Context.—:Reflex urine culture testing can reduce unnecessary cultures, limit inappropriate antibiotic use for asymptomatic bacterial presence, and lower health care costs. In pediatrics, considerations include patient age, specimen collection method, and evidence-based urinalysis criteria to identify clinically significant urinary tract infections. Objective.—:To determine how many positive urine cultures would be missed if a reflex urine culture approach were applied in a large pediatric hospital system. Design.—:A retrospective review of pediatric urine samples collected for ∼10 months with concurrent urinalysis (chemical and microscopic) and urine culture results was performed. Urinalysis was considered positive if 1 or more of the following were present: leukocyte esterase, nitrite, more than 10 white blood cells per high-power field, or bacteria. Positive urinalysis results were compared with urine culture thresholds of 1000 colony-forming units per milliliter (CFU/mL) or greater; 10 000 CFU/mL or greater; and 50 000 CFU/mL or greater in catheter and nonsterile urine collections. Results.—:Of 6926 samples, 1520 (21.9%) were catheter collections and 5406 (78.1%) were nonsterile. Applying urine culture thresholds of 10 000 CFU/mL or greater and 50 000 CFU/mL or greater for catheter and nonsterile collections, respectively, a negative urinalysis finding demonstrated a high negative predictive value (≥96.6%). A reflex culture protocol would have eliminated 3652 of 6926 cultures (52.7%) and would have missed 71 of 6926 total samples (1.0%). Organisms other than Escherichia coli were more frequently isolated from cultures that were negative by urinalysis. Conclusions.—:Implementing reflex urine culture testing based on positive urinalysis results can help reduce unnecessary urine cultures in the pediatric population with a high negative predictive value.
Context.—:The United States-Canadian Mesothelioma Reference Panel was established in 1985. Data on the first 200 cases were published in 1991. Objectives.—:To review what has changed in mesothelial pathology since the first Mesothelioma Panel article was published. Data Sources.—:Cases referred to the United States-Canadian Mesothelioma Reference Panel and published literature. Conclusions.—:Panel accessions have reached 4000. The major problems for which the first 200 cases were referred were mesothelioma versus another tumor and mesothelioma versus a benign mesothelial proliferation, and these remain the most common issues that the panel adjudicates. In the 1990s the panel depended on histochemistry and a very limited set of immunohistochemical carcinoma markers, as well as electron microscopy, to separate mesotheliomas from other tumors; currently there is an overabundance of immunohistochemical markers for this purpose, only a few of which are really specific. In the 1990s the panel depended almost entirely on morphology to separate benign from malignant mesothelial processes, but the advent of genetic analysis has led to very reliable surrogate immunohistochemical and fluorescence in situ hybridization tests for this separation. New issues and entities that the panel briefly touched on (well-differentiated papillary mesothelial tumor) or did not deal with in the 1990s, including mesothelioma genetics, cytologic diagnosis of mesothelioma, mesothelioma in situ, and solid papillary mesothelial tumor, have been addressed by panel members and are reviewed here. Mesothelioma diagnostic pathology has undergone remarkable development during the past 40 years, such that most mesotheliomas can be readily diagnosed and separated from various mimics.
Context.—:Non-US citizen international medical graduates (IMGs) represent a significant minority of individuals filling pathology positions in the Main Residency Match and actively practicing as pathologists. Prior surveys have not allowed definitive conclusions about how the citizenship status impacts pathology job search experiences. Objective.—:To improve understanding of the possible barriers to non-US citizen IMGs entering the US job market. Design.—:The College of American Pathologists Graduate Medical Education Committee developed a survey to understand the impact of US versus non-US medical graduates and citizenship status on the job search experience. Pathologists who graduated from US pathology residency and/or fellowship training programs who have been in practice for 10 years or less were targeted. Multiple distribution channels were used. Results.—:Survey responses were received from 413 individuals. Significantly fewer non-US IMGs found their first non-fellowship position in the United States and many reported greater difficulty finding a position, with a longer job search. Non-US IMGs more frequently encountered bias during their job search, most often due to visa sponsorship. Both non-US IMGs and their employers found their experiences with the immigration system to be complicated, confusing, and financially challenging. Conclusions.—:The reported survey results suggest possible opportunities for improving how non-US citizen pathology residency graduates navigate the job market, how their potential employers approach hiring them, and how professional associations assist their non-US citizen members.
