Retroperitoneal cavernous hemangiomas (RCHs) are exceedingly rare benign vascular tumors. They pose significant diagnostic challenges due to their nonspecific clinical presentations and imaging findings. This report highlights a clinically misdiagnosed case of RCH as a different retroperitoneal tumor. A 43-year-old female presented with persistent right hypochondrial pain. Imaging studies suggested a retroperitoneal mass, initially suspected to be either a gastrointestinal stromal tumor (GIST) or Schwannoma, or paraganglioma. Surgical resection of the tumor was performed, and histopathological examination confirmed the diagnosis of a cavernous hemangioma. The patient recovered well with no postoperative complications. Limited cases of RCHs have been reported in the literature. These tumors often mimic other retroperitoneal masses such as GISTs. Imaging findings are nonspecific, and definitive diagnosis typically relies on histopathological analysis. Surgical resection is the mainstay of treatment, with excellent outcomes reported across cases.

Primary mucoepidermoid carcinoma (MEC) of the liver is an extremely rare malignant tumor with nonspecific symptoms and signs.

The 2 cases included one Chinese male and one Chinese female, aged 72 and 47 years, respectively. Their clinical manifestations were hematemesis and upper abdominal pain. Imaging features were atypical, showing heterogeneous enhancement or cystic areas. After surgical resection, the pathological diagnosis was hepatic MEC, and the CRTC1-MAML2 fusion gene was found. Both patients did not undergo radiotherapy and chemotherapy after the operation, and died of tumor metastasis 3-4 months after tumor resection.

Hepatic MEC is rare and has an extremely poor prognosis. Surgical resection is the main treatment, and diagnosis requires confirmation through histopathology, immunohistochemistry, and special staining. CRTC1-MAML2 fusion can also assist in diagnosis.

Renal cell carcinoma (RCC) arises from the tubular epithelial cells in the cortex. RCC can present with metastatic disease in 25-33% of cases and has the potential to metastasize to every distant organ, with no apparent time limit for metastatic activity. Metastatic RCC to the colon is an infrequent phenomenon, making a new primary colonic adenocarcinoma an important differential. Multiple hypotheses for the mechanism of these metastases exist, including multistep hematogenous dissemination or a diffuse peritoneal seeding from an intra-abdominal or retroperitoneal tumor with colonic microperforations. Additionally, colonic metastases may outgrow their blood supply, leading to spontaneous detachment and passage in stool, a phenomenon known as autoamputation. This phenomenon has been described mostly in adnexa, ovaries, and related tumors such as teratomas, but also in polypoid carcinoma in the colon and rectum.

A 62-year-old male with a past medical history of known metastatic RCC, presented to the emergency department with multiple episodes of hematochezia and passed a large tissue-like mass in his stool. Colonoscopy revealed an ulcerated, obstructing mass in the descending colon with an inconclusive biopsy. However, the pathology from the initial mass passed through the stool revealed a clear cell-type RCC classic histologic pattern.

To the authors' knowledge, this is the first reported case of autoamputation phenomena in metastatic RCC to the gastrointestinal (GI) tract. It represents RCC's propensity to metastasize to distant sites and should be considered in the differential diagnosis of lower GI bleed.

Pulmonary tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains one of the leading causes of infectious disease-related mortality worldwide. In parallel, lung cancer represents the most lethal neoplasm, with high mortality rates globally. Emerging studies suggest that chronic Mtb infection may contribute to the development of lung cancer, particularly adenocarcinoma. Several biological mechanisms support this hypothesis. Chronic inflammation from tuberculosis creates a microenvironment enriched in proinflammatory cytokines, reactive oxygen species (ROS), and growth factors that favor cell proliferation, genomic instability, angiogenesis, and immune evasion, which are considered classic hallmarks of cancer. Additionally, both protein and non-protein virulence factors of Mtb have been shown to interfere with critical cellular signaling pathways related to tumor cell survival and invasion. Clinically, multiple observational studies and meta-analyses report an increased incidence of lung cancer among individuals with a history of tuberculosis, especially when both conditions coexist in the same pulmonary regions. Specific mutations, including EGFR, have been identified in patients with prior tuberculosis, influencing both prognosis and therapeutic response. Nevertheless, key questions remain regarding the causal nature of this association, the role of Mtb strains, and the molecular factors such as epigenetic modifications or the lung microbiome. This review proposes that infection with Mtb could function as a carcinogenic agent. Further in vitro experiments, cellular models, and clinical investigations are urgently needed to support potential reclassification of this pathogen by international agencies such as the IARC.

