Publications by authors named "Swerdlow S"

The professional identity of scientists has historically been cultivated to value research over teaching, which can undermine initiatives that aim to reform science education. Course-Based Research Experiences (CRE) and the inclusive Research and Education Communities (iREC) are two successful and impactful reform efforts that integrate research and teaching. The aim of this study is to explicate the professional identity of instructors who implement a CRE within an established iREC and to explore how this identity contributes to the success of these programs.

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The oncogenic Epstein-Barr virus (EBV) can drive tumorigenesis with disrupted host immunity, causing malignancies including post-transplant lymphoproliferative disorders (PTLDs). PTLD can also arise in the absence of EBV, but the biological differences underlying EBV(+) and EBV(-) B cell PTLD and the associated host-EBV-tumor interactions remain poorly understood. Here, we reveal the core differences between EBV(+) and EBV(-) PTLD, characterized by increased expression of genes related to immune processes or DNA interactions, respectively, and the augmented ability of EBV(+) PTLD B cells to modulate the tumor microenvironment through elaboration of monocyte-attracting cytokines/chemokines.

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Post-transplant lymphoproliferative disorders (PTLDs) remain a feared complication of transplantation, with significant morbidity and mortality. The oncogenic Epstein-Barr virus (EBV) is a key pathogenic driver in 50%-80% of cases. Numerous prognostic indices, comprising multiple clinical, epidemiological and tumor characteristics, including EBV tumor positivity, do not consistently associate with worse patient survival, suggesting a potential role for EBV genome variants in determining outcome.

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Alternative transcription start sites can affect transcript isoform diversity and translation levels. In a recently described form of gene regulation, coordinated transcriptional and translational interference results in transcript isoform-dependent changes in protein expression. Specifically, a long undecoded transcript isoform (LUTI) is transcribed from a gene-distal promoter, interfering with expression of the gene-proximal promoter.

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Article Synopsis
  • * Strong recommendations include reducing immunosuppression as an initial management step and using the anti-CD20 monoclonal antibody (rituximab), as well as chemotherapy in specific cases.
  • * There is a lack of large randomized phase III trials for treating PTLD in pediatrics, leading to reliance on clinical experience, and the report emphasizes the need for future research on this topic.
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Most Pathology residents take the Anatomic Pathology and/or Clinical Pathology primary pathology certification examination(s) near the end of their final year of training (i.e., Spring), whereas some postpone the examination(s) to the Fall administration of that year or even later.

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Seven bacteriophages were isolated from soil in Pennsylvania and Wisconsin using the host . These bacteriophages range in the number of predicted genes encoded, from 25 to 91, and are distributed across actinobacteriophage clusters EB, EC, EE, and EK.

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BabyYoda and Lynlen are two cluster EB phages that were discovered at Thiel College using NRRL B-24224. Both BabyYoda and Lynlen are predicted to be lytic, with siphovirus morphologies, with genome sizes of 41,557 and 41,448 base pairs, respectively.

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Whole-genome sequencing of longitudinal tumor pairs representing transformation of follicular lymphoma to high-grade B cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma) identified coding and noncoding genomic alterations acquired during lymphoma progression. Many of these transformation-associated alterations recurrently and focally occur at topologically associating domain resident regulatory DNA elements, including H3K4me3 promoter marks located within H3K27ac super-enhancer clusters in B cell non-Hodgkin lymphoma. One region found to undergo recurrent alteration upon transformation overlaps a super-enhancer affecting the expression of the PAX5/ZCCHC7 gene pair.

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Primary cutaneous B-cell lymphomas (PCBCLs) are lymphoproliferative disorders that appear on the skin without evidence of extracutaneous manifestations at the time of diagnosis. There is a lack of evidence-based guidelines for their clinical management due to the availability of very few large scale studies and controlled clinical trials. Here we present and discuss a series of major unmet clinical needs (UCNs) in the management of PCBCLs by a panel of 16 experts involved in research and clinical practice of PCBCL.

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  • The t(14;19)(q32;q13) chromosomal rearrangement leads to the overexpression of the BCL3 gene through its juxtaposition with the immunoglobulin heavy chain (IGH) gene, affecting various lymphoid neoplasms.
  • An analysis of 13 lymphoid neoplasms with BCL3 rearrangement identified two distinct breakpoint clusters that result in different clinical outcomes: 5' breakpoints near an IGH enhancer causing overexpression of BCL3, and 3' breakpoints leading to no overexpression.
  • The study revealed that upstream BCL3-R tumors are related to atypical chronic lymphocytic leukemia while downstream BCL3-R tumors are linked to marginal zone lymphomas,
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  • The International Pediatric Transplant Association held a conference to create guidelines for managing post-transplant lymphoproliferative disorders (PTLD) in children, focusing on how to use biomarkers like Epstein-Barr virus (EBV) levels for patient care.
  • The group recommends using "EBV DNAemia" for measuring EBV DNA in blood and advises caution when comparing results from different labs. They concluded both whole blood and plasma can be used for testing, depending on the clinical situation.
  • It is suggested that quantitative EBV DNAemia testing can help identify children at risk for PTLD, especially those who were EBV negative before their transplant, but overall routine surveillance is not recommended for
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Alternative transcription start sites can affect transcript isoform diversity and translation levels. In a recently described form of gene regulation, coordinated transcriptional and translational interference results in transcript isoform-dependent changes in protein expression. Specifically, a long undecoded transcript isoform (LUTI) is transcribed from a gene-distal promoter, interfering with expression of the gene-proximal promoter.

