Thymomas, though rare, are the most common anterior mediastinal neoplasms in adults, with incidence of 0.13 per 100,000 person-years. Due to indolent nature and lack of randomized trials, treatment relies on retrospective data. Literature on outcomes of unresectable thymomas in India is limited.

This retrospective study was conducted at a tertiary cancer centre in north India, analysing records of patients with advanced/unresectable thymic malignancies (stage III-IV) treated between January 2012 and December 2023. Clinicopathological features, response rates, progression-free survival (PFS), and overall survival (OS) were assessed.

A total of 43 patients (median age 40 years [range 22-72]; 76.7% male) were included. Histology revealed thymoma in 36 (83.7%), thymic carcinoma in 4 (9.3%), and thymic neuroendocrine tumours in 3 (7%). Common symptoms were cough (60.5%), dyspnoea (60.5%), and chest pain (55.8%). Stage distribution was - III (20.9%), IVA (46.5%), and IVB (32.6%). Liver (14%) was the most common site of distant metastasis. Myasthenia gravis and pure red cell aplasia occurred in 7% each. Forty (93%) patients received systemic therapy, primarily Cyclophosphamide-Adriamycin-Cisplatin (75%). The objective response rate for first-line systemic therapy was 37.5% (all partial responses) with a clinical benefit rate of 87.5%. Twelve (30%) underwent surgery, with R0 resection in 6 (15%). Median PFS was 16.4 months, and OS was 56 months.

Systemic therapy and surgery in selected cases provide meaningful outcomes in unresectable thymomas, emphasizing the need for prospective studies to refine treatment strategies.

Retroperitoneal sarcomas (RPS) require multidisciplinary decision-making. Following centre certification and the publication of national guidelines in German-speaking countries, the consistency and reliability of multidisciplinary team (MDT) recommendations for RPS remain unclear.

In this multi-centre study, 24 German-speaking sarcoma MDTs independently reviewed pre-treatment imaging and clinical information from 20 anonymised primary RPS cases. Centres provided standardised assessments of resectability, surgical strategy, and treatment allocation. Inter-centre agreement was quantified using percentage agreement with the per-case consensus and Krippendorff's alpha statistic (α), interpreted using established reference values.

Review of the 20 cases resulted in up to 480 MDT assessments for each item. Across 468 assessments, 411 (88%) rated the tumour as resectable and 57 (12%) as non-resectable. Centre-level agreement with the per-case consensus was 90.2%, with fair inter-centre reliability (α = 0.21). Agreement was lower in large tumours (>20 cm: 79.6%, α = 0.27) compared with smaller tumours. Agreement on surgical strategy was 65.9% (284/431; α = 0.21), with marked variability in the extent of resection and the use of compartmental versus organ-sparing approaches. Agreement on treatment allocation was 75.6% (350/463; α = 0.24) with centres pursuing different subtype-specific treatment concepts. In 8 of 20 cases, at least one centre recommended palliative treatment while others proposed a potentially curative approach.

The majority of patients were offered curative treatment options in almost all centres. Substantial variability was observed in histology-specific surgical strategies and treatment allocation. These findings indicate that centre-level interpretive frameworks substantially influence MDT recommendations. Strengthening cross-centre collaboration and refining histology-specific guidance may improve consistency in RPS care without undermining expert judgment.

Facial nerve schwannomas (FNSs) are rare benign tumors that can involve any segment of the facial nerve. Comprehensive understanding of these tumors remains limited, largely due to the paucity of reports on large surgical series in the literature, and their clinical management is particularly challenging. To balance tumor control with favorable facial nerve function, the authors have adopted nerve-preserving surgery (nonradical tumor removal and bony decompression) for moderate facial nerve palsy and conventional nerve reconstruction surgery (total tumor removal and facial nerve reconstruction) for severe or complete palsy cases. In this study, the authors evaluate the utility of a function-centered surgical strategy and a five-category, location-based classification system, based on a relatively large contemporary series.

A total of 67 consecutive FNS surgeries performed in 61 patients between 2004 and 2022 were retrospectively reviewed. The surgical strategy was selected according to the patient's preoperative facial nerve function and intraoperative electromyography (EMG) responses.

Nerve-preserving surgery was performed in 47 cases (70.1%) and was associated with improved or stable facial nerve function in 87.2%. The mean House-Brackmann grade improved from 3.5 to 3.0 in the nerve preservation group and from 4.6 to 4.0 in the nerve reconstruction group. Overall, facial nerve function improved in 50.7% and worsened in 13.4% of cases. In the nerve preservation group, tumors confined within the temporal bone (intrameatal, tympanic, and mastoid types), younger age, and favorable EMG responses were associated with better postoperative facial nerve function. During long-term follow-up (mean 87.2 months), 27.7% of this group required additional treatment.

A function-centered strategy, supported by intraoperative EMG monitoring and a tumor-centered classification, enables selective nerve preservation and was associated with favorable outcomes in FNS surgery. This strategy may serve as a practical framework for individualized surgical treatment of FNSs.

