Search Results (71)

Background: Undifferentiated pleomorphic sarcoma (UPS) is a rare, high-grade soft-tissue sarcoma characterized by a patternless proliferation of bizarre pleomorphic tumor cells lacking identifiable lineage differentiation. Its occurrence in the oral cavity is exceptionally uncommon and poses significant diagnostic challenges due to its morphological overlap with a wide spectrum of other malignancies. Material and Methods: We report a novel case of oral UPS in a 54-year-old woman, characterized by an exceptionally large size and a rapidly progressive clinical course. The diagnostic evaluation included clinical, radiological, histopathological, immunohistochemical, and molecular analyses conducted within a multidisciplinary framework. A comprehensive review of the literature on oral UPS was also performed. Results: The patient underwent an aggressive demolitive surgical approach due to the extent of the lesion. Molecular analysis revealed a previously unreported SPECC1L::TERT gene fusion. The literature review highlighted the rarity of oral UPS, its geographic predilection for Central and East Asia, possible associations with traumatic events, and its heterogeneous clinical and histopathological presentations. Conclusions: This case underscores the critical importance of a thorough diagnostic workup to ensure the accurate diagnosis and appropriate management of this rare and aggressive tumor. Multidisciplinary evaluation is essential, especially in anatomically complex and diagnostically challenging presentations such as oral UPS. Full article

Background: There is an ongoing debate about the role of perioperative chemotherapy in retroperitoneal sarcoma (RPS). The aim of this study was to evaluate the effectiveness of perioperative chemotherapy in subtypes of RPS that are considered chemosensitive, including retroperitoneal angiosarcoma, undifferentiated pleomorphic sarcoma, myxoid liposarcoma, spindle cell sarcoma, and synovial sarcoma. Methods: This is a population-based retrospective cohort study. Patients with localized retroperitoneal sarcoma who underwent surgery were included from the US National Cancer Database (NCDB). After propensity score matching for the factors age, sex, grade, margin status, and tumor size, multivariable logistic and Cox regression analyses were used to identify factors associated with systemic therapy and their potential impact on the survival of patients with localized RPS. Results: We included 851 patients who underwent surgery between 2004 and 2020 (85% white, 41% female, and mean age 62 years). Of those, 227 patients (26.7%) received perioperative chemotherapy. In multivariable logistic regression, age ≤ 60 and tumor grading GIII/IV vs. GI/II were associated with a higher probability of receiving perioperative chemotherapy. After propensity score matching, we detected no difference in overall survival between patients who received chemotherapy and those who did not (HR 0.89, CI 0.55–1.43; and log-rank p = 0.92). Patient age ≤80 and tumor grading GI/II vs. GIII/IV were associated with improved overall survival. Conclusions: In this large analysis, the use of perioperative chemotherapy was not associated with improved survival in rare, chemosensitive subtypes of retroperitoneal sarcoma. However, selection bias must be considered when interpreting these findings. Full article

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are dermal-based sarcomas that fall along a spectrum with different rates of local recurrence and metastasis. While AFX is less aggressive and confined to the dermis, PDS invades the subcutis. These tumors are most likely of mesenchymal origin, although they share common mutations with undifferentiated squamous cell carcinoma. Due to the rarity of these tumors, few studies have examined their molecular composition and gene expression. Initial studies, including exome and bulk RNA sequencing, targeted DNA sequencing of gene panels, DNA methylation, and copy number analyses, have identified recurrent UV-induced mutations in TP53, NOTCH, CDKN2A, and the TERT promoter. Recently, the first scRNA-seq dataset in AFX and PDS identified COL6A3 as a novel biomarker. In this review, we synthesize the above datasets and discuss our current understanding of the molecular drivers and prognostic biomarkers in these tumors. Full article