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Mucosa-associated lymphoid tissue (MALT) lymphomas often express IgM and IRTA1 with only a minority demonstrating plasmacytic differentiation. However, like primary cutaneous marginal zone lymphoproliferative disorders (PCMZLPD), thyroid MALT lymphomas (T-MALT-L) frequently show plasmacytic differentiation and IgG positivity. Whether T-MALT-L share other features with PCMZLPD, including frequent IgG4 positivity and infrequent IRTA1 expression, and how IRTA1 staining compares to that in Hashimoto thyroiditis (HT) are unknown.

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The International Pediatric Transplant Association (IPTA) convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorder after solid organ transplantation in children. In this report from the Prevention Working Group, we reviewed the existing literature regarding immunoprophylaxis and chemoprophylaxis, and pre-emptive strategies. While the group made a strong recommendation for pre-emptive reduction of immunosuppression at the time of EBV DNAemia (low to moderate evidence), no recommendations for use could be made for any prophylactic strategy or alternate pre-emptive strategy, largely due to insufficient or conflicting evidence.

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The International Pediatric Transplant Association (IPTA) Consensus Conference on Practice Guidelines for the Diagnosis, Prevention, and Management of Post-Transplant Lymphoproliferative Disorders after Solid Organ Transplantation in Children took place on March 12-13, 2019, and the work of conference members continued until the end of December 2021. The goal was to produce evidence-based consensus guidelines on the definitions, diagnosis, prevention, and management of PTLD and related disorders based on the critical review of the literature and consensus of experts. This report describes the goals, organization, and methodology of the consensus conference and follow-up activities.

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  • The Revised European-American Classification and subsequent WHO classifications have evolved through collaboration among experts in various fields related to hematopathology.
  • The 2022 International Consensus Classification updates the understanding of primary cutaneous lymphomas, specifically recognizing distinct subtypes and adjusting the classification of certain lymphomas to reflect their behavior.
  • Recent research has provided new insights into the biology of primary cutaneous lymphomas, revealing genetic changes that could lead to novel therapies and raising questions about classification and relationships with similar lymphomas elsewhere in the body.
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We investigated the clinicopathologic features of 5 follicular lymphomas (FLs) that transformed (tFL) morphologically to diffuse large B-cell lymphomas (DLBCLs) and had a primary mediastinal large B-cell lymphoma (PMBL)-like gene expression profile (tFL-PMBLsig-pos). None of the tFL-PMBLsig-pos cases arose in the mediastinum, all cases tested had a germinal center B-cell phenotype, 20% were CD30+, 60% CD23+, 80% MAL+, 20% CD200+, and 0% CD273/PDL2+. Whole-exome sequencing detected alterations in genes associated with both FL/DLBCL (CREBBP, KMT2C, KMT2D, ARID1A, HIST1 members, and TNFRSF14) and PMBL (JAK-STAT pathway genes, B2M, and CD58).

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  • * Recent updates have refined the understanding of these disorders, including the recognition of a new category for EBV-positive polymorphic B cell LPD and a provisional entity for primary nodal EBV+ T or NK cell lymphoma.
  • * The classification of EBV LPDs in children has also evolved, splitting into four distinct groups, while the classification of post-transplant lymphoproliferative disorders (PTLD) remains consistent with prior classifications.
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  • * A study involved whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, revealing key mutated genes and new subgroups of BL with specific genetic traits.
  • * The research findings indicate significant genetic and clinical disparities between pediatric and adult BL, suggesting that identifying these subtypes could inform better approaches to diagnosis and treatment.
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There has been a surge in COVID-19 vaccine-associated lymphadenopathy (LAD), including after the booster dose of vaccine. This can create diagnostic dilemmas in oncology patients as the relatively sudden LAD can mimic metastasis or cancer recurrence, at a risk of leading to additional but unnecessary anti-neoplastic therapy. Here we report the histopathologic features in a case of persistent LAD occurring in a patient with history of breast invasive ductal carcinoma which followed a COVID-19 vaccine booster.

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Since the 2016 WHO update, progress has been made in understanding the biology of Burkitt lymphoma (BL) and the concept of high-grade B-cell lymphomas (HGBCL) that allows some degree of refinement. The summary presented here reviews in detail the discussions of the Clinical Advisory Committee and expands upon the newly published 2022 International Consensus Classification for lymphoid malignancies (Campo et al. Blood, 2022).

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