Standards and specifications in pathology: image management, report management and terminology.

For making medical decisions, healthcare professionals require that all necessary information is both correct and easily available. Collaborative Digital Anatomic Pathology refers to the use of information technology that supports the creation and sharing or exchange of information, including data and images, during the complex workflow performed in an Anatomic Pathology department from specimen reception to report transmission and exploitation. Collaborative Digital Anatomic Pathology is supported by standardization efforts toward knowledge representation for sharable and computable clinical information. The goal of the international integrating the Healthcare Enterprise (IHE) initiative is precisely specifying how medical informatics standards should be implemented to meet specific health care needs and making systems integration more efficient and less expensive. The IHE Anatomic Pathology initiative was launched to implement the best use of medical informatics standards in order to produce, share and exchange machine-readable structured reports and their evidences (including whole slide images) within hospitals and across healthcare facilities. DICOM supplements 122 and 145 provide flexible object information definitions dedicated respectively to specimen description and WSI acquisition, storage and display. The profiles "Anatomic Pathology Reporting for Public Health" (ARPH) and "Anatomic Pathology Structured Report" (APSR) provide standard templates and transactions for sharing or exchanging structured reports in which textual observations - encoded using PathLex, an international controlled vocabulary currently being mapped to SNOMED CT concepts - may be bound to digital images or regions of interest in images. Current implementations of IHE Anatomic Pathology profiles in North America, France and Spain demonstrate the applicability of recent advances in standards for Collaborative Digital Anatomic Pathology. The use of machine-readable format of Anatomic Pathology information supports the development of computer-based decision support as well as secondary use of Anatomic Pathology information for research or public health.

Digital Imaging and Communications in Medicine Whole Slide Imaging Connectathon at Digital Pathology Association Pathology Visions 2017.

As digital pathology systems for clinical diagnostic work applications become mainstream, interoperability between these systems from different vendors becomes critical. For the first time, multiple digital pathology vendors have publicly revealed the use of the digital imaging and communications in medicine (DICOM) standard file format and network protocol to communicate between separate whole slide acquisition, storage, and viewing components. Note the use of DICOM for clinical diagnostic applications is still to be validated in the United States. The successful demonstration shows that the DICOM standard is fundamentally sound, though many lessons were learned. These lessons will be incorporated as incremental improvements in the standard, provide more detailed profiles to constrain variation for specific use cases, and offer educational material for implementers. Future Connectathon events will expand the scope to include more devices and vendors, as well as more ambitious use cases including laboratory information system integration and annotation for image analysis, as well as more geographic diversity. Users should request DICOM features in all purchases and contracts. It is anticipated that the growth of DICOM-compliant manufacturers will likely also ease DICOM for pathology becoming a recognized standard and as such the regulatory pathway for digital pathology products.

A system for sharing routine surgical pathology specimens across institutions: the Shared Pathology Informatics Network.

This report presents an overview for pathologists of the development and potential applications of a novel Web enabled system allowing indexing and retrieval of pathology specimens across multiple institutions. The system was developed through the National Cancer Institute's Shared Pathology Informatics Network program with the goal of creating a prototype system to find existing pathology specimens derived from routine surgical and autopsy procedures ("paraffin blocks") that may be relevant to cancer research. To reach this goal, a number of challenges needed to be met. A central aspect was the development of an informatics system that supported Web-based searching while retaining local control of data. Additional aspects included the development of an eXtensible Markup Language schema, representation of tissue specimen annotation, methods for deidentifying pathology reports, tools for autocoding critical data from these reports using the Unified Medical Language System, and hierarchies of confidentiality and consent that met or exceeded federal requirements. The prototype system supported Web-based querying of millions of pathology reports from 6 participating institutions across the country in a matter of seconds to minutes and the ability of bona fide researchers to identify and potentially to request specific paraffin blocks from the participating institutions. With the addition of associated clinical and outcome information, this system could vastly expand the pool of annotated tissues available for cancer research as well as other diseases.

Protein electrophoresis and immunoglobulin analysis in HIV-infected patients.

