Endometrial carcinomas cluster based on mismatch repair (MMR), TP53, and POLE exonuclease domain mutation status. Although TP53 and MMR deficiency have immunohistochemical surrogates, molecular testing is required to determine POLE status. Pathologists can identify candidates based on morphologic and immunohistochemical findings, however the outcome and limitations of pathologist-recommended molecular testing have not been investigated. We evaluated endometrial carcinomas diagnosed from 1/2022-9/2025 in which molecular testing was recommended in the pathologist's comment. Sequencing was recommended in 38 and pursued in 16 (42%). Testing impacted classification in 50% (8/16): four were POLE-mut, and four were TP53-abnormal (p53-abn) or MMR-deficient (MMRd) with molecular findings discordant with immunostaining. All POLE-mut cases were multiple classifiers diagnosed in patients >50; half were stage III; POLE-mut status down-staged one. Impactful immunohistochemical-molecular discordances occurred in two p53-abn and two no specific molecular profile (NSMP) tumors. Other unexpected molecular findings included an NSMP carcinoma with a BRCA2 mutation leading to confirmation of a germline syndrome and an MMR-deficient malignancy with TSC2 alterations which was reclassified from high-grade carcinoma to malignant PEComa. Adverse outcomes were seen in 0% of POLE-mut, 33% of p53-abn, and 67% of NSMP carcinomas. These findings suggest potential value of pathologist-directed molecular testing for identifying POLE-mut endometrial cancers, particularly in post-menopausal patients with abnormal p53 and high-grade histology, and in selected stage III patients, in whom these features might not prompt clinical consideration for molecular work-up. They also illustrate limitations of immunohistochemical surrogates and ProMisE classification, the potential for aggressive behavior in NSMP tumors with POLE-like histomorphology, and the role of molecular testing in identifying clinically impactful mutations beyond POLE.

Primary ovarian epithelioid angiosarcoma (EAS) is an exceptionally rare and highly aggressive vascular malignancy with only isolated cases reported in the literature. Owing to its nonspecific clinical presentation and overlapping radiological features, preoperative diagnosis is extremely challenging and often mimics more common gynecologic malignancies. Consequently, evidence regarding optimal diagnosis and management remains limited. A 61-year-old postmenopausal woman presented with abdominal pain and a rapidly enlarging pelvic mass. Ultrasonography, computed tomography, and magnetic resonance imaging demonstrated a giant hypervascular pelvic tumor with extensive pelvic and para-aortic lymphadenopathy, initially suggesting uterine sarcoma. Serum CA125 and lactate dehydrogenase levels were elevated. Exploratory laparotomy identified a dominant right ovarian hypervascular tumor with diffuse peritoneal dissemination and bulky pelvic and para-aortic nodal metastases. Comprehensive clinical, radiological, intraoperative, gross pathological, histopathological, and immunohistochemical assessment demonstrated a primary ovarian origin, with no evidence of an extra-ovarian primary angiosarcoma. The patient underwent radical cytoreductive surgery, including total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy, resection of visible metastatic lesions, and systematic pelvic and para-aortic lymphadenectomy, achieving complete macroscopic cytoreduction. Histopathological examination demonstrated epithelioid tumor cells with vasoformative differentiation, while immunohistochemistry showed diffuse strong positivity for CD31, CD34, and FLI1, confirming primary ovarian epithelioid angiosarcoma. The patient declined adjuvant chemotherapy, developed rapid postoperative disease progression, and died approximately 2 months after surgery. This case highlights the marked diagnostic challenges and highly aggressive biological behavior of primary ovarian EAS with extensive pelvic and para-aortic lymph node metastases and diffuse intra-abdominal dissemination. Accurate diagnosis required a comprehensive clinicopathological correlation supported by histopathological and immunohistochemical evaluation. Although complete macroscopic cytoreduction and systematic lymphadenectomy were technically feasible, their therapeutic benefit cannot be inferred from a single case. This report expands the limited literature and emphasizes the need for improved diagnostic strategies, collaborative data collection, and more effective systemic therapies for this rare malignancy.

