We report a woman in her 50s with a giant co-secreting pituitary macroadenoma producing both prolactin and growth hormone. She presented with headache, proptosis, chemosis and secondary amenorrhoea since her 20s. Workup showed hyperprolactinaemia (251 μg/L; normal ≤23 μg/L). A brain MRI showed a giant mass at the base of the skull. Repeat prolactin assay after serum dilution showed marked hyperprolactinaemia (386 020 μg/L), consistent with a giant prolactin-secreting tumour. Additional tests established the presence of growth hormone excess. She was treated with cabergoline, leading to substantial clinical improvement and progressive decrease in tumour size and prolactin. Additionally, she was initially treated with lanreotide which was ineffective. She was switched to pegvisomant therapy, resulting in insulin-like growth factor I normalisation. This case emphasises the critical importance of recognising the hook effect artefact in patients with large sellar masses. Slow uptitration of dopamine agonist therapy is advisable in patients with large tumours to minimise the risks of cerebrospinal fluid leak, apoplexy and herniation.

Paraneoplastic neurological syndromes (PNS) associated with triple-negative breast carcinoma (TNBC) are exceptionally rare. We report a case of fulminant encephalitis in a middle-aged woman with TNBC presenting with concurrent PNMA2 (Ma2/Ta), ZIC4 and recoverin antibody positivity. The patient initially developed a subacute cerebellar syndrome characterised by downbeat nystagmus, gait ataxia and diplopia. Comprehensive evaluation revealed FDG-avid left axillary lymphadenopathy and biopsy confirmed high-grade TNBC with PD-L1 CPS of 77. She received neoadjuvant chemo-immunotherapy as per standard institutional protocol (paclitaxel, carboplatin, epirubicin, cyclophosphamide and pembrolizumab). Following the sixth cycle, she developed refractory focal seizures progressing to status epilepticus with MRI findings consistent with cortical encephalitis. Despite aggressive immunosuppression including corticosteroids, intravenous immunoglobulin and rituximab, her condition proved refractory. She ultimately succumbed despite maximal supportive care. This case illustrates a rare paraneoplastic overlap syndrome combining PNMA2-associated encephalitis and ZIC4-associated cerebellar degeneration in TNBC, highlights diagnostic challenges when immune checkpoint inhibitors may amplify pre-existing onconeural immunity and underscores the dismal prognosis of intracellular antibody-mediated neurological syndromes despite aggressive immunotherapy.

A man in his 70s presented with right ocular pain, visual disturbance, forehead swelling and left iliac pain. Diagnostic imaging revealed a large right orbital-frontal mass with skull involvement, a cavitary lesion in the right upper lobe and a left iliac lesion. Histological and molecular analyses confirmed lung adenocarcinoma with a MET exon 14 skipping mutation. Initial management focused on symptom control via palliative radiotherapy to the orbital and iliac lesions which achieved rapid relief. Following molecular confirmation, tepotinib-a selective MET tyrosine kinase inhibitor-was initiated. This resulted in clinical stability and a slight radiographic reduction of the primary lung lesion. This case highlights an atypical clinical manifestation of orbital metastasis in MET-mutated non-small-cell lung cancer. It underscores the clinical necessity of prompt tissue diagnosis and molecular profiling in patients presenting with atypical metastatic sites to facilitate the timely initiation of targeted systemic therapies.

In this issue of Cancer Cell, Vuong et al. perform a cross-species functional and molecular analysis of the mechanisms of response and adaptation to VEGFR kinase inhibitors and immunotherapy, identifying SPP1⁺ tumor-associated macrophages as key players of response to therapy. They further demonstrate that chronic treatment promotes metastatic spread.

This case report discusses the anesthetic management of a 47-year-old female with recurrent adenocystic carcinoma of the trachea and dilated cardiomyopathy (DCMP) undergoing tracheal tumor debulking and stenting. The patient experienced hemodynamic collapse due to failed expiration during ventilation using a Ventrain device, necessitating a return to spontaneous bag-mask ventilation and an urgent tracheostomy to maintain the airway.

The purpose of this protocol was to evaluate the relationship between quantitative parameters derived from shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) and biological prognostic markers in breast cancer. The study included 68 patients with breast cancer and 68 healthy controls. All patients underwent SWE and CEUS imaging, and surgical specimens from the breast cancer group were analyzed using immunohistochemistry to assess the expression of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and Ki-67. Results demonstrated that breast cancer tissue exhibited significantly different elastic and perfusion characteristics compared to normal breast tissue. Specifically, the cancer group showed lower Emean values and higher Emax, Emin, peak intensity, and mean transit time (MTT) values. Correlation analysis revealed that Ki-67 expression was positively correlated with Emean, Emax, peak, and MTT, while ER was negatively correlated with all parameters except peak intensity. HER2 expression showed positive correlations with all measured imaging parameters. These findings suggest that SWE and CEUS can provide non-invasive, complementary insights to support molecular characterization and clinical evaluation of breast cancer.

