Search

Context.--Controversies and uncertainty persist in prostate cancer grading. Objective.--To update grading recommendations. Data Sources.--Critical review of the literature along with pathology and clinician surveys. Conclusions.--Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace 'tertiary grade pattern' in radical prostatectomy (RP) with 'minor tertiary pattern 5 (TP5),' and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) 'atypical intraductal proliferation (AIP)' is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice. doi: 10.5858/arpa.2020-0015-RA, Originally proposed by Donald Gleason in 1966, the Gleason grading system has evolved with several important modifications in the past 2 decades. (1-5) Cumulatively, Gleason pattern 3 has been narrowed [...]

Context.--Whole slide imaging (WSI) represents a paradigm shift in pathology, serving as a necessary first step for a wide array of digital tools to enter the field. Its basic function is to digitize glass slides, but its impact on pathology workflows, reproducibility, dissemination of educational material, expansion of service to underprivileged areas, and intrainstitutional and interinstitutional collaboration exemplifies a significant innovative movement with far-reaching effects. Although the benefits of WSI to pathology practices, academic centers, and research institutions are many, the complexities of implementation remain an obstacle to widespread adoption. In the wake of the first regulatory clearance of WSI for primary diagnosis in the United States, some barriers to adoption have fallen. Nevertheless, implementation of WSI remains a difficult prospect for many institutions, especially those with stakeholders unfamiliar with the technologies necessary to implement a system or who cannot effectively communicate to executive leadership and sponsors the benefits of a technology that may lack clear and immediate reimbursement opportunity. Objectives.--To present an overview of WSI technology--present and future--and to demonstrate several immediate applications of WSI that support pathology practice, medical education, research, and collaboration. Data Sources.--Peer-reviewed literature was reviewed by pathologists, scientists, and technologists who have practical knowledge of and experience with WSI. Conclusions.--Implementation of WSI is a multifaceted and inherently multidisciplinary endeavor requiring contributions from pathologists, technologists, and executive leadership. Improved understanding of the current challenges to implementation, as well as the benefits and successes of the technology, can help prospective users identify the best path for success. doi: 10.5858/arpa.2018-0343-RA, Pathology as a practice vitally relies on the accurate interpretation of microscopic images in order to correctly diagnose patients and guide therapeutic decision making. With the advent of whole slide [...]

To the Editor.--We read with interest the article by Lanjewar et al (1) on the 79 autopsy registers of the Grant Medical College (GMC) and J. J. Hospital (1884-1966), and [...]

Context.--Controversies and uncertainty persist in prostate cancer grading. Objective.--To update grading recommendations. Data Sources.--Critical review of the literature along with pathology and clinician surveys. Conclusions.--Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace ''tertiary grade pattern'' in radical prostatectomy (RP) with ''minor tertiary pattern 5 (TP5),'' and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDCP) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (> 50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) ''atypical intraductal proliferation (AIP)'' is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice. [ABSTRACT FROM AUTHOR]

To the Editor.--We have been following the recently published articles on microscopic photography using a smartphone with keen interest. (1,2) We agree that smartphone technology has the potential to revolutionize [...]

Context.--In 2018 the College of American Pathologists Diagnostic Immunology and Flow Cytometry Committee designed and implemented a new plasma cell neoplasia flow cytometry proficiency testing program--PCNEO--to allow clinical flow cytometry laboratories to monitor and assess their performance compared with a peer group. Objective.--To report the results from the first 4 years of the PCNEO program. Design.--Program participants were sent 2 sets of challenges per year, each including 1 wet challenge and 2 dry challenges, with associated clinical and laboratory findings. The wet challenges were composed of myeloma cell line specimens (with or without dilution in preserved whole blood) for flow cytometric analysis. The dry (paper) challenges were composed of clinical case summaries and images of flow cytometric test results from various flow cytometry laboratories of committee members. Results.--A total of 116 to 145 laboratories from 17 countries enrolled in the proficiency testing program. For the wet challenges, almost all participants (97%--100%; cumulative, 98.2%) correctly identified the presence of neoplastic plasma cell populations based on flow cytometric analysis of undiluted myeloma cell lines. Slightly fewer participants (89.0%--97.4%; cumulative, 95.2%) correctly identified the presence of neoplastic plasma cell populations based on flow cytometric analysis of diluted myeloma cell lines (10% or 50% dilutions into peripheral blood) intended to better represent a typical clinical sample. There was generally agreement among 80% or more of participants for positive or negative staining for CD38, CD138, CD19, CD20, and surface and cytoplasmic K and λ light chains. Similarly, 84% to 100% of participants were able to correctly identify the presence of neoplastic plasma cell populations in paper challenges, including the presence of small, neoplastic plasma cell populations (0.01%--5.0% clonal plasma cells) and the presence of nonneoplastic plasma cell populations (correctly identified by 91%--96% of participants). Conclusions.--Participant performance in the new proficiency testing program was excellent overall, with the vast majority of participants able to perform flow cytometric analysis and identify neoplastic plasma cell populations and to identify small plasma cell clones or expanded populations of reactive plasma cells in dry challenge flow cytometry results. This program will allow laboratories to verify the accuracy of their testing program and test interpretations for the assessment of patients suspected of having a plasma cell neoplasm. [ABSTRACT FROM AUTHOR]

Context.--Clinician feedback is an important source of information for laboratory quality improvement programs. Objective.--To pilot a program for nearly real-time solicitation and analysis of physician feedback regarding clinical laboratory services. Design.--Laboratories distributed either electronic or paper survey forms to physicians. Results were tabulated by College of American Pathologists staff. Free-text comments were shared promptly with the participating laboratories to facilitate follow-up. Results.--Forty-seven clinical laboratories participated in the study and submitted results for 987 physician surveys, including both paper and electronic forms. Of 694 responses submitted electronically within the study period, 460 (66.3%) included at least 1 free-text entry, for a total of 951 free-text comments. Conclusions.--Point-of-service solicitation of physician feedback regarding clinical laboratory services is feasible and can provide a substantial quantity of potentially useful information regarding laboratory performance from the customer perspective. [ABSTRACT FROM AUTHOR]

