搜索结果：Blood neoplasia

The goal is to design and validate a noninvasive screening model for advanced colorectal neoplasia(ACN) utilizing routine blood tumor markers and inflammatory indices, and to develop an online calculator for assessing individual risk. In this retrospective analysis, 1,290 patients who underwent colonoscopy and had full preoperative blood test results were included. Based on pathology, patients were categorized into a group with advanced colorectal neoplasms and another with non-advanced neoplasms. Patients were randomly assigned to a training set, making up 70%, and a test set, making up 30%.Candidate variables were initially screened using univariate logistic regression, and those with statistical significance were then included in a multivariate logistic regression model to determine independent predictors. To assess potential nonlinear relationships between continuous variables and the risk of advanced neoplasms, restricted cubic splines were employed. Prediction models were constructed using five machine learning algorithms and evaluated using the area under the receiver operating characteristic curve. The robustness of key predictors was further assessed through sensitivity and stratified analyses. SHAP was applied to interpret the final model, which was subsequently implemented as an online calculator. Among the 1,290 patients, 210 were diagnosed with advanced colorectal neoplasms. CEA, SII, NLR, ALB, and PLR were identified as independent predictors, and their associations remained stable across sensitivity and stratified analyses. Among the models, XGBoost achieved the best performance, with an AUC of 0.956 (95% CI 0.936-0.976). SHAP analysis identified SII as the most influential predictor. A machine learning model based on key blood markers such as CEA, SII, and NLR can effectively support noninvasive screening for advanced colorectal neoplasms. This online calculator is a convenient and practical resource for evaluating risk on an individual basis in clinical practice.

Current colorectal cancer (CRC) screening methods have limited sensitivity for precancerous lesions. Blood-based liquid biopsies are constrained by systemic dilution, highlighting the need for localized, minimally invasive molecular approaches. We evaluated whether colonoscope-derived mucus serves as a high-fidelity source of cell-free DNA (cfDNA) for detecting KRAS-mutated colorectal neoplasia. In this prospective pilot study, mucus samples (N = 43) were collected from the colonoscope sheath during routine colonoscopy. cfDNA was analyzed for KRAS codon 12 mutations using a competitive PCR assay. Diagnostic performance at variant allele frequency (VAF) thresholds (>1% and >0.1%) was compared with histology, fecal immunochemical testing (FIT), and carcinoembryonic antigen (CEA). At VAF >0.1%, mucus cfDNA achieved 80.0% sensitivity for colorectal neoplasia, outperforming FIT (40.0%) and CEA (10.0%, p = 0.005). Sensitivity reached 100% for adenocarcinoma (n=2) and 75.0% for advanced precancerous colorectal lesions. Specificity decreased to 29.6% at lower thresholds, likely due to inflammatory confounders. Importantly, KRAS mutations were detected in visually inconspicuous mucosa. Colonoscope-derived mucus is a promising localized cfDNA source for detecting early colorectal neoplasia. This approach may serve as a colonoscopy-integrated adjunct within existing screening pathways and may support post-procedure risk stratification and surveillance optimization.

CD19- and B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR T-cell) therapies have improved outcomes in relapsed or refractory B-cell lymphoid malignancies and multiple myeloma, but late hematologic complications are increasingly relevant as survivorship expands. This narrative review examines how pre-infusion clonal hematopoiesis (CH), clonal hematopoiesis of indeterminate potential (CHIP), clonal cytopenia of undetermined significance (CCUS), marrow reserve, prior genotoxic exposure, inflammatory stress, and disease-platform context shape the risks of prolonged cytopenia and therapy-related myeloid neoplasms (t-MN) after CAR T-cell therapy. Available evidence suggests that high-risk clonal architecture, particularly TP53-mutated or DNA damage response-associated clones, clonal cytopenia, larger or multiple clones, and heavy prior cytotoxic exposure, is more clinically informative than CHIP positivity alone. By contrast, associations between unstratified CH and prolonged cytopenia remain heterogeneous. CD19 lymphoma and BCMA myeloma settings share clonal-selection biology but differ in marrow ecology, treatment history, baseline cytopenia, inflammatory burden, and surveillance windows. For clinical translation, risk assessment should not rely on universal CHIP screening or binary genomic classification. Instead, clonal-risk models, hematotoxicity-risk models, baseline blood counts, inflammatory markers, prior therapy exposure, and disease-platform context should be integrated to identify patients who may benefit from intensified myeloid surveillance, supportive-care planning, and earlier marrow reassessment while preserving access to CAR T-cell therapy. CAR T-cell therapy is an important treatment for some patients with lymphoma and multiple myeloma. However, some patients may develop long-lasting low blood counts or, rarely, therapy-related myeloid neoplasms after treatment. This review explains why the condition of the bone marrow before CAR T-cell therapy matters. Some patients already have small blood-cell clones, previous exposure to chemotherapy or radiation, inflammation, or reduced marrow reserve before CAR T-cell infusion. These factors may make blood count recovery more difficult after treatment. The review emphasizes that clonal hematopoiesis or clonal cytopenia should not automatically prevent patients from receiving CAR T-cell therapy. Instead, doctors should combine blood counts, mutation type, clone size, prior treatment exposure, inflammation, and disease setting to identify patients who may need closer follow-up, earlier marrow reassessment, or more careful supportive-care planning.

Early and minimally invasive detection of colorectal neoplasia remains a major challenge in cancer prevention. Current blood-based screening approaches lack sufficient sensitivity for early-stage lesions and advanced adenomas, highlighting the need for novel circulating biomarkers. This study employs an integrative multi-phase approach combining whole-transcriptome RNA sequencing (RNA-seq) [patients with colorectal adenoma (CRA), n = 16; patients with colorectal cancer (CRC), n = 7; healthy controls, n = 10] with two-step RT-qPCR validation in tissue and plasma samples (CRA, n = 48; CRC, n = 48 for each TNM stage I-III and n = 42 for TNM IV; healthy controls n = 51). The study design encompasses discovery, validation, and liquid biopsy phases, enabling systematic prioritization of candidate genes across independent cohorts. This strategy was used to identify circulating mRNA biomarkers for early detection and monitoring of CRA (including both advanced and non-advanced adenomas) and CRC across the adenoma-carcinoma sequence, including pre- and post-operative plasma collections. RNA-seq analyses identified over 4,000 differentially expressed genes in CRA and CRC tissues compared to matched adjacent mucosa and colonic mucosa from healthy controls. Subsequent validation confirmed a consistent upregulation of several candidates, with TACSTD2 and CEMIP1 emerging as the most robust and biologically relevant. Both genes showed concordant expression patterns between tissue and plasma, supporting their detectability in liquid biopsy. TACSTD2 was markedly upregulated in CRA tissue and plasma, indicating its utility as an early biomarker of neoplastic transformation. Importantly, its elevation in premalignant lesions suggests a potential future contribution to biomarker-based risk stratification and screening settings. CEMIP1 mRNA levels were significantly elevated in CRC tissue and plasma and declined following tumor resection, reflecting a strong association with tumor burden. By integrating tissue and liquid biopsy analyses, this study identifies TACSTD2 and CEMIP1 as promising circulating mRNA biomarkers for early detection and post-surgical monitoring of colorectal neoplasia. Their complementary biological roles across different stages of tumorigenesis support their combined use in a multiplex diagnostic approach. These findings support the clinical translation of mRNA-based biomarkers into non-invasive diagnostic tools with the potential to enhance CRC screening and personalized patient management.

Myelodysplastic neoplasia (MDS) is a hematological malignancy characterized by inefficient hematopoiesis, responsible for quantitative and qualitative abnormalities of the three myeloid cell lineages, classically revealed by peripheral cytopenias and an increased risk of transformation into acute myeloid leukemia (AML). The diagnosis of these conditions is sometimes difficult, complex, and time-consuming, potentially requiring multiple examinations, relying primarily on complete blood count (CBC) data and the results of semi-quantitative and qualitative analysis of the bone marrow aspirate. Our objective through this study is to determine the epidemiological and biological profile of MDS. We included 20 patients presenting with MDS diagnosed on CBC and bone marrow aspirate analysis. Within our population, male predominance was observed, with a mean age of 61 years. Biologically, the CBC demonstrated the presence of anemia in 83.33% of cases with a mean hemoglobin concentration of 7.92 g/dl. Furthermore, thrombocytopenia was detected in 55.55%, while neutropenia was observed in only 44.44% of patients. Using the World Health Organization (WHO) 2022 classification, the entity of MDS with few blasts and multilineage dysplasia (MDS-LB-MLD) was the most frequently detected in our study (35%). According to cytogenetic analysis results, a single case of 5q- syndrome and one case of chromosome 7q deletion were identified among the 13 studies performed on all patients. Recently, MDS has attracted increased attention, particularly regarding diagnostic, prognostic, and therapeutic criteria.