We studied the prevalence and nature of immunoglobulin abnormalities in HIV-1-infected patients in the era of highly active antiretroviral therapy. Protein electrophoreses (PEP) were performed on and quantitative immunoglobulin levels obtained in samples from 320 consecutive HIV-1-infected patients. Samples with possible PEP abnormalities underwent immunofixation. The PEP pattern was normal in 83.8% of samples, 8.1% had subtle oligoclonal banding, and 4.4% had a low-concentration (<5% of total protein) monoclonal band. Hypogammaglobulinemia and polyclonal hypergammaglobulinemia accounted for 1.9% each. In multivariate analysis, younger age (odds ratio [OR], 1.06 with each decreasing year of life; 95% confidence interval [CI], 1.02-1.11; P = .016), female sex (OR, 2.4; 95% CI, 1.13-5.11; P = .02), viral load (OR, 1.50 with each increasing logarithmic viral load of 1.0; 95% CI, 1.14-1.98; P = .004), and CD4 cell count (> or =350 vs <350/microL [0.35 x 10(9)/L]) (OR, 2.71; 95% CI, 1.09-6.75; P = .032) were associated with monoclonal or oligoclonal banding. These results suggest that younger HIV-1-infected patients with a more robust immune system (higher CD4 cell count), which is stimulated by uncontrolled viremia, are most likely to have an augmented B-cell response to HIV infection. One manifestation of this B-cell response is low-concentration monoclonal banding in 4.4% of the patients studied.

Medical laboratory informatics.

Laboratory informatics is the application of computers and information systems to information management in the pathology laboratory. Effective information management is crucial to the success of pathologists and laboratorians. Informatics has become one of the key pillars of pathology, and the requirement for skilled informaticists in the laboratory has quickly grown. This article provides a wide-ranging review of pertinent aspects of laboratory informatics, and deals with important technical and management processes. Topics covered include personal computing, networks, databases, fundamentals and advanced functions of the laboratory information system, interfaces and standards, digital imaging, coding, hospital information systems and electronic medical records.

Refining DICOM for pathology--progress from the IHE and DICOM pathology working groups.

For making medical decisions, healthcare professionals require that all necessary information is both correct and easily available. We address the issue of integrating anatomical pathology department information into the electronic healthcare enterprise. The pathology workflow from order to report, including specimen processing and image acquisition was modelled. An integration profile - pathology general workflow- was created in the framework of the Integrating the Healthcare Enterprise (IHE). This Integration Profile relies on 8 transactions based on HL7 or DICOM standards. An important issue was to define information entities (order, imaging study and report) and real-world objects (specimen, tissue sample, slide, etc.). Joint efforts between IHE and DICOM WG26 has resulted in a proposed common model for "specimen" usable for both HL7 and DICOM transactions related to anatomic pathology.

Development and evaluation of an open source software tool for deidentification of pathology reports.

BACKGROUND: Electronic medical records, including pathology reports, are often used for research purposes. Currently, there are few programs freely available to remove identifiers while leaving the remainder of the pathology report text intact. Our goal was to produce an open source, Health Insurance Portability and Accountability Act (HIPAA) compliant, deidentification tool tailored for pathology reports. We designed a three-step process for removing potential identifiers. The first step is to look for identifiers known to be associated with the patient, such as name, medical record number, pathology accession number, etc. Next, a series of pattern matches look for predictable patterns likely to represent identifying data; such as dates, accession numbers and addresses as well as patient, institution and physician names. Finally, individual words are compared with a database of proper names and geographic locations. Pathology reports from three institutions were used to design and test the algorithms. The software was improved iteratively on training sets until it exhibited good performance. 1800 new pathology reports were then processed. Each report was reviewed manually before and after deidentification to catalog all identifiers and note those that were not removed. RESULTS: 1254 (69.7 %) of 1800 pathology reports contained identifiers in the body of the report. 3439 (98.3%) of 3499 unique identifiers in the test set were removed. Only 19 HIPAA-specified identifiers (mainly consult accession numbers and misspelled names) were missed. Of 41 non-HIPAA identifiers missed, the majority were partial institutional addresses and ages. Outside consultation case reports typically contain numerous identifiers and were the most challenging to deidentify comprehensively. There was variation in performance among reports from the three institutions, highlighting the need for site-specific customization, which is easily accomplished with our tool. CONCLUSION: We have demonstrated that it is possible to create an open-source deidentification program which performs well on free-text pathology reports.

Treatment outcomes in adults with favorable histologic type Wilms tumor-an update from the National Wilms Tumor Study Group.

PURPOSE: To describe the clinical outcomes in adults with favorable histologic type (FH) Wilms tumor (WT) registered in the National Wilms Tumor Studies (NWTS) 4-5. We also describe the results of patients treated in the "modern era" (1979-2001) with surgical staging, central pathology review and stage-appropriate multimodality treatment. METHODS AND MATERIALS: Twenty-three adult patients (> or =16 years of age) with FHWT after central pathology review were registered on NWTS 4-5. The tumor stage distribution was Stage I in 5, Stage II in 8, Stage III in 6, and Stage IV in 4 patients. All patients underwent primary nephrectomy followed by multiagent chemotherapy and/or radiotherapy (RT). All patients underwent tumor stage-based chemotherapy that generally followed existing NWTS Group (NWTSG) protocols. To analyze the outcomes of adult patients treated in the "modern era," the data from this report were combined with the data from 22 patients with FHWT previously reported in 1990 by the NWTSG. RESULTS: The 5-year relapse-free survival, overall survival, and disease-specific survival (DSS) rate was 77.3%, 82.6%, and 95.7%, respectively, for patients registered in the NWTS 4-5 protocols. Three patients (13%) died of chemotherapy-induced hepatic venoocclusive disease. For a total of 45 adults with FHWTs treated in the "modern era," the overall survival rate was 82%. The survival rate for those with Stage I, II, III, and IV disease was 100%, 92%, 70%, and 73%, respectively. Of the 12 Stage I-II patients treated with two drugs and no RT, the survival rate was 100%. The survival rate for Stage III and IV patients treated with three drugs and RT was 63% and 70%, respectively. CONCLUSION: The results of this report demonstrate that adults with FHWT treated with a multimodality approach similar to NWTSG protocols have good survival. We recommend that all adult patients be treated with stage-appropriate combined modality therapy, and furthermore, be entered in current Children's Oncology Group WT protocols so that coherent data can be gathered for this relatively rare tumor. Finally, all patients should be monitored for signs and symptoms of hepatic venoocclusive disease.

Pathology informatics fellowship training: Focus on molecular pathology.

BACKGROUND: Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology informatics training with molecular pathology is a natural extension, as molecular pathology is a subspecialty with high potential for application of modern biomedical informatics techniques. METHODS AND RESULTS: Pathology informatics and molecular pathology fellows and faculty evaluated the current fellowship program's core curriculum topics and subtopics for relevance to molecular pathology. By focusing on the overlap between the two disciplines, a structured curriculum consisting of didactics, operational rotations, and research projects was developed for those fellows interested in both pathology informatics and molecular pathology. CONCLUSIONS: The scope of molecular diagnostics is expanding dramatically as technology advances and our understanding of disease extends to the genetic level. Here, we highlight many of the informatics challenges facing molecular pathology today, and outline specific informatics principles necessary for the training of future molecular pathologists.

The ongoing evolution of the core curriculum of a clinical fellowship in pathology informatics.

The Partners HealthCare system's Clinical Fellowship in Pathology Informatics (Boston, MA, USA) faces ongoing challenges to the delivery of its core curriculum in the forms of: (1) New classes of fellows annually with new and varying educational needs and increasingly fractured, enterprise-wide commitments; (2) taxing electronic health record (EHR) and laboratory information system (LIS) implementations; and (3) increasing interest in the subspecialty at the academic medical centers (AMCs) in what is a large health care network. In response to these challenges, the fellowship has modified its existing didactic sessions and piloted both a network-wide pathology informatics lecture series and regular "learning laboratories". Didactic sessions, which had previously included more formal discussions of the four divisions of the core curriculum: Information fundamentals, information systems, workflow and process, and governance and management, now focus on group discussions concerning the fellows' ongoing projects, updates on the enterprise-wide EHR and LIS implementations, and directed questions about weekly readings. Lectures are given by the informatics faculty, guest informatics faculty, current and former fellows, and information systems members in the network, and are open to all professional members of the pathology departments at the AMCs. Learning laboratories consist of small-group exercises geared toward a variety of learning styles, and are driven by both the fellows and a member of the informatics faculty. The learning laboratories have created a forum for discussing real-time and real-world pathology informatics matters, and for incorporating awareness of and timely discussions about the latest pathology informatics literature. These changes have diversified the delivery of the fellowship's core curriculum, increased exposure of faculty, fellows and trainees to one another, and more equitably distributed teaching responsibilities among the entirety of the pathology informatics asset in the network. Though the above approach has been in place less than a year, we are presenting it now as a technical note to allow for further discussion of evolving educational opportunities in pathology informatics and clinical informatics in general, and to highlight the importance of having a flexible fellowship with active participation from its fellows.

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 laboratory's 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.

Different tracks for pathology informatics fellowship training: Experiences of and input from trainees in a large multisite fellowship program.

BACKGROUND: Pathology Informatics is a new field; a field that is still defining itself even as it begins the formalization, accreditation, and board certification process. At the same time, Pathology itself is changing in a variety of ways that impact informatics, including subspecialization and an increased use of data analysis. In this paper, we examine how these changes impact both the structure of Pathology Informatics fellowship programs and the fellows' goals within those programs. MATERIALS AND METHODS: As part of our regular program review process, the fellows evaluated the value and effectiveness of our existing fellowship tracks (Research Informatics, Clinical Two-year Focused Informatics, Clinical One-year Focused Informatics, and Clinical 1 + 1 Subspecialty Pathology and Informatics). They compared their education, informatics background, and anticipated career paths and analyzed them for correlations between those parameters and the fellowship track chosen. All current and past fellows of the program were actively involved with the project. RESULTS: Fellows' anticipated career paths correlated very well with the specific tracks in the program. A small set of fellows (Clinical - one or two year - Focused Informatics tracks) anticipated clinical careers primarily focused in informatics (Director of Informatics). The majority of the fellows, however, anticipated a career practicing in a Pathology subspecialty, using their informatics training to enhance that practice (Clinical 1 + 1 Subspecialty Pathology and Informatics Track). Significantly, all fellows on this track reported they would not have considered a Clinical Two-year Focused Informatics track if it was the only track offered. The Research and the Clinical One-year Focused Informatics tracks each displayed unique value for different situations. CONCLUSIONS: It seems a "one size fits all" fellowship structure does not fit the needs of the majority of potential Pathology Informatics candidates. Increasingly, these fellowships must be able to accommodate the needs of candidates anticipating a wide range of Pathology Informatics career paths, be able to accommodate Pathology's increasingly subspecialized structure, and do this in a way that respects the multiple fellowships needed to become a subspecialty pathologist and informatician. This is further complicated as Pathology Informatics begins to look outward and takes its place in the growing, and still ill-defined, field of Clinical Informatics, a field that is not confined to just one medical specialty, to one way of practicing medicine, or to one way of providing patient care.

A core curriculum for clinical fellowship training in pathology informatics.

BACKGROUND: In 2007, our healthcare system established a clinical fellowship program in Pathology Informatics. In 2010 a core didactic course was implemented to supplement the fellowship research and operational rotations. In 2011, the course was enhanced by a formal, structured core curriculum and reading list. We present and discuss our rationale and development process for the Core Curriculum and the role it plays in our Pathology Informatics Fellowship Training Program. MATERIALS AND METHODS: The Core Curriculum for Pathology Informatics was developed, and is maintained, through the combined efforts of our Pathology Informatics Fellows and Faculty. The curriculum was created with a three-tiered structure, consisting of divisions, topics, and subtopics. Primary (required) and suggested readings were selected for each subtopic in the curriculum and incorporated into a curated reading list, which is reviewed and maintained on a regular basis. RESULTS: Our Core Curriculum is composed of four major divisions, 22 topics, and 92 subtopics that cover the wide breadth of Pathology Informatics. The four major divisions include: (1) Information Fundamentals, (2) Information Systems, (3) Workflow and Process, and (4) Governance and Management. A detailed, comprehensive reading list for the curriculum is presented in the Appendix to the manuscript and contains 570 total readings (current as of March 2012). DISCUSSION: The adoption of a formal, core curriculum in a Pathology Informatics fellowship has significant impacts on both fellowship training and the general field of Pathology Informatics itself. For a fellowship, a core curriculum defines a basic, common scope of knowledge that the fellowship expects all of its graduates will know, while at the same time enhancing and broadening the traditional fellowship experience of research and operational rotations. For the field of Pathology Informatics itself, a core curriculum defines to the outside world, including departments, companies, and health systems considering hiring a pathology informatician, the core knowledge set expected of a person trained in the field and, more fundamentally, it helps to define the scope of the field within Pathology and healthcare in general.

Clinical fellowship training in pathology informatics: A program description.

