Rhabdoid differentiation has been described in various carcinomas involving different organs and is recognised as a marker of aggressive tumour behaviour. In Renal Cell Carcinoma (RCC), the current grading system of the International Society of Urologic Pathology (ISUP) has given the highest grade IV to renal cell carcinoma with rhabdoid differentiation, signifying the worst prognosis. This article delineates 6 cases of clear cell RCC with rhabdoid differentiation over four years. All patients were male with a median age of 57.5 years. Microscopically, the tumour showed clear cell areas with rhabdoid differentiation occupying 10 to 45% of tumour volume. One of the six cases showed metastasis to the small bowel at the time of presentation, highlighting the aggressive clinical course. Immunohistochemical evaluation of Ki67 labelling index ranging from 25 to 50%. Our study highlights the significance of rhabdoid differentiation in clear cell renal carcinoma, which is seen rarely but indicates aggressive behaviour.

The widespread integration of digital technologies into adolescents' daily lives has raised concerns about potential behavioral correlates, including aggression. Although prior research suggests a relationship between technology use and aggressive behavior, results are mixed and often context-dependent. This study aimed to examine the association between information technology use and aggression among Turkish adolescents. A descriptive cross-sectional study was conducted with 841 adolescents aged 11-14 years recruited from three public secondary schools in southeastern Turkey between February 3, 2025, and February 14, 2025. Data were collected using a sociodemographic questionnaire, the Information Technologies Usage Scale, and the Aggression Scale. Pearson correlation analyses and hierarchical multiple linear regression models were performed to examine associations between technology use and aggression, both before and after controlling for demographic and familial variables. Technology use was positively associated with aggression (r = 0.296, p < 0.001). In regression analyses, information technology use remained a significant predictor of aggression after adjustment for covariates (β = 0.235, p < 0.001), explaining a small proportion of variance. Among technology sub-dimensions, digital game playing and use of technological devices and applications were significantly associated with higher aggression scores, whereas virtual life preference was not. Longer daily technology use was also associated with higher aggression levels. Higher levels of technology engagement, particularly digital gaming and device use, were associated with increased aggression scores among adolescents, although the magnitude of these associations was small. Given the cross-sectional design, causal inferences cannot be drawn. The results highlight the importance of considering both the type and duration of technology use in adolescent behavioral research and underscore the need for longitudinal studies to clarify temporal relationships and underlying mechanisms.

Gut microbiota communities and their multifaceted roles in immune defense and social behavior of the red imported fire ant (Solenopsis invicta).

Behavioral issues, such as persistent or strong estrus, non-specific pain, and performance challenges in mares are frequently attributed to the estrous cycle. The objectives of this study were to analyze retrospective data on mares presented for estrus-related behavioral complaints, and to propose a structured diagnostic framework for categorizing cases during work-up at different levels of care. A retrospective study was conducted using patient records of a total of 14993 mares. In this data set, behavioral problems, pain, or poor performance were not repeatably verified to be associated with estrus in any mare. Most mares (56.8%) presented with persistent or strong estrous behavior were in diestrus at the time of presentation, suggesting misinterpretation of equine behavior. Recurrent colic, non-specific pain, and symptoms related to urination were more common in geldings than in mares. Internal medicine issues were the most common diagnoses, and they were associated with a specific stage of the estrous cycle (diestrus). Aggressive behavior was significantly associated with orthopedic diagnoses. A tiered diagnostic framework was proposed to improve client compliance, diagnostic accuracy, and management strategies, as the association between the stage of the estrous cycle and various behavioral or pain-related symptoms in the mare may be overestimated by both owners and clinicians. In conclusion, the diagnostic approach should include repeated and thorough gynecological examinations with detailed record-keeping to verify the role of the estrous cycle in each clinical case, and internal medicine or orthopedic diagnostics should be pursued as indicated.