The fecal immunochemical test (FIT) is widely used as a first-line, noninvasive colorectal cancer (CRC) screening tool due to its convenience, affordability, and high patient adherence. However, its effectiveness depends on timely follow-up colonoscopy, and failure to complete diagnostic colonoscopy after a positive FIT can result in missed or delayed detection of precancerous lesions or CRC. It remains unclear whether FIT-based screening and subsequent follow-up are equally effective across age groups and racial and ethnic populations. This study evaluates real-world differences in colonoscopy adherence and diagnostic yield following a positive FIT and examines their implications for disparities in CRC outcomes and all-cause mortality. A retrospective cohort study was conducted using de-identified patient data from the TriNetX research network. Adult patients aged ≥ 45 years who underwent colorectal cancer screening were identified using ICD-10 codes, and positive FIT results were identified using LOINC code 29,771-3. Patients were stratified into two cohorts based on whether they had a diagnostic colonoscopy performed within 1 year of the positive FIT. The study population was further stratified into three age-based cohorts (45-50, 51-64, and 65-85 years), two ethnicity-based cohorts (Hispanic and non-Hispanic), and five race-based cohorts (White, Black, Asian, Native Hawaiian or Other Pacific Islander, and American Indian or Alaska Native). To reduce selection bias and account for potential confounders, 1:1 propensity score matching was performed using demographic characteristics and relevant comorbidities. Matched cohorts were compared using odds ratios (ORs) for colonoscopy adherence, polyp detection, and colorectal cancer detection at both the 1-year and 10-year follow-up intervals. All-cause mortality was compared between matched cohorts using hazard ratios (HRs) at the same 1-year and 10-year follow-up intervals. The study included 45,598 adults with a positive FIT, of whom 17,727 completed colonoscopy within 1 year and 27,871 did not. After propensity score matching, 17,101 patients remained in each group. Patients who completed colonoscopy had higher CRC detection at 1 year (OR 2.401, 95% CI 1.771-3.257) and 10 years (OR 1.501, 95% CI 1.189-1.895), as well as higher polyp detection at 1 year (OR 17.610, 95% CI 16.534-18.756) and 10 years (OR 14.331, 95% CI 13.577-15.126). Colonoscopy completion was associated with lower all-cause mortality at 1 year (HR 0.604, 95% CI 0.516-0.707) and 10 years (HR 0.799, 95% CI 0.744-0.859). Adults aged 45-50 had higher colonoscopy adherence than those aged 51-64 (OR 1.214, 95% CI 1.111-1.326), while adults aged 51-64 had higher adherence than those aged 65-85 (OR 1.248, 95% CI 1.195-1.304). Hispanic patients demonstrated higher adherence than non-Hispanic patients (OR 1.686, 95% CI 1.537-1.848). Polyp detection was higher among Hispanic versus non-Hispanic patients (OR 1.165, 95% CI 1.059-1.282) and White versus Black patients (OR 1.111, 95% CI 1.026-1.202). No significant differences in CRC detection were observed across age, race, or ethnicity subgroups. In this large real-world cohort study, patients who underwent diagnostic colonoscopy after a positive FIT had lower all-cause mortality at both 1 and 10 years compared with those who did not. Colonoscopy adherence after a positive FIT varied by demographic group, with higher completion rates among Hispanic and Asian patients and younger adults. Polyp detection was also higher in Hispanic versus non-Hispanic patients, with no differences among age groups, while CRC detection did not vary across any subgroup. These findings highlight missed opportunities for early detection and prevention of colorectal cancer and underscore the need for targeted interventions to improve colonoscopy follow-up in lower-adherence populations.

