relatively new, has come into widespread practice during parathyroid surgery. Service delivery has evolved from a point-of-care model toward a central laboratory model, with this test serving as an illustrative example of factors that affect the balance between point-of-care and laboratory testing.

Computational Pathology: A Path Ahead

CONTEXT We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. OBJECTIVE To define the scope and needs of computational pathology. DATA SOURCES A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. CONCLUSIONS The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and nonpathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology.