Ferroptosis is a form of necrotic cell death characterized by phospholipid oxidation. The cystine-glutamate antiporter (xCT), composed of solute carrier family 7 member 11 (SLC7A11) and SLC3A2, imports cystine for glutathione synthesis. Glutathione peroxidase 4 (GPX4) requires glutathione to counteract lipid peroxidation and prevent ferroptosis. Erastin, an xCT inhibitor, and Ras-selective lethal small molecule 3 (RSL3), a GPX4 inhibitor, suppress GPX4 function and induce ferroptosis. Tumor protein p53 (TP53) has a paradoxical role in ferroptosis regulation. Mouse double minute 2 homolog (MDM2), a negative regulator of TP53, is a key oncogene in well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS). Therefore, the present study explored the role of ferroptosis in DDLPS treatment response and resistance. Publicly available expression profiles of WDLPS, DDLPS and adipose tissue were analyzed, and the differential expression of ferroptosis-related genes regulated by the MDM2-TP53 pathway was identified in WDLPS and DDLPS. In vitro experiments were performed to assess the effects of erastin and RSL3 on the viability, lipid peroxidation and apoptosis of DDLPS cell lines. The results revealed that erastin and RSL3 induced lipid peroxidation and apoptosis, thereby exerting cytotoxic effects. In addition, nutlin-3, an MDM2 inhibitor, was demonstrated to increase lipid peroxidation and cytotoxicity when applied prior to erastin treatment. Notably, nutlin-3 also upregulated SLC3A2 expression in DDLPS cell lines, thereby enhancing cystine uptake. This increase in cystine uptake was suppressed by erastin. In addition, nutlin-3-induced SLC3A2 upregulation was abolished by TP53 knockdown. Nutlin-3 combined with erastin or RSL3 reduced absolute p-4EBP-1 levels in NDDLS-1 cells and p-p70S6 levels in both cell lines, with no significant impact on the p-4EBP-1/4EBP-1 and p-p70S6/p70S6 ratios. These results indicate that ferroptosis is a therapeutic vulnerability in the response to MDM2 inhibition in DDLPS. Furthermore, combining MDM2 inhibitors with ferroptosis-inducing agents may provide a potential therapeutic strategy for DDLPS and the role of mTOR in the pro-apoptotic effect of these combinations deserve further investigation.

Canine soft tissue sarcomas (STSs) are locally aggressive mesenchymal tumors with variable recurrence rates, and often, their therapy is limited to surgical excision. CD117 (KIT) is a tyrosine kinase receptor involved in cell growth and cancer development. c-kit proto-oncogene mutations have been reported to be associated with prognosis and therapy response in human and canine cancers. However, CD117 expression and c-kit mutations have rarely been investigated in canine STSs. This study aims to assess CD117 expression and c-kit mutations in different canine STSs.

Spontaneous STSs were surgically removed, fixed, routinely processed, and stained for histological and anti-CD117 immunohistochemical analyses. Staining intensity and percentage of positivity were scored. Cases with intense CD117 expression in more than 50% of cells were analyzed for the presence of mutations in exons 8, 9, or 11 of the c-kit proto-oncogene.

Overall, 115 canine STSs were collected. Among them, CD117 was expressed in 43 STSs, with diffuse cytoplasmic staining of variable intensity. CD117 was expressed in 16 out of 27 perivascular wall tumors, 12 of 13 sarcomas of fibroblastic origin, 6 of 6 rhabdomyosarcomas, 7 of 46 liposarcomas, and 2 of 3 nerve sheath tumors. Leiomyosarcomas (20 of 20) did not show CD117 expression. Mutations were investigated in 22 cases, all of which returned negative results.

In summary, canine STSs variably expressed CD117, which suggests that tyrosine kinase inhibitors may represent a promising targeted therapy for selected canine STSs histotypes.

This case report discusses the management of a three-year-old male presenting with a pathological fracture of the distal femur due to an aneurysmal bone cyst (ABC). Due to diagnostic uncertainty and limited resources, the treatment involved an en bloc resection followed by the Masquelet technique with a fibular and cancellous graft. While this approach successfully reconstructed the bone defect, the patient developed a progressive valgus deformity and limb length discrepancy, likely due to physeal damage from the resection rather than the reconstruction technique itself. This case highlights the challenges of balancing recurrence risk, functional outcomes, and resource limitations in pediatric ABC treatment. A more physeal-sparing approach, such as curettage with bone grafting, might have mitigated complications while preserving long-term limb function.

To evaluate the clinical efficacy of nab-paclitaxel based chemotherapy in the treatment of advanced epithelioid hemangioendothelioma (EHE).

Since March 2022, chemotherapy has been recommended for patients with advanced EHE characterized by large tumors (liver tumors > 10 cm or tumors in other organs > 3 cm), rapid tumor progression, severe symptoms, serosal effusion, and treatment failure. Two chemotherapy regimens were administered: nab-paclitaxel plus bevacizumab and nab-paclitaxel plus sirolimus. Clinical data and outcomes were retrospectively analyzed.

From March 2022 to August 2024, 21 patients with histologically confirmed EHE who received nab-paclitaxel based chemotherapy were included. At baseline, 18 patients (85.7%) presented with tumor-related symptoms, and serosal effusion was detected in 12 patients (57.1%). Among patients with hepatic EHE, six (28.6%) had tumors > 10 cm, while six (28.6%) with EHE at other sites had tumors > 3 cm. Partial response and stable disease were achieved in 5 (23.8%) and 12 (57.1%) patients, respectively, resulting in a disease control rate of 80.9%. Symptom relief was observed in 15 of 18 patients (83.3%), and decreased serosal effusion was noted in 6 of 12 patients (50.0%). The 1- and 2-year progression-free survival rates were 50.7% and 13.5%, respectively, while the 1- and 2-year overall survival rates were 70.6% and 51.5%, respectively.

Nab-paclitaxel based chemotherapy may offer an effective treatment option for patients with advanced EHE exhibiting adverse prognostic factors. However, further clinical trials are required to confirm its efficacy.

Undifferentiated pleomorphic sarcoma, previously called malignant fibrous histiocytoma, is a type of malignant mesenchymal tumor (sarcoma) of soft tissue and sometimes bone. It is uncommon in the oral cavity and very sporadic in the maxillary sinus. Microscopic diagnosis of this malignancy in the maxillary sinus can be very challenging, because there is a range of features that may overlap with other benign and malignant tumors.

In this paper, we report a case of undifferentiated pleomorphic sarcoma in the maxillary sinus of a 61-year-old Iranian man who was referred to the maxillofacial surgery ward due to pain and swelling of the upper jaw and visual problems in the right eye. In the initial incisional biopsy, peripheral giant cell granuloma was diagnosed in the hospital service. Yet, on request of the surgeon, during reviewing the slides in the oral pathology service of the School of Dentistry, and using an immunohistochemical method, undifferentiated pleomorphic sarcoma was diagnosed. In this paper, a case of undifferentiated pleomorphic sarcoma in the maxillary sinus is reported, with an emphasis on the management of its problems and diagnostic errors.

This study reviews the challenges and histopathological diagnostic errors of this uncommon tumor in this rare location. This lesion may be similar to other malignant tumors, and its correct diagnosis requires a detailed and complete examination.

Soft tissue tumors (STTs) in adolescents are relatively rare, and their characteristics and behavior have not been well studied in this age group. The aim of this study was to describe the clinicopathologic patterns of STTs in adolescents aged 10-19 years according to the 2020 WHO classification.

A 10-year retrospective cross-sectional study of 632 surgical samples from adolescents was conducted at a tertiary health facility to determine the frequency, histological patterns and characteristics of STTs in this population. The data were analyzed via SPSS 23.

STTs accounted for 12.5% of all histologically diagnosed lesions in adolescents, with a mean age of 15 ± 2.9 years, 54.4% occurring in females and 35.4% in middle adolescents. The majority (64.56%) of STTs were benign, while malignant and intermediate-grade neoplasms accounted for 25.32% and 10.13%, respectively. Vascular tumours were the most common, followed by adipocytic and fibroblastic/myofibroblastic tumours, with hemangiomas being the most common. The most prevalent symptom was a painless mass (82.3%), with the head and neck (25.3%) being the most commonly involved body site. Most of the STTs patients presented within the first two years of occurrence (36.7%, n = 29/79). However, age, age group and sex were not significantly associated with the WHO grades of these STTs.

This study provided valuable insights into the characteristics and behavior of STTs in adolescents, highlighting the importance of early diagnosis and management. These findings suggest that adolescent STTs affect females more than males , involve the head and neck more and are more benign, with vascular tumours being the most common type of STT in this age group.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [15N2]-cystine and [13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

In patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear.

We retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded.

A total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS.

Surgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS.

The purpose of this study was to evaluate the additional value of dynamic contrast-enhanced (DCE) MRI and diffusion weighted MRI (DWI) in differentiation between inflammatory myofibroblastic tumor (IMT) and squamous cell carcinoma (SCC) in the sinonasal cavity.

Patients with pathologically proven IMT and SCC in the sinonasal region were enrolled in this retrospective study. All participants underwent conventional MRI and dynamic contrast-enhanced MRI, while a subset of them performed DWI. All the MRI parameters were independently analyzed by two investigators.

This retrospective study included 21 patients with IMT and 55 patients with SCC. Significant differences were found in the conventional MR imaging features including mass margin, T2 signal intensity and track sign of maxillary (p < 0.05). For DCE-MRI features, significant differences were found in progressive centripetal continual enhancement and CImax (p < 0.001 and p = 0.026, respectively). A marginal significant difference was found in ADC values between IMT (0.86 ± 0.59) and SCC (1.14 ± 0.25) (p = 0.061). The conventional MRI analysis revealed that the combination of mass margin and track sign of maxillary yielded an accuracy of 81.6%. Using a combination of progressive centripetal continual enhancement on DCE-MRI and track sign of maxillary in multivariate logistic regression analysis, the accuracy was elevated to 92.1%.

The incorporation of DCE-MRI features into conventional MRI showed improved diagnostic performance in differentiating IMT from SCC in the sinonasal region. The novel progressive centripetal continual enhancement on DCE-MRI is the most effective feature of IMT.

The aim of this case report is to assess the clinicopathological characteristics and differential diagnosis of orbital granular cell tumor (GCT).

Clinical and imaging data of a rare case of orbital GCT involving the superior rectus muscle were collected. Its clinical characteristics, imaging, and histopathological features were observed.