* Context.--Automated prostate cancer detection using machine learning technology has led to speculation that pathologists will soon be replaced by algorithms. This review covers the development of machine learning algorithms and their reported effectiveness specific to prostate cancer detection and Gleason grading. Objective.--To examine current algorithms regarding their accuracy and classification abilities. We provide a general explanation of the technology and how it is being used in clinical practice. The challenges to the application of machine learning algorithms in clinical practice are also discussed. Data Sources.--The literature for this review was identified and collected using a systematic search. Criteria were established prior to the sorting process to effectively direct the selection of studies. A 4-point system was implemented to rank the papers according to their relevancy. For papers accepted as relevant to our metrics, all cited and citing studies were also reviewed. Studies were then categorized based on whether they implemented binary or multi-class classification methods. Data were extracted from papers that contained accuracy, area under the curve (AUC), or κ values in the context of prostate cancer detection. The results were visually summarized to present accuracy trends between classification abilities. Conclusions.--It is more difficult to achieve high accuracy metrics for multiclassification tasks than for binary tasks. The clinical implementation of an algorithm that can assign a Gleason grade to clinical whole slide images (WSIs) remains elusive. Machine learning technology is currently not able to replace pathologists but can serve as an important safeguard against misdiagnosis. [ABSTRACT FROM AUTHOR]

Context.--The year 2023 marks the centenary of the Nobel Prize honoring the discovery of insulin. Little-known experimental pathologists Lydia DeWitt, MD, at the University of Michigan and Mary Kirkbride, DSc [Hon], at Columbia University, both just beginning their academic careers, made independent contributions to the discovery that have never been critically examined. This happened at a time when it was exceedingly rare for women to work in pathology. Objective.--To explore the facilitative roles of DeWitt and Kirkbride in the discovery of insulin and to examine their trail-breaking careers in academic pathology. Design.--Available primary and secondary historical resources were reviewed. Results.--DeWitt made and tested pancreatic extracts from duct-ligated atrophic pancreas (ie, Frederick Banting's great idea to prevent digestion of its hypothetical internal secretion) 15 years before Banting; Banting was unaware of her work. His idea came from reading a paper by pathologist Moses Barron. Prior duct-ligation studies had sometimes been viewed with skepticism because histologic identification of islets in atrophic duct-ligated pancreata was imperfect; Kirkbride addressed this with histochemical staining, convincing Barron and, therefore, indirectly influencing and motivating Banting. The lives and convoluted careers of these 2 early-20th-century women are explored and compared with those of other contemporary women in pathology. A unifying pattern becomes clear: careers in experimental pathology and bacteriology were accepted but performing clinical work in anatomic pathology was not. Conclusions.--Both DeWitt and Kirkbride are prototypical early-20th-century women in academic pathology whose careers were constrained by gender. However, Kirkbride made a unique and unrecognized contribution to the discovery of insulin. doi: 10.5858/arpa.2023-0060-HP, Lydia M. DeWitt, MD, and Mary B. Kirkbride, DSc, each published a sole-authored paper in the Journal of Experimental Medicine, one (1) in 1906 and the other (2) in 1912, [...]

* Context.--Gene editing--based therapies are currently in development in the areas of oncology, inherited disease, and infectious disease. These potentially life-altering therapies are derived from decades of research in both academic and industry settings that developed technologies rooted in principles and products of nature. However, with such technologic developments come many important considerations, including adverse risks, high cost, and ethical questions. Objective.--To educate pathologists about gene editing technologies, inform them of potential indications and risks, outline regulatory and practical issues that could affect hospital-based practice and laboratory testing, and advocate that pathologists need to be present at discussions among industry and regulators pertaining to gene editing--based therapies. Design.--A Gene Editing Workgroup, facilitated by the College of American Pathologists Personalized Health Care Committee and consisting of pathologists of various backgrounds, was convened to develop an educational paper to serve as a stimulus to increase pathologist involvement and inquiry in gene editing therapeutic and diagnostic implementation. Results.--Through multiple discussions and literature review, the workgroup identified potential gaps in pathologists' knowledge of gene editing. Additional topics that could impact pathology and laboratory medicine were also identified and summarized in order to facilitate pathologists as stakeholders in gene editing therapy administration and monitoring and potential use in diagnostics. Conclusions.--Gene editing therapy is a complex but potentially transformative area of medicine. This article serves as an introduction to pathologists to assist them in future discussions with colleagues and potentially identify and alter pathology practices that relate to gene editing. [ABSTRACT FROM AUTHOR]

Context.-- Mast cells are essential components of the immune system and play crucial pathogenetic roles in several digestive diseases, including mastocytic enterocolitis and eosinophilic gastrointestinal disorders. Pathologists have rarely been asked to evaluate the distribution and density of mast cells in gastrointestinal (GI) biopsy specimens. However, such requests are becoming more common because of an increasing awareness of the role of mast cells in functional GI disease and in both esophageal and nonesophageal eosinophilic gastrointestinal disorders. Objective.-- To provide pathologists with tools to incorporate the assessment of mast cells in the evaluation of esophageal, gastric, and intestinal specimens by developing a systematic approach to their evaluation, counting, and reporting. Design.-- This study consisted of a review of the literature followed by multiple consensus sessions to decide where to count mast cells and what a countable mast cell is. Results.-- We reviewed 135 papers addressing the content of mast cells in the digestive tract, selected 21 that detailed how cells were counted (microscope lens, area of high-power fields, locations evaluated, type of cells considered as countable), and summarized their data in a table. Then, drawing from both the acceptable literature and our own extensive experience, we reached a tentative consensus on: (1) the normal numbers in the different segments of the GI tract; (2) the morphology of countable mast cells; and (3) the locations and strategies for counting them. Conclusions.-- The result is a set of suggestions for reporting mast cell counts, their distribution, and their location in a way clinicians can understand and use for management decisions. [ABSTRACT FROM AUTHOR]

* Context.--In 1954, Benjamin Castleman, MD, described what was then believed to be a new entity in lymph node pathology. Initially labeled "Hyperplasia of the mediastinal node" and then "Localized mediastinal lymph node hyperplasia resembling thymoma," we now recognize the condition with the eponym "Castleman disease." We document a paper that describes the same condition, a half century before Castleman did. Objective.--To report the striking resemblance between Castleman disease and the lymph node reported in the paper published by Edwin R. LeCount, MD, titled "Lymphoma, a benign tumor representing a lymph gland in structure," published in Journal of Experimental Medicine in 1899. We also provide an overview of the remarkable achievements of LeCount. Design.--We compared the elucidation in the original paper by LeCount with the morphologic details in the papers published by Castleman et al. Material on the life of LeCount was compiled from the scientific literature, the Internet, and the files of the University of Chicago. Results.--LeCount's description and illustrations of the lymph node are uncannily similar to the onion-skinning and vascularity that Castleman documented. Conclusions.--LeCount deserves credit for his depiction of a hitherto-unreported entity. [ABSTRACT FROM AUTHOR]

