Patients with malignant peripheral nerve sheath tumors (MPNSTs) have poor outcomes despite multimodal treatment with surgery, radiation, and systemic therapy. The responses to radiotherapy (RT) are mixed, and the biologic mechanisms underlying this heterogeneity in the radiation response of MPNSTs are not understood. Here, we combined bulk and single-cell transcriptomics, genome-wide CRISPR interference screens, and multiplatform molecular analysis across MPNST cells, mouse allograft models, and patients' samples to understand the mediators of the radiation response. Our data revealed that MPNSTs, but not benign plexiform neurofibromas, induced a type I IFN signature that functionally mediated the radiation response. Moreover, irradiation of immunocompetent mouse MPNST allografts led to IFN-mediated T cell recruitment and activation. Both host mouse T cells and intact tumor IFN receptor signaling were required for RT's efficacy in mouse MPNST allografts. Analysis of human MPNST resection specimens demonstrated that increased microenvironmental and CD8+ T cell infiltration were associated with improved local control following RT. These results provide a preclinical rationale for combining immunomodulatory agents targeting IFN signaling to improve radiation responses in MPNSTs and potentially other soft tissue sarcomas.

Radiologic-pathologic correlation is essential for diagnostic accuracy, particularly when dealing with primary bone tumors. This investigation explores the unique radiographic and pathologic features of NFATC2-rearranged bone sarcomas. Inclusion criteria focused on primary bone sarcomas with NFATC2 fusions while excluding soft tissue sarcomas, benign bone cysts, and vascular neoplasms with similar fusions. Our cohort comprised 16 patients (12 males, 4 females) with a mean age of 45.6 years (range: 15 to 77y). Tumors were located in the femur (n=9), tibia (n=3), humerus (n=2), ulna (n=1), and radius (n=1). Symptoms generally followed a long latency period and several were incidentally discovered for other reasons, with a mean tumor size of 9.7cm (range: 3.0 to 19.7cm). Histologic examination revealed typical features of NFATC2-rearranged sarcomas, including uniform epithelioid, round, or spindle cells growing in cords, chains, clusters, and sheets suspended in a richly vascularized fibromyxoid to variably sclerotic stroma. Mitotic activity varied dramatically between and within tumors (from <5 to >50 per 10 HPF). By immunohistochemistry, positive stains included CD99 (12/14), NKX2.2 (7/7), AGGRECAN (3/3), SMA (6/7), CAM5.2 (3/4), SATB2 (8/9), and ERG (5/8) with more limited expression of CK AE1/AE3 (3/12) and NKX3.1 (2/8). All had an NFATC2 gene fusion, with 9 harboring FUS and 7 EWSR1 as 5' partners. Additional genetic analysis beyond the targeted fusion panel (n=7) demonstrated that all cases harbored a range of secondary genomic alterations in addition to the driver NFATC2 fusion. On radiography and CT imaging, all showed lucent lesions with peripheral sclerosis and narrow transition zones. Expansile cortical remodeling (n=8; 50%) varied from minimal to extensive. Despite generally indolent-appearing radiographic features, 87.5% (14/16) demonstrated soft tissue extension, ranging from focal to extensive. Internal septations were present in 62.5% (10/16). MRI, performed on 15 tumors, revealed hypointensity on T1-weighted images and heterogeneously hyperintense on fluid-sensitive sequences. After contrast administration, avid enhancement was seen in all tumors with perilesional edema and enhancement in 26.7% (4/15). In summary, the imaging of NFATC2-rearranged bone sarcomas differs significantly from Ewing sarcoma, suggesting a tumor of longer duration characterized by a lytic nature, areas of peripheral sclerosis, expansile cortical remodeling, and frequent extraosseous extension. However, these features may not correlate with prognosis. This study represents the first systematic radiologic evaluation of NFATC2-rearranged bone sarcomas, highlighting distinctive characteristics that may aid pathologists in their initial diagnostic assessments.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that constitute a major cause of mortality in individuals with neurofibromatosis type 1 (NF-1) and exhibit highly variable responses to radiotherapy. In this issue of the JCI, Zhu and colleagues integrated functional genomics, single-cell transcriptomics, and analysis of human tumors to show that type I IFN signaling shapes both tumor-intrinsic radiation sensitivity of MPNSTs and local recruitment and activation of T cells. Their findings establish IFN signaling as a central coordinator of the radiotherapy response in MPNSTs and suggest that incorporating targeted immunomodulation strategies may improve radiotherapy outcomes. The work also has direct implications for the role of the immune system and IFN signaling radiation-based treatment of soft tissue sarcomas beyond those involved in NF-1.

