Liquid biopsy-based circulating tumour (ct)DNA analysis of a spectrum of myeloid and lymphoid malignancies yields clinically actionable results.

AIMS: Liquid biopsy (LBx)-based next-generation sequencing (NGS) of circulating tumour DNA (ctDNA) can facilitate molecular profiling of haematopoietic neoplasms (HNs), particularly when tissue-based NGS is infeasible. METHODS AND RESULTS: We studied HN LBx samples tested with FoundationOne Liquid CDx, FoundationOne Liquid, or FoundationACT between July 2016 and March 2022. We identified 271 samples: 89 non-Hodgkin lymphoma (NHL), 43 plasma-cell neoplasm (PCN), 41 histiocytoses, 27 myelodysplastic syndrome (MDS), 25 diffuse large B-cell lymphoma (DLBCL), 22 myeloproliferative neoplasm (MPN), 14 Hodgkin lymphoma (HL), and 10 acute myeloid leukaemia (AML). Among 73.4% with detectable pathogenic alterations, median maximum somatic allele frequency (MSAF) was 16.6%, with AML (36.2%), MDS (19.7%), and MPN (44.5%) having higher MSAFs than DLBCL (3.9%), NHL (8.4%), HL (1.5%), PCN (2.8%), and histiocytoses (1.8%) (P = 0.001). LBx detected characteristic alterations across HNs, including in TP53, KRAS, MYD88, and BTK in NHLs; TP53, KRAS, NRAS, and BRAF in PCNs; IGH in DLBCL; TP53, ATM, and PDCD1LG2 in HL; BRAF and MAP2K1 in histiocytoses; TP53, SF3B1, DNMT3A, TET2, and ASXL1 in MDS; JAK2 in MPNs; and FLT3, IDH2, and NPM1 in AML. Among 24 samples, the positive percent agreement by LBx was 75.7% for variants present in paired buffy coat, marrow, or tissues. Also, 75.0% of pairs exhibited alterations only present on LBx. These were predominantly subclonal (clonal fraction of 3.8%), reflecting the analytical sensitivity of LBx. CONCLUSION: These data demonstrate that LBx can detect relevant genomic alterations across HNs, including at low clonal fractions, suggesting a potential clinical utility for identifying residual or emerging therapy-resistant clones that may be undetectable in site-specific tissue biopsies.

Critical role of pathology and laboratory medicine in the conversation surrounding access to healthcare.

Pathology and laboratory medicine are a key component of a patient's healthcare. From academic care centres, community hospitals, to clinics across the country, pathology data are a crucial component of patient care. But for much of the modern era, pathology and laboratory medicine have been absent from health policy conversations. Though select members in the field have advocated for an enhanced presence of these specialists in policy conversations, little work has been done to thoroughly evaluate the moral and ethical obligations of the pathologist and the role they play in healthcare justice and access to care. In order to make any substantive improvements in access to care, pathology and laboratory medicine must have a seat at the table. Specifically, pathologists and laboratorians can assist in bringing about change through improving clinician test choice, continuing laboratory improvement programmes, promoting just advanced diagnostic distribution, triage testing and be good stewards of healthcare dollars, and recruiting a more robust laboratory workforce. In order to get to that point, much work has to be done in pathology education and the laboratory personnel training pipeline but there also needs to be adjustments at the system level to better involve this invaluable group of specialists in these policy conversations.

Phenotypic clues that predict underlying cytogenetic/genetic abnormalities in myeloid malignancies: A contemporary review.

Precise subclassification of myeloid malignancies per the World Health Organization (WHO) classification system and the International Consensus Classification of Myeloid Neoplasms and Acute Leukaemias (ICC) requires investigation and documentation of the presence of cytogenetic and/or molecular genetic changes. These ancillary studies not only help in diagnosis, but also the prognosis of disease; however, they take time to be completed. In contrast, morphological evaluation of material from the blood and bone marrow specimens of cases where myeloid malignancies are suspected is usually completed quickly. Cytomorphological assessment may predict genetic changes and can be helpful in triaging acuity. This is especially true in haematological emergencies such as acute promyelocytic leukaemia (APL), where prompt APL-specific therapy can be life changing. Similarly, some morphological clues may help identify core binding factor leukaemias where a diagnosis of acute myeloid leukaemia (AML) could be rendered without reaching the 20% blast cutoff with immediate treatment-decision implications, or even a subset of cases of AML with FLT3 ITD/NPM1 mutation(s) which show characteristic features. Even though FISH/cytogenetics and/or PCR are still required for establishing the final diagnosis, evaluation for the presence of specific cytomorphological features that help predict genetic changes can be a useful tool to help guide early therapy.