Context.—:Transporting specimens can expose them to uncontrolled environmental factors. Whole blood viability is a commonly used preanalytic marker of quality for analysis of white blood cells. Objective.—:To evaluate whole blood viability as a marker for transportation and specimen integrity for lymphocyte subset evaluation. Design.—:More than 9000 whole blood specimens, transported during a 4-year period, and their lymphocyte subset evaluation results were analyzed retrospectively. Viability was measured by using Cellaca MX imaging cytometer, and lymphocyte and lymphocyte subset counts were determined with flow cytometry. Specimen cell viability results were stratified based on different transportation factors to discern their potential effects. Lymphocyte subset evaluation results from specimens with lower viability were compared with those from optimal viability specimens. Results.—:Cell viability of transported specimens exhibited seasonal variation, decreasing during the warm summer months (median, 77.0% versus 83.4% in other seasons). The decline in viability negatively correlated with ambient temperature during transportation (r = -0.7876). Longer transportation time (>60 hours) also caused a decrease in viability (median, 64.0%). While we observed a decrease in absolute cell counts for CD45+ lymphocytes, CD3+ T cells, CD8+ T cells, and CD19+ B cells in specimens with low viability (50%-80%), the differences were well within the assay's total allowable error. Conclusions.—:Control of preanalytic factors is critical for laboratory testing. Whole blood viability is a sensitive indicator of transport conditions and time, but it is not a specific predictor of quality for the main lymphocyte populations in cellular immunology testing.
Context.—:Prostatic acinar adenocarcinoma is the most common type of prostate cancer, while other types of cancer infrequently involve the prostate. In this review, we present an overview of contemporary updates on all types of cancers involving the prostate, with a focus on subtypes of prostatic adenocarcinoma. Unusual histological patterns and subtypes of acinar adenocarcinoma, and non-acinar forms of prostate cancers, and their prognostic and therapeutic relevance are discussed. The following summary of the contents presented in part at the 12th Princeton Integrated Pathology Symposium, Plainsboro, New Jersey, on May 10, 2025, supplemented with a relevant literature review, exemplifies the common diagnostic challenges and pitfalls for subtypes of prostate cancer, with emphasis on immunohistochemical and molecular updates when relevant. Objective.—:To describe the common lesions in the prostate, with emphasis on the diagnostic challenges and pitfalls that may arise in the pathologic assessment, and to highlight immunohistochemical workups and emerging molecular findings when relevant. Data Sources.—:Published peer-reviewed literature and personal experience are the sources for this study and presented at the course. Conclusions.—:Although most prostate cancers are acinar adenocarcinoma, other types of prostate cancer infrequently occur, which may pose diagnostic challenges. Pitfalls that arise in the pathologic assessment of prostate cancer should raise awareness. We summarize the course content, supplement it with a relevant literature review, and hope to provide a diagnostic framework for evaluating these lesions in routine clinical practice.