A 36-year-old female patient presented with a 2-year history of left eye proptosis. Magnetic resonance imaging (MRI) enhancement suggested a space-occupying lesion in the left superior rectus muscle region. On T1-weighted and T2-weighted MRI, the tumor was isointense to gray matter and significantly enhanced on the enhanced scan. Microscopic examination revealed that most tumor cells exhibited diffuse growth with unclear boundaries, and some cells were arranged in small nests. The tumor cells were large, with abundant, coarse eosinophilic granules in the cytoplasm. Occasional cells contained larger round eosinophilic droplets in the cytoplasm. Focal areas showed foamy cells, small and central round or oval nuclei with occasional nuclear enlargement and mild atypia, inconspicuous nucleoli, rare mitoses, and low proliferative activity. Immunohistochemistry results were Vimentin (+), S-100 (+), CD68 (+), Ki67 (2%+), Inhibin-a (-), CK (-), SMA (-), and Desmin (-). The pathological examination of a specimen harvested from the mass corresponded to a GCT.

Orbital GCT is rare and should be considered in the differential diagnosis of orbital tumors. It is essential to distinguish it from thyroid-associated ophthalmopathy, inflammatory pseudotumor, and myohemangioma. Definitive diagnosis requires a comprehensive analysis of clinical, histopathological, and immunohistochemical findings. Surgical excision is the primary treatment for orbital GCTs. For patients with incomplete tumor resection, close follow-up is necessary. Proton beam radiation therapy can be considered to prevent recurrence or metastasis if needed.

Solitary fibrous tumor (SFT) is a rare borderline mesenchymal tumor typically arising in the pleura and involving the orbit as its most common extra-pleural location.

We herein describe two cases of orbital SFT arising in both a 69-year-old woman presenting with progressive proptosis of the left eye and a 49-year-old woman presenting with binocular diplopia. The diagnoses relied on histopathological analysis of biopsy samples. Because of the poor local prognosis, we decided to perform an orbital exenteration in the first case. In the second case, a complete resection surgery was performed.

SFT presents classics histological features and immunohistochemical markers that are essential to the diagnosis. SFT is classified as a benign tumor, but in some cases, it can show aggressive behavior with the potential for local tissue invasion and, more scarcely, distant metastasis. This is why complete resection remains the treatment of choice for SFT.

Spindle cell tumors in the pediatric population are uncommonly reported. This case discusses an 18-month-old who presented initially with unilateral ptosis and was found to have an orbital spindle cell tumor. Pathology evaluation of the tissue was extensive with nonspecific morphologic and immunohistochemical features. Molecular testing demonstrated an MN1::TAF3 fusion on RNA sequencing, which has not been previously described in the literature in association with spindle cell neoplasms. This case highlights the challenging nature of classifying and treating a tumor with a novel fusion.

The classification of undifferentiated pleomorphic sarcoma (UPS) has been evolving with advances in immunohistochemistry and genomic profiling over the past 20 years. There is a lack of current information on UPS incidence. Due to the lack of designated histology codes for UPS in the Surveillance, Epidemiology, and End Results (SEERs) program, we estimated UPS incidence by three different definitions based on clinical opinions using the 2000-2020 data from 22 registries of the SEER program. The incidence varied widely across the three definitions with 0.06 per 100,000 persons for the least inclusive definition and 0.67 per 100,000 persons for the most inclusive definition in 2016-2020, making it challenging to estimate the exact incidence of UPS. Regardless, all the incidences decreased between 2000 and 2020. Guidelines in UPS diagnosis and classification need to be better implemented in the US.

Doege-Potter syndrome (DPS) is a very rare paraneoplastic condition that is marked by hypoglycemia brought on by a solitary fibrous tumor rather than an islet cell tumor. Soft tissue neoplasms termed as solitary fibrous tumors (SFTs) are rare and these tumors vary in the site of origin, from the pleural cavity, mediastinum, pericardium, retroperitoneal spaces, liver, thyroid, orbit, bladder, intestines, and soft tissues, while pelvic-derived fibrous tumors are incredibly unusual. There are currently extremely few documented cases and literature reviews both domestically and internationally. In this case study, we present an 82-year-old woman who developed DPS as a result of malignant pelvic SFTs. Her hypoglycemia was clinically healed after she underwent laparoscopic retroperitoneal tumor resection in our institution, and thereafter, her quality of life improved.

Undifferentiated pleomorphic sarcoma (UPS) is a frequent subtype within the heterogeneous group of soft tissue sarcomas (STS). The use of radiotherapy (RT) has become an important component of a multimodal approach to treating STS. Key studies have demonstrated that the addition of RT improves rates of local control in STS, though the effect on overall survival (OS) is less clear. Furthermore, there is very limited and conflicting evidence regarding effect of RT on overall survival in UPS. The purposes of this investigation were to examine the association between RT and OS in UPS patients undergoing surgical resection and to determine independent prognostic indicators of OS in this patient population.

This was a retrospective review of patients who underwent surgical treatment for primary UPS from 1993 to 2021. Associations between RT and OS were analyzed with Kaplan-Meier curves and log-rank testing. Cox proportional hazards regression analysis was used to determine independent prognostic factors of OS.

One hundred and fourteen patients who underwent surgical resection of primary UPS were included in the study. Ninety-six (84.2 %) patients received RT perioperatively. Use of RT was associated with improved OS on log-rank testing (hazard ratio (HR) 0.20; 95 % confidence interval (CI) 0.11-0.36; p < 0.001). On multivariate analysis, RT was an independent predictor of improved OS (HR 0.18; 95 % CI 0.09-0.39; p < 0.001) while metastasis at presentation (HR 4.82; 95 % CI 2.26-10.27; p < 0.001) and older age (HR 1.92; 95 % CI 1.20-3.36; p = 0.02) were predictive of decreased OS. Use of RT was not significantly associated with a lower rate of local recurrence in our cohort (p = 0.49).

