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* Context.--Rapid advancements in the understanding and manipulation of tumor-immune interactions have led to the approval of immune therapies for patients with non-small cell lung cancer. Certain immune checkpoint inhibitor therapies require the use of companion diagnostics, but methodologic variability has led to uncertainty around test selection and implementation in practice. Objective.--To develop evidence-based guideline recommendations for the testing of immunotherapy/immunomodulatory biomarkers, including programmed death ligand-1 (PD-L1) and tumor mutation burden (TMB), in patients with lung cancer. Design.--The College of American Pathologists convened a panel of experts in non-small cell lung cancer and biomarker testing to develop evidence-based recommendations in accordance with the standards for trustworthy clinical practice guidelines established by the National Academy of Medicine. A systematic literature review was conducted to address 8 key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, recommendations were created from the available evidence, certainty of that evidence, and key judgments as defined in the GRADE Evidence to Decision framework. Results.--Six recommendation statements were developed. Conclusions.--This guideline summarizes the current understanding and hurdles associated with the use of PD-L1 expression and TMB testing for immune checkpoint inhibitor therapy selection in patients with advanced non-small cell lung cancer and presents evidence-based recommendations for PD-L1 and tMb testing in the clinical setting. doi: 10.5858/arpa.2023-0536-CP), The advent of immune modulatory therapy has led to a radical shift in the treatment paradigm for patients with a wide range of cancers. The clinical impact of these therapies, [...]

* Context.--The US Food and Drug Administration (FDA) approved immune checkpoint inhibitor therapy for patients with advanced solid tumors that have DNA mismatch repair defects or high levels of microsatellite instability; however, the FDA provided no guidance on which specific clinical assays should be used to determine mismatch repair status. Objective.--To develop an evidence-based guideline to identify the optimal clinical laboratory test to identify defects in DNA mismatch repair in patients with solid tumor malignancies who are being considered for immune checkpoint inhibitor therapy. Design.--The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Using the National Academy of Medicine-endorsed Grading of Recommendations Assessment, Development and Evaluation approach, the recommendations were derived from available evidence, strength of that evidence, open comment feedback, and expert panel consensus. Mismatch repair immunohistochemistry, microsatellite instability derived from both polymerase chain reaction and next-generation sequencing, and tumor mutation burden derived from large panel next-generation sequencing were within scope. Results.--Six recommendations and 3 good practice statements were developed. More evidence and evidence of higher quality were identified for colorectal cancer and other cancers of the gastrointestinal (GI) tract than for cancers arising outside the GI tract. Conclusions.--An optimal assay depends on cancer type. For most cancer types outside of the GI tract and the endometrium, there was insufficient published evidence to recommend a specific clinical assay. Absent published evidence, immunohistochemistry is an acceptable approach readily available in most clinical laboratories. doi: 10.5858/arpa.2021-0632-CP, Clinical laboratory assays for detection of high levels of tumor microsatellite instability (MSI-High) or loss of DNA mismatch repair (MMR) protein expression by immunohistochemistry (IHC) are familiar to many pathologists [...]

Context.--The process for identifying patients with monoclonal gammopathies is complex. Initial detection of a monoclonal immunoglobulin protein (M protein) in the serum or urine often requires compilation of analytical data from several areas of the laboratory. The detection of M proteins depends on adequacy of the sample provided, available clinical information, and the laboratory tests used. Objective.--To develop an evidence-based guideline for the initial laboratory detection of M proteins. Design.--To develop evidence-based recommendations, the College of American Pathologists convened a panel of experts in the diagnosis and treatment of monoclonal gammopathies and the laboratory procedures used for the initial detection of M proteins. The panel conducted a systematic literature review to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were created based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework. Results.--Nine guideline statements were established to optimize sample selection and testing for the initial detection and quantitative measurement of M proteins used to diagnose monoclonal gammopathies. Conclusions.--This guideline was constructed to harmonize and strengthen the initial detection of an M protein in patients displaying symptoms or laboratory features of a monoclonal gammopathy. It endorses more comprehensive initial testing when there is suspicion of amyloid light chain amyloidosis or neuropathies, such as POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome, associated with an M protein. (Arch Pathol Lab Med. 2022;146:575-590; doi: 10.5858/arpa.2020-0794-CP), Monoclonal gammopathies (MGs) represent a spectrum of disorders with varying manifestations ranging from a completely asymptomatic condition picked up on laboratory testing to a catastrophic, life-threatening presentation in the clinic. [...]