Context.—:The College of American Pathologists (CAP) Cancer Protocols are standardized pathology reporting tools that support accurate, complete, and interoperable cancer diagnoses. Available in electronic, downloadable, and mobile formats, they are used by more than 9500 licensed users. CAP has developed a quality management system specifically for the cancer protocols with a focus on stakeholder feedback. It also maintains alignment with multiple international regulatory standards, enabling compliance with accreditation requirements. Objective.—:To describe the process for tracking, triaging, and resolving inquiries to increase transparency of the creation and maintenance of the CAP protocols. This process ensures that stakeholder feedback is fully considered and systematically incorporated into protocol updates. Design.—:Inquiries submitted in 2023-2024 were logged into 2 databases for triage within a customized task management system. For each inquiry, data were captured on volume, source, submission platform, protocol group, issue type, and resolution time. Results.—:Of 507 inquiries, 156 (31%) resulted in protocol updates. Despite 278 inquiries (55%) requiring committee input, 446 (88%) were resolved within 7 days. Most inquiries involved content (283; 56%), and technical issues were minimal (61; 12%). Submission via the preferred route (cancerprotocols@cap.org) was used for 395 inquiries (78%). Breast, gastrointestinal, genitourinary, and gynecologic protocols generated the most inquiries. Conclusions.—:Stakeholder input is used in a quality management system to create and maintain the CAP Cancer Protocols. Use of this system ensures the ongoing accuracy, usability, and interoperability of the CAP Cancer Protocols, supporting precision oncology and excellence in patient care.
Context.—:Prevalence data of human epidermal growth factor receptor 2 (HER2)-ultralow (immunohistochemistry [IHC] 0 with membrane staining in ≤10% of cells; HER2 IHC 0+) breast cancer are limited. Objective.—:To evaluate the proportion of HER2-ultralow among metastatic breast cancer samples originally scored HER2 IHC 0 (with or absent membrane staining) and 1+ and to evaluate interobserver concordance between pathologists' rescores and original scores. Design.—:Whole slide images (WSIs) from metastatic breast cancer biopsy specimens originally scored HER2 IHC 0 (with or absent membrane staining) and 1+ were rescored as HER2 IHC 0 absent membrane staining, IHC 0+ (with membrane staining), IHC 1+, or IHC 2+ by 3 pathologists. Each pathologist performed 2 blinded readings (washout period of ≥2 weeks). Results.—:Of the 246 IHC 0 WSIs, 78 (31.7%), 75 (30.5%), and 86 (35.0%) were rescored as HER2 IHC 0 absent membrane staining, 0+, and 1+, respectively. Of the 138 IHC 1+ WSIs, 3 (2.2%), 10 (7.2%), 117 (84.8%), and 6 (4.3%) were rescored as IHC 0 absent membrane staining, 0+, 1+, and 2+, respectively. Interobserver concordance was substantial (overall percentage agreement [OPA; 95% CI], 86.7% [82.9%-90.0%]; Cohen κ [95% CI], 0.781 [0.726-0.835]) to moderate (OPA [95% CI], 62.0% [59.9%-66.9%]; Cohen κ [95% CI], 0.441 [0.379-0.502]). Agreement between pathologists' consensus scores and original scores was moderate (OPA [95% CI], 72.1% [67.3%-76.5%]; Cohen κ [95% CI], 0.461 [0.381-0.541]). Conclusions.—:Scoring discrepancies highlight the potential need/benefits of training for evaluating HER2-low/HER2-ultralow cases in metastatic breast cancer, which could improve consistency in HER2 scoring by pathologists.
Context.—:In 2013, the Cytopathology Committee of the College of American Pathologists conducted its first survey on the practice patterns of laboratories performing respiratory cytology. Objective.—:To capture current laboratory practices, recognize changes in respiratory cytopathology practices over the last decade, and provide insight into future directions for improvement. Design.—:The survey was mailed to 1979 laboratories. Results.—:The survey results show a high demand for respiratory cytology. There has been a shift regarding the preferred technique to endobronchial ultrasound-guided fine-needle aspirations as one of the most frequently processed and interpreted specimens, and the most commonly performed intraprocedural assessments. The pathologist alone mostly performed intraprocedural assessments, followed by the cytotechnologist alone. The immunostaining markers used to differentiate non-small carcinomas were most commonly the panel p63, CK5/6, and p40 for squamous cell carcinoma or TTF-1 and Napsin A for adenocarcinoma, compared with a single stain for either. Molecular testing for non-small cell lung carcinomas was commonly performed, with most molecular testing being sent to an outside laboratory. Immunohistochemical stains were validated in half of the institutions, with a high number responding that they were unsure of the validation performed in their laboratories. Conclusions.—:This follow-up study of our original study has shown significant advances in the field of respiratory cytology. The data also showed a few areas, specifically validation of cytology preparations for ancillary testing and molecular testing, which may benefit from guidelines to standardize cytopathology practice and ensure quality care.
