Search Results (927)

Desmoid-type fibromatosis (DT) is a rare, locally aggressive soft tissue tumor with a frequently chronic course and substantial impact on health-related quality of life (HRQoL). While international studies have demonstrated considerable symptom burden and psychosocial impairment, data from Germany are lacking. This study aimed to assess HRQoL in German patients and to identify factors associated with HRQoL. In this cross-sectional analysis, adult patients with histologically confirmed DT completed the EORTC QLQ-C30 and the disease-specific Desmoid-Type Fibromatosis Quality of Life Questionnaire (DTF-QoL). HRQoL scores were compared with reference data from the German general population, German sarcoma patients, and international DT cohorts. Sociodemographic, disease-, tumor-, and treatment-related factors associated with HRQoL were examined using multivariate linear regression analyses. A total of 155 patients were included (69.7% female; mean age 45.0 years). Compared with the German general population, DT patients reported clinically relevant impairments in role, social, and emotional functioning and higher symptom burden, particularly pain, fatigue, and insomnia. Compared with sarcoma patients, DT patients showed better physical, role, and social functioning, while emotional functioning and symptom burden were largely comparable. German DT patients reported consistently worse HRQoL than Dutch/UK cohorts and moderately worse outcomes than Indian cohorts. Female gender, unemployment or disability pension, intensive multimodal treatment, multiple lines of systemic therapy, and tumor location in the lower extremities were independently associated with poorer HRQoL. DT is associated with sustained and clinically meaningful HRQoL impairment. HRQoL is driven primarily by psychosocial and treatment-related factors rather than disease duration, supporting the concept of DT as a chronic condition requiring long-term, multidisciplinary supportive care. Full article

Introduction: Myxoid liposarcoma (MLPS) is a rare soft tissue sarcoma comprising 5–10% of adult cases, most often in the thigh. Diagnosis is challenging due to nonspecific imaging findings and resemblance to benign lesions. Case Report: A 42-year-old male presented with a painless, enlarging upper right medial thigh mass. CT and ultrasound suggested a complex solid lesion, possibly benign. Outpatient surgical excision revealed a red, gelatinous, non-encapsulated mass. Frozen section suggested a myxomatous spindle cell tumor. Final pathology confirmed MLPS FNCLCC grade 2 (intermediate grade) with DDIT3 rearrangement on fluorescence in situ hybridization (FISH). Margins were negative but close. Postoperative PET scan and Signatera MRD assay were negative for metastasis. Given the tumor’s size (>10 cm) and known radiosensitivity, adjuvant radiotherapy (60–66 Gy) was initiated. Discussion: MLPS features myxoid stroma, plexiform vasculature, and, in high-grade tumors, a round cell component. The FUS::DDIT3 fusion gene is diagnostic. While MRI offers superior soft tissue characterization, definitive diagnosis requires pathology and molecular testing. Surgical excision with negative margins remains standard, with radiotherapy recommended for large tumors or close margins to reduce recurrence. This case highlights the limitations of preoperative imaging and the value of intraoperative pathology in guiding management. Conclusions: Early recognition, accurate diagnosis, and tailored multimodal treatment are essential for MLPS. Given the potential for recurrence, late extrapulmonary metastases, long-term surveillance with imaging, and molecular assays are critical for optimizing outcomes. Full article

Background: Timely treatment is critical for patients with bone and soft tissue tumors, but access to care may not be equitable across all populations. While treatment delays have been well studied in other cancers, disparities in time to treatment remain underexplored in orthopaedic oncology. This study aimed to determine whether racial or ethnic disparities exist in the timing of surgery, chemotherapy, or radiation for patients with sarcoma or metastatic bone disease. Methods: A retrospective cohort study was conducted using the TriNetX US Collaborative Network, a multi-institutional electronic health record database. Adult patients undergoing biopsy and subsequently diagnosed with bone sarcoma, soft tissue sarcoma, or metastatic bone disease were identified. Time to treatment was defined as the number of days between biopsy and the first recorded surgery, chemotherapy, or radiation. Patients were stratified by race and ethnicity, and statistical comparisons were performed using Mann–Whitney U tests and t-tests. Results: A total of 63,087 patients met inclusion criteria (55,697 with metastatic bone disease/bone sarcoma and 7390 with soft tissue sarcoma). In the metastatic/bone sarcoma cohort, Hispanic patients had shorter mean time to resection (58 ± 94 vs. 82 ± 239 days, p = 0.008) and fixation (35 ± 142 vs. 72 ± 315 days, p < 0.001) compared to non-Hispanic patients, although median times did not differ significantly. Among black patients, time to fixation was shorter than in White patients (mean 22 ± 103 vs. 114 ± 468 days, p < 0.001; median 0 days in both groups), while delays were observed in time to radiation (median 13 vs. 7 days; mean 85 ± 284 vs. 43 ± 203 days, p < 0.001). In the soft tissue sarcoma cohort, Black patients experienced longer mean times to resection (142 ± 293 vs. 79 ± 216 days) and radiation (141 ± 514 vs. 96 ± 364 days), though comparisons were limited by sample size. Conclusions: This large, multi-institutional study demonstrates that disparities in orthopaedic oncology differ by treatment modality and clinical context. Shorter wait times to surgery among Hispanic and Black patients in metastatic disease likely reflect more advanced disease presentation and barriers to early access, whereas delays in resection and radiation highlight inequities in accessing non-emergent, coordinated oncologic care. Reporting both means and medians provides a more complex understanding of treatment delays and underscores the need for interventions that expand early access to orthopaedic oncologists and ensure timely, equitable care. Full article

