Frailty and the brain: A narrative review of functional and pathological correlates.

Feasibility and Effectiveness of Yttrium-90 Radioembolization in Normal Lung Parenchyma: A Preclinical Study in Rabbits with Pathological Correlation to Absorbed Dose.

Psychiatric disorders such as schizophrenia, bipolar disorder, major depression, and dementia are increasingly associated with specific ocular and retinal abnormalities. These associations may reflect shared neurovascular, inflammatory, and neurodegenerative mechanisms, yet findings remain scattered and understudied. This systematic review synthesizes existing evidence on ocular and retinal pathologies across major psychiatric conditions, highlighting common retinal biomarkers that may inform future screening strategies. Following PRISMA 2020 guidelines, a systematic search of PubMed, Scopus, Web of Science, and Embase was conducted. Meta-analysis was initially planned but deemed infeasible due to significant methodological and reporting heterogeneity among eligible studies. Therefore, a structured qualitative synthesis was performed, supported by visual mapping of cross-disorder associations. Seventeen studies met inclusion criteria, covering major psychiatric conditions including schizophrenia, bipolar disorder, depression, and dementia. Across these disorders, approximately three-quarters of schizophrenia studies (≈75%) reported retinal nerve fiber layer (RNFL) thinning, and two-thirds of dementia studies (≈67%) showed retinal vascular abnormalities or RNFL loss. Glaucoma and dry eye syndrome were the most frequently observed in mood disorders, whereas microvascular dropout was reported in optical coherence tomography angiography (OCT-A) analyses of depression and bipolar disorder. The heatmap visualization highlighted overlapping neuro-ophthalmic signatures, and retinal biomarker analysis identified RNFL thinning and microvascular dropout as potential shared indicators of disease burden. This review emphasizes the emerging evidence for retinal biomarkers as accessible correlates of neuropsychiatric pathology. Although quantitative synthesis was not feasible, the qualitative patterns highlight the need for large-scale, prospective, and biomarker-validation studies integrating ophthalmology and psychiatry. These findings underscore the clinical potential of the brain-retina axis in mental health diagnostics.

We present a case of incidental PSMA uptake in the mid-esophagus on 99mTc-HYNIC-PSMA SPECT/CT in a 67-year-old man undergoing staging for high-grade prostate adenocarcinoma. While uptake in the prostate lesion was expected, unexpected focal avidity was noted in the esophagus. Given the rarity of esophageal metastases from prostate cancer, further evaluation was performed. Contrast-enhanced CT showed esophageal fluid levels, and endoscopy revealed linear ulcers in distal esophagus. Biopsy confirmed mild reflux esophagitis. This case underscores the potential for benign esophageal inflammation to mimic metastatic disease on PSMA imaging. Accurate interpretation requires careful clinical and pathologic correlation to avoid misdiagnosis.

Atypical ductal hyperplasia (ADH) carries a variable risk of upgrade at the time of surgery to ductal carcinoma in situ (DCIS) or invasive malignancy. We sought to externally validate a pragmatic upgrade risk scoring system previously demonstrated to have an upgrade rate of 0-2% in patients with a risk score of 0 out of 5. A multicenter, retrospective review of all percutaneous biopsies containing ADH was performed from 2017 to 2023. Women aged ≥ 18years who underwent diagnostic mammography and surgical excision for pathologic correlation were included. Among the 183 cases included, the mean age was 58years ± standard deviation 11, and 91 patients (50%) reported a family history of breast cancer. Most biopsies were stereotactic (75%), vacuum-assisted (84%), and used 9-gauge needles (73%). Three of 14 (21%) patients with a risk score of 0 were upgraded to DCIS following surgical excision. Seven (19%) patients had a risk score of 1 upgraded - six to DCIS and one to an estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative invasive ductal carcinoma measuring 5.45mm in largest diameter. On multivariate analysis, age, mammographic lesion size, and suspicion of DCIS on biopsy were predictive of upgrade. The risk model evaluated generally predicts the risk of upgrade of ADH at excisional biopsy but may underestimate the upgrade rate in the lowest-risk cohort. Because of the small sample size, further work is needed to determine whether the rate of upgrade is truly low enough in this lowest-risk cohort to recommend against excisional biopsy.