Local Control With Moderately Hypofractionated Definitive Radiotherapy Delivered With a Simultaneous Integrated Boost Technique to Non-extremity Soft Tissue and Bone Sarcomas.

Evidence-based quality indicators of soft tissue sarcomas in Germany 2015-2021: An analysis of the German Cancer Registry Group.

Automated 3D body composition analysis on chest CT scans for survival prediction in high-grade extremity soft tissue sarcomas.

Soft tissue sarcomas (STSs), a diverse group of mesenchymal malignancies, are characterized primarily by copy-number alterations rather than a high tumor mutation burden. In this study, we sought to identify expression-based biomarkers in complex karyotype STS (CKS) with CDK4-amplification to support improved therapeutic strategies. Using transcriptome data from National Cancer Center (NCC)-CKS samples, we selected genes whose expression levels were more than two-fold higher or less than half in tumor tissues compared with normal tissues. These genes were further filtered by CDK4-amplification status, resulting in 30 candidates, which were refined to 14 differentially expressed genes (DEGs) based on false discovery rate (FDR) significance. Bioinformatics analyses revealed enriched pathways and gene-gene networks related to redox regulation and growth-factor-driven signal transduction, indicating metabolic alterations that may promote tumor survival in CDK4-amplified CKS. A subset of the 14 genes demonstrated prognostic significance in CDK4-amplified patients from the TCGA cohort. Additionally, immune cell marker analysis showed associations between CDK4-amplification and innate immune cell signatures. Together, our findings identify promising therapeutic and prognostic targets linked to CDK4-amplification in CKS. These biomarkers warrant further investigation and may ultimately contribute to improved clinical outcomes for patients with CKS.

Inguinal "neoligament" reconstruction after groin soft tissue sarcoma resection: A novel surgical technique.

Non-thermal ultrasound-guided fractionation of human leiomyosarcoma with boiling histotripsy: an ex vivo feasibility study.

Fertility preservation via concurrent ovarian tissue cryopreservation during radical resection of pelvic retroperitoneal soft-tissue sarcoma in prepubertal girls: A case series

Multidisciplinary tumor boards (MDTs) are critical for the personalized management of soft tissue sarcomas (STS), but they are limited by time, costs, and resource demands. With recent advances in large language models (LLMs) like ChatGPT, there is growing interest in evaluating their potential role in augmenting MDT workflows. This study aimed to assess the clinical performance of ChatGPT-4o in real-world STS cases using predefined evaluation criteria, comparing its treatment suggestions with expert MDT decisions. This retrospective study included 152 patients presented to the multidisciplinary sarcoma tumor board. ChatGPT-4o was prompted to generate guideline-based treatment recommendations based on anonymized tumor board registration letters. Outputs were scored by blinded expert reviewers using a five-domain framework: diagnostic modalities, therapeutic modalities, treatment sequencing/timing, chemotherapy regimen, and clinical contextualization. Descriptive statistics and non-parametric ANOVA with post hoc tests assessed performance, including subgroup analysis by sarcoma subtype. ChatGPT-4o scores were significantly lower than the maximum achievable value of 1.0 across all five criteria (all p < 0.0001). Among individual domains, clinical contextualization significantly outperformed all other criteria in pairwise comparisons (all p < 0.05). No significant performance differences were observed across sarcoma subtypes (H = 19.74, p = 0.138). ChatGPT-4o demonstrated substantial expert-rated performance in generating tumor board recommendations for soft tissue sarcoma cases, particularly excelling in personalized contextualization. Discrepancies in treatment sequencing and chemotherapy selection highlight the need for expert oversight. These findings support the feasibility of LLM integration into oncology workflows, warranting further refinement toward safe, supportive clinical use.