Chemoradiotherapy (CRT) is a standard treatment for rectal cancer, yet patients show marked variability in response. Identifying reliable biomarkers that predict CRT response remains an unmet clinical need.

Pretreatment biopsy samples from patients who received neoadjuvant CRT were analyzed using RNA sequencing. Differentially expressed genes (DEGs) were identified between responders and nonresponders, followed by functional enrichment analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. To complement DEG-based results, gene-set enrichment analysis (GSEA) was performed to assess pathway activity across the ranked transcriptome and to prioritize biologically relevant pathways. Pathway-derived gene signatures were evaluated using receiver operating characteristic curves and validated in three independent data sets.

A total of 1,477 DEGs were detected, including 729 upregulated and 748 downregulated genes in responders. Functional enrichment analysis indicated immune activation and epithelial polarity in responders, whereas nonresponders showed enrichment of extracellular matrix organization, focal adhesion, and phosphoinositide 3-kinase-protein kinase B signaling. GSEA further identified four pathways associated with CRT response: antigen presentation, extracellular matrix-receptor interaction, focal adhesion, and drug metabolism. Among these, the antigen presentation pathway consistently predicted treatment response across data sets. Elastic net regression defined a six-gene signature (KLRC1, CTSS, HLA-DMA, HLA-DQB1, HLA-DQB2, and CIITA) with strong predictive performance, with area under the curve values ranging from 0.76 to 0.81.

These genes participate in major histocompatibility complex class II antigen-processing and immune-regulatory pathways that enhance CD4 T-cell activation. Overall, the findings indicate that an immune-active, antigen presentation phenotype underlies radiosensitivity in rectal cancer and that the six-gene signature may serve as a biomarker to guide personalized treatment strategies.

A 79-year-old man with metastatic Merkel cell carcinoma undergoing cancer-directed treatment was admitted to the hospital with 1 week of bilateral upper and lower extremity tremor and nearly continuous involuntary facial movements. These abnormal movements of his face, head, and limbs were exacerbated by purposeful movement. Examination revealed dysarthria with tremulous speech, intention tremors of the head and all extremities, distally diminished vibration sense with hyporeflexia, bilateral upper extremity dysdiadochokinesis, bilateral lower extremity dysmetria on heel-to-shin testing, and truncal ataxia. MRI of the brain showed no acute abnormalities. CSF and serum testing showed evidence of CNS inflammation with a CSF lymphocytic pleocytosis and elevated total protein. Diagnosis was ultimately made using serum and CSF studies. Here, we discuss the differential diagnosis of 2 weeks of diffuse intention tremor, involuntary facial movements, and ataxia. We discuss the workup, diagnosis, acute and nonacute management of this condition, as well as important clinical points regarding the broader category into which this diagnosis falls.

This study investigates the potential mechanisms through which the Rhubarb-Peach Kernel herb pair may exert effects in gastric cancer (GC) using network pharmacology and molecular docking approaches. Active compounds and their corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), with additional compound-target information obtained from DrugBank. Gastric cancer-related targets were collected from GeneCards, Online Mendelian Inheritance in Man (OMIM), the Therapeutic Target Database, and DrugBank. The overlapping targets were used to construct a compound-target-disease network and a protein-protein interaction network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were subsequently performed. Nine candidate compounds were docked against 8 core targets to assess their predicted structural interactions. A total of 27 active compounds were identified, among which β-sitosterol, aloe-emodin, and hederagenin were identified as major candidate compounds. Tumor protein p53, caspase 3, and JUN were among the principal network targets. Enrichment analysis indicated that the overlapping targets were mainly associated with the p53 signaling pathway and other pathways involved in cancer-related processes, including apoptosis, cell survival, and inflammatory regulation. Molecular docking revealed differences in predicted binding scores among the 9 candidate compounds and 8 core targets, with several compound-target pairs showing comparatively lower docking energies. This in silico study suggests that the Rhubarb-Peach Kernel herb pair may act through multiple compounds, targets, and biological pathways relevant to GC. However, the identified targets are not necessarily specific to GC, and the molecular docking findings represent computational predictions rather than evidence of actual biological binding. These results should therefore be considered preliminary and hypothesis-generating, and further in vitro and in vivo studies are required to evaluate their biological and therapeutic relevance.

Mixed phenotype acute leukemia (MPAL) is an uncommon hematologic malignancy characterized by the coexistence of lymphoid and myeloid lineage markers. Although adult-onset Still's disease (AOSD) is a diagnosis of exclusion, MPAL may rarely present with similar laboratory and clinical findings, resulting in delayed diagnosis and treatment.

We report a case of a 36-year-old woman who presented at 20 weeks of gestation with inflammatory polyarthritis, hyperferritinemia, lymphadenopathy, thrombocytopenia, and leukocytosis. The patient fulfilled the Yamaguchi criteria for AOSD after exclusion of autoimmune and infectious conditions and was initially treated with hydroxychloroquine and corticosteroids. An inefficient response to treatment and persistent cytopenias led to reevaluation. A repeat peripheral smear revealed blast cells, and flow cytometry confirmed MPAL. Gestation-compatible chemotherapy protocols resulted in a favorable clinical and hematologic response, with no adverse maternal or fetal outcomes.

