Schwannomas are benign nerve sheath tumors arising from Schwann cells, most commonly affecting cranial and peripheral nerves. Penile schwannomas are exceptionally rare, with fewer than 50 cases reported worldwide. Their clinical presentation often mimics other soft tissue lesions, posing diagnostic challenges for urologists. This report describes a rare case of penile schwannoma in a middle-aged Iranian man, highlighting its clinical, histopathological, and surgical features.

A 52-year-old Iranian Caucasian male presented with a painless, slow-growing, mobile mass on the dorsal glans penis, noted for 2 years with recent enlargement. Physical examination revealed a 10 × 10 mm lobulated lesion without ulceration or discharge. No lymphadenopathy or systemic findings were observed. Surgical excision was performed under local anesthesia, preserving the dorsal penile nerve. Histopathology revealed a well-defined, encapsulated biphasic spindle cell neoplasm with Antoni A and B areas, nuclear palisading, and dense chromatin. Immunohistochemistry showed strong positivity for S100 and SOX10, confirming the diagnosis of schwannoma. Postoperative follow-up over 1 year showed no erectile dysfunction or penile curvature.

Penile schwannoma, though rare, should be considered in the differential diagnosis of penile masses. Accurate diagnosis relies on histopathological and immunohistochemical evaluation. Complete surgical excision with nerve preservation offers favorable outcomes and minimal functional impairment.

Nuclear protein 1 (NUPR1) is an intrinsically disordered, stress-adaptive regulator that sits at the intersection of transcriptional plasticity and proteostatic control, broadly upregulated across malignancies and tightly associated with poor prognosis. Here, we synthesize evidence positioning NUPR1 as a central node of tumor adaptation that integrates metabolic rewiring, proteostatic balance, and cell-death checkpoints into a unified stress-response framework. NUPR1 orchestrates lipogenic and glycolytic programs, sustains lysosomal biogenesis and autophagic flux, and governs cell-fate decisions by restraining apoptosis and ferroptosis through iron and redox control. Beyond tumor-intrinsic roles, NUPR1 remodels the tumor microenvironment by driving immunosuppressive macrophage polarization and amplifying inflammatory signaling, collectively sustaining a pro-survival niche. These circuits underpin broad therapeutic resistance across modalities, spanning chemotherapy, targeted agents, endocrine therapy, and immune checkpoint blockade. We further discuss the development of small-molecule NUPR1 antagonists-including ZZW-115 and emerging chemotypes-that disrupt nuclear trafficking and stress tolerance, alongside formulation strategies to optimize pharmacodynamic potency and safety. Together, these insights establish NUPR1 as a druggable stress-response node and provide a mechanistic framework to overcome resistance and refine adaptive cancer therapy paradigms.

Cerebral gliomas represent a heterogeneous group of tumours that pose unique diagnostic and therapeutic challenges. Adolescents and young adults (AYAs, 15-39 years) often fall into a clinical gap, receiving care modelled on paediatric or adult oncology, which may not address their distinct biological and psychosocial needs. A review was conducted to systematically map the existing literature on cerebral gliomas in AYAs and identify evidence gaps in diagnosis, treatment, and prognosis. Our scoping review was conducted following PRISMA-SR guidelines, using PubMed and Scopus to identify studies on gliomas in AYAs. Eligibility criteria consisted of articles focused on gliomas in AYAs, published in English between 2000 and 2024. Studies exclusively focused on AYA populations, as well as studies including AYAs within mixed populations, were considered eligible. Extracted data included study characteristics, population, interventions, and outcomes (survival, quality of life, molecular markers), which were synthesised thematically into epidemiology, molecular/histological profiles, treatments, outcomes, and psychosocial impacts. Our systematic review identified 33 studies on gliomas in AYAs. Most of the included studies (62.5%, n = 20) were published between 2020 and 2024. Geographically, the studies were primarily conducted in the USA (25%, n = 8), followed by Canada (9.4%, n = 3) and Europe (9.4%, n = 3). From an epidemiological perspective, gliomas were the most common cerebral tumours. Molecular analyses revealed overlap between pediatric- and adult-type alterations, emphasising diagnostic ambiguity and the need for comprehensive profiling. Treatment reports underscored surgery as central, with emerging roles for proton therapy, targeted agents, and immunotherapy, although the lack of AYA-specific trials remains a barrier. Prognostic and psychosocial studies highlight survival disparities associated with molecular markers and socioeconomic factors, as well as unmet needs related to fertility preservation, neurocognition outcomes, and palliative care.