Use of RT in combination with surgery was an independent prognostic indicator of improved overall survival in UPS patients. Older age and metastasis at presentation were associated with worse overall survival. Based on this and other available studies, treatment for UPS should involve limb-sparing resection when feasible with RT to ensure optimal survival.

Solitary fibrous tumors (SFTs) represent a rare mesenchymal malignancy that can occur anywhere in the body. Due to the low prevalence of the disease, there is a lack of contemporary data regarding patient demographics and cancer-control outcomes.

Within the SEER database (2000-2019), we identified 1134 patients diagnosed with malignant SFTs. The distributions of patient demographics and tumor characteristics were tabulated. Cumulative incidence plots and competing risks analyses were used to estimate cancer-specific mortality (CSM) after adjustment for other-cause mortality.

Of 1134 SFT patients, 87% underwent surgical resection. Most of the tumors were in the chest (28%), central nervous system (22%), head and neck (11%), pelvis (11%), extremities (10%), abdomen (10%) and retroperitoneum (6%), in that order. Stage was distributed as follows: localized (42%) vs. locally advanced (35%) vs. metastatic (13%). In multivariable competing risks models, independent predictors of higher CSM were stage (locally advanced HR: 1.6; metastatic HR: 2.9), non-surgical management (HR: 3.6) and tumor size (9-15.9 cm HR: 1.6; ≥16 cm HR: 1.9).

We validated the importance of stage and surgical resection as independent predictors of CSM in malignant SFTs. Moreover, we provide novel observations regarding the independent importance of tumor size, regardless of the site of origin, stage and/or surgical resection status.

Pediatric cancer remains the leading cause of disease-related death among children aged 1-14 years. A few risk factors have been conclusively identified, including exposure to pesticides, high-dose radiation, and specific genetic syndromes, but the etiology underlying most events remains unknown. The tumor microenvironment (TME) includes stromal cells, vasculature, fibroblasts, adipocytes, and different subsets of immunological cells. TME plays a crucial role in carcinogenesis, cancer formation, progression, dissemination, and resistance to therapy. Moreover, autophagy seems to be a vital regulator of the TME and controls tumor immunity. Autophagy is an evolutionarily conserved intracellular process. It enables the degradation and recycling of long-lived large molecules or damaged organelles using the lysosomal-mediated pathway. The multifaceted role of autophagy in the complicated neoplastic TME may depend on a specific context. Autophagy may function as a tumor-suppressive mechanism during early tumorigenesis by eliminating unhealthy intracellular components and proteins, regulating antigen presentation to and by immune cells, and supporting anti-cancer immune response. On the other hand, dysregulation of autophagy may contribute to tumor progression by promoting genome damage and instability. This perspective provides an assortment of regulatory substances that influence the features of the TME and the metastasis process. Mesenchymal cells in bone and soft-tissue sarcomas and their signaling pathways play a more critical role than epithelial cells in childhood and youth. The investigation of the TME in pediatric malignancies remains uncharted primarily, and this unique collection may help to include novel advances in this setting.

Neural tumors are difficult to distinguish based solely on cellularity and often require immunohistochemical staining to aid in identifying the cell lineage. This article investigates the potential of a Convolutional Neural Network for the histopathological classification of the three most prevalent benign neural tumor types: neurofibroma, perineurioma, and schwannoma.

A model was developed, trained, and evaluated for classification using the ResNet-50 architecture, with a database of 30 whole-slide images stained in hematoxylin and eosin (106, 782 patches were generated from and divided among the training, validation, and testing subsets, with strategies to avoid data leakage).

The model achieved an accuracy of 70% (64% normalized), and showed satisfactory results for differentiating two of the three classes, reaching approximately 97% and 77% as true positives for neurofibroma and schwannoma classes, respectively, and only 7% for perineurioma class. The AUROC curves for neurofibroma and schwannoma classes was 0.83%, and 0.74% for perineurioma. However, the specificity rate for the perineurioma class was greater (83%) than in the other two classes (neurofibroma with 61%, and schwannoma with 60%).

This investigation demonstrated significant potential for proficient performance with a limitation regarding the perineurioma class (the limited feature variability observed contributed to a lower performance).

Molecular mechanisms underlying immune checkpoint inhibitor (ICI) response heterogeneity in solid tumors, including soft tissue sarcomas (STS), remain poorly understood. Herein, we demonstrate that the collagen-modifying enzyme, procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (Plod2), which is over-expressed in many tumors relative to normal tissues, promotes immune evasion in undifferentiated pleomorphic sarcoma (UPS), a relatively common and aggressive STS subtype. This finding is consistent with our earlier observation that Plod2 promotes tumor metastasis in UPS, and its enzymatic target, collagen type VI (ColVI), enhances CD8+ T cell dysfunction. We determined that genetic and pharmacologic inhibition of Plod2 with the pan-Plod transcriptional inhibitor minoxidil, reduces UPS growth in an immune competent syngeneic transplant system and enhances the efficacy of anti-Pd1 therapy. These findings suggest that PLOD2 is an actionable cancer target and its modulation could augment immunotherapy responses in patients with UPS, and potentially other sarcomas and carcinomas.