Individuals diagnosed with colorectal cancer (CRC) frequently confront a grave prognosis and exhibit poor responses to conventional treatment regimens. Immunotherapy, notably modalities centered on natural killer (NK) cells, represents a burgeoning frontier in the management of CRC. This study developed a validated prognostic model using NK-associated long non-coding RNAs (lncRNAs) to predict CRC outcomes.

Integrating single-cell RNA-seq (GSE146771_Smartseq2) and TCGA-COAD/READ bulk transcriptomic data, we identified NK-specific genes and correlated lncRNAs. A multi-step analytical approach-including univariate Cox regression for preliminary screening, LASSO regression to minimize overfitting, and multivariate Cox regression for final model optimization-yielded a robust 16-lncRNA prognostic signature with high predictive accuracy.

This model demonstrated robust predictive performance across the training set, validation set, and 76 independent clinical samples. Mechanistic investigations revealed that AC010319.3 is highly expressed in NK cells, where it attenuates NK cell cytotoxicity by suppressing the expression of IFN-γ and granzyme B, thereby promoting the proliferation and invasion of CRC cells.

This study systematically delineates the regulatory role of NK-associated lncRNAs within the CRC immune microenvironment, offering novel molecular targets and stratification strategies for CRC immunotherapy.

The tumor immune microenvironment plays a critical role in tumor progression and responses to immunotherapy. Nevertheless, its cellular complexity and heterogeneity remain incompletely understood. In this study, we employed high-resolution single-cell RNA sequencing on CD45+ immune cells isolated from ten syngeneic murine tumor models, representing seven distinct cancer types under treatment-naïve conditions, thereby enabling a comprehensive profiling of tumor-infiltrating immune cells. We identified seven principal immune cell populations and provided an in-depth characterization of T cells, NK/innate lymphoid cells, dendritic cells, monocytes/macrophages, and neutrophils. Cross-species analyses further delineated conserved immune cell states and transcriptomic features within the T cell and monocyte/macrophage compartments that are shared across syngeneic models and human tumors. To investigate the functional relevance of the predominant monocyte/macrophage compartment and the notable presence of neutrophils in syngeneic tumors, we evaluated responses to anti-PD-1 therapy across various models and analyzed the enrichment of monocyte/macrophage subsets in tumors that responded to treatment. Furthermore, we conducted neutrophil depletion experiments using anti-Ly6G antibodies, administered both as monotherapy and in combination with PD-1 blockade. Remarkably, an interferon-stimulated gene-high (ISG^high) monocyte subset was significantly enriched in models responsive to anti-PD-1 therapy. Neutrophil depletion resulted in variable antitumor effects across models but failed to enhance the efficacy of PD-1 blockade. In summary, our single-cell profiling offered a detailed atlas of the immune microenvironment across multiple syngeneic mouse tumor models, thereby enabling rational model selection for immuno-oncology studies. We uncovered an ISG^high monocyte subset enriched in anti-PD-1 responsive models, and showed the context-dependent effects of neutrophil depletion on tumor immunity and immunotherapy, underscoring the heterogeneity and functional divergence of immune cell sublineages.

N6-methyladenosine (m6A) modification has emerged as a critical epigenetic mechanism regulating gene expression in diverse physiological and pathological processes, including cancer. Methyltransferase-like 16 (METTL16), a recently identified m6A methyltransferase, has been shown to influence tumor progression through m6A-dependent regulation of key target genes. Accumulating evidence indicates that METTL16 exerts tumor-suppressive or tumor-promoting roles in a context-dependent manner, affecting cell proliferation, apoptosis, autophagy, and chemotherapeutic response across multiple cancer types such as bladder cancer, lung cancer, colorectal cancer, and acute myeloid leukemia. Mechanistically, METTL16 modifies the mRNA stability and translation of oncogenes or tumor suppressors via recognition of m6A sites, and its expression can be regulated by upstream factors including transcription factors and hypoxia-inducible signals. Recent evidence suggests that METTL16 also modulates the tumor microenvironment (TME), potentially affecting immune cell infiltration, immune checkpoint expression, and tumor immune evasion. Collectively, METTL16 emerges as a pivotal epitranscriptomic regulator linking RNA modification, tumor progression, and immune modulation, offering new avenues for precision oncology.

The GINS complex subunit 2 (GINS2) is crucial for DNA replication, but its specific roles in oral squamous cell carcinoma (OSCC) pathogenesis and tumor microenvironment (TME) modulation are poorly defined.

