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Context.--Chimeric antigen receptor T-cell (CAR-T) technology has shown great promise in both clinical and preclinical models in mediating potent and specific antitumor activity. With the advent of US Food and Drug Administration-approved CAR-T therapies for B-cell lymphoblastic leukemia and B-cell non-Hodgkin lymphomas, CAR-T therapy is poised to become part of mainstream clinical practice. Objective.--To educate pathologists on CAR-T and chimeric antigen receptor-derived cellular therapy, provide a better understanding of their role in this process, explain important regulatory aspects of CAR-T therapy, and advocate for pathologist involvement in the delivery and monitoring of chimeric antigen receptor-based treatments. Much of the focus of this article addresses US Food and Drug Administration-approved therapies; however, more general issues and future perspectives are considered for therapies in development. Design.--A CAR-T workgroup, facilitated by the College of American Pathologists Personalized Health Care Committee and consisting of pathologists of various backgrounds, was convened to develop a summary guidance paper for the College of American Pathologists Council on Scientific Affairs. Results.--The workgroup identified gaps in pathologists' knowledge of CAR-T therapy, including uncertainty in the role of the clinical laboratory in supporting CAR-T therapy. The workgroup considered these issues and summarized the findings to assist pathologists to become stakeholders in CAR-T therapy administration. Conclusions.--This manuscript serves to both educate pathologists on CAR-T therapy and serve as a point of initial discussions in areas of CAR-T science, clinical therapy, and regulatory issues as CAR-T therapies continue to be introduced into clinical practice. (Arch Pathol Lab Med. 2021;145:704-716; doi: 10.5858/arpa.2019-0632-CP, Precision medicine for cancer therapy has used both targeted molecular approaches that are directed against a specific tumor-associated molecular aberration and immunomodulatory therapies, which enhance antitumor immunity. Immunomodulatory therapies either [...]

Context.--The need for appropriate specimen use for ancillary testing has become more commonplace in the practice of pathology. This, coupled with improvements in technology, often provides less invasive methods of testing, but presents new challenges to appropriate specimen collection and handling of these small specimens, including thoracic small biopsy and cytology samples. Objective.--To develop a clinical practice guideline including recommendations on how to obtain, handle, and process thoracic small biopsy and cytology tissue specimens for diagnostic testing and ancillary studies. Methods.--The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Core needle biopsy, touch preparation, fine-needle aspiration, and effusion specimens with thoracic diseases including malignancy, granulomatous process/sarcoidosis, and infection (eg, tuberculosis) were deemed within scope. Ancillary studies included immunohistochemistry and immunocytochemistry, fluorescence in situ hybridization, mutational analysis, flow cytometry, cytogenetics, and microbiologic studies routinely performed in the clinical pathology laboratory. The use of rapid on-site evaluation was also covered. Results.--Sixteen guideline statements were developed to assist clinicians and pathologists in collecting and processing thoracic small biopsy and cytology tissue samples. Conclusions.--Based on the systematic review and expert panel consensus, thoracic small specimens can be handled and processed to perform downstream testing (eg, molecular markers, immunohistochemical biomarkers), core needle and fine-needle techniques can provide appropriate cytologic and histologic specimens for ancillary studies, and rapid on-site cytologic evaluation remains helpful in appropriate triage, handling, and processing of specimens. doi: 10.5858/arpa.2020-0119-CP, With the advances in minimally invasive sampling techniques, the ability to provide a diagnosis and perform multiple ancillary studies on limited-volume tissue samples, including small biopsy and cytology specimens, has [...]

