Two or more primary cancers that arise in two different patients are referred to as multiple primary cancers. We record those cases because optimal therapy requires interdisciplinary cooperation.

A 53-year-old male presented with intermittent hematuria for one year, fever, burning micturition, appetite loss, and a 3 kg weight loss over 2 months. His CBC showed 81% atypical cells, and bone marrow aspiration and flow cytometry indicated Precursor B-ALL. He started on the BFM-2002-protocol but had persistent hematuria. The USG of the whole abdomen revealed a urinary bladder mass. TURBT and histopathology confirmed low-grade, noninvasive papillary urothelial neoplasm. Thus, he was diagnosed with Precursor B-ALL and Low-Grade Papillary Urothelial Neoplasm Noninvasive.

A 53-year-old male with a history of anaplastic oligodendroglioma (diagnosed in 2022) presented to the emergency with altered sensorium, headache, and convulsions. He had received radiotherapy and chemotherapy for the past year. In December 2023, he experienced convulsions again due to a recurrence of the oligodendroglioma. His CBC showed an increasing total leukocyte count, reaching 100,000 over five months. Bone marrow and molecular studies indicated a myeloproliferative neoplasm, specifically chronic myeloid neoplasm (CMN) in the chronic phase, with BCR-ABL1 p210 positive. He was diagnosed with recurrent anaplastic oligodendroglioma (WHO Grade 3) and CMN in the chronic phase.

An increased prevalence of second primary malignancy is anticipated due to the rising cancer burden and the careful screening of index initial malignancy throughout therapy. Determining the best course of action requires careful staging of the cancer and discussion by a multidisciplinary team.

The immune system and inflammatory proteins influence hematologic malignancies, but causal links with immune cell phenotypes are unclear.

We applied a prespecified, multistage workflow: two-sample and multivariable Mendelian randomization (MVMR; 731 immune traits across 12 hematologic cancers), two-step mediation Mendelian randomization (MR) of 91 circulating inflammatory proteins, MAGMA/FUMA gene and pathway enrichment, and external validation with trait-specific genetic risk scores (GRSs) in UK Biobank (UKB). We then performed CCR2 perturbation assays in human monocytic leukemia cell line (THP-1) and immortalized bone marrow-derived macrophage (IBMDM) cells with artemin (ARTN) mRNA readouts and examined proteomic correlations for ARTN using the Olink inflammatory panel.

Eight immune phenotypes showed FDR-significant causal associations with malignancy, seven of which remained independent in MVMR. In acute myeloid leukemia (AML), CCR2 on CD62L ⁺ myeloid dendritic cells (DCs) was associated with lower risk, whereas BAFF-R and CD19 on transitional B cells were associated with higher risk, CD19 on IgD^-CD38^dim B cells was associated with chronic myeloid leukemia (CML), and HLA-DR⁺ NK cells were protective in non-Hodgkin lymphoma (NHL). Mediation MR identified three protein mediators-CD40L, IL-33, and ARTN, with ARTN mediating the CCR2-AML association. GRS analyses reproduced risk directions, most prominently the protective CCR2-AML association. In THP-1 and IBMDM models, CCR2 inhibition or knockdown increased ARTN mRNA expression, functionally supporting a CCR2→ARTN regulatory relationship. Proteomic correlations positioned ARTN with immune-metabolic proteins (CLEC6A, SIGLEC6, NPC2, and MTHFD2). Pathway analyses highlighted membrane-proximal processes (external plasma membrane and IgG binding) and a 16p11.2 signal.

This integrative analysis identified CCR2-ARTN as a mechanistically supported immune-inflammation axis contributing to AML risk, offering a potential therapeutic target and warrants direct validation in primary CD62L ⁺ myeloid DCs.

Venous thromboembolism (VTE) is associated with an elevated short-term cancer risk, but data on the long-term risk are conflicting. The mechanisms linking patients with VTE to elevated long-term cancer risk remain largely unknown.