The review identified major gaps, such as heterogeneous adoption of advanced diagnostic approaches, the absence of age-specific treatment protocols, and scarce research on long-term outcomes and quality of life in AYAs with gliomas. Addressing these issues requires AYA-focused clinical trials within a multidisciplinary care framework.

• Gliomas in adolescents and young adults (AYAs) present overlapping molecular and clinical features of paediatric and adult-type gliomas, determining diagnostic and therapeutic challenges in everyday care. • Current management of glioma in AYAs is usually extrapolated from paediatric or adult populations, with limited AYA-specific trials, without the presence of evidence-based guidlines.

• Our review has the aim to map the existing literature on cerebral gliomas in AYAs and to identify the major gaps in diagnosis, molecular profiling, treatment, outcome, and psychosocial aspects. • There is an urgent need to develop AYA-specific molecularly informed, multidisciplinary treatment strategies and clinical studies for gliomas focused on management and long-term outcomes.

The bidirectional occurrence of acute myeloid leukemia (AML) and plasma cell neoplasms (PCN) is rare, and clinical characteristics and survival outcomes remain poorly defined. We conducted a retrospective population-based study using the Surveillance, Epidemiology, and End Results (SEER) database (2000-2022). Patients diagnosed with both AML and PCN were identified and categorized based on diagnostic sequence. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using Kaplan-Meier methods and Cox proportional hazards models adjusting for demographic and clinical variables. The research cohort consisted mainly of elderly individuals (≥65 years old, 76.2%) and males (66.3%). The median survival time was 4.0 months (IQR: 1.0-13.0). Multivariable Cox regression analysis demonstrated that chemotherapy was associated with a significant survival benefit across all models of OS (Model III: HR = 0.54, 95% CI: 0.37-0.78, p = 0.001) and CSS (Model III: HR = 0.55, 95% CI: 0.35-0.85, p = 0.008). In contrast, radiotherapy showed no significant association with survival (all p>0.5). Kaplan-Meier analysis confirmed a significant survival advantage for patients receiving chemotherapy (log-rank p < 0.0001) but not for radiotherapy (log-rank p = 0.35). Subgroup analyses revealed that the protective effect of chemotherapy was consistent (all p for interaction > 0.5).In this population-based cohort, chemotherapy receipt was associated with improved survival among patients diagnosed with both AML and PCN. Given the observational nature of the study and limitations inherent to registry-based treatment ascertainment, these findings should be interpreted cautiously and warrant confirmation in studies designed to account for treatment timing and confounding.

Objective: To analyze the mutation status of the PIK3CA gene and the clinicopathological characteristics in lung adenocarcinoma. Methods: Lung adenocarcinoma cases that underwent next-generation sequencing (NGS) for the PIK3CA gene at the Department of Pathology, the Third People's Hospital of Henan Province and the Henan Provincial People's Hospital from January 1, 2020 to December 31, 2024 were collected. Clinicopathological indicators were recorded for statistical analysis, and follow-up was conducted. Results: A total of 127 lung adenocarcinoma patients with PIK3CA mutations were detected. There was a slight female predominance (75/127, 59.1%), the majority were non-smokers (95/127, 74.8%), and age was 65.0(57.0, 71.0)years old. Most lung adenocarcinomas were moderately differentiated (56/127, 44.1%) or poorly differentiated (44/127, 34.6%), with clinical stage Ⅳ being the most common (60/127, 47.2%). Hotspot mutations in the PIK3CA gene were present in 77 cases (77/127, 60.6%), specifically manifesting as mutations in exon 9 (E9, p.E545K/Q, p.E542K) and exon 20 (E20, p.H1047R/L/Y). Compared with E9 mutations, E20 mutations were more frequently associated with lymph node metastasis, visceral pleural invasion, airspace dissemination, poorer differentiation, and higher staging, and had a worse prognosis. Multivariate Cox analysis showed that PIK3CA hotspot mutations did not significantly affect prognosis (HR=0.586,95%CI=0.343-1.002,P=0.051). Co-existing mutations in other genes were found in 105 cases (105/127, 82.7%), with 72 cases (72/105, 56.7%) harboring concomitant EGFR mutations. Of the 62 cases receiving targeted therapy, 11 developed drug resistance, primarily due to secondary EGFR exon 20 mutations (9/11). Conclusions: Lung adenocarcinomas with PIK3CA mutations exhibit distinct clinicopathological characteristics in terms of gender, age, smoking history, differentiation degree, and clinical stage. Acquired drug resistance in lung adenocarcinoma may be accompanied by PIK3CA mutations, but PIK3CA mutation is not the main mechanism of targeted therapy resistance in lung adenocarcinoma patients.