Context.--The World Health Organization classification of tumors of the breast recognizes several special type carcinomas and benign lesions with features comparable to those of salivary gland tumors. Objective.--To discuss the histologic, immunophenotypic, molecular, and clinical features of salivary gland--like carcinomas of the breast. These breast tumors are often negative for hormone receptors and human epidermal growth factor receptor 2 (HER2), that is, triple-negative, but they generally have a much better prognosis than triple-negative breast carcinomas of no special type. We compare the immunophenotypic, molecular, and clinical features of these breast tumors with their salivary gland counterparts, highlighting similarities and differences. We also discuss benign salivary gland--like breast tumors. Finally, we highlight recent developments in understanding the molecular pathogenesis of these breast tumors and novel ancillary studies that can be used to support their diagnosis. Data Sources.--A literature review was conducted, and papers were selected for further analysis and discussion by the authors of this review based on their novelty, applicability, and impact in the field. Conclusions.--Breast tumors that exhibit morphologic overlap with salivary gland tumors have been recognized by pathologists for decades, but the similarities and differences in their molecular pathogenesis have not been understood until more recently. These developments have led to novel diagnostic tools and further knowledge of these rare breast lesions. [ABSTRACT FROM AUTHOR]

Context.--Neurotrophic receptor tyrosine kinase (NTRK) fusion testing has both diagnostic and therapeutic implications for patient care. With 2 tumor-agnostic US Food and Drug Administration--approved tropomyosin receptor kinase (TRK) inhibitors, testing is increasingly used for therapeutic decision making. However, the testing landscape for NTRK fusions is complex, and optimal testing depends on the clinicopathologic scenario. Objective.--To compare different NTRK testing methods to help pathologists understand test features and performance characteristics and make appropriate selections for NTRK fusion detection for their laboratory and individual patient specimens. Data Sources.--A literature search for NTRK gene fusions and TRK protein was performed, including papers that discussed treatment, testing methodology, and detection or prevalence of fusion-positive cases. Conclusions.--As standard of care in some tumor types, next-generation sequencing (NGS) panel testing is a cost effective and reliable way to detect a broad range of NTRK fusions. The design of the panel and use of DNA or RNA will affect performance characteristics. Pan-TRK immuno-histochemistry may be used as a rapid, less expensive screen in cases that will not undergo routine NGS testing, or on specimens unsuitable for NGS testing. Fluorescence in situ hybridization may be appropriate for low-tumor-content specimens that are unsuitable for NGS testing. Quantitative reverse transcription polymerase chain reaction is best suited for monitoring low-level disease of a specific, previously identified target. This information should help laboratories develop a laboratory-specific NTRK testing algorithm that best suits their practice setting and patients' needs. [ABSTRACT FROM AUTHOR]

* Context.--Machine learning (ML) allows for the analysis of massive quantities of high-dimensional clinical laboratory data, thereby revealing complex patterns and trends. Thus, ML can potentially improve the efficiency of clinical data interpretation and the practice of laboratory medicine. However, the risks of generating biased or unrepresentative models, which can lead to misleading clinical conclusions or overestimation of the model performance, should be recognized. Objectives.--To discuss the major components for creating ML models, including data collection, data preprocessing, model development, and model evaluation. We also highlight many of the challenges and pitfalls in developing ML models, which could result in misleading clinical impressions or inaccurate model performance, and provide suggestions and guidance on how to circumvent these challenges. Data Sources.--The references for this review were identified through searches of the PubMed database, US Food and Drug Administration white papers and guidelines, conference abstracts, and online preprints. Conclusions.--With the growing interest in developing and implementing ML models in clinical practice, laboratorians and clinicians need to be educated in order to collect sufficiently large and high-quality data, properly report the data set characteristics, and combine data from multiple institutions with proper normalization. They will also need to assess the reasons for missing values, determine the inclusion or exclusion of outliers, and evaluate the completeness of a data set. In addition, they require the necessary knowledge to select a suitable ML model for a specific clinical question and accurately evaluate the performance of the ML model, based on objective criteria. Domain-specific knowledge is critical in the entire workflow of developing ML models. [ABSTRACT FROM AUTHOR]

Context.--An abundance of clinical reports focused on specific laboratory parameters have been reported on coronavirus disease 19 (COVID-19), but a systematic analysis synthesizing these findings has not been performed. Objective.--To review and summarize the current available literature on the predictive role of various biomarkers in COVID-19 patients. Data Sources.--A literature search was performed using databases including PubMed, medRxiv, and bioRxiv. A total of 72 papers were reviewed, including 54 peerreviewed papers and 18 non--peer-reviewed preprints. Conclusions.--Although the markers are considered nonspecific, acute-phase reactants, including C-reactive protein (CRP), ferritin, serum amyloid A (SAA), and procalcitonin, were reported as sensitive markers of acute COVID-19 disease. Significantly elevated white blood cell count; marked lymphopenia; decreased CD3, CD4, or CD8 T-lymphocyte counts; high neutrophil count; thrombocytopenia; and markedly elevated inflammatory biomarkers were associated with severe disease and the risk of developing sepsis with rapid progression. Trends observed by serial laboratory measurements during hospitalization, including progressive decrease of lymphocyte count, thrombocytopenia, elevated CRP, procalcitonin, increased liver enzymes, decreased renal function, and coagulation derangements, were more common in critically ill patient groups and associated with a high incidence of clinical complications. Elevated interleukin 6 level and markedly increased SAA were most often reported in severely and critically ill patients. Indicators of systemic inflammation, such as neutrophil to lymphocyte ratio, systemic immuneinflammation index, or COVID-19 Severity Score, may be used to predict disease severity, outcome, and mortality. Interpretation of the data reported in the studies reviewed here is limited because of the study design (mostly retrospective), limited sample size, and a lack of defined clinical criteria. [ABSTRACT FROM AUTHOR]

* Context.--Laboratories of many medical college hospitals in India do not offer important diagnostic tests, most of which are routine in the West. This detracts from the service as well as the educational function of the college. Objectives.--To provide the background to pathology and laboratory medicine services and education in India, and to create a questionnaire that will put the lack of tertiary care laboratory services in perspective. This article will help illustrate the lacunae in laboratory medicine services and in the education of students. For this, we present information on the health services and pathology education facilities in India. We propose a questionnaire comprising 30 questions in various disciplines in pathology and laboratory medicine. These questions will help administrators and bureaucrats evaluate the status of the laboratories with respect to the services provided. Data Sources.--Sources include Web sites of the government of India, including that of the National Accreditation Board for Testing and Calibration Laboratories; indexed medical journal articles; and standard books and white papers on health care in India. We also used our personal experiences and interpretations of the laboratory and medical education sector in India. Conclusions.--Medical colleges in India need to offer specialized diagnostic services if they are to achieve the targets of universal health care as well as turning out competent doctors. The agencies responsible for health care in India should use the questionnaire as a first step toward improving laboratory services. Other low- and middle-income countries should also adopt this method. [ABSTRACT FROM AUTHOR]