Serum p53 antibody (s-p53-Ab) levels increase in patients with various cancer types; however, their clinicopathological relevance in pancreatic ductal adenocarcinoma (PDAC) is not well defined. The present study aimed to assess the prognostic value of s-p53-Ab status in PDAC. The present retrospective study included 124 patients who underwent surgery for PDAC between January 2012 and December 2023. Patients were categorized into s-p53-Ab(+) and s-p53-Ab(-) groups using a cutoff value of 1.3 U/ml. Prognostic significance was examined using univariate and multivariate analyses. A total of 25 patients (20%) were s-p53-Ab-positive. The isolated s-p53-Ab positivity rates in stage I and II disease were 10 and 8%, respectively. The s-p53-Ab(+) group exhibited significantly worse overall survival (P=0.038) and relapse-free survival (P=0.037) than the s-p53-Ab(-) group. Multivariate analysis revealed that s-p53-Ab(+) independently predicted poorer relapse-free survival (P=0.044) and overall survival (P=0.048). s-p53-Ab was occasionally positive in stage I/II PDAC and was associated with more aggressive disease behavior. The present study was registered as a clinical trial in the University Hospital Medical Information Network Clinical Trials Registry (registration number, UMIN000014530; date of registration, 2011/07/11).

Background: High-grade sarcomas harboring PDGFRB hotspot mutations with myogenic differentiation represent a recently characterized and aggressive subset of uterine sarcomas. First described by Dermawan et al, these tumors exhibit distinct morphological, immunophenotypic, and molecular profiles that differentiate them from conventional leiomyosarcomas. To date, only 13 gynecological tumors with this genetic alteration have been reported in the literature. Patient Presentation: We report a 56-year-old female patient who presented with a large uterine tumor with pulmonary metastases. Histological evaluation demonstrated a high-grade spindle cell neoplasm with exclusively myofibroblastic morphology and absence of key leiomyosarcoma morphological features. Immunohistochemistry showed diffuse and strong positivity for H-caldesmon and complete negativity for desmin, smooth muscle actin, myogenin, MYOD1, ALK, estrogen receptor, and progesterone receptor. Next-generation sequencing identified a PDGFRB hotspot in-frame deletion (c.2547_2558del; p.D850_R853del) along with co-occurring mutations in TP53, MED12, NOTCH3, and others. The tumor was clinically staged as FIGO Stage IVB due to lung metastases. The patient passed away 4 months after surgery. Conclusion: This tumor highlighted the importance of recognizing high-grade uterine sarcomas with PDGFRB hotspot mutations as a distinct diagnostic entity. Their aggressive clinical behavior, combined with unique histopathological and genetic features, underscores the need for molecular testing to ensure accurate diagnosis. Tyrosine kinase inhibitors such as imatinib may hold therapeutic promise, but further research is needed to optimize treatment strategies.

The WHO 2019 classification of digestive tract tumors introduced a high-grade (G3) category for well-differentiated neuroendocrine tumors (NETs). These neoplasms appear to have a better prognosis than poorly differentiated neuroendocrine carcinomas (NECs) and may not respond to platinum-based chemotherapy, which is the treatment of choice for NECs, justifying the creation of this new category. Most existing data on G3 NETs are derived from pancreatic neuroendocrine neoplasms, as the majority of G3 neuroendocrine neoplasms (NENs) arise there. G3 NETs are rare at extrapancreatic sites, and their prognosis and behavior are not well studied. We collected and analyzed a multi-institutional cohort of 24 extrapancreatic primary gastrointestinal G3 NETs based on mitotic rate and/or Ki67 index (5 gastric, 13 small bowel, 6 colorectal/anal). Mean Ki67 index was 29.3% (range: 10.5% to 50.2%). Cases generally showed typical well-differentiated NET morphology. Nodal metastases were present in 17/17 (100%) patients; 13/24 (45%) had distant metastases at initial presentation, and 7 patients developed them on follow-up. With a median of 29 months of follow-up, only 2 patients (8%) were alive without disease. Outcomes of G3 NETs were compared with a separate cohort of 125 extrapancreatic G1/G2 gastrointestinal NETs. G3 tumors presented at a higher pT-category stage ( P <0.001) and overall stage ( P =0.002), and patients with G3 disease were more likely to die than those with G1/G2 disease ( P <0.001). Our data show that, like pancreatic G3 NETs, rare extrapancreatic gastrointestinal G3 NETs exhibit aggressive behavior compared with their G1/G2 counterparts (although small bowel NETs tend to recur irrespective of grade). In most cases, the G3 designation is driven by Ki67 index, though exceptions exist, emphasizing the need for reviewing mitotic count in every case.