Human papillomavirus (HPV)-associated cervical lesions remain a significant disease burden and minimally invasive blood-based biomarkers could complement cytology and HPV testing. This study aimed to characterize the proteomic composition of plasma-derived CD9+ small extracellular vesicles (sEVs) across the morphological spectrum of HPV-associated cervical disease, from histologically normal (NILM) through low-grade (LSIL) and high-grade (HSIL) lesions to invasive squamous cell carcinoma (SCC). Plasma samples from 34 women (NILM, LSIL, HSIL, SCC) were pooled per group, and CD9+ sEVs were isolated using an electrochemically controlled immunoaffinity capture method, followed by nanoparticle tracking analysis, transmission electron microscopy, Western blotting, and label-free LC-MS/MS proteomic profiling. The core sEV proteome comprised 258 shared proteins. LSIL showed the most pronounced changes with broad enrichment of complement and coagulation components and acute-phase reactants alongside depletion of immunoglobulin chains and complement C1r-like protein (C1RL). HSIL exhibited few differential proteins, dominated by neutrophil degranulation and retinoid metabolism pathways. SCC demonstrated extensive cargo depletion (22 downregulated proteins) and a nearly sevenfold upregulation of C1RL. Five proteins (including immunoglobulin chains and GPLD1) correlated positively with lesion severity. Pathway analysis consistently implicated platelet activation, lipoprotein remodeling, and insulin-like growth factor signaling. We conclude that plasma CD9+ sEVs carry stage-specific proteomic signatures distinguishing HPV-associated cervical lesions, with C1RL emerging as a candidate biphasic marker warranting further validation.

Invasive mole is one of the most common forms of gestational trophoblastic neoplasia (GTN), characterized by hydropic chorionic villi with trophoblastic proliferation invading the myometrium. Although it usually develops after complete hydatidiform mole, occurrence following partial hydatidiform mole is uncommon. Delayed follow-up and inadequate β-human chorionic gonadotropin (β-hCG) surveillance may contribute to disease progression and severe complications. A 34-year-old woman para 2 abortus 1, presented with massive vaginal bleeding and hypovolemic shock six months after evacuation of a partial hydatidiform mole. Initial pre-evacuation β-hCG level was 1183002 mIU/mL. Due to financial constraints and inactive health insurance, post-evacuation follow-up was delayed. Serial β-hCG levels declined but remained persistently elevated for more than six months. The patient experienced continuous vaginal spotting and was diagnosed with stage I low-risk gestational trophoblastic neoplasia with a FIGO prognostic score of 4. Two weeks prior to the onset of massive bleeding, the patient had received the first cycle of single-agent methotrexate chemotherapy.Doppler ultrasonography demonstrated markedly increased myometrial vascularity suggestive of invasive mole. Despite blood transfusion, antifibrinolytic therapy, and initiation of single-agent methotrexate chemotherapy, severe vaginal bleeding persisted, resulting in profound anemia (hemoglobin 6.7 g/dL). Emergency total hysterectomy with bilateral salpingectomy was performed due to life-threatening hemorrhage. Histopathological examination confirmed invasive mole with trophoblastic invasion extending into the parametrium. No distant metastases were identified. Invasive mole following partial hydatidiform mole is rare but may lead to severe hemorrhagic complications when diagnosis and follow-up are delayed. Persistent elevation of β-hCG and abnormal uterine bleeding after molar evacuation should prompt early evaluation for gestational trophoblastic neoplasia. Multidisciplinary management, including chemotherapy, hemodynamic stabilization, and surgical intervention when indicated, is essential to achieve favorable outcomes.