* Context.--High-resolution computed tomography (HRCT) imaging has an increasingly important role in clinical decision-making in patients with interstitial lung diseases. The recent Fleischner Society white paper on the diagnostic criteria for idiopathic pulmonary fibrosis highlights the advances in our understanding of HRCT imaging in interstitial lung diseases. Objective.--To discuss the evidence and recommendations outlined in the white paper as it pertains to the radiologic diagnosis of interstitial lung disease, specifically highlighting the current limitations of HRCT in confidently predicting histopathologic findings. Data Sources.--The recent Fleischner Society white paper and other studies pertaining to the role of HRCT in predicting histopathology in interstitial lung diseases are reviewed. Conclusions.--High-resolution computed tomography is highly predictive of a usual interstitial pneumonia (UIP) pattern on histopathology when the HRCT shows a typical UIP pattern on a "confident" read by the radiologist. A probable UIP pattern is also very predictive of a UIP pattern on histopathology, and histopathologic confirmation is not needed for most patients demonstrating this pattern in the appropriate clinical setting. A UIP pattern may be seen in a substantial proportion of patients with an "indeterminate UIPV" pattern on HRCT and in many patients for whom the HRCT suggests an alternative diagnosis; histopathologic confirmation should be considered in patients demonstrating these patterns whenever feasible. [ABSTRACT FROM AUTHOR]

An introduction to a special section of the journal is presented in which the author discusses papers presented at the 2022 New Frontiers in Pathology continuing medical education conference, with topics including melodysplasia cutis, the histologic, immunohistochemical and molecular features of uncommon endometrial tumors, and features of intraplacental choriocarcinoma and chorangiocarcinoma.

Context.--Next-generation sequencing is a powerful clinical tool for cancer management but can produce incidental/secondary findings that require special consideration. Objective.--To discuss clinical and laboratory issues related to incidental or secondary germline findings in the clinical setting of tumor testing and inform future guidelines in this area. Design.--A College of American Pathologists workgroup including representation from the American Society of Clinical Oncology, the Association for Molecular Pathology, and the American College of Medical Genetics and Genomics created a review of items that should be considered when developing guidelines for incidental or secondary findings when performing clinical tumor testing. Results.--Testing recommendations should be cognizant of the differences among anticipated incidental, unanticipated incidental, and secondary findings, and whether normal tissue is also tested. In addition to defining which variants will be reported, robust recommendations must also take into account test design and validation, reimbursement, cost, infrastructure, impact on reflex testing, and maintenance of proficiency. Care providers need to consider the potential of a test to uncover incidental or secondary findings, the recommendation of upfront counseling, the need for consent, the timing of testing and counseling, and that the exact significance of a finding may not be clear. Conclusions.--As clinical oncology testing panels have become a mainstay of clinical cancer care, guidelines addressing the unique aspects of incidental and secondary findings in oncology testing are needed. This paper highlights clinical and laboratory considerations with regard to incidental/secondary findings and is a clarion call to create recommendations. [ABSTRACT FROM AUTHOR]

Context.--With the increasing development and use of iatrogenic agents, pathologists are encountering more novel foreign materials in retrieved gastrointestinal specimens. These colorful and unusual-appearing foreign materials can pose a diagnostic dilemma to those unaware of their morphology, especially if the relevant clinical history is lacking. Objective.--To discuss the histopathologic features, clinical scenarios and significance, and differential diagnosis of relatively recently described, yet quickly expanding, family of iatrogenic agents that can present as foreign materials in gastrointestinal specimens--pharmaceutical fillers (crospovidone and microcrystalline cellulose), submucosal lifting agents (Eleview and ORISE), lanthanum carbonate, hydrophilic polymers, OsmoPrep, yttrium 90 microspheres (SIR-Sphere and TheraSphere), and resins (sodium polystyrene sulfonate, sevelamer, and bile acid sequestrants). Data Sources.--We collate the findings of published literature, including recently published research papers, and authors' personal experiences from clinical sign-out and consult cases. Conclusions.--Correct identification of these iatrogenic agents is important because the presence of some novel agents can explain the histopathologic findings seen in the background specimen, and specific novel agents can serve as diagnostic clues to prompt the pathologist to consider other important and related diagnoses. Awareness of even biologically inert agents is important for accurate diagnosis and to avoid unnecessary and expensive diagnostic studies. [ABSTRACT FROM AUTHOR]

* Context.--Aldred Scott Warthin, MD, PhD, was professor of pathology and director of the pathological laboratory at the University of Michigan during the first third of the 20th century. Objective.--To explore the life and accomplishments of Dr. Warthin and his impact on academic anatomic and clinical pathology. Design.--Available primary and secondary historic sources were reviewed. Results.--After studying music, biology, and botany, Warthin attended medical school at the University of Michigan, graduating in 1891; he remained in Ann Arbor for 40 years, almost single-handedly transforming a rundown department into a top academic department. He was a dedicated teacher who produced 2 important pathology textbooks. His research interests were diverse. In 1913, he published one of the first papers unambiguously documenting heritability of cancers; subsequent research on one of his cancer families resulted in the description of Lynch Syndrome. He published extensively in the fields of surgical pathology and experimental pathology. He was a recognized expert on syphilis and pathology of aging. Conclusions.--Warthin's name is eponymously associated with Warthin-Finkeldey giant cells in measles, Warthin's tumor of the parotid, and Warthin-Starry stain for the diagnosis of syphilis as well as Warthin's sign in the clinical diagnosis of pericarditis. [ABSTRACT FROM AUTHOR]

* Context.--Recent developments in machine learning have stimulated intense interest in software that may augment or replace human experts. Machine learning may impact pathology practice by offering new capabilities in analysis, interpretation, and outcomes prediction using images and other data. The principles of operation and management of machine learning systems are unfamiliar to pathologists, who anticipate a need for additional education to be effective as expert users and managers of the new tools. Objective.--To provide a background on machine learning for practicing pathologists, including an overview of algorithms, model development, and performance evaluation; to examine the current status of machine learning in pathology and consider possible roles and requirements for pathologists in local deployment and management of machine learning systems; and to highlight existing challenges and gaps in deployment methodology and regulation. Data Sources.--Sources include the biomedical and engineering literature, white papers from professional organizations, government reports, electronic resources, and authors' experience in machine learning. References were chosen when possible for accessibility to practicing pathologists without specialized training in mathematics, statistics, or software development. Conclusions.--Machine learning offers an array of techniques that in recent published results show substantial promise. Data suggest that human experts working with machine learning tools outperform humans or machines separately, but the optimal form for this combination in pathology has not been established. Significant questions related to the generalizability of machine learning systems, local site verification, and performance monitoring remain to be resolved before a consensus on best practices and a regulatory environment can be established. [ABSTRACT FROM AUTHOR]

The article comments on a paper by B. Magnani and C. R. Taylor on the regulation of immunohistochemistry (IHC) as an assay. Topics mentioned include the challenges for achieving accuracy and precision with IHC, the impact of signal detection on how IHC and immunoassay should be regulated by government agencies in the U.S., the need to incorporate clinical immunoassay concepts into the IHC laboratory, and some developments in the staining/technical aspects of IHC.