Environmental temperatures influence most aspects of ectotherm biology, especially when fluctuating on daily and seasonal scales. The Alligator Snapping Turtle (Macrochelys temminckii) is a species of conservation concern inhabiting temperate latitudes in the southeastern United States. To study the effect of temperature and season on the bite performance of M. temminckii, we used a force transducer and high-speed videography to measure bite force and kinematics, including bite duration, jaw velocity and acceleration, and lunge velocity and acceleration, for 21 captive subadult M. temminckii. We also recorded bite behaviors, including willingness to gape and bite, and pre-bite aggressive displays. We conducted trials at 5°C, 15°C, and 25°C, and repeated our measurements in summer and winter. Maximum bite force varied significantly with temperature, albeit not to an extent likely to be biologically relevant. All bite kinematics varied significantly across at least one of the testing temperatures within seasons, with individuals performing maximally at 25°C. Willingness to bite was more affected by temperature than willingness to gape, with subjects requiring more provocation to gape and bite at 5°C than at higher temperatures and displaying fewer pre-bite aggressive behaviors. There was limited evidence of seasonal acclimation in bite kinematics, with higher summer temperatures yielding maximal performance, and measurements at lower temperatures varying little between seasons. Our findings support the need for rigorous standardization of temperature in studies of ectotherm performance and suggest that care must be taken in selecting the time of year in which temperature studies are conducted.

Fragment-based drug design coupled with AI/ML prediction enables identification of novel PARP-1 inhibitors against triple-negative breast cancer.

Odontogenic in origin, ameloblastoma is a benign tumour, characterised by its locally aggressive behaviour and high tendency for recurrence, which necessitates early recognition and meticulous management. The tumour is primarily categorised into three variants, with conventional ameloblastoma being the most common, followed by less frequently encountered forms such as unicystic and peripheral ameloblastomas and the rare entity, adenoid ameloblastoma. These different subtypes present distinct clinical, radiographic and histopathological characteristics, which can pose challenges in diagnosis and management. The present case series (3 males, 2 females) documents multiple variants of ameloblastoma, including the rare entity adenoid ameloblastoma, which was treated with no signs of recurrence on periodic follow-up. The present case series thereby illustrates the diversity of presentations, as each variant exhibits different biological behaviour, surgical considerations and recurrence potential. The present series further emphasises the importance of integrating clinical and radiological findings with histopathological confirmation to establish an accurate diagnosis. The range of treatment options outlined in the literature spans from simple bone curettage to segmental resection with staged reconstruction, thus balancing the need to minimise surgical morbidity, while ensuring a low recurrence rate. The present case series reinforces the significance of comprehensive evaluation and highlights the need for curating individualised treatment strategies to optimise patient outcomes since both conservative and radical surgical approaches have variant-specific implications. Long-term follow-up remains indispensable to monitor for recurrence, which is a persistent concern regardless of the surgical modality.

Machine learning detecting aggression among mood disorder patients visited in psychiatric emergency departments.

