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.

Perspectives from two recent medical school graduates on exposure to pathology during undergraduate medical education: A narrative inquiry.

The field of pathology is facing an inflection point where the demand for pathology services is not being met by a corresponding rise in recruitment into the field. Many of the myths about the field of pathology have been dispelled elsewhere, but there have not been many formal accounts of the experience medical students' face when finding their path to pathology. Because of challenges in the visibility of pathology as a specialty and not simply a subject required for United States Medical Licensing Examination Step 1, students tend to fall into one of two categories: early differentiators or late discoverers. Here, we provide anecdotal accounts of these two paths at institutions with different curricular designs and provide a first-hand account of the challenges we faced and opportunities discovered in our journeys to pathology. Based on these experiences, we offer suggestions for ways to address some of the issues medical students must navigate when trying to explore pathology in curricula not built for such exploration.

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.

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.

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.

Adenovirus-Associated Acute Interstitial Nephritis With Graft Survival and Novel Follow-Up Biopsy Findings Including Karyomegaly: A Case Series.

Adenoviral infections in post-transplant patients have been described in multiple organ systems, most classically the lung, liver, and alimentary tract. In the genitourinary tract, hemorrhagic cystitis is most frequently observed. Clinically apparent renal involvement with adenovirus is rare, and adenovirus-associated interstitial nephritis (AAIN) is an uncommon cause of renal allograft failure. Here, we present three cases of AAIN in patients who, after prompt diagnosis and treatment adjustment, experienced a return of allograft function. All patients were on standard triple therapy with tacrolimus levels within the target range at the time of biopsy. None of the patients had respiratory symptoms, and despite diarrhea, colon biopsies were negative. Only case one had positive adenovirus serology (IgG only) and case three had positive urine; two patients had leukopenia without neutropenia. Renal biopsies showed a characteristic granulomatous tubulocentric mixed lymphocytic and neutrophilic infiltrate. Adenovirus immunohistochemistry (IHC) showed strong staining in the tubular epithelium (nuclear and cytoplasmic) while staining for polyomavirus was negative. A follow-up biopsy two months after the diagnosis of AAIN in one patient revealed persistent cytopathic effects with negative adenoviral IHC staining while a biopsy at one year in another patient showed glomerular and tubulointerstitial scarring. AAIN is an uncommon but important etiology to consider in cases of acute renal allograft dysfunction. Although the presenting symptoms for AAIN are nonspecific, hematuria is frequently noted. Adenovirus IHC should be considered in cases with granulomatous inflammation associated with necrosis and mixed inflammatory infiltrate. As demonstrated in this single-institution case series, prompt diagnosis can result in the preservation of the renal allograft. Lasting cytopathic effects after adenoviral infection should also be considered in patients with a history, or potential history, of AAIN.

Novel Histopathologic and Ultrastructural Findings in Renal Allografts From Patients With Size and Age Mismatches: A Case Series.

While reports on the long-term pathology in mismatched allografts have been focused on the donor and recipient body surface area, evidence is emerging to support donor-recipient age difference as an additional prognostic factor. Most reports are based on pediatric recipients receiving older/bigger allografts. Here, we describe three cases with age mismatch including two cases of adult patients receiving pediatric allografts and a third case of a younger patient receiving an allograft from an older donor exhibiting findings not described in extant literature. Each of these cases exhibits unique changes seen in mismatched donor-recipient size/age post-transplant pathology. These non-rejection changes should be suspected in cases of donor-recipient size/age mismatch. In cases of allograft function decline, a full biopsy workup, including electron microscopy, should be considered.

Relationship Between Worst Pattern of Invasion and Extranodal Extension in Oral Tongue Squamous Cell Carcinomas.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is a common malignancy of the oral cavity with poor survival rates. The aim of this project is to investigate the relationship between certain histopathological factors such as Worst Pattern of Invasion (WPOI) and Extranodal Extension (ENE) in patients with oral tongue squamous cell carcinoma (OTSCC) who underwent surgical resection at Loyola University Medical Center. METHODS: This was a retrospective cohort study at a tertiary care academic medical center. All patients that underwent primary surgical resection of OTSCC between 1/1/2015 and 1/1/2022 were reviewed. Patients were identified using the Cerner CoPath Laboratory Information System. RESULTS: A total of 82 patients met inclusion criteria and were included in the study. Higher grades of WPOI (WPOI 5) were not significantly associated with the presence of ENE in our study (P = 0.82), regardless of the presence of major or minor ENE. WPOI 5 was associated with a higher incidence of local recurrence (P = 0.011). CONCLUSIONS: Higher grades of WPOI were not found to correlate with the presence of ENE, a common histopathological factor that is used as an important prognostic indicator in OTSCC. It is important for clinicians to consider these factors separately when determining whether a patient is high-risk and would benefit from aggressive multimodal treatment.