Patients with multiple myeloma (MM) who experience early relapse (ER) within 24 months of autologous stem cell transplantation (ASCT) have inferior overall survival and represent a functionally high-risk (HR) subgroup. To investigate immune features of functionally HR MM, we performed immunohistochemistry (IHC) of the bone marrow and high-dimensional flow cytometry-based phenotyping of peripheral blood to evaluate the T-cell compartment of patients with MM at day 100 after ASCT. An initial IHC-based analysis of a cohort of patients with MM (n = 110) with long-term follow-up implicated CD3+PD-1+ T cells as a marker of functionally HR disease independent of maintenance therapy or cytogenetics, suggesting a role for activated T cells as a biomarker of disease biology. Next, to further refine the immunophenotype associated with ER, we conducted flow cytometry of peripheral blood samples from Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0702 trial participants with ER (n = 45) or long-term remission (LR; n = 51), defined as no relapse for >4 years of follow-up. Unsupervised clustering followed by multivariate logistic regression identified the differential expression of HLA-DR, granzyme B, CTLA4, CD27, TIGIT, and CD38 within discrete T-cell subsets, distinguishing ER from LR patients. After variable reduction and validation, CD38 expression by CD8+Eomes+ effector memory T cells emerged as the most predictive feature segregating ER from LR patients, with an area under the curve (AUC) of 86%. This immunophenotype was corroborated in a separate standard-of-care cohort (n = 18). Thus, flow cytometric analysis of peripheral blood at day 100 after ASCT identified a CD8+CD38+ T-cell subpopulation as a key feature of immunologically HR MM.

AbstractRecent discoveries have uncovered roles for telomere length, at both short and long extremes, as a driver of inherited disease risk in children and adults. For short telomere length the predominant phenotype is degenerative, with immunodeficiency, bone marrow failure, and pulmonary disease being most common. Short telomere syndrome genetics inform clinical decisions and have transformed understanding of the etiology, natural history, and treatment of common diseases such as idiopathic pulmonary fibrosis. At the other extreme, ultra-long telomere length predisposes to neoplasia including lympho- and myeloproliferative disease. Individuals with mutations that lengthen telomeres may show features of youthfulness such as delayed hair graying but paradoxically are at risk for benign and malignant neoplasia, which are associated with aging. Their earliest events are traceable in the blood as premature onset of clonal hematopoiesis which shows complete penetrance with aging. Here, we review the genetic basis, pathophysiology, and contrasting phenotypes of Mendelian short and long telomere syndromes, emphasizing how they inform clinical decisions as well as our understanding of the fundamentals of aging and cancer.

This study aimed to investigate the levels of peripheral blood immune cells CD4+, CD8+, CD56+, and regulatory T cells (Tregs) and the expression of tumor markers K-ras and Ki-67 in pathological tissues of patients with high-risk human papillomavirus (HR-HPV)-infected cervical lesions, and to explore their correlations with HPV-DNA viral load. A total of 240 female patients with HR-HPV infection treated at Hebei Central Hospital of Petroleum between January 2022 and December 2023 were retrospectively enrolled and categorized into three groups based on histopathological diagnosis: cervical cancer group (n=80), cervical intraepithelial neoplasia (CIN) group (n=80), and chronic cervicitis group (n=80). Peripheral blood mononuclear cells (PBMCs) were isolated, and the percentages of CD4+, CD8+, CD56+, and Tregs (defined as CD4+CD25highFoxP3+ lymphocytes) were determined by flow cytometry. Immunohistochemistry (IHC) was performed to assess the expression of K-ras and Ki-67 in cervical biopsy specimens. HPV-DNA viral load was quantified by fluorescent quantitative PCR. Correlation analyses were conducted between immune cell levels, tumor marker expression, and HPV-DNA content. The cervical cancer group showed significantly lower CD4+ (31.45&#xa0;&#xb1;&#xa0;5.68%) and CD56+ (10.21&#xa0;&#xb1;&#xa0;2.15%) but higher CD8+ (29.84&#xa0;&#xb1;&#xa0;4.23%) and Tregs (8.98&#xa0;&#xb1;&#xa0;1.74%) than the CIN and cervicitis groups (all P<0.001). Proportions of K-ras+ (62.34&#xa0;&#xb1;&#xa0;10.57%) and Ki-67+ (68.45&#xa0;&#xb1;&#xa0;11.23%) cells were also highest in cervical cancer (P<0.001). HPV-DNA load increased progressively from cervicitis (median 58.16 RLU/CO) to CIN (103.83) to cervical cancer (173.68). Tregs (r=0.603) and CD8+ (r=0.628) correlated positively with HPV-DNA load, while CD4+ (r=-0.586) and CD56+ (r=-0.542) correlated negatively (all P<0.001). Both K-ras (r=0.647) and Ki-67 (r=0.689) showed positive correlations with HPV-DNA load (P<0.001). Patients with HR-HPV-infected cervical lesions exhibit distinct alterations in peripheral immune cell profiles and tumor marker expression. Assessment of these biomarkers may facilitate the early identification of cervical lesions associated with HR-HPV infection and inform the development of preventive and therapeutic strategies.