Toward a More Just System of Care in Molecular Pathology.

Policy Points American health care policy must be critically assessed to establish the role it plays in sustaining and alleviating the health disparities that currently exist in molecular genetic testing. It is critical to understand the economic and sociocultural influences that drive patients to undergo or forgo molecular testing, especially in marginalized patient populations. A multipronged solution with actions necessary from multiple stakeholders is required to reduce the cost of health care, rebalance regional disparities, encourage physician engagement, reduce data bias, and earn patients' trust. CONTEXT: The health status of a population is greatly influenced by both biological processes and external factors. For years, minority and low socioeconomic patient populations have faced worse outcomes and poorer health in the United States. Experts have worked extensively to understand the issues and find solutions to alleviate this disproportionate burden of disease. As a result, there have been some improvements and successes, but wide gaps still exist. Diagnostic molecular genetic testing and so-called personalized medicine are just now being integrated into the current American health care system. The way in which these tests are integrated can either exacerbate or reduce health disparities. METHODS: We provide case scenarios-loosely based on real-life patients-so that nonexperts can see the impacts of complex policy decisions and unintentional biases in technology without needing to understand all the intricacies. We use data to explain these findings from an extensive literature search examining both peer-reviewed and gray literature. FINDINGS: Access to diagnostic molecular genetic testing is not equitable or sufficient, owing to at least five major factors: (1) cost to the patient, (2) location, (3) lack of provider buy-in, (4) data-set bias, and (5) lack of public trust. CONCLUSIONS: Molecular genetic pathology can be made more equitable with the concerted efforts of multiple stakeholders. Confronting the five major factors identified here may help us usher in a new era of precision medicine without its discriminatory counterpart.

A Case of Primary Myelofibrosis With Transformation to Leukemia Cutis.

ABSTRACT: We report an extraordinary case of primary myelofibrosis with transformation to leukemia cutis. A 64-year-old Caucasian man with a history of JAK2-positive primary myelofibrosis presented with erythematous papulonodules on his right lower extremity. A punch biopsy revealed a normal epidermis with an underlying diffuse dermal infiltrate composed of medium-to-large-sized myeloid cells and leukocytes. Neoplastic cells were immunoreactive for LCA, CD34, CD61, CD117, and CD68 and negative for lysozyme, CD20, CD3, myeloperoxidase, and TdT. These findings were consistent with a diagnosis of leukemia cutis. A concurrent bone marrow biopsy demonstrated a markedly fibrotic, hypercellular marrow without a significant increase in blasts. With no morphologic evidence of bone marrow involvement by acute myeloid leukemia, our case suggests that the patient's primary myelofibrosis transformed to leukemia cutis. Our patient died 2 months after the onset of his skin nodules. Our case demonstrates that leukemia cutis should be included in the differential diagnosis for cutaneous nodular lesions in patients with a history of an advanced-stage hematological malignancy.

Next-Generation Scholarship: Rebranding Hematopathology Using Twitter: The MD Anderson Experience.

Hematopathologists are witnessing very exciting times, as a new era of unsurpassed technological advances is unfolding exponentially, enhancing our understanding of diseases at the genomic and molecular levels. In the evolving field of precision medicine, our contributions as hematopathologists to medical practice are of paramount importance. Social media platforms such as Twitter have helped facilitate and enrich our professional  interactions and collaborations with others in our field and in other medical disciplines leading to a more holistic approach to patient care. These platforms also have created a novel means for instantaneous dissemination of new findings and recent publications, and are proving to be increasingly useful tools that can be harnessed to expand our knowledge and amplify our presence in the medical community. In this Editorial, we share our experience as hematopathologists with Twitter, and how we leveraged this platform to boost scholarly activities within and beyond our subspecialty, and as a powerful medium for worldwide dissemination of educational material and to promote our remote teaching activities during the COVID-19 pandemic.