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.

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.

Genome Sequences of Hemolytic and Nonhemolytic Listeria innocua Strains from Human, Food, and Environmental Sources.

This report describes genome sequences for nine Listeria innocua strains that varied in hemolytic phenotypes on sheep blood agar. All strains were sequenced using Pacific Biosciences (PacBio) single-molecule real-time (SMRT) chemistry; overall, the average read length of these sequences was 2,869,880 bp, with an average GC content of 37%.

Heterotopic Mesenteric Ossification With Trilineage Hematopoiesis.

Heterotopic ossification (HO) histologically refers to extraskeletal bone formation in non-ossifying tissues, most commonly noted in the extremities, buttocks, abdominal wall, and hip joints. HO developing in the mesentery (heterotopic mesenteric ossification, HMO) is very rare, with fewer than 100 cases reported in the literature. It usually occurs in adult male patients with a history of repeated abdominal trauma. So far, only two cases of HMO have been reported with the development of hematopoietic bone marrow. Here, we report the third case of HMO with true trilineage hematopoiesis in a 66-year-old female with suspicious mesenteric-retained foreign material from prior surgical procedures, including hysterectomy for endometrial adenocarcinoma and multiple repairs for incisional hernia.

Nodular Histiocytic/Mesothelial Hyperplasia Mimicking Mesenteric Metastasis.

Nodular histiocytic/mesothelial hyperplasia (NHMH) is a rare histologic entity, characterized by localized benign reactive proliferation of histiocytes and mesothelial cells. The presence of this rare entity poses a challenge in differential diagnosis, both in radiological findings and pathological interpretations under certain circumstances, and consequently has been misdiagnosed as malignancy. Here, we report a case of mesenteric NHMH in a patient with colonic mucinous adenocarcinoma. Histology shows numerous large calretinin (+) mesothelial cells mixed with CD68 (+) histiocytes by immunohistochemistry. In contrast to almost all previously reported cases with typical features of histiocytic predominance, the current case of NHMH mainly consists of mesothelial cells with intermixed histiocytes. The findings expand the histologic spectrum of NHMH and contribute to awareness of this entity in the differential diagnosis.

Orphan Nuclear Receptor NR4A2 Is Constitutively Expressed in Cartilage and Upregulated in Inflamed Synovium From hTNF-Alpha Transgenic Mice.

Orphan nuclear receptor 4A2 (NR4A2/Nurr1) is a constitutively active transcription factor with potential roles in the onset and progression of inflammatory arthropathies. NR4A2 is overexpressed in synovium and cartilage from individuals with rheumatoid arthritis (RA), psoriatic arthritis, and osteoarthritis. This study documents the expression and tissue localization of NR4A2 and upstream regulator nuclear factor kappa B (NF-κB) in the human tumor necrosis factor-alpha (hTNF-α) transgenic mouse model of RA. Since TNF-α is a potent inducer of NR4A2 in vitro, we hypothesized that NR4A2 would also be upregulated and active during disease progression in this model. Expression levels of NR4A2, related receptors NR4A1 (Nur77) and 3 (NOR1), and NF-κB1 transcripts were quantified by RT-qPCR in hTNF-α and wild-type joints at three stages of disease. The protein distribution of NR4A2 and NF-κB subunit RelA (p65) was analyzed by quantitative immunohistochemistry. Global gene expression of 88 RA-related genes was also screened and compared between groups. Consistent with previous reports on the hTNF-α model, transgenic mice exhibited significant weight loss and severely swollen paws by 19 weeks of age compared to age-matched wild-type controls. NR4A1-3 and NF-κB1 were constitutively expressed at disease onset and in healthy joints. NF-κB1 transcript levels increased 2-fold in hTNF-α paws with established disease (12 weeks), followed by a 2-fold increase in NR4A2 at the late disease stage (19 weeks). NR4A2 and RelA proteins were overexpressed in inflamed synovium prior to symptoms of arthritis, suggesting that gene expression changes documented in whole paws were largely driven by elevated expression in diseased synovium. Broader screening of RA-related genes by RT-qPCR identified several differentially expressed genes in hTNF-α joints including those encoding inflammatory cytokines and chemokines, matrix-degrading enzymes and inhibitors, cell surface receptors, intracellular signaling proteins and transcription factors. Consensus binding sites for NR4A receptors and NF-κB1 were enriched in the promoters of differentially expressed genes suggesting central roles for these transcription factors in this model. This study is the first comprehensive analysis of NR4A2 in an animal model of RA and validates the hTNF-α model for testing of small molecules and genetic strategies targeting this transcription factor.