Context.--The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery led to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings. Objective.--To develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma. Design.--The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were derived based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework. Results.--Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma. Conclusions.--Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions on specimen suitability, diagnostic capabilities, and correct use of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment. (Arch Pathol Lab Med. 2021;145:269-290; doi: 10.5858/arpa.2020-0261-SA), The diagnosis and classification of lymphoma has evolved into a complex, multimodal process that requires rigorous attention to and quality assurance of numerous preanalytical, analytical, and postanalytical details. After exclusion [...]

The American Society of Clinical Oncology (ASCO) recently issued the guideline Molecular Biomarkers in Localized Prostate Cancer, (1) which was published in the Journal of Clinical Oncology and endorsed by [...]

* Context.--ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA. Objectives.--To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making. Design.--The College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology convened an expert panel to conduct a systematic review of the literature to develop an evidence-based guideline with recommendations for optimal HER2 testing in patients with GEA. Results.--The panel is proposing 11 recommendations with strong agreement from the open-comment participants. Recommendations.--The panel recommends that tumor specimen(s) from all patients with advanced GEA, who are candidates for HER2-targeted therapy, should be assessed for HER2 status before the initiation of HER2-targeted therapy. Clinicians should offer combination chemotherapy and a HER2-targeted agent as initial therapy for all patients with HER2-positive advanced GEA. For pathologists, guidance is provided for morphologic selection of neoplastic tissue, testing algorithms, scoring methods, interpretation and reporting of results, and laboratory quality assurance. Conclusions.--This guideline provides specific recommendations for assessment of HER2 in patients with advanced GEA while addressing pertinent technical issues and clinical implications of the results. (Arch Pathol Lab Med. 2016;140:1345-1363; doi: 10.5858/arpa.2016-0331-CP; 10.5858/arpa.2016-0331CP.s1), Gastroesophageal adenocarcinoma (GEA) is estimated to represent up to 43 280 cancer cases in the United States in 2016, (1) and represents the eighth (esophageal) and fifth (stomach) most common [...]

Context.--Additional reviews of diagnostic surgical and cytology cases have been shown to detect diagnostic discrepancies. Objective.--To develop, through a systematic review of the literature, recommendations for the review of pathology cases to detect or prevent interpretive diagnostic errors. Design.--The College of American Pathologists Pathology and Laboratory Quality Center in association with the Association of Directors of Anatomic and Surgical Pathology convened an expert panel to develop an evidence-based guideline to help define the role of case reviews in surgical pathology and cytology. A literature search was conducted to gather data on the review of cases in surgical pathology and cytology. Results.--The panel drafted 5 recommendations, with strong agreement from open comment period participants ranging from 87% to 93%. The recommendations are: (1) anatomic pathologists should develop procedures for the review of selected pathology cases to detect disagreements and potential interpretive errors; (2) anatomic pathologists should perform case reviews in a timely manner to avoid having a negative impact on patient care; (3) anatomic pathologists should have documented case review procedures that are relevant to their practice setting; (4) anatomic pathologists should continuously monitor and document the results of case reviews; and (5) if pathology case reviews show poor agreement within a defined case type, anatomic pathologists should take steps to improve agreement. Conclusions.--Evidence exists that case reviews detect errors; therefore, the expert panel recommends that anatomic pathologists develop procedures for the review of pathology cases to detect disagreements and potential interpretive errors, in order to improve the quality of patient care. (Arch Pathol Lab Med. 2016; 140:29-40; doi: 10.5858/arpa.2014-0511-SA), The test cycle in surgical pathology and cytology is similar to the test cycle of other laboratory tests. (1-4) It is composed of the preanalytic, analytic, and postanalytic phases. The [...]