Chronic myeloid leukemia-leukemia cutis mimicking a neutrophilic panniculitis-like leukemia cutis: Report of a rare case.

While drug-induced panniculitis is not uncommon in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor therapy, it is rare for CML to initially present as a leukemic panniculitis. We present the case of a 45-year-old male with no relevant prior medical history presenting with 6 months of migratory nodules, 2 months of drenching night sweats, and a 20 pound weight loss. Physical examination showed firm subcutaneous nodules with overlying ecchymoses present on the right lateral thigh and left lower back. Biopsy of a nodule from the right thigh showed a subcutaneous lobular panniculitis involved by a dense infiltrate of neutrophils and granulocyte precursors. Fluorescent in-situ hybridization (FISH) was positive for t(9;22)(q34;q11.2)BCR-ABL1 fusion. A concurrent hemogram revealed a white blood cell count elevation of 600,000 K/µL. Bone marrow biopsy examination showed marked myeloid expansion with an increase in granulocyte precursors and Philadelphia chromosome positivity by FISH, consistent with bone marrow involvement by CML. Herein, we describe this unusual and rare case of CML initially presenting as a neutrophilic panniculitis-like leukemia cutis. Arriving at this challenging diagnosis may be easily missed without clinical and laboratory correlation, which would certainly lead to the patient's not receiving life-saving treatment.

Fatigue in primary Sjögren's syndrome (pSS) is associated with lower levels of proinflammatory cytokines: a validation study.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune rheumatic disease with symptoms including dryness, fatigue, and pain. The previous work by our group has suggested that certain proinflammatory cytokines are inversely related to patient-reported levels of fatigue. To date, these findings have not been validated. This study aims to validate this observation. Blood levels of seven cytokines were measured in 120 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 30 age-matched healthy non-fatigued controls. Patient-reported scores for fatigue were classified according to severity and compared to cytokine levels using analysis of variance. The differences between cytokines in cases and controls were evaluated using Wilcoxon test. A logistic regression model was used to determine the most important identifiers of fatigue. Five cytokines, interferon-γ-induced protein-10 (IP-10), tumour necrosis factor-α (TNFα), interferon-α (IFNα), interferon-γ (IFN-γ), and lymphotoxin-α (LT-α) were significantly higher in patients with pSS (n = 120) compared to non-fatigued controls (n = 30). Levels of two proinflammatory cytokines, TNF-α (p = 0.021) and LT-α (p = 0.043), were inversely related to patient-reported levels of fatigue. Cytokine levels, disease-specific and clinical parameters as well as pain, anxiety, and depression were used as predictors in our validation model. The model correctly identifies fatigue levels with 85% accuracy. Consistent with the original study, pain, depression, and proinflammatory cytokines appear to be the most powerful predictors of fatigue in pSS. TNF-α and LT-α have an inverse relationship with fatigue severity in pSS challenging the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions.

The Conundrum of Diagnosing Cutaneous Composite Lymphoma in the Molecular Age.

INTRODUCTION: Cutaneous composite lymphoma (CCL) is extremely rare. When 2 potentially distinct lymphoid lesions occur at one skin site, distinguishing between one neoplastic clone and a secondary reactionary lymphoid response versus a second neoplasm is difficult. In this study, we describe a unique case of CCL along with a review of reported cases in literature to identify clues and discuss issues that are relevant to the diagnosis of CCL. DESIGN: Review of a CCL case from our institution and a systematic review of reported cases of CCL in the literature. RESULTS: A total of 18 studies describing 22 cases and a case report from our institution are included. The mean age at diagnosis was 68 years. Most cases herein presented with multiple skin lesions (67%) and reported a history of immune suppression (76%). Nineteen cases (83%) had a combination of T-cell and B-cell neoplasms, whereas the remaining cases had 2 distinct B-cell clones. Clonal differentiation was confirmed based on morphology and immunohistochemistry in all cases, and by polymerase chain reaction studies in 19 cases. Complete remission was achieved in only one quarter of reported cases. CONCLUSION: Diagnosing CCL can be challenging because accurate differentiation of 2 or more clonal populations at 1 site is tedious. A stepwise approach and integration of clinical, morphologic, immunohistochemistry, and molecular data along with an understanding of the prognosis of the lymphomas in question is essential for an accurate diagnosis and necessary because of therapeutic and prognostic implications.