Objective: Vulvar and vaginal melanoma are rare gynecologic malignancies with aggressive clinical behavior and poor prognosis. Due to their low incidence and exclusion from most clinical trials, treatment decisions are often extrapolated from cutaneous melanoma data. This study aims to provide real-world insights into the clinical course and outcomes of vulvar and vaginal melanoma in the context of modern systemic therapy. Methods: We retrospectively analyzed 39 patients with vulvar or vaginal melanoma treated at a single tertiary cancer center between 2011 and 2023. Clinical and pathologic data, including tumor site, stage, treatment modalities, and outcomes, were collected. Systemic therapy regimens included anti–PD-1 antibody monotherapy (either pembrolizumab or nivolumab), anti–PD-1 + anti-CTLA4 combination therapy (ipilimumab and nivolumab), and chemotherapy combined with interleukin-2. Progression-free survival and overall survival were evaluated. Results: Patients frequently presented with locally advanced disease. High rates of multifocality, positive margins, and repeated local recurrence were observed, particularly in vulvar primaries. Among those treated for advanced disease (n = 28), combination immunotherapy yielded the most durable responses. Vulvar melanoma was associated with longer progression-free survival and overall survival compared with vaginal melanoma (median progression-free survival: 33 vs. 5 mo, HR = 3.8; median overall survival: 42 vs. 10 mo, HR = 7.8). Conclusions: Vulvar and vaginal melanoma present unique diagnostic and therapeutic challenges in gynecologic oncology. Site-specific prognosis and distinct response patterns to immunotherapy underscore the importance of individualized management strategies and multidisciplinary coordination in this rare population.

Abstract Papillary thyroid carcinoma (PTC), the most prevalent thyroid malignancy, exhibits aggressive behavior in subsets with metastasis. Despite advances in risk stratification, biomarkers predicting metastatic potential remain limited. Here, we identify lactate as a critical driver of PTC metastasis through lactylation of carnitine palmitoyltransferase 1 A (CPT1A), the rate-limiting enzyme in fatty acid β-oxidation (FAO). Multi-omics profiling of 27 paired PTC tissues revealed elevated lactate levels and FAO activation, corroborated by TCGA data. Functional assays demonstrated that exogenous lactate enhances PTC cell migration via CPT1A-dependent FAO. Mechanistically, lactate upregulated CPT1A transcription by promoting histone H3K18 lactylation (H3K18la), simultaneously stabilized CPT1A protein via lactylation of CPT1A at K180/K285 to suppress its ubiquitin-proteasomal degradation. Genetic or pharmacological inhibition of CPT1A abolished lactate-driven migration and FAO activity. In vivo, lactylation-deficient CPT1A mutants (K180R/K285R) attenuated lung metastasis and subcutaneous tumor growth in nude mice. This study reveals that lactate-CPT1A axis synergistically amplifies FAO to fuel PTC progression, suggesting CPT1A lactylation as a therapeutic vulnerability for metabolic intervention.

This study investigates the effectiveness of a structured psychological intervention based on enhancing psychological well-being in reducing aggressive behavior among primary school students in a conflict-affected context. Despite the growing recognition of positive psychology frameworks, limited empirical research has examined their applicability among children exposed to chronic socio-political stressors, particularly in the Gaza Strip. Accordingly, this study aims to evaluate the impact of a well-being-based counseling program on modifying aggressive behavior among fifth-grade male students. A quasi-experimental design was employed using a pre–post–follow-up approach with a control group. The sample consisted of 24 students (aged 10–11 years) selected purposively based on high levels of aggressive behavior and low psychological well-being. Participants were divided equally into experimental and control groups. The intervention comprised a 12-session counseling program integrating self-awareness, emotional expression, social skills, decision-making, and adaptive coping strategies. Data were collected using researcher-developed scales for psychological well-being and aggressive behavior, with established validity and reliability. Statistical analyses were conducted using non-parametric tests, including Mann–Whitney, Wilcoxon, and Friedman tests. The findings revealed a statistically significant reduction in aggressive behavior among the experimental group in the post-test compared to the pre-test, as well as significant differences between the experimental and control groups in favor of the experimental group. Furthermore, results indicated sustained effects of the intervention at follow-up, although partial regression was observed in physical aggression and aggression toward property. These findings highlight the effectiveness of well-being-based interventions in promoting adaptive behavioral outcomes among children in high-stress environments. The study contributes to the literature by providing a context-sensitive model for integrating psychological well-being into behavioral intervention programs and offers practical implications for school-based mental health practices in conflict-affected settings.

