Citations

Abstract Objective To describe the presenting symptoms, treatment regimens, and outcomes associated with oropharyngeal adenoid cystic carcinoma. Data Sources Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, and Scopus via Elsevier. Review Methods This review followed the Preferred Reporting Items for Systematic Reviews and Meta‐analyses. A medical librarian conducted the literature search using controlled vocabulary and keywords, with investigator input. Eligible articles were clinical trials and observational studies reporting on clinical features, treatment, or outcomes for oropharyngeal adenoid cystic carcinoma. Results Our search identified 233 unique citations, with 44 articles included covering 195 patients. The female‐to‐male ratio was 1.7:1, and the base of the tongue was the most common subsite (73%). Presenting symptoms were mainly pain/discomfort (n = 31), followed by a palpable mass (n = 19) and dysphagia (n = 12). At diagnosis, 22.3% (29 patients) had positive lymph nodes. Treatment was primarily surgical (n = 102), with definitive radiation therapy used in 58 cases. Disease progression was noted in 86 patients, 36% (n = 31) of whom developed distant metastases—primarily to the lungs (n = 26). Long‐term outcomes (n = 76) showed 3‐ and 5‐year overall survival rates of 71.5% to 100% and 47.6% to 79.0%, and disease‐free survival rates of 54.7% to 70.0% and 21.9% to 44.0%, respectively. Conclusion Among patients with available data, oropharyngeal adenoid cystic carcinoma appeared more common in women and has a predilection for the base of the tongue. However, this finding should be interpreted with caution, given the high proportion of missing data. These tumors appear to carry a higher risk for nodal metastases and may lead to poor outcomes.

Abstract Recent single-cell transcriptomic studies of follicular lymphoma (FL) have revealed heterogeneity among malignant B (MB) cells and selected components of the tumor microenvironment (TME), but have been constrained by relatively small sample sizes and a lack of spatial context. We performed comprehensive cellular profiling and spatial dissection of over five million cells by integrating single-nucleus RNA sequencing (snRNA-seq) from 182 samples (FL, n = 167; control, n = 15) with single-cell spatial transcriptomics (ST) from 386 samples (FL, n = 365; control, n = 21). After stringent quality control, 1,289,073 and 3,968,427 cells from snRNA-seq and ST data, respectively, were analyzed. Unsupervised clustering of snRNA-seq data identified 58 TME cell subtypes. To extend this classification to the ST dataset, we integrated snRNA-seq and ST data by co-embedding them into a shared principal component space, enabling robust batch correction and cell-type label transfer across modalities. Using this supervised annotation framework, ST data recapitulated 54 TME cell subtypes. MB, proliferating MB (MBprolif), and healthy B (HB) cells were classified using sample-level unsupervised clustering in ST. Macrophages exhibited previously uncharacterized heterogeneity in transcriptomic profiles and spatial distribution. We identified CXCL13-expressing macrophage subtypes with high intra- and peri-follicular abundance, termed follicular macrophages (FMs). Non-negative matrix factorization of intrafollicular cell fractions identified five TME archetypes: FM, follicular stroma, two follicular T, and HB archetypes. The FM archetype was enriched for intrafollicular macrophages, including FMs, and showed a significantly higher proportion of grade 3A/3B cases (53.4%) compared to other archetypes (≤16.5%). It was also associated with a higher frequency of high tumor burden requiring treatment initiation rather than a watch-and-wait (WW) approach. Among patients managed by WW, those with the FM archetype showed significantly shorter event-free survival (EFS) compared to those with non-FM archetypes, whereas this association was not observed among treated patients. The percentage of intrafollicular macrophages (IFMP) showed excellent predictive performance for the FM archetype (area under the curve: 0.90). IFMP calculated in a published multiplex spatial protein imaging dataset from an independent cohort of 242 FL patients validated the associations between high IFMP and both pathology grade 3A/3B and shorter EFS in WW patients. Consistently, spatial neighborhood and cell–cell communication analyses revealed co-localization of FMs and MBprolif cells, forming a distinct niche with activated signaling mediated by FM-derived CXCL13, APRIL, and BAFF. Our integrative multi-modal analysis defines previously unrecognized cellular heterogeneity and spatial architecture in FL and highlights macrophage-enriched follicular ecosystems associated with aggressive clinicopathological features, providing a framework for improved biological understanding and patient management. Citation Format: Yoshiaki Abe, Bijal Thakkar, Atish Kizhakeyil, Ashley Wilson, Andrew L. Feldman, Jared Henderson, Amy Ayers, Sara Borgschatz, R. Andrew Harkins, Priya Lakra, Daisuke Kaji, Jonathon B. Cohen, David Russler-Germain, Eric Mou, Francisco Vega, Jennifer Chapman, Giorgio Inghirami, Carla Casulo, Izidore S. Lossos, Jean L. Koff, Chijioke Nze, Peter Martin, Sergei Syrbu, Kiran Vij, David L. Jaye, James R. Cerhan, Christopher R. Flowers, Anne J. Novak, Richard Burack, Dai Chihara, Mamiko Sakata-Yanagimoto, Joshua Tobin, Xubin Li, Michael R. Green. Spatially resolved microenvironment profiling reveals distinct follicular lymphoma archetypes [abstract]. In: Proceedings of the Fifth AACR International Meeting on Advances in Malignant Lymphoma: From Discovery to Clinical Impact; 2026 Jun 24-27; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2026;7(3_Suppl):Abstract nr A049.