Soft-tissue sarcomas (STSs) comprise a rare, heterogeneous group of mesenchymal malignancies in which histologic grade remains the strongest determinant of outcome, metastatic risk, and therapeutic strategy. Intermediate/high-grade STSs exhibit a pronounced propensity for early distant relapse, yet growing evidence indicates that metastatic behaviour is not uniform. Within this spectrum, an oligometastatic phenotype, characterised by a limited number of metastases, often confined to the lung, has emerged as a clinically and biologically distinct state associated with more indolent metastatic kinetics and improved survival when treated with aggressive local interventions. However, the criteria that define true oligometastatic STSs remain unsettled, and prospective evidence is lacking. Emerging molecular and immunological correlates provide a potential framework for biological triage. Low genomic complexity (low-risk CINSARC), a B-cell/TLS-rich tumour microenvironment, high immune-cytotoxic signatures, and persistently low or undetectable circulating tumour DNA (ctDNA) are each linked to reduced metastatic competence and may underpin oligometastatic trajectories. Conversely, high chromosomal instability, immunosuppressive microenvironments, and elevated ctDNA levels align with covertly polymetastatic biology despite limited radiographic disease. In this context, artificial intelligence and machinelearning approaches applied to computational genomics, immune profiling, imaging, and liquid-biopsy data offer a powerful strategy to integrate these multi-dimensional features and refine predictions of metastatic behaviour in STS. Oligometastatic STS therefore represents a biologically definable subset amenable to multimodal management integrating local ablative therapies, systemic agents, and immune-based strategies. Prospective, biomarker-stratified trials are needed to validate selection frameworks and optimise treatment sequencing in this evolving therapeutic space. Full article

Soft tissue sarcomas are rare malignant mesenchymal tumors for which accurate diagnosis, prognostic stratification, and therapeutic decision-making remain challenging. Although histopathology and immunohistochemistry are essential diagnostic tools, they frequently fail to capture the molecular complexity underlying tumor aggressiveness and treatment resistance. In this study, we evaluated the utility of RNA-based next-generation sequencing for the molecular characterization of STS and for elucidating transcriptomic mechanisms associated with aggressive tumor behavior. An observational cohort of 24 patients with histologically confirmed soft tissue sarcomas was analyzed, using adipose and skeletal muscle tissue as controls. RNA was extracted from tumor samples, libraries were prepared with a targeted pan-cancer panel, and sequencing was performed on the Illumina platform, followed by bioinformatic analysis using DRAGEN pipelines and DESeq2. RNA-NGS identified a predominance of single-nucleotide polymorphisms and significant differential gene expression, with overexpression of proliferation-related genes (TOP2A, MKI67, BUB1B), extracellular matrix and microenvironment-associated genes (COL11A1, SPP1), and developmental regulators (HOXD13, MELK). Subgroup analysis revealed a distinct transcriptomic profile in leiomyosarcoma, while gene fusion analysis detected clinically relevant alterations. These findings demonstrate that RNA-NGS provides biologically and clinically meaningful insights into the molecular landscape of soft tissue sarcomas and supports its integration into precision medicine-oriented diagnostic workflows. Full article