This study systematically compared and ranked the effects of different martial arts styles on youth aggression using a network meta-analysis. Data were retrieved from Web of Science, MEDLINE, PsycINFO, SPORTDiscus, PubMed, and the Cochrane Central Register of Controlled Trials up to July 2025. A random-effects model was applied to account for study variability, and study quality was assessed using the NIH Quality Assessment Tool. Results showed that in experimental studies, traditional non-combat martial arts (TNC-MA) significantly reduced aggression compared with inactive controls (standardized mean differences [SMD] = -0.41 [-0.73, -0.10]), with non-contact sports (NC-S) being the second most effective (SMD = -0.41 [-0.73, 0.10]). Multi-style martial arts (MS-MA) and combat-oriented martial arts (CO-MA) showed generally weak or non-significant effects, and contact sports (C-S) had the smallest effect, with occasional slight increases in aggressive tendencies. Similar patterns were observed in observational studies, where participation in TNC-MA (SMD = -0.63 [-0.88, -0.39]) and NC-S (SMD = -0.60 [-0.91, -0.29]) was associated with lower aggression levels. MS-MA and CO-MA showed weaker or non-significant associations, and C-S had the smallest association. Subgroup analyses suggested that individuals older than 12 years exhibited lower aggression levels. In conclusion, TNC-MA and NC-S showed the most consistent evidence for reducing aggression in experimental studies and for being associated with lower aggression in observational studies, whereas CO-MA, MS-MA, and C-S showed weaker or non-significant effects across both study designs. These findings highlight the value of non-competitive programs that foster mental discipline to mitigate aggression and support positive psychosocial development.

Aggression may be behaviorally distinguished by reactive or appetitive properties. Here, we use a model of operant aggression administration, in which outbred male CD-1 mice lever press (contingent) or do not lever press (non-contingent) to attack an intruder mouse, to examine behavioral differences in aggression reinforcement. Contingent reinforcement identifies the behavioral and neural basis of appetitive, or rewarding, aggression self-administration, while non-contingent reinforcement isolates reactive, or involuntary, components. Females are not used in this study due to their low propensity to attack. We applied supervised machine-guided behavioral classification and Shapley additive scores (SHAP) to describe differences and similarities in attack behavior features. We find that behavioral sequences of an attack bout are similar whether aggression reinforcement is contingent or non-contingent, though underlying neural mechanisms differ. Fos immunolabeling following operant reinforcement reveals distinct network activity patterns between contingent and non-contingent groups, supporting distinct neural mechanisms in appetitive or reactive aggression. We further identify high Fos activity in nucleus accumbens in both contingent and non-contingent groups. Nucleus accumbens (NAc) activity and changes in NAc neuroligin-2 (NLGN2) expression are associated with aggressive behavior. We find that the number of attack bouts is negatively correlated with NAc NLGN2 immunolabeling, regardless of contingent or non-contingent intruder presentation. As a result, molecularly dissociable features do not necessarily reflect operant behavioral repertoires.Significance Statement: Aggressive behavior presents for different reasons, and two important clinical presentations include appetitive (sought after) and reactive (fight or flight) aggression. Understanding how these phenotypes differ in their behavioral and neural signatures is essential for identifying mechanisms at the intersection of neuropsychiatric disease and maladaptive aggression. Using an operant model in outbred male CD-1 mice, we combined explainable machine learning and forebrain Fos mapping to compare contingent (appetitive) and non-contingent (reactive) aggression. We find that, although behavioral repertoires are notably similar across contingency contexts, neural activity and nucleus accumbens neuroligin-2 expression distinguish aggression severity and phenotype. These findings reveal that molecular features can diverge from behavior, providing new insight into the neurobiology of contingent and non-contingent aggression.