* Context.--To date, the College of American Pathologists (CAP) has developed 17 laboratory practice guidelines (LPGs) including updates. In 2013, the CAP was awarded a 5-year cooperative agreement grant from the United States Centers for Disease Control and Prevention to increase the effectiveness of LPGs. Objective.--To assess the awareness and adoption of 2 CAP LPGs: immunohistochemical (IHC) assay validation and initial workup of acute leukemia. Design.--Baseline surveys for each LPG were conducted in 2010 and 2015, respectively. To measure the adoption of guideline recommendations and inform future updates, a follow-up study consisting of surveys, telephone interviews, and focus group sessions was conducted in laboratories that indicated they perform IHC testing. A follow-up study for the acute leukemia LPG is planned. Results.--For the IHC Validation LPG, a total of 1624 survey responses, 40 telephone interviews, and discussions with 5 focus group participants were analyzed. The response rate for the aforementioned 3 modalities was 46%, 13%, and 3%, respectively. All modalities indicated most respondents were aware of the LPG and had adopted most or all of its recommendations. Respondents expressed needs for continued communication, increased specificity, and more prescriptive recommendations when the guideline is updated. Conclusions.--While data-driven development of evidence-based LPGs requires significant resources, active data collection to identify gaps and assess adoption contributes to improved laboratory testing practices in support of patient care. The CAP identified sustainable modalities to track metrics and developed multiple tools that should improve guideline development, adoption, and implementation. Of these modalities, written or electronic surveys were the most logistically feasible and had the highest response rate. (Arch Pathol Lab Med. 2020;144:83-89; doi: 10.5858/arpa.2018-0276-CP), The United States Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) established minimum requirements for assuring the quality of laboratory testing in US clinical laboratories. (1) To ensure accurate diagnosis [...]

* Biospecimens acquired during routine medical practice are the primary sources of molecular information about patients and their diseases that underlies precision medicine and translational research. In cancer care, molecular analysis of biospecimens is especially common because it often determines treatment choices and may be used to monitor therapy in real time. However, patient specimens are collected, handled, and processed according to routine clinical procedures during which they are subjected to factors that may alter their molecular quality and composition. Such artefactual alteration may skew data from molecular analyses, render analysis data uninterpretable, or even preclude analysis altogether if the integrity of a specimen is severely compromised. As a result, patient care and safety may be affected, and medical research dependent on patient samples may be compromised. Despite these issues, there is currently no requirement to control or record preanalytical variables in clinical practice with the single exception of breast cancer tissue handled according to the guideline jointly developed by the American Society of Clinical Oncology and College of American Pathologists (CAP) and enforced through the CAP Laboratory Accreditation Program. Recognizing the importance of molecular data derived from patient specimens, the CAP Personalized Healthcare Committee established the Preanalytics for Precision Medicine Project Team to develop a basic set of evidence-based recommendations for key preanalytics for tissue and blood specimens. If used for biospecimens from patients, these preanalytical recommendations would ensure the fitness of those specimens for molecular analysis and help to assure the quality and reliability of the analysis data. (Arch Pathol Lab Med. 2019;143:1346-1363; doi: 10.5858/arpa.2019-0009-SA), OVERVIEW: THE CRITICAL ROLE OF PREANALYTICS IN THE MOLECULAR ANALYSIS OF PATIENT BIOSPECIMENS Biospecimens acquired during routine medical practice are the primary sources of the molecular information about patients and [...]

* Context.--In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing.Objective.--To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update.Design.--The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations.Results.--Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline.Conclusions.--The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes (ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to 'rule in' targetable mutations when tissue is limited or hard to obtain.(Arch Pathol Lab Med. 2018;142:321-346; doi: 10.5858/arpa.2017-0388-CP), Patients with advanced lung cancer have a poor prognosis, with a median survival of 1 year. However, for many patients whose tumors harbor certain specific molecular alterations (eg, activating alterations [...]

Context.--Laboratories must demonstrate analytic validity before any test can be used clinically, but studies have shown inconsistent practices in immunohistochemical assay validation. Objective.--To assess changes in immunohistochemistry analytic validation practices after publication of an evidence-based laboratory practice guideline. Design.--A survey on current immunohistochemistry assay validation practices and on the awareness and adoption of a recently published guideline was sent to subscribers enrolled in one of 3 relevant College of American Pathologists proficiency testing programs and to additional nonsubscribing laboratories that perform immunohistochemical testing. The results were compared with an earlier survey of validation practices. Results.--Analysis was based on responses from 1085 laboratories that perform immunohistochemical staining. Of 1057 responses, 65.4% (691) were aware of the guideline recommendations before this survey was sent and 79.9% (550 of 688) of those have already adopted some or all of the recommendations. Compared with the 2010 survey, a significant number of laboratories now have written validation procedures for both predictive and nonpredictive marker assays and specifications for the minimum numbers of cases needed for validation. There was also significant improvement in compliance with validation requirements, with 99% (100 of 102) having validated their most recently introduced predictive marker assay, compared with 74.9% (326 of 435) in 2010. The difficulty in finding validation cases for rare antigens and resource limitations were cited as the biggest challenges in implementing the guideline. Conclusions.--Dissemination of the 2014 evidencebased guideline validation practices had a positive impact on laboratory performance; some or all of the recommendations have been adopted by nearly 80% of respondents. (Arch Pathol Lab Med. 2017;141:1247-1254; doi: 10.5858/arpa.2016-0558-CP), The College of American Pathologists (CAP) Pathology and Laboratory Quality Center (the CAP Center) develops and maintains evidence-based laboratory practice guidelines (LPGs) that follow the US Institute of Medicine's Clinical [...]