BACKGROUND: In 2007, our healthcare system established a clinical fellowship program in pathology informatics. In 2011, the program benchmarked its structure and operations against a 2009 white paper "Program requirements for fellowship education in the subspecialty of clinical informatics", endorsed by the Board of the American Medical Informatics Association (AMIA) that described a proposal for a general clinical informatics fellowship program. METHODS: A group of program faculty members and fellows compared each of the proposed requirements in the white paper with the fellowship program's written charter and operations. The majority of white paper proposals aligned closely with the rules and activities in our program and comparison was straightforward. In some proposals, however, differences in terminology, approach, and philosophy made comparison less direct, and in those cases, the thinking of the group was recorded. After the initial evaluation, the remainder of the faculty reviewed the results and any disagreements were resolved. RESULTS: The most important finding of the study was how closely the white paper proposals for a general clinical informatics fellowship program aligned with the reality of our existing pathology informatics fellowship. The program charter and operations of the program were judged to be concordant with the great majority of specific white paper proposals. However, there were some areas of discrepancy and the reasons for the discrepancies are discussed in the manuscript. CONCLUSIONS: After the comparison, we conclude that the existing pathology informatics fellowship could easily meet all substantive proposals put forth in the 2009 clinical informatics program requirements white paper. There was also agreement on a number of philosophical issues, such as the advantages of multiple fellows, the need for core knowledge and skill sets, and the need to maintain clinical skills during informatics training. However, there were other issues, such as a requirement for a 2-year fellowship and for informatics fellowships to be done after primary board certification, that pathology should consider carefully as it moves toward a subspecialty status and board certification.

Pathology informatics fellowship retreats: The use of interactive scenarios and case studies as pathology informatics teaching tools.

BACKGROUND: Last year, our pathology informatics fellowship added informatics-based interactive case studies to its existing educational platform of operational and research rotations, clinical conferences, a common core curriculum with an accompanying didactic course, and national meetings. METHODS: The structure of the informatics case studies was based on the traditional business school case study format. Three different formats were used, varying in length from short, 15-minute scenarios to more formal multiple hour-long case studies. Case studies were presented over the course of three retreats (Fall 2011, Winter 2012, and Spring 2012) and involved both local and visiting faculty and fellows. RESULTS: Both faculty and fellows found the case studies and the retreats educational, valuable, and enjoyable. From this positive feedback, we plan to incorporate the retreats in future academic years as an educational component of our fellowship program. CONCLUSIONS: Interactive case studies appear to be valuable in teaching several aspects of pathology informatics that are difficult to teach in more traditional venues (rotations and didactic class sessions). Case studies have become an important component of our fellowship's educational platform.

Standardizing the use of whole slide images in digital pathology.

Whole slide imaging/images (WSI) offers promising new perspectives for digital pathology. We launched an initiative in the anatomic pathology (AP) domain of integrating the healthcare enterprise (IHE) to define standards-based informatics transactions for integrating AP information and WSI. The IHE integration and content profiles developed as a result of this initiative successfully support the basic image acquisition and reporting processes in AP laboratories and provide a standard solution for sharing or exchanging structured AP reports in which observations can be explicitly bound to WSI or to regions of interest (ROI) in images.

Recent advances in standards for Collaborative Digital Anatomic Pathology.

CONTEXT: Collaborative Digital Anatomic Pathology refers to the use of information technology that supports the creation and sharing or exchange of information, including data and images, during the complex workflow performed in an Anatomic Pathology department from specimen reception to report transmission and exploitation. Collaborative Digital Anatomic Pathology can only be fully achieved using medical informatics standards. The goal of the international integrating the Healthcare Enterprise (IHE) initiative is precisely specifying how medical informatics standards should be implemented to meet specific health care needs and making systems integration more efficient and less expensive. OBJECTIVE: To define the best use of medical informatics standards in order to share and exchange machine-readable structured reports and their evidences (including whole slide images) within hospitals and across healthcare facilities. METHODS: Specific working groups dedicated to Anatomy Pathology within multiple standards organizations defined standard-based data structures for Anatomic Pathology reports and images as well as informatic transactions in order to integrate Anatomic Pathology information into the electronic healthcare enterprise. RESULTS: The DICOM supplements 122 and 145 provide flexible object information definitions dedicated respectively to specimen description and Whole Slide Image acquisition, storage and display. The content profile "Anatomic Pathology Structured Report" (APSR) provides standard templates for structured reports in which textual observations may be bound to digital images or regions of interest. Anatomic Pathology observations are encoded using an international controlled vocabulary defined by the IHE Anatomic Pathology domain that is currently being mapped to SNOMED CT concepts. CONCLUSION: Recent advances in standards for Collaborative Digital Anatomic Pathology are a unique opportunity to share or exchange Anatomic Pathology structured reports that are interoperable at an international level. The use of machine-readable format of APSR supports the development of decision support as well as secondary use of Anatomic Pathology information for epidemiology or clinical research.