To investigate long-term cancer risk after VTE and whether this risk pertained predominantly to cancers sharing risk factors with VTE.

Using nationwide Danish registries, we followed patients with first-time VTE (1996-2022) until cancer diagnosis, death, emigration, or December 31, 2022, whichever occurred first. We used the Aalen-Johansen estimator to compute cumulative cancer incidence, treating death as a competing event. Standardized incidence ratios (SIRs) compared observed events with expected events based on general population rates. We analyzed cancer incidence overall and by site-specific and etiology groups for smoking-, obesity-, alcohol-, hormone-, and infection-related cancers, and "all other" cancers.

We followed 138,049 patients for a median of 5.5 years. The 1-year cancer risk was 4.0%. The 1-year SIR was 3.45 (95% CI, 3.36-3.55), then ranged from 1.09 to 1.16 over 20 years of follow-up, reaching 1.00 (95% CI, 0.90-1.11) thereafter. SIR was elevated in all cancer groups within 1 year and afterward, but was driven by site-specific cancers often related to smoking, obesity, and alcohol (lung, pharynx, larynx, esophagus, stomach, liver, pancreas, and colon), as well as hematological cancers.

Compared with the general population, patients with VTE had an increased cancer risk for up to 20 years. Shared risk factors, such as lifestyle-related factors and genetic predisposition, may contribute to this increased risk.

Flow cytometry (FCM) is a co-criterion in myelodysplastic neoplasms (MDS) diagnostics, currently not used for prognostication. This study aimed to develop an FCM-score predicting overall survival (OS) in MDS to improve early clinical patient prognostication. FCM of bone marrow samples was performed for diagnostic purposes in 509 therapy-naïve MDS patients and 77 healthy donors. The following methodology was used: (1) uni- and multivariate Cox proportional hazards regression and Kaplan-Meier curves for OS to assess FCM-parameters' prognostic value; (2) receiver operating characteristic (ROC) curves to test the prognostic superiority of FCM-parameters versus established FCM-scores and clinical risk-scores; and (3) development of a FCM-prognostic score (FCM-PS) based on six FCM-parameters with independent prognostic impact. The final FCM-PS included aberrancies of progenitor cells (increased CD45 mean fluorescence intensity [MFI]-ratio of lymphocytes and myeloid progenitor cells, decreased % of lymphatic progenitor cells), granulopoiesis (increased CD33 MFI, decreased sideward scatter [SSC]-ratio of granulopoiesis and lymphocytes), lymphocytes (increased % of B-lymphocytes), and plasmacytoid dendritic cells (increased %). FCM-PS outperformed established scores for OS (hazard ratio [HR] 4.08 [95% CI 2.54-6.55] vs. Ogata-score: 2.44 [1.61-3.70], International Prognostic Scoring System-Revised [IPSS-R]: 2.37 [1.61-3.49], International Prognostic Scoring System-Molecular [IPSS-M]: 0.816 [0.303-2.196]). Patients in the FCM-PS low score category showed significantly better OS (P < 0.0001). Further, FCM-PS allowed discrimination within IPSS-R area under the curve [AUC]: 0.70 vs. 0.62) and IPSS-M (AUC: 0.75 vs. 0.48) subgroups. Validation of the prognostic FCM-PS in an independent patient cohort confirmed good discrimination performance (AUC: 0.70). We introduce a unique, easy-to-use prognostic FCM-PS score (panel: CD45/CD34/CD117/CD33/CD19/CD123/HLA-DR) for OS in MDS, allowing refined risk stratification for IPSS-R subgroups.

Surgical decision-making in patients with spinal metastases remains complex due to the need to balance potential surgical benefits with limited survival and common frailty. Predictive models can assist in this process, but their clinical utility is often limited by complexity and lack of validation.

To externally validate a simple three-predictor frailty model for 90-day survival and complications, and to compare its performance with other commonly used tools.

Prospective external validation study conducted at a single tertiary cancer center.