* 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. [ABSTRACT FROM AUTHOR]

* Context.--This article presents a review of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), including its separation from follicular variant of papillary carcinoma of the thyroid, its evolution, and current definition and pathologic characteristics. Objectives.--To emphasize the understanding of the concept of NIFTP as a neoplasm based on molecular analyses, its critical histopathologic features, the microscopic findings that exclude the diagnosis, and the importance of complete sectioning of the tumor to exclude neoplasms that should be diagnosed as carcinomas. Important distinctions are discussed including difficulties with literature that shows NIFTP with metastases, inadequacy of sectioning of the tumor, and lack of descriptive histology of the surrounding thyroid and possible other lesions. Data Sources.--Review of articles in the English literature on NIFTP, as well as comparative papers showing differences and distinctions between this entity and papillary carcinomas. Conclusions.--This article concludes that with the current state of knowledge on NIFTP with studies from all over the world, this entity is a low-risk neoplasm that, when diagnosed using appropriate criteria, should not be associated with metastatic or recurrent disease, at least on intermediate length of follow-up. This review includes discussion of multifocal NIFTP, as well as the recently defined micro-NIFTP (1 cm or less), and describes features of the tumor that remain to be studied and correlated with outcome: oncocytic variants of NIFTP, percentage of allowable solid areas of growth in the lesions, and definitions of true neoplastic papillae and hyperplastic ones and how these should influence the diagnosis of NIFTP. [ABSTRACT FROM AUTHOR]

* Context.--The World Health Organization Classification of Tumours: Digestive System Tumors, 5th edition, was published in 2019 and shows several impactful changes as compared with the 4th edition published in 2010. Changes include a revised nomenclature of serrated lesions and revamping the classification of neuroendocrine neoplasms. Appendiceal goblet cell adenocarcinoma is heavily revised, and intrahepatic cholangiocarcinoma is split into 2 subtypes. New subtypes of colorectal carcinoma and hepatocellular carcinoma are described. Precursor lesions are emphasized with their own entries, and both dysplastic and invasive lesions are generally recommended to be graded using a 2-tier system. Hematolymphoid tumors, mesenchymal tumors, and genetic tumor syndromes each have their own sections in the 5th edition. New hematolymphoid lesions include monomorphic epitheliotropic intestinal T-cell lymphoma; duodenal-type follicular lymphoma; intestinal T-cell lymphoma, not otherwise specified; and indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. This paper will provide an indepth look at the changes in the 5th edition as compared with the 4th edition. Objective.--To provide a comprehensive, in-depth update on the World Health Organization classification of digestive tumors, including changes to nomenclature, updated diagnostic criteria, and newly described entities. Data Sources.--The 5th edition of the World Health Organization Classification of Tumours: Digestive System Tumours, as well as the 4th edition. Conclusions.--The World Health Organization has made many key changes in its newest update on tumors of the digestive system. Pathologists should be aware of these changes and incorporate them into their practice as able or necessary. [ABSTRACT FROM AUTHOR]

* Context.--Point-of-care testing (POCT) is inherently spatial, that is, performed where needed, and intrinsically temporal, because it accelerates decision-making. POCT efficiency and effectiveness have the potential to facilitate antimicrobial resistance (AMR) detection, decrease risks of coinfections for critically ill patients with coronavirus infectious disease 2019 (COVID-19), and improve the costeffectiveness of health care. Objectives.--To assess AMR identification by using POCT, describe the United States AMR Diagnostic Challenge, and improve global standards of care for infectious diseases. Data Sources.--PubMed, World Wide Web, and other sources were searched for papers focusing on AMR and POCT. EndNote X9.1 (Clarivate Analytics) consolidated abstracts, URLs, and PDFs representing approximately 500 articles were assessed for relevance. Panelist insights at Tri•Con 2020 in San Francisco and finalist POC technologies competing for a US $20,000,000 AMR prize are summarized. Conclusions.--Coinfections represent high risks for COVID-19 patients. POCT potentially will help target specific pathogens, refine choices for antimicrobial drugs, and prevent excess morbidity and mortality. POC assays that identify patterns of pathogen resistance can help tell us how infected individuals spread AMR, where geospatial hotspots are located, when delays cause death, and how to deploy preventative resources. Shared AMR data "clouds" could help reduce critical care burden during pandemics and optimize therapeutic options, similar to use of antibiograms in individual hospitals. Multidisciplinary health care personnel should learn the principles and practice of POCT, so they can meet needs with rapid diagnostic testing. The stakes are high. Antimicrobial resistance is projected to cause millions of deaths annually and cumulative financial loses in the trillions by 2050. [ABSTRACT FROM AUTHOR]

* Context.--Machine learning (ML) allows for the analysis of massive quantities of high-dimensional clinical laboratory data, thereby revealing complex patterns and trends. Thus, ML can potentially improve the efficiency of clinical data interpretation and the practice of laboratory medicine. However, the risks of generating biased or unrepresentative models, which can lead to misleading clinical conclusions or overestimation of the model performance, should be recognized. Objectives.--To discuss the major components for creating ML models, including data collection, data preprocessing, model development, and model evaluation. We also highlight many of the challenges and pitfalls in developing ML models, which could result in misleading clinical impressions or inaccurate model performance, and provide suggestions and guidance on how to circumvent these challenges. Data Sources.--The references for this review were identified through searches of the PubMed database, US Food and Drug Administration white papers and guidelines, conference abstracts, and online preprints. Conclusions.--With the growing interest in developing and implementing ML models in clinical practice, laboratorians and clinicians need to be educated in order to collect sufficiently large and high-quality data, properly report the data set characteristics, and combine data from multiple institutions with proper normalization. They will also need to assess the reasons for missing values, determine the inclusion or exclusion of outliers, and evaluate the completeness of a data set. In addition, they require the necessary knowledge to select a suitable ML model for a specific clinical question and accurately evaluate the performance of the ML model, based on objective criteria. Domain-specific knowledge is critical in the entire workflow of developing ML models. (Arch Pathol Lab Med. 2023;147:826-836; doi: 10.5858/ arpa.2021-0635-RA), Machine learning (ML) (1) has emerged as a powerful tool for analyzing and interpreting laboratory test results as well as integrating clinical findings with laboratory data. (2) In recent years, [...]