Abstract The purpose of this study was to explore epigenetic dysregulation resulting from deleterious SPEN mutations in diffuse large B cell lymphoma (DLBCL). Truncating (tr) SPEN mutations are among defining variants in LymphGen:BN2 and DLBclass:C1. We previously found SPEN mutations enriched in DLBCL that failed to reach EFS24, and inferior survival was observed in SPEN-tr vs all other BN2 and C1. Differential gene expression (DEG) in these groups identified >1000 DEGs including upregulation of IKZF3 and BCL2 and downregulation of MHC-II, overall suggesting an alternative, aggressive biology for a subset of BN2/C1 cases generally thought to have favorable outcomes. In healthy cells, SPEN is a dynamic epigenetic regulator with roles in chromatin formation and as a NOTCH co-repressor. We hypothesized that loss of SPEN reprograms the epigenetic landscape to drive the aggressive phenotype in affected DLBCL. Methods: OCI-LY3 cell line with CRISPR/Cas9-induced SPEN-tr mutations was analyzed by ATAC and RNA-seq. Diagnostic DLBCL FFPE tumor biopsies from the Molecular Epidemiology Resource (MER) were analyzed by 850k/EPIC methylation array (n=164). SPEN-depleted OCI-LY3 cells displayed significant (|Log2FC|>2) peaks of open (n=3083) and closed (n=1729) chromatin indicative of systemic epigenetic reprogramming, with enriched peaks (FDR<0.01, |Log2FC|>2) converging on pro-survival and immune evasion (ATP11C, BCL11B, RAG1/2 genes) and negatively enriched for cell cycle and apoptotic pathways (CDK6, TP63, CD80 genes). Chromatin accessibility featured enrichment for TCF3/4 and ZEB1 binding motifs and depletion of EBF1, REL, and NFKB1/2 motifs (FDR<0.0001, |Z-score|>5), suggesting a shift to an activated, post-germinal center program (via open TCF3/4 motifs) with reduced reliance on NF-kB signaling. Footprinting analysis further revealed decreased occupancy at NFKB2 and REL/B motifs, and reduced occupancy at HES1 with elevated occupancy at Rbpjl motifs (p<0.05, |Score|>0.2) indicating downregulation of NF-kB is in favor of non-canonical Notch transcription programming. Merging gene expression and accessibility, gene-peak concordance was observed for elevated CXCR4 and IL6 expression and decreased SOCS1, CD274 (PD-L1), and CCND1 expression (FDR<0.01, |Log2FC|>1), suggesting expression programs feature uncontrolled JAK/STAT signaling (via high IL6, low SOCS1) with immune evasion mechanisms independent of PD-L1. By methylation array, strong epigenetic reprogramming was observed in SPEN-tr DLBCL (n=8), where differential methylation analysis vs WT (n=146), vs BN2 (n=4), and vs C1 (n=15) samples revealed hypermethylation signatures (p<0.05, |FC|>1) indicative of reduced cell-cell signaling and antigen presentation pathways (including HLA-A/G/H). In conclusion, SPEN-depletion triggers systemic epigenetic reprogramming to enhance immune evasion and non-canonical Notch target genes. SPEN-tr DLBCL should be considered with heightened risk estimation and as prime candidates for personalized treatments beyond standard therapy. Citation Format: Janek S. Walker, Joseph P. Novak, Abigail R. Dropik, Zilin Xianyu, Michelle K. Manske, Matthew J. Maurer, Eric Mou, Rebecca L. King, Stephen M. Ansell, Thomas M. Habermann, Thomas E. Witzig, James R. Cerhan, Anne J. Novak. Deleterious SPEN mutations induce epigenetic reprogramming to promote survival and enhance immune evasion pathways in an aggressive subset of BN2/C1 DLBCL tumors [abstract]. In: Proceedings of the Fifth AACR International Meeting on Advances in Malignant Lymphoma: From Discovery to Clinical Impact; 2026 Jun 24-27; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2026;7(3_Suppl):Abstract nr A006.