Background/Objectives: Tumor thrombus is an uncommon but serious finding in sarcoma, with limited pediatric data. While adult cases indicate a median survival of ~14 months, outcomes in children remain poorly understood. Methods: A retrospective review (1990–2025) was conducted at a single pediatric tertiary center. Patients &lt;18 years with pathologically confirmed bone or soft tissue sarcoma and radiographic or histologic evidence of tumor thrombus were included. Minimum follow-up was 3 years or until end of life. The primary outcome was survival after tumor thrombus diagnosis. Results: Thirteen patients (nine males, four females) met the inclusion criteria. The median age at sarcoma diagnosis was 10.5 years. Osteosarcoma was the most common subtype (69.2%), with 76.9% of tumors arising in bone. Disease was localized in 53.8% and metastatic in 46.2% at presentation. Tumor thrombus was contiguous in 61.5% and noncontiguous in 38.5%. The median time from sarcoma diagnosis to death was 44.2 months; from tumor thrombus diagnosis to death, this was 15.2 months. The overall survival after tumor thrombus diagnosis was 30.8%. Conclusions: Pediatric sarcoma with tumor thrombus is associated with poor prognosis, and surgical intervention did not appear to result in long-term survival in this small series. Tumor thrombus may be noncontiguous from the primary tumor, emphasizing the importance of advanced imaging and its implications for treatment planning and counseling.

Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas with peripheral nerve differentiation. A wide surgical resection with negative margins is the mainstay of treatment but is not always curative. Here, we present clinical outcomes of patients who underwent surgical resection for MPNST. We identified and collected data on patients who underwent surgical resection for their MPNST at The Johns Hopkins Hospital, from 2010 to 2024. We generated Kaplan-Meier curves and performed univariable and multivariable analyses to determine factors associated with progression-free survival (PFS) and overall survival (OS). We identified 123 MPNST patients. On univariable analysis, older age (hazard ratio [HR] 1.02), radiation-induced etiology (HR 1.59), spinal tumors (HR 3.27), high-grade pathology (HR 2.6), and postoperative complications (HR 3.07) were each associated with worse OS. Neurofibromatosis type 1 (NF1)-related etiology (HR 0.54), gross total resection (HR 0.48), negative margins (HR 0.58), R0 resection status (HR 0.46), and preoperative ambulatory status (HR 0.26) were each associated with improved OS. The results of the univariable analysis were similar for PFS and for OS and PFS within the NF1-related subgroup. On multivariable analysis, nonextremity MPNST (Spine adjusted hazard ratio [aHR] 3.28, Brachial Plexus aHR 5.51, Head/Neck aHR 6.23), recurrent tumor status (aHR: 2.64), and postoperative complications (aHR 3.27) were independently significantly associated with poor OS. MPNST are aggressive sarcomas that present challenges in diagnosis and treatment. In our series, NF1-related MPNST patients had the highest OS, likely associated with close monitoring for MPNST among the high-risk NF1-population. Nonextremity tumor locations, recurrent tumors, and postoperative complications were associated with inferior OS and PFS. Multi-institutional studies are warranted to investigate the impact of these prognostic factors in a larger, more heterogeneous MPNST patient cohort and examine the utility of surveillance in the neurofibromatosis patient population under a multidisciplinary team.