Background: Primary intracardiac tumors may be diagnosed incidentally, sometimes in the case of complications. Case Report: This case report presents a 64-year-old woman who was admitted to the emergency department with cardiac complications, including heart palpitations and shortness of breath. Initial investigations revealed the presence of ground glass opacity in the left lung and significant mediastinal adenopathy. Transthoracic echocardiography (TTE) indicated severe mitral stenosis caused by a mass attached to the mitral valve, and the transesophageal echocardiography (TEE) confirmed the presence of a tumor, raising concerns about a myxoma with a high risk of embolism. The patient experienced transitory neurological dysfunction, and subsequent imaging uncovered a thrombus occluding the left internal carotid artery. An emergency surgical procedure was performed, including extracorporeal circulation and rapid deep cooling, to facilitate safe mass excision and carotid embolectomy. Histopathological analysis of the extracted tissue revealed undifferentiated pleomorphic sarcoma (FNCLCC Grade 3). Following the surgery, the patient needed extended mechanical ventilation and subsequently underwent a tracheostomy because of her ongoing respiratory support requirements. Conclusions: Despite the complexity of the surgical intervention, the prognosis remained poor due to the aggressive nature of the tumor and neurologic complications. This case underscores the rarity of primary cardiac sarcomas, the challenges in diagnosis, and the need for prompt surgical intervention to mitigate risks associated with embolic events. Full article

Background and Clinical Significance: Undifferentiated pleomorphic sarcoma (UPS) is a highly malignant soft tissue tumor formerly known as malignant fibrous histiocytoma. In the fifth edition of the WHO classification (2020), UPS is classified as an undifferentiated/unclassifiable sarcoma diagnosed via exclusion. While UPS commonly occurs in the extremities, its incidence in the head and neck region is rare (3%), with only a few reported cases in the oropharynx. Surgical resection is the primary treatment; however, tumors at the tongue base pose significant challenges due to the complex anatomy and the presence of critical neurovascular structures. This case highlights a rare instance of tongue-base UPS successfully treated with transoral videolaryngoscopic surgery (TOVS), demonstrating its feasibility as a minimally invasive approach. Case Presentation: A 68-year-old male presented with pharyngeal discomfort, dysphagia, and nocturnal dyspnea. Clinical examination revealed a pedunculated tumor originating from the left tongue base, occupying the pharyngeal cavity. Imaging studies showed a 5 cm mass without lymph node metastasis. A biopsy confirmed UPS (cT3N0M0). Given the tumor’s characteristics, TOVS was performed using an FK-WO TORS laryngo-pharyngoscope retractor. The tumor was resected with a ≥10 mm margin, achieving complete histological resection. The patient’s dyspnea resolved immediately, and oral intake resumed the next day. No adjuvant radiotherapy was administered, and no recurrence was observed for 50 months. Conclusions: This is the first reported case of UPS of the tongue base successfully resected using TOVS. This minimally invasive approach provides a safe and effective alternative for managing oropharyngeal UPS. Full article

Background/Objectives: To correlate size changes in undifferentiated pleomorphic sarcoma (UPS) on magnetic resonance imaging (MRI) after neoadjuvant chemoradiation therapy (nCRT) with pathological response, risk of local recurrence, and therapeutic regimens. Methods: This retrospective study analyzed clinical, pathological, and imaging data from 39 biopsy-proven UPS subjects. Four readers measured the tumor dimensions before and after nCRT, including two perpendicular axial diameters and the longest coronal/sagittal diameter. Three cross-sectional areas and bounding volume were also calculated. Responders (pR) were defined as having ≤10% viable cells and non-responders (pNR) as having more. Inter-reader agreement was evaluated using Kendall’s concordance coefficient. Changes in tumor size were compared between pR and pNR using one-way ANOVA and Tukey’s HSD test for multiple comparisons of means. Results: pR showed a greater increase in size across all measurements compared to pNR. For the longest axial diameter, the mean increase was 30% ± 35% for pR and 14% ± 31% for pNR, with a mean difference (pR-pNR) of 16% (95% CI: 6–27%, p = 0.003). In tumors treated with radiotherapy alone, pR exhibited larger size increases in all dimensions compared to pNR. In contrast, in the chemoradiation group, pR showed a slight increase, while pNR generally shrank, although these differences did not reach statistical significance. Notably, pNR with local recurrence exhibited a reduction in all tumor dimensions compared to pNR without local recurrence. Conclusions: This exploratory study suggests that tumor size changes may predict pathological response and local recurrence after nCRT in UPS; however, the small sample size limits the generalizability of these findings. Full article