Abstract Background: Although some vaccines seem to be associated with a lower risk of lymphoma, their impact on outcomes is largely unknown. Methods: Data from a large prospective lymphoma cohort study were utilized to estimate associations of self-reported history of vaccination against hepatitis A, hepatitis B, influenza, and yellow fever with event-free survival (EFS) and overall survival (OS) using Cox proportional hazard models. Results: None of the vaccines were associated with EFS [hazard ratio (HR) 0.77–1] or OS (HRs 0.96–1.04). Similarly, there were no significant associations between the vaccines and outcomes for each lymphoma subtype. Conclusions: Prior vaccination against selected viruses was not associated with EFS or OS among patients with lymphoma. Impact: We did not find evidence for an impact of prior vaccination on lymphoma prognosis.

Chronic pelvic pain (CPP) represents a complex condition where peripheral nociceptive drivers and central nervous system processes produce symptoms that extend beyond the pelvis. Central sensitization (CS) is a state of heightened neuronal responsiveness with amplified pain signaling and diminished inhibitory control, in which patients experience multifocal pain, fatigue, sleep disturbance, cognitive difficulties, and hypersensitivity to sensory stimuli. Management of CS requires a multimodal and comprehensive approach, including pain neuroscience education, targeted pelvic physical therapy, and behavioral therapies. As the field advances, incorporating sensitization science offers a more accurate, patient-centered framework to reduce symptom burden and improve quality of life.

Abstract Background Approximately 12,000 adolescents and young adults (ages 15-39, AYAs) are diagnosed with a primary central nervous system (CNS) tumor each year. DNA methylation profiling has transformed CNS tumor classification by refining diagnostic accuracy and identifying biologically distinct subtypes, but its application has not been systematically evaluated in the AYA population. In this study, we examined the spectrum of CNS tumor types across age groups, with a focus on the AYA population. Methods We assembled a large dataset of CNS tumor samples with age annotations and methylation profiles matching with high confidence to a CNS tumor type using the NCI/Bethesda classifier. Prevalence of tumor type, methylation class and DNA copy number aberrations were compared across age strata (pediatric, AYA and adult). Results The cohort of 21,099 CNS tumors included 5139 tumors from AYAs (24%), which showed a mixed pattern, with tumors typical of childhood (e.g. medulloblastoma) as well as those common in older adults (e.g. glioblastoma). Several tumor types were specifically enriched in the AYA, including IDH-mutant astrocytoma, pleomorphic xanthoastrocytoma, posterior fossa group B ependymoma, and diffuse hemispheric glioma, H3 G34-mutant, among others. Distinct methylation subclasses of multiple tumor types were observed in the AYA, and patterns of genomic aberrations showed age-specific distributions. Conclusion Large-scale methylation profiling revealed unique classification patterns of CNS tumors in AYAs, with specific tumor types, subclasses, and genomic alterations enriched in this population. These data may serve as a valuable reference resource for better understanding the spectrum of CNS tumors affecting AYA patients.

Through a Delphi process, all 33 panelists reached consensus on topics relating to MRI reporting of knee meniscus lesions, demonstrating that interdisciplinary and multi-institutional standardization is possible.