Human Intestinal Spirochetosis Incompatible With Dysplastic Adenomatous Epithelium.

Human intestinal spirochetosis (HIS) refers to the colonization of spirochetal bacteria in the human intestinal tract. HIS caused by Brachyspira spp. has been recognized for decades, but their pathological and clinical significance is largely unclear. The coincidence of dysplasia in adenoma or adenocarcinoma and HIS is very rare, and whether spirochetes can colonize on dysplastic epithelium remains controversial. Here, we report a case that showed abrupt abolition of mucosal surface fringe formation on a tubular adenoma (TA) and increased cytoplasmic MUC1 expression in the dysplastic epithelial cells compared with adjacent nondysplastic colonocytes. The findings support the hypothesis that the epithelial colonization of spirochetes is significantly reduced by dysplasia likely due to loss of microvilli, and an increase of epithelial MUC1 expression might contribute to reduced spirochetal colonization in colonic mucosa.

Hemophagocytic Lymphohistiocytosis.

CONTEXT.­: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder of immune regulation that can eventually result in end-organ damage and death. HLH is characterized by uncontrolled activation of cytotoxic T lymphocytes, natural killer cells, and macrophages that can lead to a cytokine storm. The diagnosis of HLH is often challenging due to the diverse clinical manifestations and the presence of several diagnostic mimics. The prognosis is generally poor, warranting rapid diagnosis and aggressive management. OBJECTIVE.­: To provide a comprehensive review of the pathogenesis, clinical features, diagnosis, and management of HLH. DATA SOURCES.­: Peer-reviewed literature. CONCLUSIONS.­: HLH is a condition where a complete understanding of the pathogenesis, early diagnosis, and proper management has an important role in determining patient outcome. Genetic mutations causing impairment in the function of cytotoxic T lymphocytes and natural killer cells have been identified as the root cause of familial HLH; however, the specific pathogenesis of acquired HLH is unclear. The HLH-2004 protocol used in the diagnosis of HLH was originally developed for the pediatric population. The HLH-2004 protocol still forms the basis of the diagnosis of HLH in adults, although its use in adults has not been formally validated yet. Treatment of HLH is primarily based on the HLH-94 protocol, which involves suppressing the inflammatory response, but the treatment needs to be modified in adults depending on the underlying cause and comorbidities.

The Implementation and Effectiveness of PathElective.com.

The COVID-19 pandemic put most in-person pathology electives on-hold as departments adapted to changes in education and patient care. To address the subsequent void in pathology education, we created a free, virtual, modular, and high-quality pathology elective website. Website traffic from June 1, 2020, to October 1, 2020, was monitored using the built-in analyses on Squarespace. Twitter engagement was analyzed using Twitter analytics and the Symplur Social Graph Score. A voluntary satisfaction survey was sent to all PathElective users and results were analyzed. During this time, the site saw 25 467 unique visitors, over 34 988 visits, 181 302 page views, and 4449 subscriptions from 99 countries. Countries with the highest traffic are the United States (14 682), India (5210), and the Philippines (2195). PathElective's Twitter social graph score increased from 63.59 to 89.3 with the addition of 1637 followers. Data from surveyed users (n = 177) show most to be pathology residents (41%). Most subscribers (89%) are committed to a career in pathology. The majority heard of the website via Twitter (55%). Almost half of those surveyed engaged with the PathTwitter community on Twitter and of those who participated, 99% found that interaction useful. In all survey questions surrounding satisfaction and usefulness, a large majority of the users were either satisfied or very satisfied. PathElective is a novel pathology elective that offers a unique opportunity to educate medical students and residents from around the globe and demonstrates high effectiveness and satisfaction among users.