Context.--The coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coagulation dysfunction is a hallmark in patients with COVID-19. Fulminant thrombotic complications emerge as critical issues in patients with severe COVID-19. Objective.--To present a review of the literature and discuss the mechanisms of COVID-19 underlying coagulation activation and the implications for anticoagulant and thrombolytic treatment in the management of COVID-19. Data Sources.--We performed a systemic review of scientific papers on the topic of COVID-19, available online via the PubMed NCBI, medRxiv, and Preprints as of May 15, 2020. We also shared our experience on the management of thrombotic events in patients with COVID-19. Conclusions.--COVID-19-associated coagulopathy ranges from mild laboratory alterations to disseminated intravascular coagulation (DIC) with a predominant phenotype of thrombotic/multiple organ failure. Characteristically, high D-dimer levels on admission and/or continuously increasing concentrations of D-dimer are associated with disease progression and poor overall survival. SARS-CoV-2 infection triggers the immune-hemostatic response. Drastic inflammatory responses including, but not limited to, cytokine storm, vasculopathy, and NETosis may contribute to an overwhelming activation of coagulation. Hypercoagulability and systemic thrombotic complications necessitate anticoagulant and thrombolytic interventions, which provide opportunities to prevent or reduce "excessive" thrombin generation while preserving "adaptive" hemostasis and bring additional benefit via their anti-inflammatory effect in the setting of COVID-19. [ABSTRACT FROM AUTHOR]

Context.--Point-of-care testing (POCT), diagnostic testing at or near the site of patient care, is inherently spatial, that is, performed at points of need, and also intrinsically temporal, because it produces fast actionable results. Outbreaks generate geospatial "hotspots." POC strategies help control hotspots, detect spread, and speed treatment of highly infectious diseases. Objectives.--To stop outbreaks, accelerate detection, facilitate emergency response for epidemics, mobilize public health practitioners, enhance community resilience, and improve crisis standards of care. Data Sources.--PubMed, World-Wide Web, newsprint, and others were searched until Coronavirus infectious disease-19 was declared a pandemic, the United States, a national emergency, and Europe, the epicenter. Coverage comprised interviews in Asia, email to/from Wuhan, papers, articles, chapters, documents, maps, flowcharts, schematics, and geospatial-associated concepts. EndNote X9.1 (Clarivate Analytics) consolidated literature as abstracts, ULRs, and PDFs, recovering 136 hotspot articles. More than 500 geospatial science articles were assessed for relevance to POCT. Conclusions.--POCT can interrupt spirals of dysfunction and delay by enhancing disease detection, decision-making, contagion containment, and safe spacing, thereby softening outbreak surges and diminishing risk before human, economic, and cultural losses mount. POCT results identify where infected individuals spread Coronavirus infectious disease-19, when delays cause death, and how to deploy resources. Results in national cloud databases help optimize outbreak control, mitigation, emergency response, and community resilience. The Coronavirus infectious disease-19 pandemic demonstrates unequivocally that governments must support POCT and multidisciplinary healthcare personnel must learn its principles, then adopt POC geospatial strategies, so that onsite diagnostic testing can ramp up to meet needs in times of crisis. [ABSTRACT FROM AUTHOR]

Context.--The novel coronavirus disease 2019 (COVID-19) pandemic is significantly changing methodologic approaches in all branches of the health system. From a forensic point of view, this event is partly changing the manner in which forensic pathologists and all those who work in autopsy services operate, but above all, it is changing the patterns established for years by which cadavers are analyzed postmortem. Objective.--To present a review of the literature and a proposal for COVID-19 autopsy protocols. To contain the infection risk, a revision of all the protocols that until now have been applied to the examination of bodies that require autopsy services is required. Data Sources.--Currently, the diagnosis and postmortem analysis of positive or suspected COVID-19 cases plays a crucial role in scientific research. A review of the main recommendations proposed by international scientific societies regarding the risk of infection during autopsy was carried out. Scientific papers currently available via the PubMed NCBI search engine on COVID-19 postmortem diagnosis were also examined. Conclusions.--Throughout the history of medicine, autopsy has been fundamental to the understanding of multiple pathogenic processes that are investigated postmortem. The purpose of the study is to propose an operating protocol that can be useful for all clinical and forensic autopsies, with particular reference to the correct methods to be applied to the examination of positive or suspected COVID-19 cases, regarding both the autopsy procedure and the collection and analysis of biological samples. [ABSTRACT FROM AUTHOR]

* Context.--Solid pseudopapillary neoplasm of the pancreas is a low-grade malignant tumor generally associated with a good prognosis. Solid pseudopapillary neoplasms show peculiar morphologic features, but sometimes the differential diagnosis with other pancreatic neoplasms (ie, pancreatic neuroendocrine tumors) can be a challenging task, especially in cytologic or biopsy specimens. In these cases immunohistochemistry is a useful tool, but the diagnostic utility of several proposed immunohistochemical markers is questionable. In recent years, despite several attempts to characterize the pathogenetic, molecular, and prognostic features of solid pseudopapillary neoplasms, they still remain unclear. Objective.--To give the reader a comprehensive update on this entity. Data Sources.--The PubMed database (US National Library of Medicine) was searched using the following string: pseudopapillary tumor [AND/OR] neoplasm [AND/OR] pancreas. All articles written in English were included. In addition, because a heterogeneous terminology has been used in the past to define solid pseudopapillary neoplasms, the reference lists of each paper selected in the PubMed database were also reviewed. Conclusions.--This review gives a comprehensive update on the pathologic, clinical, and molecular features of solid pseudopapillary neoplasms, particularly addressing issues and challenges related to diagnosis. In addition, we have tried to correlate the molecular alterations with the morphologic and clinical features. [ABSTRACT FROM AUTHOR]