Objective: To investigate the clinicopathological and molecular features of meningioma, and to analyze the characteristic molecular changes in high-grade meningioma (WHO grades 2-3). Methods: A total of 139 meningioma specimens from 134 patients treated at Xuanwu Hospital, Capital Medical University from 2015 to 2020 were collected, including 49, 62 and 28 samples of WHO grades 1, 2 and 3 meningiomas, respectively. Clinical data and pathological diagnoses were reviewed. Next-generation sequencing (NGS) was conducted to analyze the associations of molecular biomarkers with clinicopathological features and prognosis. Results: Among the 134 patients, 59 patients (44.0%) were male, and 75 (56.0%) were female, age 57 (49, 66) years old. The most common genetic alteration was NF2 mutation (43.2%, 60/139). In non-NF2 mutated meningiomas, the hotspot genes of detectable mutations were AKT1 (13.7%, 19/139), TRAF7 (9.4%, 13/139), KLF4 (5.7%, 8/139), SMO (5.7%, 8/139), and PIK3CA (1.4%, 2/139). Twelve of the 13 cases TRAF7 alterations co-occurred with other genetic changes. Some molecular alterations were associated with histological subtypes. For instance, NF2 mutations were most frequently detected in psammomatous meningiomas (2/2) and fibrous meningiomas (8/9), while all secretory meningiomas harbored KLF4 mutations (6/6). Some molecular alterations were associated with tumor grade and prognosis. JAK3 mutations (4.3%, 6/139), TERT promoter mutations (3.6%, 5/139), and homozygous deletion of CDKN2A/B (4.3%, 6/139) were exclusively found in high-grade meningiomas. TERT promoter mutations and CDKN2A/B homozygous deletion (versus normal) were both independently associated with poorer prognosis (P<0.001 for both). JAK3 mutation was also associated with shorter overall survivals (P=0.031). Conclusions: NF2 is the most frequently mutated gene in meningiomas. TERT promoter mutations and CDKN2A/B homozygous deletion occur exclusively in high-grade meningiomas, link to unfavorable prognosis, and can serve as independent diagnostic markers for WHO grade 3 meningioma. JAK3 mutation seems also to be associated with high-grade meningiomas and shorter survivals.

Objective: To evaluate the performance of a deep learning framework based on the PathOrchestra pathology foundation model for predicting key driver gene mutations (VHL, PBRM1, BAP1, and SETD2) in clear cell renal cell carcinoma (ccRCC), and to analyze the associations of these mutations with clinicopathological characteristics and prognosis using whole-exome sequencing data. Methods: Whole-slide images and matched whole-exome sequencing data were collected from 319 patients with pathologically confirmed ccRCC at the First Affiliated Hospital of Air Force Medical University between March 2018 and July 2023. Image features of the whole slide imaging were extracted using the PathOrchestra foundation model. An attention-based multiple-instance learning model was developed to predict gene mutations. Model performance was evaluated on an independent test set, with the UNI model serving as a baseline control. The associations of the mutation status with clinicopathological parameters and patient prognosis were also analyzed. Results: On the independent test set, the PathOrchestra model achieved area under the receiver operating characteristic curve values of 0.87 for VHL, 0.84 for PBRM1, 0.95 for BAP1, and 0.88 for SETD2, showing higher predictive performances than the UNI baseline for BAP1 and SETD2. Clinicopathological correlation analysis based on whole-exome sequencing data revealed that BAP1 mutation was associated with higher WHO/ISUP grade (χ²=17.694,P=0.001), tumor relapse/metastasis (χ²=4.257,P=0.039), and shorter progression-free survival (P=0.045). Conclusions: The PathOrchestra-based deep learning approach can effectively identify key driver gene mutations in ccRCC using whole slide images of HE-stained slides, providing a feasible method for inferring genetic alterations from pathological images. The association of BAP1 mutation in ccRCC with poor prognosis further supports its value in prognostications. Moreover, the model visualization reveals morphological signatures associated with gene mutations, offering preliminary insights into genotype-morphology relationships.