Bacteriophage-mediated decolonization of Klebsiella pneumoniae in a novel Galleria mellonella gut colonization model with Enterobacteriaceae.

Galleria mellonella larvae have emerged as an invertebrate model for investigating bacterial pathogenesis and potential therapies, addressing ethical concerns related to mammalian models. This model has the advantage of having a simple gut microbiome, which is suitable for gut colonization studies. Intestinal colonization by Enterobacteriaceae significantly contributes to the spread of antibiotic resistance. This study aimed to establish a novel Enterobacteriaceae gut colonization larval model and assess its suitability for evaluating distinct antimicrobial efficacies. Larvae were force-fed sequentially with bacterial doses of K. pneumoniae and E. coli at 0, 24, and 48 h, with survival monitoring at 24 h intervals. Bacterial counts were assessed after 48 h and 120 h of force-feeding. Successfully colonized larvae were subjected to one-time force feeding of a bacteriophage cocktail (107 PFU/larvae) or MIC-based meropenem and ciprofloxacin. The colonized bacterial load was quantified by CFU count. Three doses of 106 CFU/larvae resulted in stable gut colonization, independent of the K. pneumoniae or E. coli strain. Compared with the control, force-feeding of the bacteriophage reduced the colonization of the strain Kp 419614 by 5 log10 CFU/larvae, while antibiotic treatment led to a 3 log10 CFU/larval reduction. This novel G. mellonella model provides a valuable alternative for gut colonization studies, facilitating proof-of-concept investigations and potentially reducing or replacing follow-up experiments in vertebrate models.

Implementing PathElective as an organized means of supplementing pathology education in an osteopathic medical school-the New York Institute of Technology College of Osteopathic Medicine experience.

Pathology is not traditionally chosen by medical students applying to residency. In osteopathic medical schools, limited access to dedicated pathology faculty further complicates this issue. Because of a lack of pathology experiences, osteopathic medical students may not be as familiar with a pathology career. The purpose of this brief report is to describe the pilot experience of implementing a pre-existing web-based, free virtual platform for pathology education as alternative, supplemental exposure to pathology for osteopathic medical students at our institution. We began to offer the online pathology elective for Academic Year 2022-2023. Using the online free service of PathElective, this course provided a valuable exposure to pathology with multiple modules in anatomic, clinical, and digital/molecular pathology, before and after assessments, recorded videos by pathology experts, handouts, and reading assignments. During the first week, three introductory modules were required followed by weeks 2-4, in which the students would complete a total of 10 modules of their own choice. In total, 14 students participated in this virtual rotation from August 2022-May 2023. All chose cardiac pathology as the most popular module. Three of the 14 students matched into pathology residencies. This small cohort of 4th year medical students at our osteopathic medical school successfully completed a virtual elective rotation with the resources of PathElective. We report the success of this experience and hope to continue monitoring progress.

Evolving educational landscape in pathology: a comprehensive bibliometric and visual analysis including digital teaching and learning resources.

AIMS: Pathology education is a core component of medical training, and its literature is critical for refining educational modalities. We performed a cross-sectional bibliometric analysis to explore publications on pathology education, focusing on new medical education technologies. METHODS: The analysis identified 64 pathology journals and 53 keywords. Relevant articles were collected using a web application, PaperScraper, developed to accelerate literature search. Citation data were collected from multiple sources. Descriptive statistics, with time period analysis, were performed using Microsoft Excel and visualised with Flourish Studio. Two article groups were further investigated with a bibliometric software, VOSViewer, to establish co-authorship and keyword relationships. RESULTS: 8946 citations were retrieved from 905 selected articles. Most articles were published in the last decade (447, 49.4%). The top journals were Archives of Pathology & Laboratory Medicine (184), Human Pathology (122) and the American Journal of Clinical Pathology (117). The highest number of citations was found for Human Pathology (2120), followed by Archives of Pathology & Laboratory Medicine (2098) and American Journal of Clinical Pathology (1142). Authors with different backgrounds had the greatest number of articles and citations. 12 co-authorship, 3 keyword and 8 co-citation clusters were found for the social media/online resources group, 8 co-authorship, 4 keyword and 7 co-citation clusters for the digital pathology/virtual microscopy/mobile technologies group. CONCLUSIONS: The analysis revealed a significant increase in publications over time. The emergence of digital teaching and learning resources played a major role in this growth. Overall, these findings underscore the transformative potential of technology in pathology education.