There has been noteworthy progress in molecular characterisation and therapeutics in soft tissue sarcomas. Novel agents have gained regulatory approval by the FDA. Examples are the tyrosine kinase inhibitors avapritinib and ripretinib in gastrointestinal stromal tumours (GIST), the immune check point inhibitor atezolizumab in alveolar soft part tissue sarcoma, the γ-secretase inhibitor nirogacestat in desmoid tumours, the NTRK inhibitors larotrectinib and entrectinib in tumours with NTRK fusions, the mTOR inhibitor nab-sirolimus in PEComa, and the EZH-2 inhibitor tazemetostat in epithelioid sarcoma. The FDA has also recently granted accelerated approval for autologous T-cell therapy with afami-cel in patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. There are other promising treatments that are still investigational, such as MDM2 and CDK4/6 inhibitors in well-/dedifferentiated liposarcoma, immune checkpoint inhibitors in the head and neck angiosarcoma and a subset of patients with undifferentiated pleomorphic sarcoma, and PARP inhibitors in leiomyosarcoma. The challenges in drug development in soft tissue sarcoma are due to the rarity and the molecular heterogeneity of the disease and the fact that many subtypes are associated with complex karyotypes or non-targetable molecular alterations. We believe that progress maybe possible with a better understanding of the complex biology, the development of novel compounds for difficult targets such as proteolysis targeting chimeras (Protacs), the utilisation of modern clinical trial designs, and enhanced collaboration of academia with industry to develop treatments with a strong biologic rationale. Full article

Background: Undifferentiated pleomorphic sarcoma (UPS) is a highly malignant mesenchymal tumor that ranks as one of the most common types of soft tissue sarcoma. Even though chemotherapy increases the 5-year survival rate in UPS, high tumor heterogeneity frequently leads to chemotherapy resistance and consequently to recurrences. In this study, we characterized the cell composition and the transcriptional profile of UPS with resistance to chemotherapy at the single cell resolution. Methods: A 58-year-old woman was diagnosed with a 13.6 × 9.3 × 6.0 cm multi-nodular tumor with heterogeneous cysto-solid structure at the level of the distal metadiaphysis of the left thigh during magnetic resonance tomography. Morphological and immunohistochemical analysis led to the diagnosis of high-grade (G3) UPS. Neoadjuvant chemotherapy, surgery (negative resection margins), and adjuvant chemotherapy were conducted, but tumor recurrence developed. The UPS sample was used to perform single-cell RNA sequencing by chromium-fixed RNA profiling. Results: Four subpopulations of tumor cells and seven subpopulations of tumor microenvironment (TME) have been identified in UPS. The expression of chemoresistance genes has been detected, including KLF4 (doxorubicin and ifosfamide), ULK1, LUM, GPNMB, and CAVIN1 (doxorubicin), and AHNAK2 (gemcitabine) in tumor cells and ETS1 (gemcitabine) in TME. Conclusions: This study provides the first description of the single-cell transcriptome of UPS with resistance to two lines of chemotherapy, showcasing the gene expression in subpopulations of tumor cells and TME, which may be potential markers for personalized cancer therapy. Full article