The College of American Pathologists (CAP) made a strategic decision 10 years ago to develop and publish evidence-based laboratory practice guidelines (LPGs). As the CAP had worked previously with the [...]

Context.--A cooperative agreement between the College of American Pathologists (CAP) and the United States Centers for Disease Control and Prevention was undertaken to measure laboratories' awareness and implementation of an evidence-based laboratory practice guideline (LPG) on immunohistochemical (IHC) validation practices published in 2014. Objective.--To establish new benchmark data on IHC laboratory practices. Design.--A 2015 survey on IHC assay validation practices was sent to laboratories subscribed to specific CAP proficiency testing programs and to additional non subscribing laboratories that perform IHC testing. Specific questions were designed to capture laboratory practices not addressed in a 2010 survey. Results.--The analysis was based on responses from 1085 laboratories that perform IHC staining. Ninety-six percent (809 of 844) always documented validation of IHC assays. Sixty percent (648 of 1078) had separate procedures for predictive and nonpredictive markers, 42.7% (220 of 515) had procedures for laboratory-developed tests, 50% (349 of 697) had procedures for testing cytologic specimens, and 46.2% (363 of 785) had procedures for testing decalcified specimens. Minimum case numbers were specified by 85.9% (720 of 838) of laboratories for non-predictive markers and 76% (584 of 768) for predictive markers. Median concordance requirements were 95% for both types. For initial validation, 75.4% (538 of 714) of laboratories adopted the 20-case minimum for non-predictive markers and 45.9% (266 of 579) adopted the 40-case minimum for predictive markers as outlined in the 2014 LPG. The most common method for validation was correlation with morphology and expected results. Laboratories also reported which assay changes necessitated revalidation and their minimum case requirements. Conclusions.--Benchmark data on current IHC validation practices and procedures may help laboratories understand the issues and influence further refinement of LPG recommendations. (Arch Pathol Lab Med. 2017;141:1255-1261; doi: 10.5858/arpa.2016-0559-CP), In 2015, the College of American Pathologists (CAP) conducted a survey of laboratory practices to examine the current state of immunohistochemical assay (IHC) validation procedures, assess general awareness of the [...]

Objectives.--To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. Methods.--The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. Results.--Twenty-one guideline statements were established. Conclusions.--Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented. (Arch Pathol Lab Med. 2017; 141:625-657; doi: 10.5858/arpa.2016-0554-CP), Molecular testing to select targeted and conventional therapies for patients with colorectal cancer (CRC) has been the focus of a number of recent studies and is becoming standard practice for [...]

Context.--Genomic sequencing for cancer is offered by commercial for-profit laboratories, independent laboratory networks, and laboratories in academic medical centers and integrated health networks. The variability among the tests has created a complex, confusing environment. Objective.--To address the complexity, the Personalized Health Care (PHC) Committee of the College of American Pathologists proposed the development of a cancer genomics resource list (CGRL). The goal of this resource was to assist the laboratory pathology and clinical oncology communities. Design.--The PHC Committee established a working group in 2012 to address this goal. The group consisted of site-specific experts in cancer genetic sequencing. The group identified current next-generation sequencing (NGS)-based cancer tests and compiled them into a usable resource. The genes were annotated by the working group. The annotation process drew on published knowledge, including public databases and the medical literature. Results.--The compiled list includes NGS panels offered by 19 laboratories or vendors, accompanied by annotations. The list has 611 different genes for which NGS-based mutation testing is offered. Surprisingly, of these 611 genes, 0 genes were listed in every panel, 43 genes were listed in 4 panels, and 54 genes were listed in 3 panels. In addition, tests for 393 genes were offered by only 1 or 2 institutions. Table 1 provides an example of gene mutations offered for breast cancer genomic testing with the annotation as it appears in the CGRL 2014. Conclusions.--The final product, referred to as the Cancer Genomics Resource List 2014, is available as supplemental digital content. (Arch Pathol Lab Med. 2015; 139:989-1008; doi: 10.5858/arpa.2014-0330-CP), The last 10 years have seen a transformation in genomic medicine and its application to cancer research and clinical care. (1, 2) Comprehensive sequencing efforts have identified at least 140 [...]