Gestational trophoblastic neoplasia (GTN) encompasses a spectrum of pregnancy-related disorders and poses significant clinical challenges. Understanding its prevalence, clinical characteristics, and associated risk factors is essential for timely diagnosis and management. This study aimed to evaluate the prevalence, clinical and biochemical features, and associated factors of GTN patients admitted to a tertiary referral center in northwestern Iran. A cross-sectional, descriptive-analytical study was conducted on all women diagnosed with GTN at Imam Reza Hospital, Kermanshah, between 2017 and 2022. Data were collected retrospectively from both electronic and paper-based medical records using a standardized checklist. Variables included demographics, obstetric and medical history, clinical signs, biochemical markers (&#x3b2;-hCG), treatment modalities, and metastatic status. Descriptive statistics were analyzed using SPSS v26. Among 30,133 deliveries during the study period, 382 GTN cases were identified, yielding a prevalence of 1.27%. Complete mole was the most frequent subtype (56.8%), followed by partial mole (37.7%). Vaginal bleeding (85.6%) and uterine enlargement (74.6%) were the most common clinical presentations. Blood group A was the most prevalent (47.4%), and 15.4% of patients had a history of consanguineous marriage. Uterine evacuation was the primary treatment (85.3%), with chemotherapy and hysterectomy used as indicated. Metastatic disease was observed in 7.6% of patients, predominantly affecting the lungs. GTN represents a notable health concern in this region, with complete mole being the most common form. Age, educational level, blood group, and prior molar pregnancy were identified as relevant factors. Early recognition based on clinical and biochemical markers, alongside structured follow-up, is crucial to optimizing outcomes. These findings underscore the importance of awareness, education, and comprehensive care strategies for high-risk populations.

Myeloid sarcoma (MS) is a rare extramedullary manifestation of myeloid neoplasia that may present as an isolated disease without concurrent bone marrow involvement, primary disease or secondary to an antecedent myeloid neoplasm. The molecular landscape and prognostic determinants of these groups remain incompletely defined. This multi-institutional retrospective cohort study of 145 histologically confirmed MS cases from multiple academic centers incorporates clinical, cytogenetic, and next-generation sequencing data to characterize disease biology and outcomes. Patients with primary MS (56.6% of cases) more often received stem cell transplant and achieved remission, while those with secondary disease (43.4%) were more likely to receive local irradiation and less likely to achieve remission. Isolated MS (20.7% of cases) demonstrated preserved peripheral blood counts and significantly lower mutational burden. Myelodysplasia-related (MR) mutations (44.5% of cases) were associated with higher mutational burden and increased cytogenetic abnormalities but did not influence outcomes. Secondary MS exhibited more frequent TET2 mutations, consistent with evolution from antecedent myeloid neoplasia. NPM1 mutations (52.6% of cases) were associated with skin involvement, higher remission/relapse rates, and frequent FLT3 co-mutation. Additional mutations, including ASXL1 and NRAS, were associated with distinct clinical features but not survival differences. Overall, this comprehensive study highlights clinical and molecular heterogeneity in MS. Outcomes appear to be influenced by an interplay of disease context, clonal architecture, and therapeutic strategy rather than individual mutations alone, underscoring the need for integrated molecular profiling and prospective studies to guide management. This study highlights that MS with MR mutations may follow different cellular pathways to evolution.