Medulloblastoma (MB) is the most common childhood brain cancer, with Group 3 (G3) as the most aggressive subgroup, being prone to relapse and treatment resistance. A small subset of stem-like cells contributes to this recurrence, but the mechanisms behind their transformation are not fully understood. In this study, we employed therapeutically relevant in vitro and in vivo chemoradiotherapy (CRT) models of G3 MB and discovered a significant activation of SRC kinase following CRT treatment, while other kinases such as AKT and ERK were unaffected. Remarkably, SRC activation was exclusive to G3 MB cells and was absent in the less aggressive Sonic Hedgehog and Group 4 MB, as well as in normal brain cells. SRC activation in CRT-treated G3 MB cell and tumors corresponded with increased stemness, as evidenced by elevated levels of stemness factors SOX2, NOTCH1, OCT4, Nanog and phosphorylated STAT3, alongside a reduction in the differentiation marker βIII-tubulin/TUBB3. Conversely, SRC knockout or pharmacological inhibition promoted differentiation and reduced aggressiveness in CRT-resistant G3 MB cells, which could be rescued by re-expression of SRC in SRC knockout cells. Additionally, SRC inhibition significantly reduced the viability of CRT-treated G3 MB cells by inducing both apoptosis and necroptosis, while sparing the proliferation and stem-like properties of normal neural stem cells, indicating a promising toxicity profile. Importantly, in a therapeutically relevant orthotopic G3 MB model, administration of the re-purposed blood-brain-barrier permeable SRC inhibitor, Saracatinib, in conjunction with CRT, significantly reduced tumor burden and improved animal survival compared to CRT treatment alone without any neurotoxic side effects. Overall, our results underscore the pivotal role of SRC in enhancing stemness and aggressive behavior in CRT-resistant recurrent G3 MB. Targeting SRC not only promotes cell death through apoptosis and necroptosis but also encourages differentiation, positioning it as a promising therapeutic target for rapid clinical interventions.

Introduction. Basal cell carcinoma is the most common malignant cutaneous neoplasm and accounts for most non-melanoma skin cancers. Despite its low metastatic potential, it may exhibit locally aggressive behavior, particularly in high-risk anatomical regions such as the nose and in aggressive histological subtypes, including the micronodular variant. Involvement of the nasal ala represents a significant therapeutic challenge, as management must integrate the principles of complete oncologic resection with optimal functional and aesthetic reconstruction. In this context, local flaps represent a valuable reconstructive option, and the bilobed flap remains a reliable technique for small to medium-sized nasal defects due to its versatility, favorable tissue match, and ability to achieve reconstruction in a single surgical stage. Objective. To describe the diagnostic approach, surgical management, and immediate reconstruction of a micronodular basal cell carcinoma located on the left nasal ala, as well as to highlight the utility of the bilobed flap as a reconstructive option for nasal defects following oncologic resection. Materials and Methods. A 54-year-old female patient is presented, with a history of systemic arterial hypertension, chronic occasional tobacco use, and prior superficial parotidectomy for benign disease, who presented with a dermal lesion on the left nasal ala of one year’s duration with progressive growth. On physical examination, a nodular lesion measuring approximately 1 cm was identified, with poorly defined borders, pigmentation, and central ulceration, without evidence of deep tissue invasion. An incisional biopsy was performed on October 10, 2025, yielding a histopathological diagnosis of ulcerated, pigmented micronodular basal cell carcinoma. Given the high-risk histological subtype and the anatomical location, surgical treatment was indicated. A wide three-dimensional excision with 1 cm safety margins was performed, followed by immediate reconstruction using a bilobed flap designed according to nasal subunit principles. The procedure was completed without complications, and the flap demonstrated adequate viability in the immediate postoperative period. Results. During the surgical procedure, an exophytic nodular lesion measuring approximately 1 cm in diameter was identified on the left nasal ala. A wide three-dimensional excision was performed, with adequate circumferential and deep margins to ensure optimal oncologic control. The resulting defect was immediately reconstructed using a bilobed flap, allowing coverage with local tissue of similar characteristics, appropriate redistribution of tension, and preservation of the nasal contour. In the immediate postoperative period, the patient remained hemodynamically stable, with a Glasgow Coma Scale score of 15, fully oriented, without evidence of active bleeding, and with adequate flap viability, with no immediate complications. Conclusions. Micronodular basal cell carcinoma located on the nasal ala represents a high-risk entity due to both its anatomical location and its infiltrative histological pattern, requiring a surgical approach with strict adherence to oncologic principles. Wide three-dimensional excision followed by immediate reconstruction using a bilobed flap constitutes a safe and effective option in selected cases, as it allows adequate tumor control while achieving functional and aesthetic restoration in a single surgical stage. In this context, the bilobed flap remains a valuable reconstructive tool in facial plastic surgery, particularly for small to medium-sized defects of the distal nasal third.