Context.--Both the regulations in the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and the checklists of the College of American Pathologists (CAP) Laboratory Accreditation Program require clinical laboratories to verify performance characteristics of quantitative test systems. Laboratories must verify performance claims when introducing an unmodified, US Food and Drug Administration-cleared or approved test system, and they must comply with requirements for periodic calibration and calibration verification for existing test systems. They must also periodically verify the analytical measurement range of many quantitative test systems. Objectives.--To provide definitions for many of the terms used in these regulations, to describe a set of basic analyses that laboratories may adapt to demonstrate compliance with both CLIA and the CAP Laboratory Accreditation Program checklists for performing calibration verification and for verifying the analytical measure ment range of test systems, to review some of the recommended procedures for establishing performance goals, and to provide data illustrating the performance goals used in some of the CAP's calibration verification and linearity surveys. Data Sources.--The CAP's calibration verification and linearity survey programs, the CLIA regulations, the Laboratory Accreditation Program requirements, and published literature were used to meet these objectives. Conclusions.--Calibration verification and linearity and analytical measurement range verification should be performed using suitable materials with assessment of results using well-defined evaluation protocols. We describe the CAP's calibration verification and linearity programs that may be used for these purposes. (Arch Pathol Lab Med. 2014;138:1173-1181; doi: 10.5858/arpa.2013-0051-CP), Clinical laboratories that are regulated by the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and/or accredited by the College of American Pathologists (CAP) are required to demonstrate acceptable performance criteria [...]

Objectives: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery lead to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings.the Aim Of This Review Is To: develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma.Methods: The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of the literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, recommendations were derived based on the available evidence, the strength of that evidence, and key judgments as defined in the GRADE Evidence to Decision framework.Results: Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma.Conclusions: Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions about specimen suitability, diagnostic capabilities, and correct utilization of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment. [ABSTRACT FROM AUTHOR]

Context.--Measured plasma or serum creatinine concentration is a primary component of equations used to calculate estimated glomerular filtration rate (eGFR). In recent years, most assay manufacturers have adopted creatinine calibration procedures that are traceable to the National Institute of Standards and Technology's Standard Reference Material 967. Objectives.--To examine the current performance of creatinine assays, to compare changes in assay performance since 2003, and to examine the reliability of laboratory eGFR calculations. Design.--Serum samples spiked with different concentrations of creatinine were analyzed by participating laboratories in the College of American Pathologists' LN24 survey. Participants' reported values were compared against values measured by liquid chromatography-isotope dilution mass spectrometry. Participants were asked to calculate the eGFR for certain samples, and results were compared with those obtained from the 4-parameter Modification of Diet in Renal Disease equation. Results.--Biases among current creatinine methods are in the range of -5% to 10%, compared with -7% to 34% seen in a 2003 study. This degree of bias in eGFR calculations is of clinical significance only for concentrations near the cut points used to stage chronic kidney disease. Approximately 20% of laboratories report eGFR values that exceed ±1 mL/min per 1.73 [m.sup.2] from the expected eGFR using the 4-parameter Modification of Diet in Renal Disease equation. Conclusions.--Since 2003, there have been improvements in the performance of creatinine assays, which appear to be related to the adoption of standard reference materials for calibration. The effect of the observed method biases in clinical practice now appears minimal. Laboratories should continue to monitor the accuracy of eGFR calculations. (Arch Pathol Lab Med. 2013;137:496-502; doi: 10.5858/arpa.2012-0134-CP), Measurement of plasma or serum creatinine is indicated for the assessment of renal function. That measurement is a primary component of the equations that provide estimated glomerular filtration rate (eGFR) [...]

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. [ABSTRACT FROM AUTHOR]

Context: ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA., Objectives: To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making., Design: The College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology convened an expert panel to conduct a systematic review of the literature to develop an evidence-based guideline with recommendations for optimal HER2 testing in patients with GEA., Results: The panel is proposing 11 recommendations with strong agreement from the open-comment participants., Recommendations: The panel recommends that tumor specimen(s) from all patients with advanced GEA, who are candidates for HER2-targeted therapy, should be assessed for HER2 status before the initiation of HER2-targeted therapy. Clinicians should offer combination chemotherapy and a HER2-targeted agent as initial therapy for all patients with HER2-positive advanced GEA. For pathologists, guidance is provided for morphologic selection of neoplastic tissue, testing algorithms, scoring methods, interpretation and reporting of results, and laboratory quality assurance., Conclusions: This guideline provides specific recommendations for assessment of HER2 in patients with advanced GEA while addressing pertinent technical issues and clinical implications of the results., (© 2016 College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)