Proper treatment of intra-articular tumor/tumor-like lesions (tenosynovial giant cell tumor, synovial chondromatosis, synovial hemangioma / intra-articular venous malformations, lipoma arborescens, etc.) depends on an accurate diagnosis. This review highlights the imaging findings of intra-articular tumor/tumor-like lesions and the other synovial diseases (gout, amyloid arthropathy, rheumatoid arthritis, ganglion, and postoperative intra-articular tumor) to determine whether they could help in establishing the correct diagnosis. Many synovial proliferative diseases have specific imaging characteristics and an awareness of these characteristics along with their pathological and anatomical features can allow for an accurate diagnosis. Even though a wide spectrum of diseases may involve the synovium, careful MRI assessment used in conjunction with clinical information can lead to a substantial narrowing of the differential diagnosis.

This study aims to analyze and compare the clinical and pathological characteristics of anorectal malignant melanoma (AMM) among Chinese patients and those from East Asia. Clinical data of 17 AMM patients who were treated at Jiangsu Province Hospital (JPH) in China from 2013 to 2023 were collected, and further compared with 544 East Asia AMM patients reported in 20 literature materials from 2011 to 2023. Furthermore, the 4-fold table of the Pearson Chi-square test was used to calculate and compare the pathological characteristics of AMM patients in JPH and East Asia. Fisher exact probability was performed to statistically analyze the relationship between clinical–pathological indicators and lymphatic metastasis in AMM patients in JPH. The median age of initial diagnosis for AMM patients in JPH and East Asia were 69 years and 61.4 years, respectively. Several medical indicators are similar between the JPH and East Asian patients, and the differences are not statistically significant (P > .05), including gender, S-100 Protein, Human Melanoma Black 45, Ki-67, tumor size, lymphatic metastasis, and surgical approach. Moreover, indicators showed differences (P < .05) are tumor location, Melanoma Antigen Recognized by T cells 1, depth of invasion, clinical stage, and adjuvant therapy. In AMM patients in JPH, lymphatic metastasis is significantly correlated with tumor size and depth of invasion (P = .017 and .004, respectively). In AMM patients from JPH, lymphatic metastasis is significantly correlated with tumor size and depth of invasion. More indicators are similar between AMM patients in JPH and East Asia populations, such as gender, S-100 Protein, Human Melanoma Black 45, Ki-67, tumor size, lymphatic metastasis, and surgical approach, while less indicators have differences.

Objectives: Spinal cord injury (SCI) disrupts the microstructure of the spinal cord, triggers reorganization of the brain network, and causes motor deficits. However, the temporal dynamics and interrelationships of these alterations remain unclear. Methods: Eight monkeys underwent spinal cord hemisection and were randomly assigned to either the SCI-only group or the treatment group that received neurotrophin-3-chitosan implants. Longitudinal brain structural/resting-state magnetic resonance imaging and spinal cord diffusion tensor imaging (DTI) were conducted. Concurrently, hindlimb motor function was assessed. The brain network topology was characterized through graph theory. The generalized additive mixed model (GAMM) was employed to analyze the longitudinal trajectories of network metrics, while the linear mixed-effects model (LMM) was used to evaluate the moderating effect of treatment on correlations between network metrics and motor/DTI parameters. Results: The SCI-only group exhibited sustained functional network segregation, aberrant structural topology, and lower fractional anisotropy (FA). These findings collectively reflect chronic maladaptive plasticity. In the treatment group, the therapy not only enhanced white matter integrity, reflected by increased FA values, but also reduced the clustering coefficient (Cp) in brain structural network, indicating a shift away from maladaptive segregation. Critically, the LMMs further revealed that treatment moderated the pathological correlations between global efficiency (Eg), local efficiency, Cp, and locomotor parameters. Moreover, spinal FA exerted a significant main effect on Eg of brain functional networks. Conclusions: These findings suggest that treatment-induced brain reorganization underlies motor function following SCI, and progressive brain reorganization correlates with changes in spinal cord microstructure, revealing a systems-level mechanism of neural repair.

Research Background: Bronchial cysts are congenital disorders resulting from abnormal embryonic development of the trachea and bronchi, leading to ectopic formation. Clinical symptoms are often subtle, but as the cysts enlarge, they may compress adjacent tissues and organs, causing symptoms. Surgical resection is the preferred treatment method. Objective: To summarize the clinical features, imaging manifestations and surgical treatment experience of posterior mediastinal bronchial cyst. Methods: By summarizing and analyzing the case data and reviewing the literature, we summarize one case of infected bronchial cyst of the posterior mediastinum treated by thoracoscopy in our department. Results: Infected thick-walled bronchial cysts, due to prolonged inflammatory stimulation, exhibit tight adhesions between the cyst wall and surrounding tissues such as the esophagus and bronchi. Complete surgical resection is challenging, and dissection may cause esophageal rupture. Segmented resection offers a safe and feasible approach. Conclusion: Posterior mediastinal bronchial cyst is a relatively common benign disease, but infected thick-walled cystic lesions are relatively rare, and surgical resection needs to pay attention to the anatomical relationship of the cyst wall with the esophagus and pericardium.