The clinical overlap between the manifestations of AOSD and MPAL may occasionally result in misdiagnosis and delayed detection of an underlying malignancy. In patients presenting with presumed AOSD, careful exclusion of hematologic cancers is essential, particularly in the presence of atypical features such as persistent systemic inflammation, cytopenias, or poor therapeutic response.

This case describes a rare association between the manifestations of AOSD and MPAL. In addition, it highlights the importance of recognizing warning signs that may indicate an underlying malignancy in patients presenting with AOSD-like symptoms.

Pyelonephric giant cell tumor of soft tissue represents an exceptionally uncommon neoplasm of the urinary tract with limited malignant potential. It typically follows a benign clinical trajectory, with distant metastases occurring infrequently; reports of aggressive disease culminating in lethal multiorgan dissemination are exceedingly rare. The present case seeks to augment the clinical dataset and elucidate the features of its malignant transformation.

A 72-year-old male presented with a 3-day history of persistent right-sided low back pain, without fever, gross hematuria, or dysuria. Contrast-enhanced abdominal computed tomography imaging revealed wall dilation and hypertrophy of the right renal pelvis-ureteral transitional segment with lipomatous enhancement, measuring approximately 3.3 × 2.7 cm.

Combined with imaging manifestations and postoperative pathological examination results, the patient was definitively diagnosed with a pyelonephric soft tissue giant cell tumor.

The patient underwent radical nephroureterectomy after systematic preoperative evaluation.

Regular postoperative follow-up was performed. Adrenal gland and pulmonary metastatic lesions were detected at 6 months postoperatively. The patient died of continuous tumor progression at 15 months after surgery.

This case illustrates that soft tissue giant cell tumor is a rare neoplasm, with renal pelvis soft tissue giant cell tumor being exceedingly uncommon. Diagnosis primarily relies on histopathological examination. Clinicians should include renal pelvis soft tissue giant cell tumor in differential diagnoses. When feasible, en bloc surgical resection is recommended. Postoperative surveillance should be intensified to facilitate early detection of recurrence, as some patients harbor potential relapse, and prognosis remains cautiously guarded.

The molecular mechanisms by which KMT2A-rearranged (KMT2A-r) leukemias maintain the oncogenic FLT3 expression remain largely unclear, limiting therapeutic opportunities. Here, we identify the RNA binding protein MBNL1 as an unexpected positive regulator of FLT3 by DepMap dataset exploration and combinatorial CRISPR screens. MBNL1 promotes leukemia cell survival in cell lines and primary tumors by sustaining FLT3 expression in a KMT2A-r context-dependent manner. Mechanistically, we discover that MBNL1 recognizes a structured single-stranded DNA (ssDNA) element containing five consecutive guanines within the FLT3 enhancer, through MBNL1's zinc finger domains and the carboxyl-terminal unstructured region. Such MBNL1 protein/ssDNA interaction was evident in KMT2A-r leukemia using ChIP-seq and KAS-seq. Mutations of key amino acids of MBNL1's ssDNA binding surface or the critical guanines in ssDNA markedly abrogate the protein-ssDNA interactions. These findings implicate MBNL1 as a distinct FLT3 activator by recognizing a structured enhancer ssDNA element, highlighting an unexpected role for RNA binding proteins in transcriptional regulation through direct ssDNA recognition.

Adoptive T cell therapy requires T cells to infiltrate vascular tissues and preserve immune function. In solid tumor treatment, however, the surrounding microenvironment produces abnormal vasculature that impedes T cell infiltration. An approach that enables vascular normalization and enhances adoptive T cell function in parallel is essential for effective therapy but has not been reported. Here, we report the use of lenvatinib (LEN) to induce transient vascular normalization, thereby facilitating T cell infiltration. Moreover, LEN enhances T cell persistence by promoting the differentiation of T cells toward a memory phenotype. Our results indicate that the differentiation is by suppressing the PI3K-AKT-mTOR pathway, which drives effector differentiation, and by activating FOXO1, a transcription factor that promotes memory formation. To coordinate the transient vascular normalization and T cell enhancement, we link LEN-loaded, PD-L1-blocking micelles to T cells through acid-labile click chemistry, forming pH-responsive T cell-nanodrug conjugates. The conjugates synchronize the intratumoral release of LEN and the PD-L1 antagonist peptide OPBP-1, thereby coordinating vascular normalization, T cell differentiation, and checkpoint blockade. In vivo, the conjugates increased intratumoral CD8⁺ T cells and splenic memory T cells by over sixfold in B16-OVA tumors and achieved complete regression in a subset of MC38-OVA tumors without systemic toxicity, providing a promising strategy for solid tumor immunotherapy.