Abstract Patients with atypical variants of Alzheimer's disease (AD) often present at a younger age with predominantly non‐amnestic impairments and a more aggressive disease course. Historically, individuals with atypical presentations have not been included in large‐scale clinical trials, which typically focus on late‐onset, sporadic amnestic‐predominant AD. Consequently, treatment options and research efforts specific to atypical AD remain limited. The emergence of amyloid‐targeting therapies that slow disease progression underscores these challenges, as evidence supporting their efficacy in early‐onset amnestic and non‐amnestic AD variants is scarce. This perspective article argues that atypical AD represents an excellent disease model for clinical trials and proposes strategies to address critical gaps in clinical trial design for this population. Key considerations include optimizing participant selection approaches, establishing syndrome‐specific or surrogate biological and clinical endpoints, and fostering advocacy to enhance early and accurate diagnosis, equitable representation, and outcomes for these populations.

Background: Self-expanding metal stents (SEMS) are recommended for the endoscopic palliation of distal malignant biliary obstruction (DMBO). Placement of SEMS during endoscopic retrograde cholangiopancreatography (ERCP) has been associated with an increased risk of post-ERCP pancreatitis (PEP). Objectives: The aim of this study is to evaluate rates of PEP in patients who underwent SEMS placement for pancreatic versus non-pancreatic malignancy. Design: Retrospective Cohort Study. Methods: Patients who underwent SEMS placement for DMBO between June 2017 and May 2021 were identified retrospectively from a procedural billing database. PEP incidence was compared between pancreatic and non-pancreatic DMBO groups and multivariate logistic regression was performed to identify risk factors for PEP. Results: A total of 488 individuals were identified, with 395 (80.9%) cases of DMBO due to pancreatic and 93 (19.1%) due to non-pancreatic malignancy. Stent types included 124 (25.4%) fully covered (FCSEMS) and 364 (74.6%) uncovered metal stents (UCSEMS). The overall rate of PEP in the cohort was 6.3% with no significant difference between pancreatic and non-pancreatic etiologies (6.1% vs 7.5%, p = 0.606). When adjusted for age <50 years old, female sex, and pancreatic stent placement, a non-pancreatic malignancy was not associated with an increased risk of PEP (OR 0.83, 95% CI 0.36–2.15). Conclusion: No statistically significant difference in PEP rates was seen after biliary sphincterotomy and SEMS placement for palliation of DMBO in patients with pancreatic versus non-pancreatic malignancies.

Abstract Workplace stress is one of the main sources of stress for adults, although physiological and cognitive factors may impact each person's stress response. Numerous studies have shown heart rate, heart rate variability, neural activity, and cognitive performance are affected by stress. Additionally, visual and auditory stimuli in one's environment have been shown to affect individuals' reaction to stressful events. To our knowledge, few studies have examined how each of these physiological and cognitive measures relate to one's perception of stress, the ability to recover from stress, and what environmental factors may help with stress recovery. Here, 80 healthy adults performed a laboratory-controlled stress induction task where they experienced and recovered from an acute psychological stressor (Trier Social Stress Test, TSST, using verbal math skills and a public presentation that was videotaped). Throughout the assessment, heart rate, heart rate variability, and neural activity were measured using wearable devices to assess changes before, during, and after the stressor. Additionally, participants were assessed their perceived stress levels at specific times throughout the assessment. After the psychological stressor, participants were randomly assigned to one of four recovery conditions within a multisensory relaxation room: Control (C), Auditory Only (A), Visual Only (V), or Combined Auditory and Visual (AV). During the stressor, anxiety, heart rate, and beta EEG power increased and high-frequency power and heart rate variability decreased, confirming participants reactivity to the stressor ( P < 0.01 for all vs. baseline). Only the V and AV conditions led to notable reductions in anxiety (15 and 17%, respectively) vs. the C condition, but these did not reach statistical significance. There was no difference between V and AV, suggesting a stronger impact of V. We observed no differences between conditions during recovery for HR and HRV. Overall, these findings suggest the visual features of the relaxation room impacted self-reported anxiety, however physiological and neurological effects did not demonstrate a statistically meaningful response.