De novo neuroendocrine carcinoma (NECa) of the prostate is a rare, aggressive malignancy distinct from therapy-related forms, that remains poorly characterized at the molecular level. Here we analyzed six cases, including pure and mixed forms with adenocarcinoma, using histopathology, immunohistochemistry, next-generation sequencing, and genome-wide DNA methylation profiling. Morphologically, prominent intraductal extension of NECa was a frequent and striking feature. In mixed tumors, NECa and adenocarcinoma components shared pathogenic genetic alterations and highly concordant DNA methylation profiles. Frequent aberrations in tumor suppressor proteins p53, RB, and PTEN/AKT were observed, mirroring molecular features described in therapy-related NECa and correlating with tumor behavior. Notably, a null pattern of p53 immunoreactivity represented the predominant aberrant expression pattern. In addition, a previously unreported NRAS mutation was detected in one case. Collectively, we describe the morphological, genetic and epigenetic features of six cases of de novo NECa of the prostate. These findings, if verified in larger cohorts of patients, will provide new insights into the biology and histogenesis of de novo prostatic NECa and may inform future diagnostic and therapeutic strategies.

Spontaneous hemothorax, defined as bleeding into the pleural cavity without trauma or coagulopathy, is rare. Especially, it is uncommon in patients with primary epithelial lung cancer. We report a rare autopsy case of lung adenocarcinoma harboring both an anaplastic lymphoma kinase (ALK) rearrangement and a tumor protein p53 (TP53) mutation, in which hemothorax led to the formation of a giant pleural hematoma.A 75-year-old man with stage IVB lung adenocarcinoma presented with mediastinal and cervical lymph node metastases and right pleural effusion at diagnosis. Molecular testing revealed an ALK rearrangement and a TP53 mutation. He was treated sequentially with alectinib, lorlatinib, and brigatinib. After disease progression and treatment-related complications, he presented to the emergency department with acute dyspnea and a rapid decrease in hemoglobin level. Contrast-enhanced computed tomography showed encapsulated fluid retention with faint high attenuation in the right pleural cavity, and magnetic resonance imaging findings were consistent with a hematoma. Given his poor performance status and the absence of active bleeding on imaging, invasive intervention was not performed. Despite supportive management, he died one week after admission from respiratory failure and hemodynamic deterioration.Autopsy revealed a giant pleural hematoma above the diaphragm, surrounded by pleural metastases. Although no definite source vessel was identified, active bleeding from a metastatic pleural lesion was observed, suggesting persistent tumor-related hemorrhage as the cause of the hemothorax.This case represents an extremely rare presentation of ALK-rearranged lung adenocarcinoma complicated by spontaneous hemothorax. Neither ALK rearrangement nor TP53 mutation has been directly linked to hemothorax, but the aggressive biological behavior associated with this molecular profile may have contributed to the catastrophic pleural bleeding. In lung cancer patients, rapid pleural fluid accumulation with hyperdense imaging findings should raise suspicion for hemothorax.

Tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme of serotonin synthesis in the CNS, has been associated with numerous behavioural traits and psychiatric disorders. Tph2 modified mice present altered sensitivity to stress, and excessively aggressive behaviour that develops even in female animals. We have measured histochemically the activity of cytochrome c oxidase (COX) in 106 brain regions in wildtype, Tph2 heterozygous and total knockout male and female mice (n=78). In addition to direct comparisons by sex and genotype, COX activity co-variation in putative aggression networks was examined. Overall, female mice have higher COX activity than males. In regions affected by Tph2 inactivation a consistent pattern emerged, where Tph2[±] mice had the lowest, Tph2[-/-] mice had the highest COX activities, and Tph2[+/+] in-between. Tph2 inactivation induced broad changes and an extensive reorganisation of neural activity as revealed by regional activity co-variation matrices of COX. These patterns of inter-regional correlations differed between sexes. Co-variation of COX activity also differed between males and females in the proposed networks for aggressiveness. In male mice, Tph2 inactivation disrupted co-variation of COX activity of the dorsal raphe and the periaqueductal grey matter with limbic regions. The septum appears as a hub of altered connectivity in females but not in males. Serotonin deficiency is associated with altered regional neural activity patterns as revealed by COX histochemistry. These alterations are profoundly different in male and female mice, and suggest that serotonin plays a partly sex-dependent role in the regulation of behaviour.