Navigating The 2022 International Consensus and World Health Organization Classifications of Hematopathology: A Call for Unified Diagnostic Language.

CONTEXT.­: In 2022, 2 distinct guidelines for the diagnosis of myeloid neoplasms became available: the 5th edition of the World Health Organization guideline (WHO2022) solely and the International Consensus Classification (ICC). Despite major overlap, there are important differences that can have important implications. OBJECTIVE.­: To explore the current opinions and diagnostic practices of hemato-oncologists and hematopathologists across the United States. DESIGN.­: An online anonymous survey was created using REDCap, and a secure link was shared via email to fellowship program leaderships and via posts on social media. RESULTS.­: A total of 310 responses were obtained. Only 33 of 309 respondents (10.7%) reported using solely the 2016 World Health Organization guideline to make diagnoses, whereas 167 of 309 (54%) supplemented it with other guidelines. The rest were either not sure (17; 5.5%), used WHO2022 solely (46; 14.9%), or used ICC solely (6; 1.9%). The choice of guideline was not related to region (P = .15), practice setting (P = .86), or hospital size (P = .22). More than 90% reported it is a source of confusion in clinical diagnosis, management, trial design, and other areas. CONCLUSIONS.­: Overall, our study found that having 2 distinct guidelines could be a source of confusion for physicians and calls for a unified diagnostic language.

Osteopathic physician trainees and pathways to pathology.

Currently, there are few osteopathic physician trainees who choose to pursue pathology residencies when compared to allopathic students and international medical graduates. Although the amount of residency positions filled by osteopathic students has increased in recent years, the percentage of osteopathic students choosing pathology has not changed much from 2011 to 2022 (about 0.16% increase), and, in 2022, pathology had the third lowest percentage of filled post-graduate year 1 residency positions by osteopathic applicants when compared to fifteen other major medical specialties. Potential explanations for this disparity may include relatively few total numbers of osteopathic applicants when compared to allopathic and international medical graduate trainees, as well as potential institutional educational limitations (i.e., pathology exposure differences among academic-based versus community-based hospital settings). This review suggests ways pathologists and educational institutions may help improve pathology exposure to osteopathic physician trainees, such as pathology interest groups, post-sophomore fellowships, rotating pathology electives, and through social media (e.g., Twitter). Utilizing these (and other) pathways may help improve osteopathic physician recruitment to pathology during subsequent applicant-residency match cycles.

Polyamine catabolism is concentrated in tumor-associated histiocytes in diffuse large B-cell lymphoma and classic Hodgkin lymphoma.

Polyamines are cationic molecules necessary for cell survival, growth, and replication [1-5]. Polyamines come in a variety of structural forms and are principally regulated by two enzymes, spermine/spermidine acetyltransferase-1 (SAT1) and ornithine decarboxylase-1 (ODC1). SAT1 targets the polyamines spermidine and spermine for degradation via acetylation, while ODC1 is involved in converting the polyamine precursor molecule to more complex polyamines [6-8]. Polyamines and their regulatory enzymes have been implicated in tumor metastasis [9,10] and in crosstalk between oncogenes [11-13] in numerous types of cancer, but their role has never been evaluated in B-cell malignancies. In this study, we examine the expression of SAT1 in diffuse large B-cell lymphoma (DLBCL) and classic Hodgkin lymphoma (HL). We found that SAT1 is expressed in all examined cases of DLBCL (n = 15) and HL (n = 5), though the levels of expression across cases vary. We also note that SAT1 expression appears to be concentrated in tumor-associated histiocytes, rather than tumor cells in both DLBCL and HL. We propose that these findings indicate that the polyamine catabolic enzyme, SAT1, plays an unappreciated role in the pathogenesis of B-cell neoplasms.