Context.—:Critical limits represent quantitative boundaries of life-threatening diagnostic results that demand urgent clinician notification and potentially, lifesaving intervention. Objectives.—:To document 35-year changes in glucose critical limits, characterize decision thresholds at independent and network hospitals, identify US geographic risk differences, report point-of-care testing results, and align critical notifications, pathophysiological risk, and consensus recommendations to improve outcomes. Design.—:We gathered critical limit notification lists from 417 hospitals comprising university, trauma, and heart centers, and network and community hospitals in all 50 states and Washington, District of Columbia, then extracted glucose critical limits for adults and newborns. Results.—:All hospitals listed low and high glucose critical limits. Between 1990 and 2025, low glucose critical limits increased significantly (P < .001) with medians of 45 (range, 30-70) versus 50 (range, 35-60) mg/dL, respectively. Histograms documented striking inconsistencies. Matched pairs (N = 73) of laboratory versus point-of-care low glucose critical limits at the same hospitals did not differ significantly. A US risk level map identified geographic discrepancies relative to the neuroglycopenic impaired awareness threshold of 54 mg/dL. There were statistically significant changes in newborn low and high distributions with 2025 medians of 40 (range, 20-55) and 200 (range, 120-500) mg/dL, respectively. Conclusions.—:An increased median low critical limit of 50 mg/dL does not match the 54 mg/dL threshold for neuroglycopenic loss of awareness that places patients at risk. The median high critical limit of 450 mg/dL at network hospitals decreases the risks of extreme hyperglycemia. The risk map revealed geographic inconsistencies, lack of harmonization, and poor alignment with consensus clinical recommendations.
Context.— Preanalytical errors account for 60% to 70% of total laboratory errors and represent a significant threat to laboratory quality and patient safety. Despite their impact, systematic risk assessment approaches remain underutilized in clinical laboratories, particularly in resource-limited settings. Objective.— To implement a structured risk assessment framework for identifying, evaluating, and mitigating preanalytical process vulnerabilities in a stand-alone diagnostic laboratory, and to measure the impact of targeted interventions on error reduction. Design.— A quality improvement initiative was conducted at Vedant Diagnostic Center, a National Accreditation Board for Testing and Calibration Laboratories (NABL)–accredited stand-alone diagnostic laboratory in Rajkot, Gujarat, India, processing approximately 4000 tests monthly. Nine critical preanalytical processes were systematically evaluated with a Severity × Probability risk matrix. Processes were classified as low (1–4), medium (5–9), high (10–15), or extreme risk (16–25). Corrective and preventive actions (CAPAs) were implemented. Results.— One process (11%) was classified as extreme risk, 2 (22%) as high risk, and 6 (67%) as medium risk. Baseline error rate was 1.0% (40 errors per 4000 tests monthly). Following CAPA implementation—including phlebotomist training, expiry verification, and temperature monitoring—error rate decreased to 0.3% (12 errors monthly), representing a statistically significant 70% reduction (χ 2 = 21.8; P < .001). Conclusions.— Systematic risk assessment combined with targeted corrective actions achieved substantial reduction in preanalytical errors. This reproducible, resource-appropriate methodology enables laboratories to enhance preanalytical quality and patient safety, particularly where NABL or other laboratory accreditation requirements drive continuous improvement.