Artificial body tactile stimulation (TS) has been shown to improve fish welfare by reducing aggressive behavior and stress, thereby serving as a sensory enrichment. Here, we tested the effect of TS on aggressive behavior and stress response in the Siamese fighting fish (Betta splendens), an ornamental species reared worldwide and renowned for its high aggressiveness. Twenty isolated male fish were exposed either to TS (provided by a frame with vertical plastic sticks lined with silicone bristles, inserted in the middle of the tank) or to a control treatment (sticks without bristles) for 22 days. Individual aggressive behavior was evaluated before and after the treatment period using mirror tests and staged pair fights. We measured cortisol, brain serotonin (5-HT), and dopamine (DA) to infer stress and possible associations with aggressiveness and the reward system. Although fish actively interacted with the bristles, TS did not alter overt physical fighting but significantly increased frontal and lateral displays. Furthermore, TS elevated cortisol levels, decreased 5-HT, and increased the 5-HIAA/5-HT turnover ratio. DA levels remained unchanged, indicating no activation of neural reward pathways. Contrary to our expectations, TS did not mitigate aggressiveness in this species but rather seemed to prompt an increase in both behavioral and physiological reactivity (cortisol levels and 5-HT activity) to fighting. Our findings indicate that artificial selection for high aggression in B. splendens may alter sensory processing to touch, causing physical contact to act as a stressor rather than an enrichment.

Alveolar rhabdomyosarcoma (RMS), an aggressive pediatric soft tissue cancer, is driven by the oncogenic fusion transcription factor PAX3::FOXO1 (P3F) or PAX7::FOXO1. In a subset of fusion-positive (FP)-RMS cases, amplification of the MIR17HG locus leads to overexpression of the miR-17-92 cluster of microRNAs (miRNAs). However, miR-17-92 is also highly expressed in FP-RMS tumors lacking this amplification, suggesting alternative regulatory mechanisms. Here, we show that P3F and MYCN cooperatively drive miR-17-92 expression in FP-RMS. CRISPR/Cas9-mediated knockout of P3F or MYCN in FP-RMS cell lines substantially reduced miR-17-92 expression. Using a human myoblast line or low P3F FP-RMS variant with inducible P3F or MYCN expression, P3F or MYCN alone induces minimal to low miR-17-92 expression whereas introduction of both MYCN and P3F leads to robust activation of the miR-17-92 cluster and acquisition of oncogenic phenotypes. Chromatin immunoprecipitation sequencing (ChIP-seq) revealed a P3F binding motif located 1.84 Mb upstream of the MIR17HG promoter. CRISPR-mediated deletion of this region in the myoblast system resulted in marked reduction of miR-17-92 expression and impaired oncogenic transformation. Functional inhibition of mature miRNAs of this cluster in FP-RMS cells using miRNA-sponge constructs suppressed proliferation and transformation. In the myoblast model system, transduction studies with exogenous miR-17-92 or miRNA-sponge expression constructs indicated that miR-17-92 is necessary but not sufficient for oncogenic transformation. Implications: These findings establish a cooperative transcriptional axis in FP-RMS involving P3F and MYCN that activates MIR17HG through a distal regulatory element, thereby contributing to oncogenic behavior and uncovering a novel mechanistic vulnerability.

Radiation-induced sarcoma (RIS) is a rare but aggressive long-term complication of radiotherapy. It typically develops within previously irradiated tissues after a prolonged latency period and is associated with poor prognosis because of its locally invasive behavior and high recurrence rates. Breast cancer survivors who receive adjuvant radiotherapy remain at risk for secondary malignancies, including sarcomas arising within the radiation field. We report the case of a 78-year-old woman who developed a progressively enlarging chest wall mass 25 years after mastectomy and adjuvant radiotherapy for breast cancer. Initial clinical and radiological findings raised concern for local recurrence; however, histopathological examination with immunohistochemistry confirmed a high-grade pleomorphic dermal sarcoma arising within the previously irradiated field. The patient initially received gemcitabine and docetaxel chemotherapy, but follow-up fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) demonstrated disease progression. She subsequently underwent extensive chest wall resection with pulmonary resection and prosthetic reconstruction, followed by palliative radiotherapy for metastatic disease. This case highlights the importance of maintaining a high index of suspicion for RIS in patients presenting with new lesions decades after radiotherapy, as early biopsy with histopathological and immunohistochemical evaluation is essential for accurate diagnosis and appropriate management.

Although peer victimization and school refusal tendencies are well documented in early adolescence, the specific within-person directional associations between the two remain underexplored. Employing a three-wave Random Intercept Cross-Lagged Panel Model (RI-CLPM), this study disentangled stable between-person differences from within-person fluctuations in a sample of 510 Chinese early adolescents (53.92% boys; Mage at T1 = 10.30 years, SD = .61), and explored potential gender differences in these processes. Results showed that at the within-person level, peer victimization significantly predicted prospective school refusal tendencies-a directional transmission most prominent during the initial wave interval (T1-T2)-whereas school refusal tendencies did not predict prospective peer victimization. Multi-group analysis indicated no significant gender differences in these cross-lagged associations. These findings highlight the developmentally sensitive role of peer victimization in precipitating school avoidance and emphasize the need for trait-controlled, timely peer interventions.