This detailed review focuses on retroperitoneal undifferentiated pleomorphic sarcoma (UPS), a particularly aggressive soft-tissue sarcoma that poses unique diagnostic and therapeutic challenges due to its rarity and complex presentation. By documenting a new case of retroperitoneal UPS and conducting a comprehensive review of all known cases, this article aims to expand the existing body of knowledge on the epidemiology, molecular pathogenesis, and treatment strategies associated with this rare disease. The complexity of diagnosing UPS is emphasized given that it rarely occurs in the retroperitoneal space and its histological and molecular complexity often complicates its recognition. This review highlights the need for specialized diagnostic approaches, including advanced imaging techniques and histopathological studies, to accurately diagnose and stage the disease. In terms of treatment, this paper advocates a multidisciplinary approach that combines surgery, radiotherapy and chemotherapy and tailors it to individual patients to optimize treatment outcomes. This review highlights case studies that illustrate the effectiveness of surgical intervention in the treatment of these tumors and emphasize the importance of achieving clear surgical margins to prevent recurrence. Furthermore, this review discusses the potential of new molecular targets and the need for innovative therapies that could bring new hope to patients affected by this challenging sarcoma.

Desmoid Tumors (DT) are rare neoplasms with higher incidence in younger women.

Retrospective, single-center analysis of patients with DT. Variables were age, sex, biopsy, treatment and recurrence. The disease-free survival (DFS) was calculated with the Kaplan-Meier method.

242 patients were evaluated, mean age was 34 years, 70.7% women, 44.4% originated in the trunk/abdomen and 54.5% had size > 5cm. Surgery was performed in 70.2%, 31% with negative margin and only 57% with previous biopsy. Recurrence rate was 38% and 1,2,5-year DFS was 75.3%, 64.2%, 57.8%, respectively. Size (p = 0.018) and tumor location in the dorsum (p = 0.001), extremities (p = 0.003) and pelvis (p = 0.003) were related to higher relapse rate.

our data reinforces the need to gather data from real world practice and the importance of awareness of DT and medical education about DT behavior and best approach due to the high rates of surgery and elevated number of patients treated without biopsy. Level of Evidence III; Retrospective Comparative Study.

Epithelioid hemangioma (EH) is an intermediate locally aggressive tumor that consists of epithelioid cells and endothelial cell differentiation, which can occur at any age, but is most common between the ages of 30 and 40 years. EH in the thoracic spine is rare, and accurate diagnosis is critical to treatment planning. Our aim was to explore the imaging and clinical data of thoracic spine EH to improve the understanding of this rare disease.

From January 1, 2018 to June 30, 2023, a database of thoracic spine masses was retrospectively reviewed. Five patients with histologically proven thoracic spine EH and complete imaging available were identified and analyzed. Computed tomography (CT) and magnetic resonance imaging (MRI) findings were evaluated separately by two radiologists with more than 10 years of experience. Positron emission tomography (PET)/CT was conducted by two nuclear medicine diagnostic technologists with at least 5 years of experience.

The patients included three male and two female patients aged 23 to 56 years (mean age was 38.4 ± 14.3 years). All patients underwent CT, MRI, and 18F-FDG PET/CT examination before treatment. Four patients were limited to one vertebral involvement, only one patient had multiple vertebral involvement, and all tumors involved the accessories, including one involving the posterior ribs. The maximum diameter of the tumor ranged from 2.7 to 4.3.

CT, MRI, and 18F-FDG PET/CT findings of thoracic spine EH have certain characteristics, and understanding these imaging findings will help to obtain accurate diagnosis before surgery.

Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available.

The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution.

This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in trials for which results are not yet published were excluded.

Thirty-six patients with advanced/metastatic pleomorphic sarcomas were included. The median age was 52 years. A total of 26 patients (72%) had UPSs and 10 patients (28%) had other high-grade pleomorphic sarcomas. The median follow-up time was 8.8 months. The median PFS was 2.9 months. The 3-month PFS and 6-month PFS were 46% and 32%, respectively. The median OS was 12.9 months. The 12-month OS and 24-month OS were 53% and 29%, respectively. The best response, previous RT, and type of ICB treatment were significantly and independently associated with shorter PFS (p = 0.0012, p = 0.0019 and p = 0.036, respectively). No new safety signal was identified, and the toxicity was overall manageable with no toxic deaths and only four patients (11%) stopping treatment due to toxicity.

Real-world retrospective data are consistent with the published literature, with a promising 6-month PFS of 32%. Partial or stable responders to ICB treatment have significantly improved PFS compared to progressors.

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

Cutaneous fibrous histiocytoma (FH) is considered a benign dermal tumor. The cellular variant is rare and poorly documented. Besides presenting a high risk of local recurrence, it has a low but serious metastatic potential. We present a case of metastatic cellular FH and also review the literature on this tumor, given its unusual metastatic development. A 47-year-old male patient presented with a lesion in the anterior surface of the right thigh, which has been present since adolescence but had grown during last year. Anatomopathological evaluation revealed a cellular FH, and the lesion was completely removed. Six months later, tumor recurrence with multiple compartment muscle involvement and pulmonary metastasis were detected. Both lesions were completely resected and after 3 years of follow-up, the patient is asymptomatic and free of the disease. We conclude that FH should be carefully sampled to detect variants with high local recurrence rates or with some metastatic risk such as the cellular one. We recommend wide surgical resection and a close follow-up including chest x-rays or thorax computed tomography (CT) in all cellular FH cases with local recurrence.