A consecutive cohort of 126 patients who underwent open posterior surgery with instrumentation for spinal metastases from solid tumors between 2018 and 2024.

Primary outcomes were 90-day survival and the occurrence of postoperative complications. Secondary outcomes included 30-day, 180-day and overall survival. Model performance was evaluated through discrimination (AUC), risk stratification, accuracy for surgical indication and calibration.

The Anzuategui model (three predictors: tumor growth rate, comorbidities, and lymphocyte count) was applied preoperatively, along with four other three-predictor models (Tomita, Modified Bauer, Van der Linden, and Sioutos). Discrimination was assessed using ROC curves. Risk stratification was evaluated using predefined low-, moderate-, and high-risk categories, analyzed through Kaplan-Meier curves and complication rates. Model accuracy for surgical indication was calculated using a 90-day survival threshold as the reference. Calibration for both 90-day survival and postoperative complications was performed by comparing category-specific predicted probabilities derived from the development cohort with observed event rates in the validation cohort.

The Anzuategui model demonstrated predictive performance for the primary outcomes comparable to the other models under evaluation. It achieved an AUC of 0.78 (95% CI: 0.70-0.85) for 90-day survival and 0.68 (95% CI: 0.59-0.76) for postoperative complications. Risk stratification showed clear separation between survival curves across the three predefined categories. Accuracy for predicting appropriate surgical indication was 70% (95% CI: 61-78), with a sensitivity of 64% and specificity of 85%. Tomita and Modified Bauer models showed comparable accuracy (75% and 74%, respectively) but lower specificity. Calibration indicated overestimation of 90-day mortality (intercept -1.75; slope 2.05) and modest miscalibration for postoperative complications (intercept -0.40; slope 0.67).

The Anzuategui model demonstrated acceptable external performance, with greater validity for predicting 90-day survival than for postoperative complications. Its simplicity and frailty-centered structure make it a practical bedside tool, particularly in urgent or resource-limited settings. Integrating this approach with established prognostic models may support more balanced decision-making across diverse clinical scenarios.

Fibrous hamartoma of infancy (FHI) is a rare benign soft tissue tumor of early childhood, often misdiagnosed due to its clinical and/or radiological resemblance to vascular malformations or pediatric soft tissue neoplasms.

A 7-month-old male presented with a rapidly enlarging, firm, non-pulsatile subcutaneous mass involving the anterior aspect of almost the entire right arm. MRI suggested a low-flow vascular malformation; however, due to clinical concern for alternative pathology and the lesion's benign appearance, large size, superficial location, and resectability, complete excision was performed. Histopathology revealed the characteristic triphasic pattern confirming fibrous hamartoma of infancy. The patient recovered well with no recurrence at 3-month follow-up.

This case highlights the diagnostic pitfalls of FHI, which may closely mimic vascular anomalies on imaging, and underscores the importance of surgical excision for both definitive diagnosis and curative treatment. To our knowledge, this represents the first reported case of FHI from Palestine.

Esophageal cancer (ESCA), a leading cause of cancer-related mortality, lacks reliable biomarkers for early detection and prognosis. Dysregulated microRNAs (miRNAs) have emerged as pivotal regulators of tumor progression, yet their context-specific roles and interactions with target genes in ESCA remain underexplored.

Multi-omics data from The Cancer Genome Atlas-esophageal cancer (TCGA-ESCA) and Gene Expression Omnibus (GEO) datasets were integrated to identify differentially expressed miRNAs and mRNAs. A miRNA-mRNA regulatory network was constructed using FunRich and validated through functional assays, including dual-luciferase reporter, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in vitro proliferation/migration/invasion experiments. Prognostic signatures were developed using Cox regression, least absolute shrinkage and selection operator (LASSO)-Cox and nomogram analysis.