Much has been written recently about the remarkable transformation new DNA sequencing technologies are bringing to medicine, delivering vast amounts of genetic information speedily and with ever-decreasing cost. Glib references [...]

The article by Bass et al titled, 'A review of pre-analytical factors affecting molecular, protein, and morphological analysis of formalin-fixed, paraffin-embedded (FFPE) tissue: how well do you know your FFPE [...]

Context.--The College of American Pathologists surveys are the largest laboratory peer comparison programs in the world. These programs allow laboratories to regularly evaluate their performance and improve the accuracy of the patient test results they provide. Proficiency testing is offered twice a year to laboratories performing microsatellite instability testing. These surveys are designed to emulate clinical practice, and some surveys have more challenging cases to encourage the refinement of laboratory practices. Objective.--This report summarizes the results and trends in microsatellite instability proficiency testing from participating laboratories from the inception of the program in 2005 through 2012. Design.--We compiled and analyzed data for 16 surveys of microsatellite instability proficiency testing during 2005 to 2012. Results.--The number of laboratories participating in the microsatellite instability survey has more than doubled from 42 to 104 during the 8 years analyzed. An average of 95.4% of the laboratories correctly classified each of the survey test samples from the 2005A through 2012B proficiency challenges. In the 2011B survey, a lower percentage of laboratories (78.4%) correctly classified the specimen, possibly because of overlooking subtle changes of microsatellite instability and/or failing to enrich the tumor content of the specimen to meet the limit of detection of their assay. Conclusions.--In general, laboratories performed well in microsatellite instability testing. This testing will continue to be important in screening patients with colorectal and other cancers for Lynch syndrome and guiding the management of patients with sporadic colorectal cancer. (Arch Pathol Lab Med. 2014; 138:363-370; doi: 10.5858/arpa.2013-0159-CP), Although most cases of colorectal cancer (CRC) are sporadic, approximately 2% to 3% are due to the hereditary CRC syndrome known as hereditary nonpolyposis CRC (1) or Lynch syndrome (LS). [...]

The College of American Pathologists offers these templates to assist pathologists in providing clinically useful and relevant information when reporting results of biomarker testing. The College regards the reporting elements [...]

The College of American Pathologists offers these templates to assist pathologists in providing clinically useful and relevant information when reporting results of biomarker testing. The College regards the reporting elements [...]

This issue of Archives of Pathology & Laboratory Medicine includes a white paper commissioned by the College of American Pathologists (Dash RC, et al) that describes the many elements that [...]

* Context.--Molecular pathology is a rapidly growing area of laboratory medicine in which DNA and RNA are analyzed. The recent introduction of array technology has added another layer of complexity involving massive parallel analysis of multiple genes, transcripts, or proteins. Objective.--As molecular technologies are increasingly implemented in clinical settings, it is important to bring uniformity to the way that test results are reported. Data Sources.--The College of American Pathologists Molecular Pathology Resource Committee members summarize elements that are already common to virtually all molecular pathology reports, as set forth in the College of American Pathologists checklists used in the laboratory ac creditation process. Consensus recommendations are proposed to improve report format and content, and areas of controversy are discussed. Resources are cited that promote use of proper gene nomenclature and that describe methods for reporting mutations, translocations, microsatellite instability, and other genetic alterations related to inherited disease, cancer, identity testing, microbiology, and pharmacogenetics. Conclusions.--These resources and recommendations provide a framework for composing patient reports to convey molecular test results and their clinical significance to members of the health care team. (Arch Pathol Lab Med. 2007;131:852-863), The physician who orders a molecular test expects the laboratory report to state what test was done and the result that was obtained. Many clinicians find it helpful if the [...]

* Context.--The diagnosis of B-cell lymphoid malignancy can frequently be substantiated by detecting clonal immunoglobulin heavy chain (IGH) gene rearrangements, which is typically done by polymerase chain reaction (PCR) amplification [...]

The College of American Pathologists offers these templates to assist pathologists in providing clinically useful and relevant information when reporting results of biomarker testing. The College regards the reporting elements in the templates as important elements of the biomarker test report, but the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice. [ABSTRACT FROM AUTHOR]