Primary lung cancer encompasses heterogeneous histopathological subtypes with distinct clinical and radiological features. Accurate correlation of CT patterns with histology can improve diagnostic assessment and contribute to earlier recognition of aggressive tumor behavior. A retrospective study was conducted on 33 patients (25 males, 8 females; mean age 67.3 years) with histologically confirmed primary lung cancer. Demographic factors, smoking history, histological subtype, and CT characteristics—including lesion size, lobar and segmental distribution, necrosis, and metastatic spread—were analyzed. Radiological staging was performed according to the TNM system, and findings were correlated with histopathology. Results: Histology: Adenocarcinoma was the most frequent subtype (51.5%), followed by squamous cell carcinoma (27.3%), with fewer cases of large cell, small cell, mixed, and plano-cellular carcinomas. Adenocarcinoma predominated in both smokers and non-smokers, whereas squamous carcinoma was more frequent among smokers. Tumor size and location: Mean lesion diameter was 5.9 cm (range: 1.5–13 cm). The most common sites were the right lower lobe (33.3%) and right upper lobe (30.3%), particularly in posterior basal and posterior segments. Necrosis: Present in 54.5% of tumors, necrosis was more frequent in squamous carcinomas (44.4%) compared with adenocarcinomas (33.3%), while adenocarcinomas were more often necrosis-free (75%). Metastases: Distant spread occurred in 27.3% of patients, predominantly to adrenal glands (44.4%) and brain (22.2%), with additional involvement of liver (11.1%) and lymph nodes/contralateral lung (55.6%). Adenocarcinoma accounted for two-thirds of metastatic cases. Staging: Advanced disease predominated, with stage IIIB (27.3%) and stage IVA (18.2%) most frequent. Only 24.2% of patients were diagnosed at early operable stages (IA–IIB). CT–pathology correlation demonstrated that adenocarcinoma is the predominant subtype across smoking categories, whereas squamous carcinoma more frequently exhibited necrosis. Most patients presented with large tumors and advanced disease, with metastases reflecting typical spread patterns. These findings underscore the diagnostic value of CT in characterizing histological subtypes, staging, and guiding clinical management, while reinforcing the need for earlier detection and screening strategies.

Objectives: Pancreatic cystic lesions (PCLs) are increasingly detected due to the widespread use of imaging techniques. The identification of pancreatic mucinous cysts is especially important since these carry a risk of malignant transformation and require follow-up or surgical resection. The aim of this study was to determine the diagnostic yield of the molecular analysis of K-RAS (Kirsten RAt Sarcoma virus) and GNAS (Guanine Nucleotide-binding protein, Alpha Stimulating protein activity) gene mutations in pancreatic cyst fluid (PCF) obtained by endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA). Methods: In this prospective trial, we assessed the sensitivity, specificity, and positive and negative predictive values of K-RAS and GNAS mutation analysis in differentiating mucinous versus non-mucinous cysts and the subsequent impact on decision-making in daily clinical practice. The reference standard used comprised the combination of morphology on cross-sectional imaging and EUS, string sign, cyst fluid cytology, intracystic carcinoembryonic antigen (CEA), and glucose levels, with subsequent correlation of surgical pathology in resected cases. Fluid samples of 47 cysts obtained by EUS-FNA over a 39-month period were analyzed. Mutation analysis of KRAS (exon 2) was performed in all cases, and additionally, GNAS (exon 8) in 28 cases using Sanger sequencing. Results: 33 out of 47 PCLs were classified as mucinous cysts and 14 as non-mucinous cysts defined using conventional standards, including morphological characteristics, string-sign, cytology, cyst fluid testing, and histology in resected cases. Of these 33 mucinous cysts, KRAS mutation was detected in 14 samples. A further 23 mucinous lesions were additionally tested for GNAS mutation, which was detected in 10 of the 23 cysts. A 42.4% sensitivity for KRAS and 43.5% for GNAS mutation analysis was calculated, with a specificity of 92.9% and 100%, respectively, for detecting mucinous lesions. The clinical management was altered through the genetic testing results in one single case. Conclusions: In this cohort, K-RAS and GNAS mutational analysis in cyst fluid did not improve the detection of mucinous pancreatic cysts significantly after conventional testing. However, the method may be useful due to its high specificity in uncertain cases.