Objective: To analyze the clinical characteristics of lower urinary tract dysfunction (LUTD) in school-age children, examine their correlation with emotional-behavioral problems, and explore the potential influencing factors for such problems in this population. Methods: This case-control study enrolled 130 LUTD patients aged 6-12 years who were admitted to Shanxi Children's Hospital from June 2024 to October 2025, comprising the LUTD group. A control group of 125 age- and gender-matched children undergoing routine health check-ups at the hospital's outpatient department during the same period was also established. All participants were assessed by using a general information questionnaire, the dysfunctional voiding and incontinence scoring system (DVISS) and the Achenbach Child Behavior Checklist (CBCL) to evaluate lower urinary tract symptoms and emotional-behavioral problems. Independent sample t test, Mann Whitney U or χ[2] test were used for comparison between groups. Multiple linear regression was applied to analyze the risk factors for emotional and behavioral problems in the LUTD group. Spearman rank correlation analysis was used to examine the correlation between emotional and behavioral problems and DVISS scores in the LUTD group. Results: The LUTD group consisted of 72 males and 58 females, with age of (8.5±1.7) years, while the control group included 66 males and 59 females, with age of (8.9±1.7) years. The scores of the total CBCL score, depression, hyperactivity, aggression, boy social problems and schizoid traits were all higher in the LUTD group than in the control group (t=4.78, Z=2.71, 4.76, 3.60, 2.17, 2.10, all P<0.05). Multiple linear regression analysis revealed that low educational level of caregivers, poor academic performance, family conflict and abnormal DVISS score were associated with emotional and behavioral problems in children with LUTD (β=4.99, 5.85, 2.87, 5.75, all P<0.05). In the LUTD group, DVISS scores were all positively correlated with the scores of social withdrawal, hyperactivity, aggression, social problems, obsessive-compulsive symptoms and the total CBCL score (r=0.24, 0.22, 0.21, 0.27, 0.29, 0.51, all P<0.05). Conclusions: School-aged children with LUTD are more likely to develop emotional-behavioral problems than healthy children. These problems are associated with the educational level of caregivers, severity of lower urinary tract symptoms, academic performance, and family relationships.

Sexual aggression (SA) is a major public health concern with serious consequences for victims and significant costs for society. The majority of acts are committed by men from the general population who are rarely prosecuted. The Confluence Model (CM) is one of the most empirically supported frameworks for explaining SA, primarily tested in samples from the United States of America. However, its cross-cultural validity remains understudied. This study aimed to evaluate the explanatory power of the CM in relation to SA perpetrated by Argentinian men without criminal records for sexual offenses. A total of 354 cisgender heterosexual or bisexual men from the general population completed an anonymous online survey. Hierarchical multiple regression and structural equation modeling were used. Results partially replicated the original model: hostile masculinity had a stronger and more consistent association with SA than impersonal sex, which was removed in the most parsimonious model. Childhood victimization, adolescent antisocial behavior, and tolerant attitudes toward violence showed indirect effects. The findings contribute to an assessment of the CM in a Latin America context and underscore the importance of culturally grounded prevention strategies that integrate risk factors proposed by the model. Implications for future research and practice are discussed.

The Displaced Aggression Questionnaire (DAQ) assesses the trait tendency to aggress against innocent targets, following unrelated provocation. In a primary aim, interpersonal concepts and methods and other measures were used to evaluate the construct validity of DAQ subscales (i.e., angry rumination, revenge planning, behavioral displaced aggression). A second aim evaluated the extent to which partialing altered interpersonal and other correlates of the DAQ subscales. A representative online sample of 999 U.S. adults completed the DAQ, interpersonal circumplex measures of trait social behavior and problems, agentic and communal values, negative interpersonal experiences, social support, loneliness, and subjective social status, as well as measures of self-regulatory processes. In Structural Summary Method analyses, DAQ subscales had expected associations with hostile interpersonal style and more severe interpersonal problems. Additional correlations with interpersonal processes and self-regulation generally supported predictions. However, partialing DAQ subscales from each other severely undermined this otherwise supportive evidence of construct validity.