Context.--There is a wide disconnect between patients and the pathologists who make their diagnoses. Recent literature highlights successful programs in which patients meet with pathologists to review their pathology reports and see their tissue under a microscope. We do not know how many patients are interested in such a service, nor do we understand what drives interested patients to want to meet with their pathologist and what specific value it may provide. Objective.--To quantify patient interest in a patientpathologist consultation program and qualitatively assess motivations for patient interest or disinterest. Design.--Subjects were recruited from an academic cancer center and a local community cancer support group to respond to a survey about their interest in a patientpathologist consultation program. Both online forms and paper surveys were available. The online survey was promoted via social media. Results.--There was a high level of patient interest, with 75% of respondents indicating they were definitely interested in a patient-pathologist consultation program. Key themes of interest were enhanced understanding of the diagnosis and disease, an opportunity to demystify the diagnostic process, and the perception that additional knowledge would empower the patient. Conclusions.--In a select group of cancer patients, there is a very high level of interest in a patient-pathologist consultation program. Pathologists, clinicians, and hospital leadership should work together to pilot these programs in diverse settings. Additional quantitative work to scale interventions for the interested population and qualitative work to design effective, patient-centered consultation programs and to assess value are needed. [ABSTRACT FROM AUTHOR]

Context.--Myriad forces are changing teaching and learning strategies throughout all stages and types of pathology education. Pathology educators and learners face the challenge of adapting to and adopting new methods and tools. The digital pathology transformation and the associated educational ecosystem are major factors in this setting of change. Objective.--To identify and collect resources, tools, and examples of educational innovations involving digital pathology that are valuable to pathology learners and teachers at each phase of professional development. Data Sources.--Sources were a literature review and the personal experience of authors and educators. Conclusions.--High-quality digital pathology tools and resources have permeated all the major niches within anatomic pathology and are increasingly well applied to clinical pathology for learners at all levels. Coupled with other virtual tools, the training landscape in pathology is highly enriched and much more accessible than in the past. Digital pathology is well suited to the demands of peer-to-peer education, such as in the introduction of new testing, grading, or other standardized practices. We found that digital pathology was well adapted to apply our current understanding of optimal teaching strategies and was effective at the undergraduate, graduate, postgraduate, and peer-to-peer levels. We curated and tabulated many existing resources within some segments of pathology. We identified several best practices for each training or educational stage based on current materials and proposed high-priority areas for potential future development. doi: 10.5858/arpa.2021-0473-RA, We could just as well be writing this paper with a manually powered typewriter, or with ink drawn from a well by a quill pen, had not a series of [...]

Context.--In 2016 the World Health Organization published a revised classification of testicular neoplasms based upon advances in understanding their pathogenesis and molecular biology. The rationale for this revision and additional clinically relevant observations were the topics of a talk given to the Houston Society of Clinical Pathologists in April 2017. This paper summarizes that talk. Objective.--To summarize and explain the most important changes to the classification of testicular neoplasms in the World Health Organization 2016 revision. Data Sources.--Peer-reviewed published literature and contributions by individuals with expertise in this area that were also reviewed by genitourinary pathologists. Conclusions.--Most changes occurred in the germ cell tumor classification, including replacement of the terms intratubular germ cell neoplasia unclassified and carcinoma in situ by germ cell neoplasia in situ; subdivision of the tumors into 2 main categories, those derived from germ cell neoplasia in situ and those not derived from germ cell neoplasia in situ; distinction of germ cell neoplasia in situ from germ cells with delayed maturation and pre-germ cell neoplasia in situ; expansion of the trophoblastic tumor category to include epithelioid trophoblastic tumor and cystic trophoblastic tumor; and substitution of spermatocytic tumor for spermatocytic seminoma and its placement in the non-germ cell neoplasia in situ group. Other revisions included eliminating sclerosing Sertoli cell tumor as a distinct entity; the recognition of intratubular hyalinizing Sertoli cell tumor; and acceptance of the role of undifferentiated gonadal tissue in the pathogenesis of gonadoblastoma. [ABSTRACT FROM AUTHOR]

* This paper reports the results of a collaborative lung cancer study between City of Hope Cancer Center (Duarte, California) and CIRECA, LLC (Cambridge, Massachusetts), comprising 328 samples from 249 patients, that used an optical technique known as spectral histopathology (SHP) for tissue classification. Because SHP is based on a physical measurement, it renders diagnoses on a more objective and reproducible basis than methods based on assessing cell morphology and tissue architecture. This report demonstrates that SHP provides distinction of adenocarcinomas from squamous cell carcinomas of the lung with an accuracy comparable to that of immunohistochemistry and highly reliable classification of adenosquamous carcinoma. Furthermore, this report shows that SHP can be used to resolve interobserver differences in lung pathology. Spectral histopathology is based on the detection of changes in biochemical composition, rather than morphologic features, and is therefore more akin to methods such as matrix-assisted laser desorption ionization time-of-flight mass spectrometry imaging. Both matrixassisted laser desorption ionization time-of-flight mass spectrometry and SHP imaging modalities demonstrate that changes in tissue morphologic features observed in classical pathology are accompanied by, and may be correlated to, changes in the biochemical composition at the cellular level. Thus, these imaging methods provide novel insight into biochemical changes due to disease. [ABSTRACT FROM AUTHOR]

The author explores the issues surrounding informed consent for genetic testing in autopsy. Topics covered include the importance of reviewing autopsies performed under authority of a state's law governing medical examiners or coroners (ME/C), the highlights of the position paper of the National Association of Medical Examiners (NAME) on genetic testing and details of some of the legal cases in the U.S. about informed consent.

* Context.--Cervical adenocarcinomas span a diverse group of tumors with several distinct histologic tumor types, which include endocervical, endometrioid, intestinal, villoglandular, gastric, signet ring, serous, clear cell, and mesonephric. Diagnosis of cervical adenocarcinoma, especially early diagnosis, poses a significant challenge. Objective.--To review the pathogenesis, diagnostic criteria, immunohistochemical markers, and differential diagnosis of various subtypes of human papillomavirus (HPV)-positive and HPV-negative cervical adenocarcinomas. The paper presents a concise summary of the issues that may be particularly difficult in histopathologic diagnosis, such as differentiating neoplastic lesions from benign mimics, determining the tumor type, differentiating early invasive lesions from adenocarcinoma in situ, measuring the depth of invasion, and, finally, differentiating primary cervical adenocarcinoma from uterine endometrioid adenocarcinoma and tumors metastatic from other primary sites. Data Sources.--The study employed a PubMed search of recently published reports. Conclusions.--Early detection of HPV-positive tumor types may be aided with the expansion of HPV testing; however, early diagnosis of HPV-negative cervical adenocarcinomas will continue to pose a challenge and may require the development of additional molecular testing techniques. [ABSTRACT FROM AUTHOR]