This longitudinal study investigates the bidirectional relationship between personal values and aggressive behavior among immigrant adolescents from the Former Soviet Union residing in Israel. Using a 4-wave cross-lagged latent difference score modeling approach over 2 years, we examined the reciprocal associations between personal values and aggressive behaviors over time. The sample included 180 adolescents (mean age = 14.36 years, SD = 1.35; 44.5% girls) and their primary caregivers, with youth reporting on personal values and both youth and parents reporting on adolescent aggression. Separate models were estimated for youth- and parent-reported youth aggression. Our findings indicated that immigrant youth aggression predicted changes in personal values over time, but not vice versa. For youth-reported models, adolescents' aggressive behavior predicted increases in self-enhancement and openness to change values and decreases in self-transcendence and conservation values. For parent-reported models, youth aggressive behavior predicted increases in youth self-enhancement values over time. These results highlight the asymmetry in the value-behavior dynamic during adolescence, particularly as immigrant youth navigate and integrate into a new socio-cultural environment. Our findings highlight the role of behavioral adaptation in shaping value systems during adolescence, offering insights into mechanisms underlying immigrant youth adjustment. Our findings emphasize the importance of targeting aggressive behaviors in interventions to foster adaptive values and enhance social integration.

Tumours harbouring FET::CREB fusions, particularly those involving EWSR1/FUS and CREM, represent an emerging group that is distinct from and unclassifiable into established categories such as angiomatoid fibrous histiocytoma, clear cell sarcoma of soft tissue, or malignant gastrointestinal neuroectodermal tumour. This study aims to further delineate the clinicopathological, immunohistochemical, and molecular features of these rare mesenchymal neoplasms with EWSR1/FUS::CREM fusions, focusing on diagnostic challenges and aggressive potential. We analysed seven cases of mesenchymal neoplasms with EWSR1/FUS::CREM fusions through detailed clinicopathological evaluation, extensive immunohistochemical profiling, and molecular genetic analysis [RNA sequencing and fluorescence in situ hybridization (FISH)]. The cohort included five females and two males (age range: 5-55 years) with tumours involving diverse intra-abdominal and extra-abdominal locations. Histologically, all tumours were composed predominantly of monomorphic epithelioid to round cells, with one case showing focal spindling. The neoplastic cells were arranged in solid sheets, nests, and trabeculae, set within a variably collagenous stroma. Mitotic activity was variable, and tumour necrosis was present in two cases. A prominent lymphoplasmacytic infiltrate was noted in three cases. Immunohistochemistry revealed a strikingly heterogeneous profile, which directly led to a wide spectrum of initial misdiagnoses. These included: epithelial malignant mesothelioma in two intra-abdominal tumours co-expressing AE1/AE3 and WT1; Ewing sarcoma in one CD99-positive tumour; a sex cord-stromal tumour in one ovarian neoplasm co-expressing S100, SOX10, and α-inhibin; epithelioid hemangioendothelioma in one case co-expressing CD34 and ERG; a neurogenic tumour in one case with synaptophysin expression; and metastatic carcinoma in a lymph node in one case, which was misdiagnosed due to diffuse expression of AE1/AE3 and a dense lymphoplasmacytic infiltrate mimicking a nodal metastasis. Molecular analysis via targeted RNA sequencing identified in-frame EWSR1::CREM fusions in five cases and a FUS::CREM fusion in two cases, all of which were confirmed by FISH. Clinically, two patients presented with disseminated disease, and all three with follow-up had aggressive courses (recurrence or metastasis). Our series solidifies epithelioid mesenchymal neoplasms with EWSR1/FUS::CREM fusions, which constitute a distinct sarcoma characterized by a misleading immunophenotype, with potential for aggressive clinical behaviour. Accurate diagnosis requires molecular confirmation to avoid diagnostic pitfalls and guide management.