Context.—:One objective of the College of American Pathologists/American College of Medical Genetics Cytogenetics Committee is to ensure the accurate detection and clinical interpretation of abnormalities observed by fluorescence in situ hybridization (FISH) analysis when evaluating hematologic neoplasms. Objective.—:To report a 20-year performance summary (2005-2024) of FISH challenges focusing on hematologic neoplasms. Design.—:A retrospective review was performed from 2005 through 2024 to identify FISH challenges specifically addressing hematologic neoplasms. The overall performance of participants was evaluated to identify potential recurring errors of clinical relevance. Results.—:A total of 124 hematologic neoplasm FISH challenges from 2005 to 2024 were provided to participating laboratories, including 45 paper challenges (results and/or images were provided for interpretation purposes), 43 liquid challenges (bone marrow aspirate or peripheral blood), and 36 formalin-fixed paraffin-embedded (FFPE) tissue challenges. Of the 124 challenges, 120 (97%) exceeded the required 80% consensus for grading purposes. Of the 4 failed challenges (3%), 2 (1 liquid, 1 paper) involved the interpretation of atypical FISH signal patterns; 1 (paper) involved the interpretation of FISH signal patterns correlating involvement by myeloid versus lymphoid interphase nuclei; and 1 (liquid) likely involved a specimen processing or handling error that resulted in discordant participant responses. All 36 FFPE tissue challenges exceeded the 80% consensus for grading purposes. Conclusions.—:This 20-year retrospective review demonstrates that clinical cytogenomic laboratories have been and continue to be highly proficient in the detection and interpretation of FISH abnormalities associated with hematologic neoplasms.
Context.—:Human epidermal growth factor receptor 2 (HER2) alterations occur in several solid tumors, including urothelial carcinoma. Although HER2-targeted therapies, such as trastuzumab deruxtecan, have shown promising results in HER2-positive bladder cancer, optimal immunohistochemistry (IHC) scoring criteria for urothelial carcinoma remain unclear. Objective.—:To compare American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) HER2 IHC scoring criteria for breast and upper gastrointestinal (GI) cancers in urothelial carcinoma and to correlate HER2 expression with histologic subtypes, metastatic sites, temporal heterogeneity, and next-generation sequencing (NGS) findings. Design.—:A total of 139 specimens from 129 patients with urothelial carcinoma were evaluated. HER2 IHC was scored using both breast and upper GI CAP criteria across histologic subtypes and metastatic sites. Temporal heterogeneity was assessed in paired primary and metastatic specimens (n = 11). Results.—:Using upper GI criteria, 43 of 105 cases (41%) were HER2 3+ compared with 35 of 105 (34%) HER2 3+ with breast criteria, with 12 of 139 cases (9%) showing higher scores using upper GI criteria. ERBB2 mutations were found in 15 of 96 (16%) and amplification in 4 of 96 (4%) of sequenced cases. HER2 3+ staining was enriched in micropapillary (11 of 14; 79%) and plasmacytoid (3 of 5; 60%) subtypes. Brain metastases had the highest proportion (6 of 15; 40%) of HER2 3+ cases. In paired samples, HER2 scores in metastases were the same (9 of 12; 75%) or higher (3 of 12; 25%) than primaries. Conclusions.—:Upper GI and breast scoring criteria yield divergent scores in a significant subset of urothelial carcinomas, potentially affecting eligibility for targeted therapy. Associations with histologic subtype and metastatic site support disease-specific diagnostic and therapeutic strategies.