Herpesviruses, such as Epstein-Barr virus (EBV), are thought to potentially play a significant role in multiple disease processes, including neoplasia, multiple sclerosis (MS), and more recently, Alzheimer's disease (AD). Animal models remain vital tools for understanding these diseases and developing therapeutics. Callitrichine herpesvirus 3 (CalHV-3) was identified in the early 2000s in the common marmoset (Callithrix jacchus). Although phylogenetically related to human EBV, the biological similarities between CalHV-3 and EBV have not been thoroughly characterized. Over 450 marmosets from five biomedical research colonies in the United States were screened for CalHV-3 using droplet digital PCR (ddPCR). Peripheral blood mononuclear cells (PBMCs) were magnetically separated to determine viral loads in B-cell enriched and B-cell depleted populations. A CalHV-3 infected cell line was reactivated to determine gene expression profiles using quantitative-Reverse Transcription PCR (q-RT-PCR). Archived cases of lymphoma in the marmoset were immunophenotyped by immunohistochemistry (IHC). In the neoplastic tissue, CalHV-3 viral loads were measured by ddPCR, and viral transcripts were visualized using RNAscope. The prevalence of CalHV-3 in these research colonies ranged from 19-63%. The virus was detected longitudinally in PBMCs and saliva. Infected marmosets had CalHV-3 viral loads enriched in B-cells. All cases of B-cell lymphoma in the marmoset were positive for CalHV-3 DNA, with transcripts of EBV latent and lytic gene homologs detected in neoplastic tissue. Like EBV, CalHV-3 is characterized by persistent infection, shedding in saliva, B-cell tropism, latent and lytic gene expression profiles, and lymphomagenesis in a subset of infected animals. These results further suggest that CalHV-3 in the common marmoset may serve as a translational model of EBV infection and associated diseases.

Composite indolent B-cell lymphomas may remain unrecognized when one component dominates the clinical presentation. Apparent relapse after therapy may, therefore, represent the emergence of a biologically distinct lymphoma rather than the recurrence of the original disease. An 82-year-old woman presented with systemic low-grade B-cell lymphoma that was most consistent with marginal zone lymphoma (MZL). Staging demonstrated peripheral blood involvement and multifocal FDG-avid disease. Treatment with the CD20&#xd7;CD3-bispecific antibody mosunetuzumab resulted in complete metabolic remission. During surveillance, a new, isolated cervical lymph node developed despite sustained systemic response. Biopsy revealed follicular lymphoma (Grade 1-2) with a germinal center phenotype and a BCL2 rearrangement, findings discordant with recurrence of MZL. Retrospective review of the original specimen identified in situ follicular neoplasia within the initial biopsy. The disease course was, therefore, reinterpreted as a synchronous composite lymphoma in which treatment of the dominant MZL unmasked a previously clinically silent B-cell neoplasm with follicular lineage. Local radiotherapy achieved remission of the follicular component. New disease following treatment of an indolent lymphoma should not automatically be interpreted as relapse. Discordant clinical behavior, particularly focal progression after systemic response, warrants repeat biopsy and integrated pathologic reassessment. This case illustrates how therapy may reveal preexisting clonal heterogeneity and emphasizes the importance of temporality in distinguishing relapse from composite lymphoma. The authors have confirmed clinical trial registration is not needed for this submission.

The submandibular glands are salivary glands located under the mandible that secrete saliva into the oral cavity. The occurrence of heterotopic submandibular glands is an uncommon anatomical variation that is usually found unilaterally. There are few known reports of bilateral heterotopic submandibular glands; this paper describes a rare case of bilateral heterotopic submandibular glands that were discovered incidentally during routine dissection of a cadaver for medical education purposes and subsequent histological examination. The heterotopic glands were located in the carotid triangle at the level of the hyoid bone and appeared to receive blood supply from the facial artery and innervation from the facial nerve, similar to that of typical submandibular glands in normal anatomical location. Venous drainage was into the facial vein and communicating jugular vein. Dissection of each bilateral heterotopic submandibular gland revealed a duct oriented toward the oral cavity, suggesting that it was a functional salivary gland. Histological analysis of the glands and nearby deep cervical chain lymph nodes revealed normal salivary gland and lymph node structure, with no evidence of neoplasia. Encountering such anatomical variations during cadaveric dissection as part of medical education is an irreplaceable learning experience that increases the understanding of pathologies and clinical competency.