We identified 1,131 differentially expressed mRNAs and 69 miRNAs in ESCA. The miR-15b-5p/BTG2 axis emerged as a central regulatory hub. miR-15b-5p was significantly upregulated in ESCA tissues and showed an inverse correlation with B-cell translocation gene 2 (BTG2) expression. Survival analyses established both molecules as independent prognostic factors. Mechanistically, miR-15b-5p directly targeted BTG2 3'UTR, suppressing its expression. Functional studies demonstrated that miR-15b-5p overexpression promoted proliferation, migration and invasion in ESCA cells, whereas BTG2 restoration reversed these effects. A prognostic nomogram integrating miR-15b-5p, BTG2 and clinical parameters demonstrated robust predictive accuracy (C-index: 0.78).

The miR-15b-5p/BTG2 axis represents a novel regulatory mechanism in ESCA progression with significant potential as both a prognostic biomarker and therapeutic target.

Glioma, the most frequent primary intracranial tumor, is characterized by infiltrative growth in the central nervous system, pronounced invasiveness, high malignancy, and poor clinical prognosis. The existing treatment methods include surgery, radiotherapy and chemotherapy, but the efficacy is still limited. Analysis of The Cancer Genome Atlas (TCGA) dataset reveals marked downregulation of acid-sensing ion channel 2 (ASIC2) expression in glioma tissues, which significantly correlates with reduced patient survival. Moreover, ASIC2 expression is inversely associated with the extent of immune cell infiltration and glioma stem cell markers. Functional experiments demonstrate that both knockdown and overexpression of ASIC2 critically regulate glioma cell proliferation, invasion, and metastatic potential through mechanisms mediated by matrix metalloproteinase 2 (MMP2), calcineurin, and nuclear factor of activated T cells 1 (NFAT1) signaling pathways. These findings delineate a pivotal role for ASIC2 in governing glioma malignant behavior and establish its relevance as a potential molecular target for therapeutic intervention.

Long non-coding RNAs (lncRNAs) constitute a large class of ribonucleic acids, participating in multiple biological events within tumor cells, especially the regulation of transcription. A growing body of literature has revealed that abnormalities of lncRNA expression could result in carcinogenesis and oncogenesis by exerting inhibition or oncogenic effects. LINC01094 is a recently identified lncRNA found to be dys-regulated in an assortment of cancer tissues and control multiple biological processes via competing endogenous RNA (ceRNA) mechanisms. Specifically, LINC01094 functions as a ceRNA to modulate tumor cell growth, invasion, and migration by regulating critical signaling pathways including PI3K/AKT, PTEN/AKT, and Wnt/β-catenin, while also exerting oncogenic effects through transcriptional regulatory networks. Numerous recently published reports have shown that LINC01094 exerts critical functions during the regulation of malignant cell growth, migrating ability, and invasiveness, thereby controlling cancer cell growth and metastasis. In this review, multiple cancer biology functions of LINC01094 documented in published literature are summarized, aiming to inspire innovations in the management of human malignancies under laboratory and clinical settings.

Perinephric myxoid pseudotumor of fat (PMPF) is a rare and highly heterogeneous disease consisting of mature fat, myxoid stroma with spindled or stellate stromal cells histologically. Here, we present 2 cases of PMPF occurring in an allograft and a native kidney, and a systematic review that included 120 previously reported cases was subsequently conducted. Notably, 89% of PMPF cases with documented medical history had comorbidities. The most common comorbidities were urologic neoplasm (45%), chronic kidney disease (23%), allograft kidney (16%), and urinary tract obstruction (5%). We propose a classification of PMPF based on comorbidities and discovered that patients with concomitant urologic neoplasm or obstruction tended to have significantly smaller tumors, and active surveillance of PMPF after treating the primary disease might be an appropriate approach. In contrast, for patients with kidney transplants, chronic kidney disease, or no identifiable primary disease, the tumors were generally larger; therefore, surgical intervention should be considered. Regardless of the classification method used, for tumors exhibiting a slow growth rate, active surveillance should be considered. Our findings aimed to facilitate more accurate differential diagnosis and optimize treatment options.