Cancer reprogramming is an important facilitator of cancer development and survival, with tumor cells exhibiting a preference for aerobic glycolysis beyond oxidative phosphorylation, even under sufficient oxygen supply condition. This metabolic alteration, known as the Warburg effect, serves as a significant indicator of malignant tumor transformation. The Warburg effect primarily impacts cancer occurrence by influencing the aerobic glycolysis pathway in cancer cells. Key enzymes involved in this process include glucose transporters (GLUTs), HKs, PFKs, LDHs, and PKM2. Moreover, the expression of transcriptional regulatory factors and proteins, such as FOXM1, p53, NF-κB, HIF1α, and c-Myc, can also influence cancer progression. Furthermore, lncRNAs, miRNAs, and circular RNAs play a vital role in directly regulating the Warburg effect. Additionally, gene mutations, tumor microenvironment remodeling, and immune system interactions are closely associated with the Warburg effect. Notably, the development of drugs targeting the Warburg effect has exhibited promising potential in tumor treatment. This comprehensive review presents novel directions and approaches for the early diagnosis and treatment of cancer patients by conducting in-depth research and summarizing the bright prospects of targeting the Warburg effect in cancer.

Primary lymphoma of the bone (PLB) is a rare entity, with a majority of pediatric cases presenting in the metaphysis of long bones. There have been only seven reported cases to date of pediatric lymphoma of the bone arising from the epiphysis, of which only two have been described in the proximal tibia. We report a pediatric case of PLB in the tibial epiphysis which presented initially with knee pain. Imaging was performed with X-ray, MRI, CT, and PET-CT with bone biopsies revealing diffuse large B-cell lymphoma. This patient also showed a second, synchronous lesion in the left iliac bone, which was also biopsy proven to diffuse large B-cell lymphoma. Lymphoma in the epiphysis for children is rare and often confused with infectious etiologies or other types of tumors. Misdiagnosis may result in inappropriate treatment and possible progression of the disease, thus making early identification important to initiate therapy.

Solitary Fibrous Tumor (SFT) is a rare mesenchymal tumor with a higher incidence of benign than malignant, most common location in the pleura. Although this tumor has been found in other locations in the body such as the head and neck region, retroperitoneal space, and intra-abdominal omentum, SFT of the gallbladder remains extremely rare in the medical literature. In this article, we present the imaging characteristics of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) of gallbladder SFT, thereby contributing to providing information in the study of this rare pathology.

Solitary fibrous tumor (SFT) is an uncommon mesenchymal tumor that can manifest in a variety of locations, including the retroperitoneum. The most effective standard diagnostic approach and treatment is yet to be determined due to unpredictable behavior of SFT, including retroperitoneal SFT.

A 43-year-old female with a retroperitoneal SFT presented with a palpable mass and symptomatology. Surgical exploration disclosed a tumor encompassing the left renal artery and vein, necessitating left nephrectomy and retroperitoneal mass removal. Initial histological examination suggested rhabdomyosarcoma, but subsequent immunohistochemistry confirmed the diagnosis of retroperitoneal SFT. No adjuvant therapy was administered, and there was no detectable mass on follow-up imaging. The patient remained symptom-free.

Retroperitoneal SFTs are difficult to diagnose due to their non-specific morphology, thus immunohistochemistry plays a crucial role in confirming its diagnosis. Surgical excision with negative resection margins continues to be the standard treatment. Recurrence rates are low in comparison to other retroperitoneal sarcomas, hence routine chemotherapy or radiation therapy is not advised.

This case demonstrates the significance of contemplating SFT as the differential diagnosis of retroperitoneal tumors and the role of immunohistochemistry in confirming the diagnosis. The optimal management strategies for retroperitoneal SFTs should be determined by additional research.

Parameningeal location of rhabdomyosarcoma (PM RMS) is known to be an unfavorable prognostic factor. Scarce data are available on radiotherapy (RT) concepts with regard to outcome.

Treatment and outcome of 395 children with PM RMS registered within two Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry (1995-2021) were evaluated.

Patients were IRS group II (n = 15) and III (n = 380) and received systemic treatment according to the enrolled protocols: I2VA (n = 172), VAIA/CEVAIE (n = 223). Delayed resection was performed in 88/395 (22%) patients, and RT was additionally given in 79/88 (90%) resected patients. RT was the predominant local treatment in 355/395 (90%) patients: hyperfractionated accelerated photon (HART; n = 77), conventionally fractionated photon (n = 91) or proton beam (n = 126), brachytherapy (n = 4), heavy ions (n = 1), not available (n = 56). In the subgroup of RT as only local treatment (n = 278), no intracranial tumor extension and complete remission at end of treatment were significant positive prognostic factors. No significant difference on tumor outcome was seen between different radiotherapy concepts. Long-term toxicity with mostly endocrinological and visual deficiencies was reported in 161/279 (58%) surviving patients with a lower trend after proton beam RT (48%) when compared to HART or conventionally fractionated photon RT (71% and 72%, respectively). Ten-year event-free and overall survival in the overall group were 62% (±5, 95% confidence interval [CI]) and 67% (±5, 95% CI); in the RT-only group 67% (±6, 95% CI) and 71% (±6, 95% CI), respectively.

CWS data confirm the recent RT concept in PM RMS. Long-term sequelae as endocrinological and visual deficiencies need to be addressed.

To determine whether the combination of nab-paclitaxel with gemcitabine has activity in patients with pretreated soft tissue sarcoma (STS).