GINS2 expression was analyzed using TCGA data and validated in OSCC patient tissues and cell lines via qPCR, Western blot (WB), and immunohistochemistry (IHC). Functional assays (CCK-8, colony formation, wound healing, Transwell invasion) and in vivo xenograft models assessed the impact of GINS2 knockdown (sh-GINS2) or overexpression (OE-GINS2) on OSCC cell behavior and tumorigenesis. Mechanistic links involving PTP4A1 and PKM2 were explored using Co-immunoprecipitation (Co-IP) and immunofluorescence (IF). Immune correlations were assessed in TCGA/TIMER2.0 (PDCD1, LAG3, CTLA4, HAVCR2), and PD-1/TIM-3 on CD8⁺ T cells were quantified by flow cytometry in co-culture. Neutrophil features (PD-L1 expression) and interventions (neutrophil depletion, anti-PD-L1) were evaluated in vitro and immune-reconstituted in vivo settings.

GINS2 was significantly upregulated in OSCC tissues and cell lines, correlating with advanced clinical stage and higher pathological grade. GINS2 knockdown suppressed proliferation, colony formation, migration, and invasion in vitro, and inhibited tumor growth in vivo. At the protein level, GINS2 physically associated with PTP4A1 and monotonically modulated its steady-state abundance; PTP4A1 interacted and co-localized with PKM2. In TCGA, GINS2 expression positively correlated with T-cell exhaustion markers, and altering GINS2 in OSCC cells changed PD-1 and TIM-3 on co-cultured CD8⁺ T cells. GINS2 expression also correlated with neutrophil infiltration; GINS2 overexpression increased tumor-associated neutrophils (TANs) in vivo, and Ly6G neutrophil depletion attenuated GINS2-driven tumor enhancement. OSCC-associated neutrophils exhibited elevated PD-L1 expression, correlating positively with GINS2 levels. GINS2 knockdown sensitized OSCC models to anti-PD-L1 therapy, reducing tumor growth and Ki67 expression, particularly when combined with T cells and neutrophils.

GINS2 acts as a key oncogenic driver in OSCC, promoting tumor progression and facilitating immune evasion. Its effects appear to involve a proximal GINS2-PTP4A1-PKM2 module and the recruitment/polarization of PD-L1⁺ neutrophils linked to T-cell dysfunction. Targeting the GINS2 axis-potentially in combination with PD-L1 blockade-warrants further investigation in OSCC, with downstream signaling mechanisms to be clarified in future work.

Despite the revolutionized diagnostic effect of fluorine-18 -fludeoxyglucose ([¹⁸F]-FDG) as a positron emission tomography (PET) radiotracer in oncological divisions, lack of specificity and sensitivity in discovery of some tumor subtypes was inevitable. Fibroblast activation protein (FAP) is overexpressed in a vast majority of neoplasms, particularly in more than 90% of epithelial tumors which could be an appropriate target for evaluation of tumor's molecular and metabolic functions by FAP inhibitor (FAPI) ligands. Considerably extensive radiolabeled FAPIs have been investigated during clinical trials for diagnostic as well as theranostic applications with encouraging outcomes. In the same cancers, PET/CT imaging by FAPIs are demonstrating to be valuable alternative to [¹⁸F]-FDG in assessment of cancers in which [¹⁸F]-FDG PET performance is suboptimal due to [¹⁸F]-FDG high background uptake or relatively low avidity. Furthermore, the propensity to specifically target FAP expression through FAP-targeted medications or radiotracer therapy creates prospects for image-guided treatment in both cancer and non-cancer indications. FAPI PET will remain a fascinating field of study in the future years.

Chemoresistance represents a significant challenge in the chemotherapy of colorectal cancer (CRC), limiting the effectiveness. In this regard, gene expression heterogeneity plays a critical role, influencing cancer cell adaptability and survival under chemotherapy. Our previous data revealed that ribosomal protein uL3 positively correlates with both chemoresistance and poor prognosis in CRC patients. This study explores the combination of 5-fluorouracil (5-FU), the first-line treatment of CRC, with G-quadruplex (G4) ligands, which have recently emerged as promising candidates for cancer therapy, to overcome uL3-mediated chemoresistance. We found that resistant p53-deficient and uL3-silenced CRC cells showed increased levels of G4 structures compared to both sensitive p53-deficient and p53-proficient cells, thereby exhibiting vulnerability to the cytotoxic effects of two well-established G4 ligands, pyridostatin (PDS) and RHPS4. The combination of 5-FU with PDS or RHPS4 exhibited a synergistic effect, selectively targeting tumor cells. This approach enabled a >10-fold reduction in the 5-FU dose, improving treatment efficacy. The effectiveness of this combination was further validated in vivo using uL3-silenced CRC cell-derived xenografts in a chicken embryo model. Overall, our findings highlight a novel and promising combination strategy that targets chemoresistance in CRCs characterized by non-functional p53 and reduced levels of uL3.