BACKGROUND Genitourinary sarcomas include testicular sarcomas and are the most common subtype of sarcoma within the genitourinary system. Undifferentiated pleomorphic sarcoma is a subtype of soft tissue sarcomas that may affect the extremities and retroperitoneum. However, the presence within the testicle is rare. Here, we present a case of an undifferentiated testicular pleomorphic sarcoma, which will explore the presentation and treatment of a rare type of testicular cancer. CASE SUMMARY Here we present a 56-year-old male who comes to the urology clinic for left testicular swelling. The patient then underwent left radical orchiectomy via an inguinal approach for a left testicular mass seen on examination and on scrotal ultrasound. Pathology revealed undifferentiated pleomorphic sarcoma (Federation of the French Cancer Centres grade 3), 9.5 cm in size, and it was limited to the testicle. The surgical margins were negative. A follow-up positron emission tomography computed tomography scan was obtained, which showed no evidence of hypermetabolic lymph nodes or masses in the abdomen or pelvis. CONCLUSION Testicular sarcomas are a rare type of soft tissue sarcoma. The standard treatment of the testicular mass usually begins with radical inguinal orchiectomy. Patients with scrotal sarcomas are at high risk of local and distant recurrence, emphasizing the importance of surgical excision and wide margins. There is little studied regarding the integration of radiotherapy and chemotherapy for these cases as neoadjuvant or adjuvant therapies. This case highlights the presentation and treatment of a patient with a rare phenotype of testicular pleomorphic sarcoma treated by radical inguinal orchiectomy. In this study, our patient continued without nodal or distant disease in his initial positron emission tomography computed tomography scan after surgery.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma characterised by myxoid matrix, multilobular architecture, eosinophilic ovoid to short spindle cells arranged in cords, clusters or reticular patterns and NR4A3 gene rearrangement. However, some EMCs show morphological variations or non-EWSR1::NR4A3 fusion. We described herein five cases of variant EMCs. The five patients included two females and three males, aged 24-59 years (median: 49 years). The tumours were located in the dorsal region, buttock, thigh, paravertebral region and elbow, respectively. Grossly, the tumour sizes ranged from 4.0 to 16.0 cm (median: 6.5 cm) in greatest dimension. Morphological examination revealed tumours with varied growth patterns, including solid variants with eosinophilic proteinaceous fluid (n = 2), classic EMC morphology with rhabdoid cells (n = 1), a biphasic variant, composed of fibroblastic/myofibroblastic-like cells and oval to short spindle-shaped cells (n = 1), and a spindle-cell morphology with a myxoid stroma and prominent haemorrhagic cystic spaces (n = 1). Immunohistochemically, all cases showed variable expression of CD117. Next-generation sequencing (NGS) identified an EWSR1::NR4A3 fusion, a novel FUS::NR4A2 fusion, a novel ACTB::NR4A3 fusion, and two FUS::NR4A3 fusions. Follow-up for all five patients showed no signs of local recurrence or distant metastasis. These five cases of EMC highlight the continuous morphological spectrum of this tumour, demonstrating significantly greater histological diversity than classically described. The identification of novel fusion partners further expands its genetic landscape.

Myxofibrosarcoma (MFS) is a rare malignant soft tissue sarcoma, typically affecting elderly patients and commonly arising from the extremities. Its occurrence in older individuals with atypical locations, such as retroauricular, is uncommon. A 50-year-old female presented with a history of recurrent left huge retroauricular mass, a painless and hard mass, not mobile, not tender, attached to the skin, approximately 4*3 cm. Initial imaging suggested a benign lesion; however, histopathological results of the excised mass revealed a spindle cell neoplasm with a lot of myxoid changes that indicate High-grade Myxofibrosarcoma. Immunohistochemistry confirmed a diagnosis of high-grade MFS. The patient underwent surgical excision of the retroauricular mass with clear margins and remains under regular follow-up with no signs of recurrence to date. In this case, the diagnostic tools of MFS are mainly used in elderly patients with atypical anatomical locations. The imaging is a nonspecific tool to confirm diagnosis, and the histopathological examination is an accurate diagnostic tool for MFS. The mainstay of MFS treatment is surgical excision, and in this case, the patient received Adjuvant Radiotherapy and systemic chemotherapy therapy (doxorubicin and ifosfamide) due to high-grade or multiple recurrences, adjuvant therapy and Regular follow- up; are essential to prevent local recurrence. This case contributes to the limited data on MFS in sub-Saharan Africa, to increase awareness and reporting, and to better understand epidemiology and management strategies in this region.

The impact of non-centralised surgical treatment on local recurrence, amputation rate and survival in patients with extremity soft tissue sarcoma.