Background/Introduction: Soft tissue sarcomas (STS) represent a diverse group of rare cancers that have variable responses to chemotherapy. Although tumor size is an established prognostic factor, its influence on the benefit of chemotherapy within specific histologies is not well understood. Methods: We conducted a retrospective analysis of 3890 patients with five STS subtypes using SEER data from 2000 to 2021. Patients were stratified by tumor size (<5 cm, 5–10 cm, >10 cm) and propensity score matched within each subtype-size cohort to control for confounders. Cox regression assessed the impact of chemotherapy on overall survival, with results presented as hazard ratios (HR) and 95% confidence intervals (95%-CI). Inverse probability of treatment weighting (IPTW) was used to improve selection bias. Results: Chemotherapy use in UPS demonstrated worse survival in smaller tumors <5 cm (HR = 2.65, 95%-CI = 1.19–5.92, p = 0.018) and 5–10 cm tumors (HR = 1.45, 95%-CI = 1.03–2.04, p = 0.031). In larger UPS tumors (>10 cm), a directionally protective association observed in matched analysis attenuated after inverse probability of treatment weighting (IPTW) (HR = 0.82, 95%-CI = 0.60–1.12, p = 0.211). Fibromyxosarcoma 5–10 cm tumors demonstrated worse survival with chemotherapy (matched HR = 3.74, 95%-CI = 2.30–6.10, p < 0.001), which remained consistent after IPTW (HR = 4.47, 95%-CI = 2.63–7.60, p < 0.001), along with >10 cm tumors (IPTW HR = 2.16, 95%-CI = 1.07–4.34, p = 0.031). DDLPS >10 cm tumors demonstrated a directionally harmful association (HR = 1.49, 95%-CI = 0.96–2.29, p = 0.073). Synovial sarcoma 5–10 cm tumors demonstrated a directionally protective trend that remained statistically non-significant across analyses. Conclusions: The effect of chemotherapy on survival in localized STS depends on both histologic subtype and tumor size. However, subgroup estimates with confidence intervals approaching 1.0 should be interpreted cautiously. Full article

Background: Soft tissue sarcomas are rare and highly heterogeneous malignant tumors, often asymptomatic in the early stages. Accurate diagnosis and reliable assessment of the risk of metastasis, classified as low, intermediate, or high, are therefore essential for effective clinical decision-making. However, the application of Artificial Intelligence (AI) approaches to these diseases is often limited by the small size and quality of available datasets, which can compromise model robustness and reliability. Methods: The use of formal methods, based on mathematical modeling and logical verification, can be an alternative to AI techniques. When integrated with radiomics, formal methods provide a structured and interpretable approach to support disease diagnosis. Results: The proposed methodology yielded encouraging results, in line with those reported in the literature. A process was conducted to extract several first- and second-order radiomic classes, which were then selected based on their significance. The resulting models were evaluated using standard performance metrics and obtained 80% accuracy, 83% precision, and 83% recall. Conclusion: The transparency of formal methods improves the interpretability of models and radiomic features, allowing new links with clinical practice to be discovered. The proposed approach is presented as a feasibility and proof-of-concept framework aimed at improving interpretability. Given the very small cohort size, performance metrics should be considered preliminary and descriptive, as they require validation on larger external datasets before any clinical applicability can be claimed. Full article

Background: Inguinoscrotal sarcomas are a rare sarcoma subtype. The treatment of choice is radical inguinal orchiectomy with wide local resection of the surrounding soft tissues. However, consensus regarding prognostic factors is lacking. We present our experience at a referral sarcoma center concerning the management, oncologic results, and prognostic factors pertaining to this disease. Methods: We conducted a retrospective analysis of patients who underwent surgery for inguinoscrotal sarcomas between 2005 and 2023 at a sarcoma referral hospital. Results: The study included 39 patients. The most frequent histology was liposarcoma. Seven patients required surgical reconstruction with a microvascularized free flap. Four patients presented major postoperative complications. Mean follow-up was 46 months. Overall survival rates were 97.4%, 81.7%, and 64.8% at one, three, and five years. High-grade tumors were correlated with worse overall and disease-free survival. Conclusions: The chance finding of a sarcoma in the inguinal region poses a diagnostic and therapeutic dilemma when considering options for treatment with curative intent. Vascular and muscle resection followed by vascular and/or free flap reconstruction may be necessary to achieve complete surgical resections; therefore, a multidisciplinary approach is needed. A preoperative biopsy should be performed to establish the histological grade, which may be the main prognostic factor. Full article