NAPAGE is a phase Ib/II clinical trial investigating the combination of nab-paclitaxel (nab-pc) with gemcitabine employing two cohorts. One of a dose-de-escalation phase and one of expansion. In phase I, nab-pc was given at 150 mg/m2 in combination with gemcitabine 1000 mg/m2 every two weeks, until disease progression or unacceptable toxicity. This dose was recommended for phase II (RP2D), as there was no dose limiting toxicity (DLT) or discontinuations due to adverse events (AEs). The primary endpoint of the phase II was progression-free rate (PFR) at 3 months (H0: 20%, H1:40%). The secondary endpoints included progression free survival (PFS), overall survival (OS), AEs, objective response and patient-reported outcomes (PRO). Efficacy analysis was by intention to treat.

The 3-month PFR was 56.4% (95% confidence interval CI: 39.6-72.2%). The 3-month and 6-month PFS were 58.4% (95% CI: 41.3-72.1%) and 44.6% (95% CI: 28.4-59.5%), respectively. Median PFS was 5.3 months (95% CI: 1.4-8.2) and median OS was 12.8 months (95% CI: 10.5-39.2). The most common treatment-related grade ≥ 3 AE were neutropenia (18%), followed by anemia (2.6%), hypertension (2.6%) and alanine aminotransferase increase (2.6%). Grade 1 and grade 2 peripheral sensory neuropathy (PNP) occurred in 15.4% and 20.5%, respectively. No grade 3-4 PNP was reported.

Combining nab-pc and gemcitabine is safe. Promising activity is observed in pretreated STS patients with manageable toxicity. This regimen should be considered for further exploration.

Rhabdomyosarcomas (RMS) constitute a heterogeneous spectrum of tumors with respect to clinical behavior and tumor morphology. The paternal uniparental disomy (pUPD) of 11p15.5 is a molecular change described mainly in embryonal RMS. In addition to LOH, UPD, the MLPA technique (ME030kit) also determines copy number variants and methylation of H19 and KCNQ1OT1 genes, which have not been systematically investigated in RMS. All 127 RMS tumors were divided by histology and PAX status into four groups, pleomorphic histology (n = 2); alveolar RMS PAX fusion-positive (PAX+; n = 39); embryonal RMS (n = 70) and fusion-negative RMS with alveolar pattern (PAX-RMS-AP; n = 16). The following changes were detected; negative (n = 21), pUPD (n = 75), gain of paternal allele (n = 9), loss of maternal allele (n = 9), hypermethylation of H19 (n = 6), hypomethylation of KCNQ1OT1 (n = 6), and deletion of CDKN1C (n = 1). We have shown no difference in the frequency of pUPD 11p15.5 in all groups. Thus, we have proven that changes in the 11p15.5 are not only specific to the embryonal RMS (ERMS), but are often also present in alveolar RMS (ARMS). We have found changes that have not yet been described in RMS. We also demonstrated new potential diagnostic markers for ERMS (paternal duplication and UPD of whole chromosome 11) and for ARMS PAX+ (hypomethylation KCNQ1OT1).

The tumor microenvironment is a dynamic network of stromal, cancer, and immune cells that interact and compete for resources. We have previously identified the Vanin1 pathway as a tumor suppressor of sarcoma development via vitamin B5 and coenzyme A regeneration. Using an aggressive sarcoma cell line that lacks Vnn1 expression, we showed that the administration of pantethine, a vitamin B5 precursor, attenuates tumor growth in immunocompetent but not nude mice. Pantethine boosts antitumor immunity, including the polarization of myeloid and dendritic cells towards enhanced IFNγ-driven antigen presentation pathways and improved the development of hypermetabolic effector CD8+ T cells endowed with potential antitumor activity. At later stages of treatment, the effect of pantethine was limited by the development of immune cell exhaustion. Nevertheless, its activity was comparable with that of anti-PD1 treatment in sensitive tumors. In humans, VNN1 expression correlates with improved survival and immune cell infiltration in soft-tissue sarcomas, but not in osteosarcomas. Pantethine could be a potential therapeutic immunoadjuvant for the development of antitumor immunity.

The therapeutic approach of pleomorphic liposarcoma (PLPS), a rare high-grade subgroup of soft tissue sarcoma, is commonly extrapolated from the management of other LPS subtypes. Only published retrospective data on PLPS currently serve as a guide for oncologists without clear recommendations or specific guidelines. In the advanced setting, specific systemic therapy such as eribulin and trabectedin showed promising activity in comparison to conventional therapy (doxorubicin- and gemcitabine-based protocols), which currently remains the current standard of care at initial stages of the disease. The better understanding of soft tissue sarcoma (STS) pathophysiology and disease course has led to the development of adapted clinical trial designs for rare STS histotypes with specific treatment approach.

Otological solitary fibrous tumors (SFT) are exceedingly rare. There has been no report of SFT localized to the tympanic membrane. To report on a rare case of solitary fibrous tumor of the tympanic membrane and provide systematic review of the literature pertaining the demographics and pathophysiology of otological SFTs.

This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. A search of PubMed, Google Scholar, and Cochrane Library databases was conducted to identify English-language articles on solitary fibrous tumor of the ear, with emphasis on the tympanic membrane, published through 2022. A combination of Boolean operators and the following keywords were included in the search strategy: "solitary fibrous tumor", "tympanic membrane", and "ear".

We found 12 previous reports of solitary fibrous tumors of the ears, none of which were in the tympanic membrane. All cases underwent surgical resection, with or without perioperative embolization, or radiation. There was no evidence of distant diseases in any cases.