We evaluated the survival rate/survivor characteristics following first progression/relapse of metastatic rhabdomyosarcoma (M1 RMS), using pooled European and US collaborative group data from the INternational Soft Tissue saRcoma ConsorTium (INSTRuCT). Patients with first diagnosis of M1 RMS aged 0-40 years were identified within the INSTRuCT database (Upfront Cohort; UC). The First Event Cohort (FEC) included UC patients with first event of disease progression/relapse. Clinical features and survival of FEC patients were described. UC included 1095 eligible M1 RMS patients. 5-year Overall and Event Free Survival were 32.0% (95% Confidence Interval (CI) 29.2-34.9) and 27.5% (95% CI 24.8-30.2) respectively. Median time to event was 13.9 months (range 1 day-172.6 months). Among UC patients, 727 with first event of progression/relapse were included in FEC. 3-year Overall Survival for FEC from first event was 8.0% (95% CI 6.1-10.2). Thirty-four (4.7%) FEC patients were alive with > 3 years follow up ("disease free") and 16 (2.2%) with < 3 years follow up. FEC patients alive > 3 years were significantly more likely than deceased FEC patients to have: younger age (p = 0.0031); no locoregional lymph node involvement (p = 0.0013); fewer metastatic sites (p = 0.006); no bone and/or bone marrow disease (p < 0.001 for each); lower Oberlin scores (p < 0.0001); time to first event > 18 months (p < 0.0001). Univariate and multivariable analyses conducted in FEC to investigate factors impacting OS showed that Oberlin score ≥ 2 (Hazard Ratio (HR) 1.295, 95% Confidence Limits (CL) 1.07-1.57, p = 0.0074) and involvement of loco-regional lymph nodes at diagnosis (HR 1.28, 95% CL 1.08-1.52, p = 0.0053) were associated with worse outcome. Outcomes following first progression/relapse of M1 RMS are dismal. Survivors had fewer adverse prognostic features at first presentation and later first events. Further work is required to predict survivors of first relapse more reliably.

Trabectedin is standard for r/r soft tissue sarcomas. tTF-NGR accumulates in tumor vasculature leading to tumor vascular occlusion and tumor infarction. Both compounds in sequence could trap trabectedin inside tumors and increase its efficacy, which then optimizes the pro-coagulatory activity of tTF-NGR. This report summarizes translational data and results of the safety run-in patient cohort of the TRABTRAP trial combining trabectedin plus tTF-NGR. A dose of trabectedin of 1.5mg/m2 (24h, day 1) combined with 1.0mg/m2 of tTF-NGR (1h, days 2 and 3, q day 22) represents the approx. Maximum tolerated dose (MTD) and with 0.5mg/m2 tTF-NGR (days 2 and 3) the recommended starting dose for the randomized part of TRABTRAP. None of the 6 patients on 0.5mg/m2 tTF-NGR had dose-limiting toxicity (DLT). Higher doses or additional days of application of tTF-NGR led to grade 3 DLT including early troponin T high sensitivity increase, a reversible non-ST-elevation myocardial infarction in one patient, and reversible thromboembolic events. Pharmacokinetics explain the difference of the MTD between the phase I study and in TRABTRAP. Experimental and clinical efficacy and tolerability of the combination between trabectedin and tTF-NGR supports the active randomized part of TRABTRAP.

Superficial leiomyosarcoma is a rare soft tissue sarcoma that typically presents as a firm, painful nodule in adults older than 50 years. We report a unique case of a 35-year-old woman with a slow-growing, mobile, subcutaneous nodule on the upper arm, initially presumed to be a benign lesion, most likely an angiolipoma. After excisional biopsy, histopathologic evaluation revealed an intermediate-grade leiomyosarcoma with focal dedifferentiation, demonstrating an abrupt transition from well-differentiated leiomyosarcoma to a high-grade, immunophenotypically undifferentiated sarcoma. Immunohistochemical staining showed loss of smooth muscle actin and desmin in the central dedifferentiated region, with retention of these stains at the peripheral lower-grade components. Wide local excision achieved clear margins, and imaging revealed no metastasis. Only 2 prior cases of cutaneous dedifferentiated leiomyosarcoma have been reported, both in the head and neck and with a more classic clinical presentation of a firm and immobile nodule. Our case is unusual in its location and deceptively benign clinical presentation. Given its aggressive potential and high reported rates of metastasis and mortality, prompt recognition and excisional biopsy are essential for diagnosis. This case highlights the importance of maintaining clinical suspicion for malignancy in persistent subcutaneous nodules and adds to the limited literature on dedifferentiated cutaneous leiomyosarcoma.