Virtual Pathology Elective, Real Education: The PathElective.com Experience as a Model for Novel Pathology Pedagogy and a Primer for Curricular Evolution.

CONTEXT.­: PathElective.com was created in response to the pandemic's restrictions on interactions with trainees, and since has been incorporated into many training programs worldwide, serving as a unique means of delivering high-quality pathology and laboratory medical education at multiple levels of training. OBJECTIVE.­: To analyze student usage, performance, and satisfaction to provide insight into the effectiveness of virtual education to guide curricular evolution. DESIGN.­: Squarespace (Squarespace, Inc) was used for website development and to collect website analytics. Students were assessed before and after course participation using a dual-form crossover quiz design. Quiz data were anonymous and analyzed with a paired t test to account for varying student background. A novel analysis was performed aimed at examining the attrition rate of students across multiple modules. RESULTS.­: Over the study period (May 1, 2020 to October 31, 2021), PathElective.com received 577 483 page views, 126 180 visits, 59 928 unique visitors, and 10 278 registered users who earned 15 305 certificates. A total of 7338 premodule and postmodule quiz pairs were analyzed. The overall average increase in score was 13.83% (P = .02). All but 5 of the 56 courses experienced a statistically significant increase in score. All courses received median scores of Very Satisfied/Satisfied in all 6 assessment domains. Aggregate attrition data revealed a unique, negative polynomial relationship (R2 = 0.656). CONCLUSIONS.­: PathElective.com is a free, effective means of enhancing anatomic/clinical pathology training in medical education. These analyses offer a unique perspective on the online user experience and could guide the development of future online medical education resources.

Improving Transparency in the Residency Application Process: Survey Study.

BACKGROUND: Increasing numbers of residency applications create challenges for applicants and residency programs to assess if they are a good fit during the residency application and match process. Applicants face limited or conflicting information as they assess programs, leading to overapplying. A holistic review of residency applications is considered a gold standard for programs, but the current volumes and associated time constraints leave programs relying on numerical filters, which do not predict success in residency. Applicants could benefit from increased transparency in the residency application process. OBJECTIVE: This study aims to determine the information applicants find most beneficial from residency programs when deciding where to apply, by type of medical school education background. METHODS: Match 2023 applicants voluntarily completed an anonymous survey through the Twitter and Instagram social media platforms. We asked the respondents to select 3 top factors from a multiple-choice list of what information they would like from residency programs to help determine if the characteristics of their application align with program values. We examined differences in helpful factors selected by medical school backgrounds using ANOVA. RESULTS: There were 4649 survey respondents. When responses were analyzed by United States-allopathic (US-MD), doctor of osteopathic medicine (DO), and international medical graduate (IMG) educational backgrounds, respondents chose different factors as most helpful: minimum United States Medical Licensing Examination (USMLE) or Comprehensive Osteopathic Medical Licensing Examination (COMLEX) Step 2 scores (565/3042, 18.57% US-MD; 485/3042, 15.9% DO; and 1992/3042, 65.48% IMG; P<.001), resident hometown region (281/1132, 24.82% US-MD; 189/1132, 16.7% DO; and 662/1132, 58.48% IMG; P=.02), resident medical school region (476/2179, 22% US-MD; 250/2179, 11.5% DO; and 1453/2179, 66.7% IMG; P=.002), and percent of residents or attendings underrepresented in medicine (417/1815, 22.98% US-MD; 158/1815, 8.71% DO; and 1240/1815, 68.32% IMG; P<.001). CONCLUSIONS: When applying to residency programs, this study found that the factors that respondents consider most helpful from programs in deciding where to apply differ by educational background. Across all educational groups, respondents want transparency around standardized exam scores, geography, and the racial or ethnic backgrounds of residents and attendings.

Pathology Education Powered by Virtual and Digital Transformation: Now and the Future.

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.