Patients with tuberous sclerosis complex (TSC1/TSC2 mutations) exhibit variable expressivity of autism spectrum disorder (ASD), and maternal immune activation is known to heighten ASD risk. Interleukin-6 (IL-6) is a pleiotropic cytokine with well-established roles in immune regulation, inflammation, and neuroinflammatory processes. It is produced by multiple immune cell types in response to infection or tissue injury, and is commonly characterized as a pro-inflammatory mediator. Notably, IL-6 can cross the blood-brain barrier and has been implicated in neuroinflammation and inflammation-associated neuropsychiatric conditions, including autism spectrum disorder (ASD) and intellectual disability (ID). Here, we describe a protocol to induce systemic inflammatory signaling in zebrafish by delivering IL‑6 into the bloodstream through injection into the duct of Cuvier. This approach enables controlled and reproducible inflammatory responses to study inflammation-driven changes in early development. The protocol details the essential steps for IL-6 preparation, microinjection, and downstream experimental applications in zebrafish models of disease and neuroinflammation, including studies designed to probe gene-environment interactions. By enabling controlled induction of systemic inflammatory signaling, this approach provides a versatile platform for examining how genetic susceptibility and inflammatory exposures intersect to shape developmental outcomes.

Accurate segmentation of colorectal polyps is crucial for the early prevention and diagnosis of colorectal cancer. However, due to the high heterogeneity of polyps in terms of shape, size, and texture, as well as the complexity of the intestinal environment (such as folds, specular reflections, and fecal residues), existing methods still face significant challenges in boundary localization and small-polyp detection. To address these issues, this paper proposes a Polyp Segmentation Network based on Pinwheel Convolution and Dual Attention (PWD-Net). The proposed network adopts a U-shaped encoder-decoder architecture, where a pretrained ResNet is employed as the encoder to extract multi-level local features. Specifically, a Pinwheel Convolution Module (PCM) is introduced at the bottleneck layer to capture the global geometric structure and multi-directional contextual information of polyps through multi-angle rotated convolution kernels. A Dual-Attention Mechanism (DAM) that integrates channel attention and spatial attention is designed to adaptively suppress background noise and enhance polyp-region features. In addition, a Multi-scale Feature Fusion (MSF) strategy is employed to combine deep semantic information with shallow boundary details, ensuring both completeness and precision of segmentation results. Experiments conducted on the Kvasir-SEG and CVC-ClinicDB datasets demonstrate that PWD-Net achieves average Dice coefficients of 0.865 and 0.944, and IoU scores of 0.765 and 0.892, respectively, significantly outperforming existing state-of-the-art methods. Ablation studies verify the effectiveness of each module, and cross-dataset evaluations confirm the strong generalization ability of the model. This study provides a high-precision and robust solution for clinical polyp segmentation, offering significant value for the early diagnosis of colorectal precancerous lesions and supporting computer-aided intervention.

Tamoxifen is a key endocrine therapy for estrogen receptor-positive (ER⁺) breast cancer, but acquired resistance limits long-term efficacy. The molecular mechanisms remain complex, and predictive biomarkers are lacking. Gene expression data related to tamoxifen resistance were obtained from GEO (GSE67916), and differentially expressed genes (DEGs) were identified using the limma algorithm. Functional enrichment analyses (GO and KEGG) revealed involvement in immune processes, antiviral responses, endocytosis, lysosome pathways, and estrogen signaling. Three machine learning algorithms (LASSO, SVM-RFE, and RF) identified six hub genes (CAMK1D, CHAC1, KIAA0513, MED13, NDRG1, STXBP5). A prognostic risk model based on these genes was constructed using TCGA-BRCA data, effectively stratifying patients into high- and low-risk groups with significantly different overall survival. The model demonstrated good predictive accuracy (AUC = 0.70) and stable performance in time-dependent ROC analyses, validated in an independent cohort. This study provides a robust tamoxifen resistance-related gene signature and a multigene prognostic model, offering novel insights into resistance mechanisms and potential guidance for individualized prognosis and therapy in ER⁺ breast cancer.

Inflammatory myofibroblastic tumor (IMT) is an uncommon mesenchymal neoplasm of intermediate biological potential, characterized by proliferating myofibroblastic spindle cells with a prominent inflammatory infiltrate. Although IMT occurs more commonly in children and young adults, primary involvement of the anterior mediastinum is exceedingly rare, particularly in older male patients, and may mimic more common anterior mediastinal tumors such as thymoma or thymic carcinoma. The authors report on a 68-year-old male patient with an incidentally detected anterior mediastinal mass. Contrast-enhanced chest computed tomography and magnetic resonance imaging revealed a 6.6 × 3.6-cm anterior mediastinal soft-tissue lesion with heterogeneous enhancement, peripheral delayed enhancement, central hypoenhancement, restricted diffusion, and an indistinct interface with adjacent pericardial structures. The patient underwent complete surgical resection via median sternotomy. Histopathological examination showed spindle-cell proliferation with a prominent lymphoplasmacytic infiltrate, supporting the diagnosis of IMT. Immunohistochemistry showed anaplastic lymphoma kinase (ALK) negativity. Additional ancillary studies showed negative staining for CD21, CD23, and CXCL13 and negative Epstein-Barr virus (EBV)-encoded small RNA in situ hybridization, arguing against follicular dendritic cell sarcoma and EBV-associated lesions. Fluorescence in situ hybridization showed no rearrangements involving ALK, ROS1, RET, or PDGFRB. The patient recovered well without adjuvant therapy, postoperative CA125 and neuron-specific enolase levels returned to the normal range, and no recurrence or metastasis was observed during 2 years of follow-up. This rare case highlights that ALK-negative anterior mediastinal IMT should be considered in the differential diagnosis of anterior mediastinal masses across age groups. Complete resection may provide durable disease control in selected resectable cases, but the single-case nature of this report and the known recurrence potential of IMT support cautious interpretation and long-term surveillance.