In the context of a tympanic membrane mass with associated pain and hearing loss, our findings suggest that solitary fibrous tumor should be included in the differential diagnosis.

Primary retroperitoneal masses have numerous differential diagnoses, many of which are rare entities. These can be neoplastic or nonneoplastic. Among the rare conditions are solitary fibrous tumors, which can either be benign or malignant. It is a mesenchymal, spindle-cell tumor, reported first in 1931 as a pleural tumor by Klemperer et al. A 20-year-old lady, with abdominal pain for 6 months, was diagnosed with a retroperitoneal mass on the left lower abdomen on USG which was confirmed by an MRI scan of the abdomen. The patient underwent laparoscopy-assisted excision of the mass. The final histopathological reports and immunohistochemistry reports revealed a solitary fibrous tumor. Solitary fibrous tumors (SFTs) are rare tumors in the retroperitoneum. In our search, fewer than a hundred cases have been reported. It has a characteristic "patternless pattern" in a microscopic study. Adverse outcomes of SFTs are associated with atypical features in histology, such as nuclear pleomorphism, necrosis, increased cellularity, and mitoses >4/10 HPF and size more than 10 cm. The standard of care is surgical excision with clear margins. Open surgeries have been done traditionally; we present a case where we performed the excision laparoscopically.

Neoadjuvant tyrosine kinase inhibitor (TKI) therapy has reduced tumor burden and improved survival in both primary and recurrent gastrointestinal stromal tumors (GISTs). However, no clear guidelines exist on optimal patient selection for neoadjuvant therapy (NAT). Our aim was to analyze factors and outcomes associated with the therapeutic sequence of TKI therapy before and/or after surgery for gastric GISTs.

We performed a retrospective study of patients surgically treated for a gastric GIST utilizing the 2006-2018 National Cancer Database. We examined demographic, clinical, and pathological characteristics associated with NAT versus adjuvant therapy (AT) using logistic regression.

Of the 3732 patients, 20.4% received NAT and 79.6% had AT. Among patients receiving therapy, NAT significantly increased over our study period (12% to 30.7%). A majority of the AT group received a partial gastrectomy (77.9%) compared with the NAT group who received more near-total/total gastrectomy or gastrectomy with en bloc resection (p < 0.001). In a multivariable model, patients were more likely to receive NAT when insured (private, aOR: 2.37, 95% CI: 1.31-4.29), treated at an academic/research program (aOR: 1.83, 95% CI: 1.49-2.56), had tumors located in the proximal stomach (aOR: 1.40, 95% CI: 1.06-1.86), tumor size > 10 cm (aOR: 1.88, 95% CI: 1.41-2.51), and received near-total/total gastrectomy (aOR: 1.81, 95% CI: 1.42-2.29). There were no differences in outcomes.

NAT for gastric GIST has increased in utilization. NAT was used in patients with larger tumors and who underwent more extensive resection. Despite these factors, outcomes were similar to patients receiving only AT. More studies are required to determine the therapeutic sequence for gastric GISTs.

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that typically arise from the pleura but can also occur in various locations throughout the body. Although there are increasingly more reports of extra-pleural SFTs, reports of SFTs in bone are very rare, and a malignant SFT accompanying recurrence of pelvis has not yet been reported.

We herein present the case of a 15-year-old male who experienced intermittent numbness in his right buttock, accompanied by radiating pain in his lower limbs for 6 months. Radiological examinations revealed an expansive, heterogeneous enhanced mass in the sacral and iliac regions, with a branch of the right internal iliac artery feeding the tumor.

The histological examination suggest a diagnosis of a malignant SFT with high proliferation activity.

The sacral mass was surgically excised.

Following the surgery, the patient experienced a local recurrence of the tumor at 9 months and was administered adjuvant imatinib treatment. Recent magnetic resonance imaging contrast-enhanced displayed shrinkage of the tumor, which may provide certain evidence for chemotherapy for the treatment of recurrence of malignant SFTs in the pelvic region.

Complete surgical excision is the recommended treatment for this rare disease entity, and the role of adjuvant therapies is controversial due to their rarity. Our case underscores the challenges in managing recurrent malignant SFTs and highlights the importance of a thorough diagnostic workup. Further research is needed to establish the role of adjuvant therapies in the management of these tumors.

Undifferentiated pleomorphic sarcoma (UPS), also known as malignant fibrous histiocytoma, is a rare mesenchymal tumor that occurs mostly in the soft tissue of the limbs and retroperitoneum. UPS of the breast is extremely rare, with less than 20 cases reported in the literature.

We present a case of UPS of the right breast in a 56-year-old female. The growth of tumor could not be impeded by chemotherapy and radiotherapy. Then, she underwent right modified radical mastectomy with axillary lymph node dissection. The patient died eventually due to severe respiratory failure. UPS of the breast is a rare and aggressive tumor that presents with a rapidly growing mass. It can be difficult to diagnose as it shows no specific histological features and can mimic other spindle cell tumors of the breast.

Breast sarcomas are categorized in very rare malignancies, and the mortality of this type of cancers are significantly high as they often are not diagnosed in early stages.

The treatment of UPS of the breast is mostly surgical, with adjuvant radiotherapy and chemotherapy depending on the tumor characteristics and response to neoadjuvant chemotherapy. Long-term follow-up is necessary as these tumors have a high rate of local recurrence and distant metastasis.