BackgroundPathogenic tau accumulation drives neurodegeneration in Alzheimer’s disease (AD). Enhancing the aging brain’s resilience to tau pathology would lead to novel therapeutic strategies. DAP12 (DNAX-activation protein 12), highly and selectively expressed by microglia, plays a crucial role in microglial immune responses. Previous studies have shown that tauopathy mice lacking DAP12 exhibit higher tau pathology but are protected from tau pathology-induced cognitive deficits. However, the exact mechanism behind this resilience remains elusive.MethodsWe investigated the effects of DAP12 deletion on tau pathology, as well as tau-induced brain inflammation and neurodegeneration, in homozygous human Tau P301S transgenic mice. In addition, we conducted single-nucleus RNA sequencing of hippocampal tissues to examine cell type-specific transcriptomic changes at the single-cell level. Furthermore, we utilized the CellChat package to profile cell-cell communication in the mouse brain and investigated how these interactions are affected by tau pathology and Dap12 deletion.ResultsWe demonstrated that Dap12 deletion reduced tau processing in primary microglia and increased tau pathology in female tauopathy mice, with minimal effects on males. Despite this, Dap12 deletion markedly reduced brain inflammation, synapse loss, and demyelination, indicating enhanced resilience to tau toxicity. Single-cell transcriptomic profiling revealed that Dap12 deletion blocked tau-induced alterations in microglia, neurons, and oligodendrocytes. CellChat analysis identified aberrant tau-induced SLIT2 signaling from excitatory neurons to oligodendrocytes. Dap12 deletion suppressed Slit2 upregulation and mitigated demyelination, while lentiviral-Slit2 overexpression induced myelin loss in tauopathy mice. Elevated SLIT2 levels were associated with demyelination in tauopathy mouse model and human AD brains. Spatial transcriptomics revealed a spatial correlation of SLIT2 expression and tau pathology in AD brain tissue.ConclusionsOur study identifies a novel DAP12-dependent mechanistic link between upregulated Slit2 expression in excitatory neurons and oligodendrocyte-dependent myelination loss in tauopathy. Despite elevating tau load, the absence of microglial Dap12 ameliorates neuroinflammation and improves brain functions in tauopathy mice. Our study suggests that selectively targeting the toxic aspects of DAP12 signaling while preserving its beneficial functions may be a promising strategy to enhance brain resilience in AD.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13024-025-00903-3.

To analyze the experience at our institutions with liposclerosing myxofibrous tumor (LSMFT) regarding radiographic reporting, pathologic correlation, and follow-up for malignant transformation. A retrospective search of imaging and pathology databases at two tertiary institutions (1987-2022) identified cases with LSMFT in the diagnosis or differential diagnosis. Clinical records, imaging reports, and follow-up data were reviewed. Two fellowship-trained musculoskeletal radiologists independently assessed imaging features and two bone tumor pathologists independently reviewed the pathology findings. Among over 11 million imaging reports, 149 cases included LSMFT in the imaging report differential diagnosis, with pathologic correlation available in 18 patients (8 men, 10 women; median age 41.9years [range, 16.5-68.3years]). All patients presented with hip pain. Radiography was performed in all 18 cases, CT in 7 cases, and MRI in 15 cases. On imaging, lesions appeared well-defined with a sclerotic margin (14/18) and were most commonly central (14/18) and intertrochanteric (16/18) in location. Mean diameter was 5.9cm in greatest dimension (range, 3.2-11.5cm). Histopathology revealed low-grade benign neoplastic and non-neoplastic lesions in all cases, most commonly fibrous dysplasia (9/18). Two out of 18 cases were found with LSMFT in the pathology report impression. No malignant transformations were observed on follow-up. When radiography shows findings described as possible LSMFT, the pathology diagnosis generally corresponds to other benign lesions. No malignant transformations were observed in our cohort. In the absence of symptoms or aggressive imaging features, we do not routinely pursue surveillance cross-sectional imaging, biopsy, or surgical management.