Context.—:The prevalence of paracoccidioidomycosis remains unknown; current estimates rely primarily on hospital-based records from Brazil, where approximately 80% of reported cases occur. In Brazil, paracoccidioidomycosis ranks as the eighth leading cause of death among chronic infectious diseases. Objective.—:To present data on cases of paracoccidioidomycosis identified at autopsy in a teaching hospital and to compare these findings with previously published autopsy case series. Design.—:Autopsy records from 1989 to 2024 were reviewed to identify paracoccidioidomycosis cases. Demographic, epidemiologic, and clinical data were extracted from the corresponding medical charts. Results.—:Among 2397 autopsies, 17 cases of paracoccidioidomycosis (0.71%) were confirmed. Twelve patients (70.5%) were male, with a median age of 44.6 years. Nine patients (52.9%) were HIV (human immunodeficiency virus)-positive, 5 of whom (55.5%) received both diagnoses within the same year. Including the present study, 12 published autopsy case series of paracoccidioidomycosis have summarized the findings from 325 cases. Most cases demonstrated disseminated fungal disease involving multiple organs, with frequencies ranging from 42.8% to 100% for the lungs; 28.5% to 100% for lymph nodes; 17.6% to 83.3% for mucosal sites; 11.8% to 80.5% for the adrenal glands; and 2.8% to 64.3% for the skin. Conclusions.—:This study, consistent with other autopsy series, confirms the systemic nature of this mycosis, particularly in HIV-infected patients. HIV infection appears to alter the natural history of paracoccidioidomycosis, resulting in a more acute, severe, and disseminated clinical course. All non-HIV-infected patients were diagnosed post mortem and had less extensive systemic organ involvement. The HIV-infected cases herein included represent the largest autopsy cohort of HIV-paracoccidioidomycosis coinfection reported to date.
Context.—:TPIT (TBX19 [T-box transcription factor 19]) immunohistochemistry is widely used to classify corticotroph tumors, yet unexpected nuclear staining has been observed in chordoma with certain commercial clones, raising concerns about diagnostic cross-reactivity. Objective.—:To investigate the molecular basis of cross-reactivity of the TPIT antibody clone OTI2G1 in chordoma and assess the potential diagnostic pitfall in tumors of the sellar region. Design.—:We compared TBX19 and TBXT (Brachyury [T-box transcription factor T]) by T-box domain sequence alignment and structural modeling/superposition. Immunohistochemistry for TPIT (OTI2G1, CL6251) and Brachyury was performed on pituitary tissues, corticotroph tumors, and chordomas. Colocalization of OTI2G1 and Brachyury was quantified by multiplex immunofluorescence. Results.—:TBX19 and Brachyury T-box domains showed marked structural similarity (Cα root mean square deviation, 0.071 Å), and the OTI2G1 immunogen (TBX19 amino acids [aa] 1-238) overlapped the Brachyury T-box. OTI2G1 showed diffuse nuclear staining in chordomas, whereas CL6251 showed negativity. Multiplex immunofluorescence demonstrated OTI2G1 signal in 77.6% of Brachyury-positive chordoma cells (95% CI, 77.5%-77.6%; P < .001). Conclusions.—:Diffuse nuclear "TPIT" staining with OTI2G1 in chordoma reflects cross-reactivity driven by conserved T-box structure rather than true TBX19 expression. For the differential diagnosis of sellar lesions, especially poorly differentiated chordoma versus pituitary neuroendocrine tumor, use of more specific clones (eg, CL6251) is recommended.
Context.—:The diagnosis and characterization of well-differentiated neuroendocrine tumors (WDNETs) on cytology is challenging, with recognized pitfalls that may have therapeutic and prognostic implications. Objective.—:To analyze data curated by the College of American Pathologists educational slide program for accuracy in the cytologic diagnosis of WDNET. The current state of cytologic diagnosis of WDNET is also reviewed for educational purposes. Design.—:The study cohort included non-gynecologic cytology slides reviewed by participants in the College of American Pathologists Non-Gynecologic Cytopathology Education program. Individual responses for cytotechnologists or cytologists (CT) and pathologists were collated for WDNET. The data were analyzed for concordance with the correct general diagnosis and concordance with the correct reference diagnosis. The exact reference diagnosis available for each site was "pancreatic neuroendocrine tumor," "liver, well/moderately differentiated neuroendocrine tumor," and "lung, well/moderately differentiated neuroendocrine tumor." Performance measures were assessed. Results.—:The WDNET analysis includes 8941 responses from 1382 laboratories. The selection of the general diagnosis of "malignant" or "suspicious for malignancy" was greater than 90% in all body sites. Pathologists correctly identifying WDNET was highest in the pancreas (2501/2738, 91.3%) compared with the lung (805/1019, 79.0%) and liver (1444/1966, 73.4%). Pathologists had better concordance with the diagnosis of WDNET in all sites than CTs (P < .001). Conclusions.—:This large study, encompassing pathologists and CTs, confirms that although participants can identify WDNET on cytology, opportunities for greater accuracy and education persist. The most common incorrect response in the pancreas was adenocarcinoma, while the most common misdiagnosis was small cell carcinoma in the lung and liver.