Background: Fusion-negative rhabdomyosarcoma (FNRMS) represents the most prevalent subtype of rhabdomyosarcoma, the most common pediatric soft-tissue sarcoma. Although its invasion is a leading cause of recurrence and poor prognosis, its underlying mechanism remains unclear. We investigated how extracellular matrix density regulates FNRMS progression via mechano-transduction. Methods: We used three-dimensional spheroid invasion assays with FNRMS cells embedded in varying collagen concentrations. Mechanistic insights were gained through immunofluorescence, sequencing reanalysis, calcium live-cell imaging, and pharmacological inhibition of the YAP–PIEZO1 axis. Results: High extracellular matrix density significantly enhanced invasive spreading, correlating with increased YAP nuclear localization. YAP overexpression was sufficient to promote invasive spreading, while its inhibition attenuated the matrix-enhanced phenotype. We identified PIEZO1 as a direct transcriptional target of YAP. High extracellular matrix density stimulated PIEZO1-dependent calcium influx, which was required for invasion. Furthermore, elevated PIEZO1 expression was significantly associated with poorer overall survival in FNRMS patients. Targeting YAP effectively suppressed both calcium flux and invasion. Conclusions: Our findings establish a YAP–PIEZO1 axis linking extracellular matrix density to FNRMS invasion. This mechanosensitive pathway represents a potential therapeutic vulnerability in aggressive FNRMS. Full article

Background: The necessity of a pre-therapeutic biopsy for soft tissue tumors is assessed differently depending on imaging. We examined the concordance of histopathological and radiological imaging-based diagnoses of soft tissue tumors in a monocentric, multidisciplinary sarcoma board. Methods: From October 2022 to December 2024, we prospectively included 184 patients presenting with preoperative imaging but without prior histology who are presented at the multidisciplinary sarcoma board of the University Hospital of Erlangen. We evaluated tumor dignity (benign/malignant) and most probable tumor subtype based on cross-sectional imaging assisted by the demographic and anatomic characteristics of individual cases. This assessment was then compared with the final pathological results. Results: We classified 75 tumors as benign and 109 tumors as malignant. Of the 75 patients with a suspected benign tumor, 66 (88%) had a benign diagnosis confirmed by pathological assessment, while two (2.7%) had a malignant tumor and seven (9.3%) an intermediate biology tumor. Of the 109 patients with suspected malignant tumors, 69 (63.3%) had a malignant pathology, while 30 (27.5%) had a benign pathology, and 10 (9.2%) an intermediate tumor. Matching the multidisciplinary sarcoma board’s assessment with the pathological results revealed significant sensitivity and a negative predictive value for malignant tumors, as well as a significant positive predictive value and specificity for benign tumors. Conclusions: The study shows that, despite the high degree of predictability at an experienced sarcoma center, imaging cannot completely replace biopsies and caution should be exercised when deciding against a biopsy. It is emphasized that the decision not to perform a biopsy can only be made in cases where lipomatous tumors appear benign in imaging procedures, and only in an experienced center. Full article

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 <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. Full article

Objectives: Intramuscular myxomas (IMMs) are rare benign soft tissue tumors arising within large skeletal muscles. Their etiology is incompletely understood, but they are frequently associated with mutations (e.g., GNAS) and may occur in syndromic conditions such as Mazabraud and McCune–Albright syndromes. This study retrospectively analyzed clinical, radiological, histopathological, and molecular features of IMMs, including syndromic associations. Methods: A retrospective analysis was performed on 41 patients diagnosed with IMM who underwent biopsy or surgical resection between September 2011 and September 2022. Clinical, imaging, histopathological, and molecular data were evaluated using descriptive statistics. Results: The cohort included 27 females and 14 males with a mean age of 52.8 years. The most common tumor location was the quadriceps femoris, followed by other thigh muscles. Most patients presented with mild symptoms due to slow tumor growth. MRI was performed in all but one case, with additional imaging in 12 patients. Radiological differential diagnoses commonly included soft tissue sarcoma and hematoma. Complete tumor resection was achieved in 90.2% of patients. Immunohistochemistry was performed in 78.0%, most frequently showing CD34 positivity. GNAS mutation analysis was conducted in 85.4% of cases and was positive in 57.1%. Complications occurred in 9.8%, and no recurrences were observed during follow-up. Conclusion: IMMs are rare benign tumors that can be reliably diagnosed using histology supported by immunohistochemistry and GNAS mutation analysis. Complete surgical resection provides excellent outcomes with a low risk of complications or recurrence. Mazabraud syndrome should be considered in patients with multiple or recurrent IMMs and GNAS mutations. Full article