Context.--Inappropriate laboratory test ordering has been shown to be as high as 30%. This can have an important impact on quality of care and costs because of downstream consequences such as additional diagnostics, repeat testing, imaging, prescriptions, surgeries, or hospital stays. Objective.--To evaluate the effect of computerized clinical decision support systems on appropriateness of laboratory test ordering. Data Sources.--We used MEDLINE, Embase, CINAHL, MEDLINE In-Process and Other Non-Indexed Citations, Clinicaltrials.gov, Cochrane Library, and Inspec through December 2015. Investigators independently screened articles to identify randomized trials that assessed a computerized clinical decision support system aimed at improving laboratory test ordering by providing patient- specific information, delivered in the form of an on-screen management option, reminder, or suggestion through a computerized physician order entry using a rule-based or algorithm-based system relying on an evidence-based knowledge resource. Investigators extracted data from 30 papers about study design, various study characteristics, study setting, various intervention characteristics, involvement of the software developers in the evaluation of the computerized clinical decision support system, outcome types, and various outcome characteristics. Conclusions.--Because of heterogeneity of systems and settings, pooled estimates of effect could not be made. Data showed that computerized clinical decision support systems had little or no effect on clinical outcomes but some effect on compliance. Computerized clinical decision support systems targeted at laboratory test ordering for multiple conditions appear to be more effective than those targeted at a single condition. [ABSTRACT FROM AUTHOR]

The article discusses various papers published in this special section including one by Xue et al. on embolization procedures in liver explants, one by S. Li et al. on the treatment with monoclonal antibodies, and one by Xue et al. on a compendium of histomorphologic changes that pathologists may observe in liver.

Context.--There are a number of critical factors that can lead to incorrect results if the diagnostic pathologist performing immunohistochemistry is unaware of, or not vigilant about, their influence. Objective.--To highlight 3 arenas in which errors may be introduced. Data Sources.--For choosing the correct primary antibody, selection of the most appropriate antibodies for a given clinical application can be aided by obtaining information from the vendor; however, this can yield incomplete information. There are a number of online databases that have comparisons of antibodies from different vendors, particularly with respect to their use and properties. Reading the published literature can assist in this process, particularly with respect to determining antibody sensitivity and specificity, but it is a daunting task to keep up with all of the immunohistochemistry-related papers published. Finally, Web sites of a number of quality assurance organizations are accessible and can provide a wealth of information comparing the "real world" performance characteristics of different antibodies to the same target protein. False-positive signals can result from a number of factors, including the use of inappropriately high antibody concentration, and "pseudospecific" signal that is in the wrong compartment of the cell. False-negative signal can result from factors such as use of a nonoptimized epitope retrieval method. It is critical that epitope retrieval methods be optimized for each antibody employed in the laboratory. Conclusions.--By paying attention to these potential problems, the "black box" of diagnostic immunohistochemistry can be made more transparent. [ABSTRACT FROM AUTHOR]

Immunodeficient individuals are prone to develop a number of opportunistic infections and unique neoplasms. Epstein-Barr virus--associated smooth muscle tumor is an uncommon neoplasm associated with immunodeficiency. It has been described in patients infected with human immunodeficiency virus, in the posttransplant setting, and in those with congenital immunodeficiency. Different anatomic sites can be involved by Epstein-Barr virus-associated smooth muscle tumor, and even multiple locations can contain these unique lesions within the same patient. The presence of variable numbers of intratumoral lymphocytes and primitive round cell areas are the unique defining features for this tumor. Histopathologic features may vary considerably in terms of cellular atypia, mitotic activity, and necrosis, with no correlation to the clinical behavior. Demonstration of Epstein-Barr virus infection by in situ hybridization within tumor cell remains critical for the diagnosis. The mechanism for Epstein-Barr virus infection of progenitor cells and neoplastic transformation has been an area of interest and conjecture. Different treatment strategies are proposed according to underlying disease status. This paper reviews the clinicopathologic features of this uncommon neoplasm with detailed discussion of the role of Epstein-Barr virus in the pathogenesis. [ABSTRACT FROM AUTHOR]

The approval of anti-programmed death receptor (PD)-1 therapies for non-small cell lung cancer has directed the spotlight on programmed death ligand-1 (PD-L1) immunohistochemistry as the latest predictive biomarker potentially required in this disease. Several other drugs in this class will likely be approved in the future and each has been developed with a unique anti-PD-L1 immunohistochemistry test. The prospect of 5 drugs competing in the same treatment area, each possibly requiring PD-L1 immunohistochemistry testing, presents a challenge for pathologists unlike any previously faced. The key issue is whether laboratories will attempt to deliver the trial-validated assays for one or more of these treatments, or introduce instead one or more laboratory developed tests, or attempt to provide a single PD-L1 immunohistochemistry assay for all possible anti-PD-1 and anti-PD-L1 treatments that may be used. This paper discusses some of the issues, challenges, hazards, and possible solutions that have recently emerged in this most complex interface between cancer therapeutics and laboratory biomarker testing. [ABSTRACT FROM AUTHOR]

Context.--Telepathology is a particular form of telemedicine that fundamentally alters the way pathology services are delivered. Prior reviews in this area have mostly focused on 2 themes, namely technical feasibility issues and diagnosis accuracy. Objectives.--To synthesize the literature on telepathology implementation challenges and broader organizational and societal impacts and to propose a research agenda to guide future efforts in this domain. Data Sources.--Two complementary databases were systematically searched: MEDLINE (PubMed) and ABI/ INFORM (ProQuest). Peer-reviewed articles and conference proceedings were considered. The final sample consisted of 159 papers published between 1992 and 2013. Conclusions.--This review highlights the diversity of telepathology networks and the importance of considering these distinctions when interpreting research findings. Various network structures are associated with different benefits. Although the dominant rationale in single-site projects is financial, larger centralized and decentralized telepathology networks are targeting a more diverse set of benefits, including extending access to pathology to a whole region, achieving substantial economies of scale in workforce and equipment, and improving quality by standardizing care. Importantly, our synthesis reveals that the nature and scale of encountered implementation challenges also varies depending on the network structure. In smaller telepathology networks, organizational concerns are less prominent, and implementers are more focused on usability issues. As the network scope widens, organizational and legal issues gain prominence. [ABSTRACT FROM AUTHOR]

Information on papers that critically review new entities on general surgical pathology that were presented at the 16th spring seminar of the Korean Pathologists Association of North America (KOPANA) in 2018 is presented. Topics include diffuse gliomas for nonneuropathologists, p16 immunohistochemistry (IHC) in melanocytic lesions, and the 2-tier grading system for laryngeal squamous precursor lesions. The seminar featured pathologists including Eunlee S. Yi, Eun Y. Lee, and Jae Y. Ro.