MicroRNAs (miRNAs) are pivotal regulators of gene expression, influencing key cellular processes such as proliferation, differentiation, apoptosis, and metastasis. In the realm of sarcomas—a diverse group of malignant tumors affecting soft tissues and bone sarcomas—miRNAs have emerged as crucial players in tumorigenesis and tumor progression. This review delves into the intricate roles of miRNAs across various soft tissue sarcoma subtypes, including rhabdomyosarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, fibrosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma (UPS), and malignant peripheral nerve sheath tumor (MPNST). We explore how dysregulated miRNAs function as oncogenes or tumor suppressors, modulating critical pathways that define the aggressive nature of these cancers. Furthermore, we discuss the diagnostic and prognostic potential of specific miRNAs and highlight their promise as therapeutic targets. By understanding the miRNA-mediated regulatory networks, this review aims to provide a comprehensive overview of current research while pointing towards future directions for miRNA-based therapies. Our findings underscore the potential of miRNAs to transform the landscape of sarcoma treatment, offering hope for more precise, personalized, and effective therapeutic strategies. Full article

Purpose: Brain metastases (BM) in sarcomas occur rarely and are associated with poor prognosis. This study is a large retrospective cohort describing the demographic and clinical characteristics of these patients, treatment strategies, and survival outcomes. Methods: In total, 81 patients with BM from sarcomas were identified across five sarcoma centers. Demographic data, clinical presentation, and treatment modalities were analyzed. Results: The most common histologies were leiomyosarcoma (12.3%) and undifferentiated pleomorphic sarcoma (12.3%). The median time from sarcoma diagnosis to brain metastases was 1.9 years. Upon presentation, 88.9% of patients with BM from sarcomas were symptomatic with the most common presenting symptom being focal neurological deficits (37.9%) and headaches (22.1%). Higher-grade sarcomas were more likely to metastasize and were usually preceded by metastases to other sites, most commonly the lungs. One-year overall survival was 31% from initial sarcoma diagnosis, and the median time from diagnosis of BM until death was 6.0 months. For treatment, 60 (74.1%) patients had radiation, 39 (48.1%) patients had systemic therapy, and 29 (35.8%) patients had surgery. In a multivariate analysis, surgery (HR 0.30) and chemotherapy (HR 0.23) were found to be significantly correlated with improved survival outcomes. Although radiation as a whole was not found to significantly correlate with survival, improved outcomes were seen with stereotactic radiosurgery (SRS, mOS 11.6 mo) as opposed to whole-brain radiation therapy (WBRT, mOS 8.3 mo). Additionally, patients with leptomeningeal disease were significantly less likely to survive more than one year compared to patients with brain metastases only. Conclusions: Our findings identify that patients with metastatic sarcoma to the brain have poor prognoses, often have concurrent metastasis, and have a median survival of only 6 months. Additionally, our study found that leptomeningeal metastases is a rare presentation with poor survival outcomes. There are various treatment modalities for sarcomas with BM; however, there are no guidelines, unlike in other malignancies. Further research is necessary to evaluate the role of therapeutic measures in terms of type, timing, and outcomes. Full article

Undifferentiated pleomorphic sarcoma (UPS) is an aggressive soft tissue sarcoma with a poor prognosis. The patients are usually found to have metastasis when the primary tumor is diagnosed. Eccrine syringofibroadenoma (ESFA) is a rare cutaneous adnexal lesion of eccrine duct origin. There are five subtypes, one of which is reactive ESFA, known to occur in reaction to an inflammatory or neoplastic process. In this article, we report a case of the co-existence of both UPS and ESFA in a 70-year-old male patient, presenting with a painless, erythematous, irregular surface nodule with a peripherally extended brownish hyperkeratotic plaque on the right palm. The histologic findings revealed an ill-defined dermal tumor of atypical epithelioid and spindle-shaped cells with large pleomorphic hyperchromatic nuclei and abundant eosinophilic cytoplasm. Some of those cells were multinucleated giant cells in the stroma with vascular proliferation and mixed inflammatory cell infiltrate. The tumor cells, which were only positive for vimentin, supported the diagnosis of undifferentiated pleomorphic sarcoma (UPS). Meanwhile, the overlying epidermis demonstrated hyperkeratosis, papillated epidermal hyperplasia, and proliferation of anastomosing slender cords and strands of cuboid cells within loose fibrovascular stroma. These findings are the characteristics of eccrine syringofibroadenoma (ESFA). We describe here a patient in whom reactive ESFA occurred on and surrounded the UPS tumor. Full article