Imaging and pathology correlation in schwannomatosis: insights from a case series

Background: Preoperative timelines may lengthen due to tailored evaluation and system constraints. We examined whether two complementary measures of time-to-surgery (TTS)—admission-to-surgery (A-TTS) and biopsy-result-to-surgery (B-TTS)—behave similarly and whether parallel tracking offers service value. Methods: In a single-center retrospective cohort of eligible women undergoing upfront surgery for invasive breast cancer (2010–2021; n = 167), we reported quality indicators for timeliness (target attainment, agreement and discordance, the interval gap, and the surgery-to-adjuvant interval), while analyzing recurrence as the primary endpoint and overall survival as secondary. Discrimination analyses, logistic regression, and Cox models were used; non-proportional hazards were handled with a log–time interaction centered at 24 months. Results: The two time measures were not interchangeable: discordant cases were frequent and pointed to different bottlenecks. A-TTS ≤ 24 days was independently associated with recurrence (OR 3.16; 95% CI 1.13–8.82) and showed a large early hazard for death at 24 months that attenuated over time (HR 22.83; 95% CI 6.44–80.98; interaction HR 0.06; 95% CI 0.02–0.21), whereas B-TTS showed no association. Conclusions: Lymphovascular invasion remained the strongest pathologic correlate of survival. Tracking both intervals, paired with brief, reason-coded reviews of discordant cases, may support scheduling, quality dashboards, and breach governance better than a single TTS metric.

The adrenal gland integrates stress, metabolic, immune, and circadian signals to safeguard organismal homeostasis, yet its aging biology has been comparatively overlooked. Converging evidence from recent primate single-nucleus atlases, functional perturbations in human adrenal cells, human pathology, and multi-organ proteome aging resources reveals a coherent mechanistic picture: adrenal aging is region-specific, substrate-limited, and constrained by proteostasis, characterized by decline of dehydroepiandrosterone sulfate (DHEA-S) and aldosterone, while preserved cortisol output on average with diurnal flattening and higher prevalence of autonomous cortisol secretion with ageing. These endocrine trajectories implicate heightened vulnerability of the zona reticularis (ZR) and zona glomerulosa (ZG) versus the zona fasciculata (ZF). At the cellular level, ZR cells exhibit senescence, immune activation, and lipid metabolic disruption, including downregulation of androgen sulfation. Broad reduction of LDLR across cortex limits cholesterol import reduces DHEA-S, linking substrate scarcity to endocrine decline. Proteostatic lesions including aggresomes, amyloid, and lipofuscin accumulate across zones, aligning adrenal changes with systems-level proteome aging and vascular susceptibility. Key pathological correlates like ZR thinning, accumulation of aldosterone-producing cell clusters (APCCs), and higher prevalence of adrenal tumors underscore an age-biased remodeling of zonal identity and control hierarchies. Developmental and sex-dimorphic programs, including WNT/FRZB signaling and extracellular matrix remodeling, likely preconfigure later-life vulnerability. In this perspective, we synthesize these advances into a mechanistic model connecting centripetal differentiation, cholesterol trafficking, proteostasis collapse, inflammaging, and vascular aging to endocrine dysfunction and highlight biomarker strategies to index "adrenal age". We also outline near-term clinical deployment opportunities in older adults with adrenal incidentalomas or frailty using combined hormonal and plasma proteomic readouts, supported by human multi-organ proteomic evidence of proteostasis and vascular aging, aiming to restore cholesterol handling, reinforce proteostasis, and modulate senescence and niche signals.