Background: Vascular leiomyosarcoma (LMS) is an exceptionally rare and aggressive soft tissue sarcoma arising from the smooth muscle cells of the vascular wall. They account for approximately 0.5–2% of adult soft-tissue sarcomas and are the most frequent primary malignancy of vascular origin. Among venous sites, the inferior vena cava (IVC) is the most frequently involved, accounting for more than half of reported vascular LMS cases, with rarer occurrences in peripheral veins, including the internal saphenous vein and the external iliac vein. Case Presentation: We report a case series comprising two distinct presentations of vascular LMS involving the internal saphenous vein and the inferior vena cava, respectively. Each case highlights unique clinical manifestations, radiologic features, histopathologic diagnosis, and therapeutic challenges inherent to the involved vascular territory. Surgical resection with clear margins was the primary treatment modality, complemented by adjuvant therapies tailored according to tumor grade and extent. Literature Review: An updated literature review contextualizes these findings, detailing epidemiology, diagnostic challenges, prognostic factors, and current management approaches. It emphasizes the rarity of leiomyosarcomas originating from major venous pathways and highlights variability in clinical presentation, tumor size, growth patterns, and outcomes. Achieving complete surgical removal with negative margins continues to be the primary treatment goal and the most significant prognostic factor. Conclusions: Given the paucity of cases, our series contributes valuable insights into the clinical spectrum and multidisciplinary approach necessary for optimal outcomes in vascular LMS. Early recognition and aggressive treatment remain paramount to improving survival in this rare malignancy. Full article

Chondrosarcoma (ChS) is a rare bone malignancy with heterogeneous behavior, the molecular and immunological background of which remains unknown. No effective systemic treatment for advanced ChS patients is available. The aim of this study was to develop an immune–mutational classification of ChS and to search for novel prognostic factors and molecular targets. We performed an immunological–molecular profiling of 99 patients diagnosed with primary ChS G1–G3 and dedifferentiated ChS. An expression of 20 immune response markers was assessed by IHC and targeted the next-generation sequencing of 409 genes was performed. Immunological and mutational profiles were correlated with overall survival using a multivariate LASSO-penalized Cox model. Three immunophenotypes were described—“cold” (IMP1), “hot” (IMP2), and “intermediate” (IMP3). IMP1 was the most prevalent in G1 cases, while IMP2 was the most prevalent in dedifferentiated cases. IDH1/2 or TP53 mutations were associated with high-grade ChS (FDR < 0.05). IMP2 was characterized by a higher number of immune infiltrates in the central region of the tumor (HR: 3.3; CI: 1.13–9.8; p < 0.05). IDH1 mutations were present most often in IMP2 cases (HR: 3.8; CI: 1.75–8.1; p < 0.001). Tumor size, dedifferentiated subtype, IDH1 mutation and the presence of IMP2 were identified as independent negative prognostic survival factors in ChS. An immune–mutational classification system for ChS patients was proposed, which may be used to identify those potentially suited for immunotherapy combined with IDH-mutant inhibitors in future research. Full article

Background: Dendritic and histiocytic cell sarcoma (DHCS) and clear cell sarcoma (CCS) are ultra-rare soft-tissue sarcomas characterized by diagnostic ambiguity, limited treatment guidelines, and poor outcomes. Their rarity has restricted the development of evidence-based management strategies, leaving clinical decisions reliant on small case series and institutional experience. DHCS typically presents without a unifying molecular driver and is often misclassified without comprehensive immunophenotyping. CCS is defined by EWSR1-ATF1/CREB1 fusions but exhibits low responsiveness to conventional chemotherapy. There remains a clear need to clarify natural history, therapeutic responses, and molecular characteristics in both. Methods: We conducted a retrospective cohort study of adult patients with histologically confirmed DHCS or CCS seen at The Ohio State University Comprehensive Cancer Center between 2010 and 2022. Demographics, treatment modalities, clinical outcomes, and molecular profiles were extracted and analyzed descriptively. Time to progression (TTP) and progression rates by treatment modality were recorded. A structured literature review was conducted to provide context for the findings. Results: Outcomes are descriptive and cohort-specific, reflecting institutional experience rather than generalizable estimates. A total of 10 patients with DHCS and 5 with CCS were evaluable. Most DHCS patients presented with metastatic disease. Among DHCS patients who received systemic therapies, 5 of 8 (62.5%) experienced progression during or shortly after treatment. Among CCS patients who received systemic therapies, 3 of 4 (75%) progressed during or shortly after treatment. Overall mortality occurred in 4 of 10 DHCS patients (40%) and 3 of 5 CCS patients (60%). TP53 mutations were identified in 4 of 7 next-generation sequencing (NGS)-tested DHCS cases, and PD-L1 positivity was detected in 5 of 7 tested DHCS cases and 1 of 5 tested CCS cases. Conclusions: Despite multimodal treatment, this referral-based cohort of patients with ultra-rare DHCS and CCS showed high rates of progression and mortality. Our findings underscore the urgent need for multi-institutional collaboration and biomarker-driven clinical trials to guide management of these ultra-rare sarcoma subtypes. Full article