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. Full article

Myxofibrosarcoma (MFS), an aggressive soft tissue sarcoma, is one of the undifferentiated pleomorphic sarcomas; it has a low incidence, affecting people in the sixth to eighth decades of life. It usually involves the extremities and is painless with a slow-growing pattern. Based on the case of a 52-year-old female patient who presented with a painful, massive, rapid-growing, ulcerated tumor of the anterior surface of the left thigh, we performed a literature review regarding the current standard of care for patients with MFS. Computed tomography examination, followed by magnetic resonance imaging and surgical biopsy with histopathological examination, confirmed the diagnosis and the presence of lung and inguinal lymph node metastases. Due to the rapid-growing pattern and the local aggressiveness, our tumor board team recommended emergency excisional surgery, with subsequent reconstructive procedures followed by referral to an oncological center. This review emphasizes the importance of proper and rapid diagnosis, followed by multidisciplinary management, for MFS cases with atypical presentation and distal metastases to improve overall outcomes. Full article

Poor long-term survival in localized high-risk soft tissue sarcomas (STSs) of the extremities and trunk highlights the need to identify new prognostic factors. CXCR4 is a chemokine receptor involved in tumor progression, angiogenesis, and metastasis. The aim of this study was to evaluate the association between CXCR4 expression in tumor tissue and survival in STSs patients treated with neoadjuvant therapy. CXCR4 expression was retrospectively determined by immunohistochemical analysis in serial specimens including initial biopsies, tumors post-neoadjuvant treatment, and tumors after relapse. We found that a positive cytoplasmatic expression of CXCR4 in tumors after neoadjuvant treatment was a predictor of poor recurrence-free survival (RFS) (p = 0.003) and overall survival (p = 0.019) in synovial sarcomas. We also found that positive nuclear CXCR4 expression in the initial biopsies was associated with poor RFS (p = 0.022) in undifferentiated pleomorphic sarcomas. In conclusion, our study adds to the evidence that CXCR4 expression in tumor tissue is a promising prognostic factor for STSs. Full article

Radiation-associated sarcomas (RASs) are rare tumors with limited contemporary data to inform prognostication and management. We sought to identify the clinical presentation, patterns of care, and prognostic factors of RASs. RAS patients treated at a single institution from 2015 to 2021 were retrospectively reviewed for clinicopathologic variables, treatment strategies, and outcomes. Thirty-eight patients were identified with a median follow-up of 30.5 months. The median age at RAS diagnosis was 68.4 years (27.9–85.4), with a median latency from index radiotherapy (RT) of 9.1 years (3.7–46.3). RAS histologies included angiosarcoma (26%), undifferentiated pleomorphic sarcoma (21%), and osteosarcoma (18%). Most were high-grade (76%). Genomic profiling revealed low tumor mutational burden, frequent inactivating TP53 mutations (44%), CDKN2A deletions (26%), and MYC amplifications (22%), particularly in breast angiosarcomas. Of 38 patients, 33 presented with localized disease, 26 of whom were treated with curative intent. Overall, the median progression-free survival (PFS) was 9.5 months (1.4–34.7), and the overall survival (OS) was 11.1 months (0.6–31.6). Patients with localized vs. metastatic RASs had a longer PFS (HR, 3.0 [1.1–8.5]; p = 0.03) and OS (HR, 3.0 [1.04–8.68]; p = 0.03). Among localized RAS patients, high grade was associated with shorter OS (HR, 4.6 [1.04–20.30]; p = 0.03) and resection with longer OS (mean 58.8 vs. 6.1 months, HR, 0.1 [0.03–0.28]; p < 0.001). Among patients undergoing resection, negative margins were associated with improved OS (mean 71.0 vs. 15.5 months, HR, 5.1 [1.4–18.2]; p = 0.006). Patients with localized disease, particularly those undergoing R0 resection, demonstrated significantly better outcomes. Novel strategies are urgently needed to improve treatment outcomes in this challenging group of diseases. Full article