To compare MRI and contrast-enhanced CT in assessing neoadjuvant therapy (NAT) response for locally advanced esophageal squamous cell carcinoma (ESCC). In this prospective single-center study (July 2019-August 2024), 122 ESCC patients (cT2-T4a/N0-N3/M0; mean age 63.2 ± 7.0 years; 95 male) underwent pre-/post-NAT MRI and contrast-enhanced CT before esophagectomy. Two blinded radiologists independently evaluated treatment response on CT and MRI images using Response Evaluation Criteria in Solid Tumors (RECIST) and MR tumor regression grade (mrTRG). Postoperative pathologic TRG (pTRG) served as the reference standard. Categories included pathological complete response (pCR: pTRG0, n = 32) vs non-pCR (pTRG1-3, n = 90), and pathological good response (pGR: pTRG0-1, n = 48) vs non-pGR (pTRG2-3, n = 74). Imaging assessments were compared with pathological findings using χ2 test and Cohen's kappa value. CT demonstrated accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 63.9%, 25.0%, 77.8%, 28.6%, and 77.8%, respectively, in differentiating CR from non-CR, while MRI showed superior performance with respective values of 93.4%, 90.6%, 94.4%, 85.3%, and 96.6%. Cohen's kappa coefficient revealed high concordance between MRI findings and postoperative pathology in CR evaluation (κ = 0.834, p < 0.001), whereas CT showed no statistically significant agreement (κ = 0.029, p = 0.748). mrTRG had excellent correlation with pTRG (κ = 0.917 for CR/non-CR; κ = 0.710 for GR/non-GR, p < 0.001). MRI outperformed CT in post-NAT response evaluation using RECIST for locally advanced ESCC. The mrTRG system enables precise TRG stratification, suggesting MRI as the preferred imaging modality for RECIST implementation in ESCC management. Question Can RECIST be applied to CT or MRI, accurately assess NAT response in locally advanced ESCC, and which modality demonstrates superior performance? Findings MRI surpassed CT in discriminating complete response (CR) from non-CR using RECIST and provided a mrTRG system. Clinical relevance MRI-based RECIST evaluation, combined with the mrTRG, enables precise risk stratification and personalized treatment planning for locally advanced ESCC, with better clinical utility and pathological correlation compared to CT-based measurements.

Peri-implantitis is a common complication after dental implant restoration, and its occurrence is closely related to the dynamic evolution of plaque biofilm on the surface of implants. This article systematically reviews the formation mechanism and influencing factors of plaque biofilm and its pathological correlation with peri-implantitis. Studies have shown that implant surface roughness, material properties, and host immune status jointly regulate the composition and virulence of plaque biofilms. Excessive proliferation of Gram-negative anaerobic bacteria leads to inflammation and bone resorption by releasing virulence factors. Future research should focus on surface modification technology and the development of personalized maintenance strategies to reduce the risk of peri-implantitis.

Limited literature exists on the extent of eating concerns among adolescents. This study examines the extent of eating disorder pathology and psychosocial correlates among 11- to 18-year-olds. School pupils (N=382; 52% female; 72.8% Caucasian) provided demographic information and completed measures of eating disorder pathology (using a cut-off of > 3.64 on the seven-item Eating Disorders Examination-Questionnaire), psychosocial impairment, body shape dissatisfaction and mood. Levels of comorbid problems were compared across adolescents with low- and high-risk for eating disorders, using Mann-Whitney tests and Chi-squared tests and an alpha of 0.001 (to account for exploratory analyses). A fifth (20.7%) of pupils exhibited clinical levels of eating disorder pathology, and they scored significantly worse on the other measures of psychopathology than those without such eating concerns. The majority (89.9%) of pupils with eating disorder pathology scores were above the clinical threshold in one or more comorbid areas. Eating disorder pathology and measures of comorbidity were all significantly intercorrelated. A fifth of pupils were at-risk of eating disorder pathology, and almost all demonstrated substantial comorbidity. Contrary to the 'white female' eating disorder stereotype, many of those with eating concerns were non-white and over a third did not identify as female. These findings require further work on the screening technology, but highlight the pressing need for access to eating disorder prevention and treatment for a diverse population of such adolescents.

Abstract Introduction/Objective Pseudomyogenic hemangioendothelioma (PMHE) is a rare, locally aggressive vascular tumor that typically affects young adults’ soft tissue or bone and demonstrates limited metastatic potential. We report such a case in a 14-year-old male with detailed clinical history and pathologic correlations. Methods/Case Report The patient initially presented with a pathological fracture of the left femur following a month-long history of hip pain. Imaging revealed multiple suspicious lytic lesions throughout the proximal femur, concerning for a neoplastic process. Open biopsy confirmed PMHE based on characteristic histopathology, including sheets of epithelioid and spindled cells with eosinophilic cytoplasm, and immunophenotype positive for keratin AE1/3, ERG, CD31, and FOSB, with negative CD34 and desmin stain. Despite initial surgical intervention with open reduction and pinning, the patient experienced significant local progression, requiring radical resection and reconstruction of the left proximal femur. Pathological analysis of the resected specimen confirmed a 7.5 cm tumor involving the bone and soft tissue, with a positive lateral soft tissue margin. NGS Sarcoma Fusion Panel confirmed an ACTB::FOSB fusion, thus supporting the diagnosis of PMHE. Results NA Conclusion This case underscores the diagnostic challenge and aggressive nature of PMHE, highlighting the importance of immunohistochemistry and molecular testing for FOSB rearrangements in confirming the diagnosis.