Context.-Pathology is essential to global health care, yet disparities remain in access to education and training. The College of American Pathologists (CAP) Foundation addresses these gaps through grants and awards that support trainees, early-career pathologists, and initiatives promoting equity worldwide. Since 2015, total funding has increased from $18,400 to $84,098, an astounding 357%. Objective.-To evaluate the CAP Foundation Grants and Awards Program during a 10-year period, assessing financial investment, award distribution, recipient characteristics, and impact. Design.-A mixed-methods retrospective study integrated (1) quantitative analysis of program data, (2) qualitative feedback from awardees, and (3) a quantitative award impact survey of past CAP Foundation awardees. Variables included demographics, award type, funding amounts, geographic distribution, and career stage. Surveys assessed professional development, mentorship, and long-term engagement with CAP. Results.-From 2015 to 2024, a total of 744 applicants submitted 760 applications, resulting in 355 awards across 14 categories. Applications increased more than 8-fold, peaking in 2023, with surges during the COVID-19 pandemic. Medical student applications grew from 1 in 2020 to 17 in 2024 (76% annual growth); 9 of 12 Medical Student Travel Award recipients (75%) entered pathology residency. Geographic disparities were noted, with smaller residency programs showing higher per capita application rates. Among 174 survey respondents, 129 (74%) reported networking benefits, 127 (73%) learning benefits, and 99 (57%) mentorship benefits, though only 49 (28%) sustained long-term mentoring relationships. Conclusions.-The CAP Foundation's awards program has expanded access, supported career development, and fostered future pathologists. Strengthening long-term mentorship and bridging education-to-practice gaps may further enhance its impact.
center dot Context.-Clinical laboratories are increasingly implementing pharmacogenomic (PGx) testing. Although PGx is similar to genetic testing for other indications, there are unique aspects that laboratories should consider. Objective.-To aid clinical laboratories that are implementing clinical PGx testing by describing characteristics of PGx test design and validation, as well as approaches to reporting. Resources that are useful for clinical laboratories performing PGx testing will be highlighted. Design.-The College of American Pathologists formed a workgroup composed of laboratorians with expertise in clinical PGx testing. The workgroup included representatives from the Association for Molecular Pathology and the American College of Medical Genetics and Genomics. The workgroup reviewed pertinent literature, as well as experience from proficiency testing and from members' laboratories. Results.-The workgroup recommends that laboratories implementing PGx consider the following concepts: testing platform, test design (ie, selection of pharmacogenes and variants/alleles), use of reference materials during test development and as controls during clinical runs, star allele and standard nomenclature systems, translations from genotype to predicted phenotype, and considerations for result reporting including making medication recommendations. The workgroup provides considerations when using report vendors, emphasizing the clinical laboratory's role and responsibility when implementing such reporting tools from vendors. Conclusions.-Clinical laboratories should be familiar with the fundamentals of PGx, ensure that PGx testing meets the applicable regulatory requirements for all aspects of the clinical laboratory testing process, and follow recommendations for standardization of nomenclature and reporting. ( (Arch Pathol Lab Med. 2026;150:339-353; doi: 10.5858/ arpa.2025-0179-CP)