A 13-year-old neutered female domestic shorthair cat was referred for weight loss, polyphagia, polyuria, polydipsia and intermittent vomiting. Blood work demonstrated diabetes mellitus; abdominal ultrasonography revealed a hypoechoic, thickened pancreas with two large fluid-filled cavities within the body and right limb. Cytology of the aspirated fluid indicated suppurative inflammation with bacterial infection, which cultured Pasteurella multocida. Medical management for diabetes mellitus and pancreatic abscessation was initiated. After approximately 4 months of antimicrobial therapy and five percutaneous drainages, clinical signs improved; nevertheless, serial abdominal ultrasonography demonstrated persistent pancreatic abscessation, while repeated cultures and antibiograms documented progressively resistant bacterial infections. The condition culminated in abscess rupture and septic peritonitis, prompting surgical drainage and omentalisation. Histopathological examination of the pancreatic parenchyma revealed severe lymphoplasmacytic pancreatitis with glandular atrophy, while evaluation of the pancreatic tissue associated with the abscess demonstrated a suspected pancreatic exocrine neoplasm, most compatible with a well-differentiated adenocarcinoma. This case highlights the need for earlier consideration of surgical intervention in cases of recurrent pancreatic abscessation and underscores the importance of including concurrent pancreatic neoplasia as a differential diagnosis in chronic, non-resolving presentations.

Risk of some diseases of cats increases with age, including chronic kidney disease (CKD) and hyperthyroidism, but clinical signs can be dismissed by caregivers as age-related changes. Quantify the prevalence of disease and other major clinical findings in older cats. Data from cats (&#x2265;8&#x2009;years old) that underwent routine health screening at 2 United Kingdom (UK)-based primary care veterinary clinics over a 52-month period (October 2, 2018 to February 14, 2023) were analyzed. At screening visits, history, physical examination, and blood tests for plasma biochemistry with or without plasma total thyroxine concentration were performed. When possible, systolic blood pressure measurement (97.1% of cases; Doppler method) and urinalysis (41.3% of cases; 98.2% by cystocentesis; and bacterial culture if indicated based on sediment examination) were performed. A total of 549 cats were screened with a median age of 13.5 (IQR: 11.3-15.8) years old. Diagnoses of hyperthyroidism, azotemic CKD, and hypertension were made in 89/464 (19.2%; 95% CI, 15.9%-23.0%), 62/542 (11.4%; 95% CI, 9.0%-14.4%), and 37/524 (7.1%; 95% CI, 5.2%-9.6%) of cats, respectively. Severe dental disease was present in 32/522 (6.1%; 95% CI, 4.4%-8.5%) and bacteriuria was identified in 22/227 (9.7%; 95% CI, 6.5%-14.2%) of urine samples. Other diagnoses included suspected neoplasia (8 cats), diabetes mellitus (8 cats), and suspected primary gastrointestinal disease (4 cats). Routine medical health screening in older cats is useful in detecting diseases, many of which would benefit from prompt veterinary intervention. These results can assist veterinarians in explaining the value of health screening to cat caregivers.

Tumor protein p53 (TP53) alterations are frequently reported in canine cancers but remain incompletely characterized due to differences in reference genomes and sequencing cost. To evaluate a cost-efficient primer-walking approach for TP53 variant screening in dogs with spontaneous tumors. Tumor tissue (n = 10) or blood (n = 16) was collected from 26 dogs with suspected neoplasia. Interpretable TP53 sequences spanning introns and exons 2-11, excluding long intron 1 and non-protein-coding exon 1, were obtained by primer-walking polymerase chain reaction and Sanger sequencing. Bidirectional reads were compared with the Ensembl ROS_Cfam_1.0 v114 reference sequence. TP53 gene sequence variations were observed in 18/26 sequenced tumor cases, including one exonic frameshift insertion and 17 noncoding variants: 13 intronic variants and 4 variants in the 5' untranslated region. Recurrent substitutions and deletions occurred in the intron 8-10 region. Variants were detected in lymphomas and carcinomas, including cases from several small breeds, but no significant association with tumor type or breed was demonstrated. Primer-walking Sanger sequencing can screen TP53 regions beyond coding exons in canine tumor samples. Matched tumor-normal sequencing is needed to determine somatic versus germline origin and to evaluate noncoding TP53 variants as potential biomarkers or drivers.