Search Results (565)

Background: Soft tissue sarcomas (STSs) are a rare and heterogeneous group of mesenchymal tumors with limited response to current therapies, particularly in advanced stages. STS tumors were traditionally considered “cold” tumors, characterized by limited immune infiltration and low immunogenicity. However, emerging evidence is challenging this perception, highlighting a potentially critical role for the immune system in STS biology. Objective: Building on our previous findings suggesting impaired natural killer (NK) cell activity in STS patients, we aimed to perform an in-depth characterization of peripheral NK cells in STS. Methods: Peripheral blood samples from STS patients and sex- and age-matched healthy donors were analyzed to assess NK cell degranulation, IFNγ production, and receptor repertoire. Results: Functional assays revealed a notable reduction in both degranulation and IFNγ production in NK cells from STS patients. STS patients also exhibited dysregulated expression of activating and inhibitory NK cell receptors. Principal component analysis (PCA) identified CD27 and NKp44 as critical markers for distinguishing STS patients from healthy donors. Increased CD27 expression represents a shift towards a more regulatory NK cell phenotype, and we found that CD27 expression was negatively correlated with NK cell degranulation and IFNγ production. ROC curve analysis demonstrated strong potential to distinguish between the groups for both CD27 (AUC = 0.85) and NKp44 (AUC = 0.94). Conclusion: In conclusion, STS patients exhibited impaired NK cell function, altered receptor repertoire, and a shift towards a less cytotoxic and more regulatory phenotype. Full article

Background and Clinical Significance: Myxoid liposarcoma (MLS) is a malignant soft tissue tumor that often presents as a painless, slow-growing mass and is known for its atypical extrapulmonary metastatic pattern. Although sciatic nerve involvement is rare, when present, it usually causes neurologic symptoms. In this case, a large MLS silently expanded and completely encased the sciatic nerve without causing deficits, highlighting the importance of early imaging, multidisciplinary planning, and individualized surgical strategy in managing complex soft tissue sarcomas. Case Presentation: This case report describes a 67-year-old male with a 30 cm encapsulated myxoid liposarcoma of the posterior left thigh. The tumor had grown insidiously over one year and completely encased the sciatic nerve without causing pain, paresthesia, or motor impairment. Selective embolization was performed preoperatively to minimize blood loss. A posteromedial surgical approach allowed for en bloc resection with negative margins and preservation of sciatic nerve integrity. Histopathology confirmed a myxoid liposarcoma composed primarily of spindle-shaped tumor cells. The patient experienced no postoperative complications or neurologic deficits. At the two-year follow-up, he remains disease-free with full functional recovery. Conclusions: This case illustrates the potential for large, asymptomatic myxoid liposarcomas to encase critical neurovascular structures without infiltration. Preoperative embolization as part of a multidisciplinary plan was key to achieving safe resection and excellent functional outcomes. Full article

Osteosarcoma is one of the most common primary bone malignancies, typically occurring around the knee. However, the forearm is a rare site, with tumors in the proximal ulna being extremely uncommon. Primary sarcoma in this location presents a surgical challenge due to the complex anatomy and limited reconstructive options. We report a rare case of a 19-year-old female with non-metastatic, high-grade giant cell-rich osteosarcoma involving the right proximal ulna. To our knowledge, this is only the second reported adult case of this histological subtype in this location. The patient was treated at a specialized oncology center with neoadjuvant and adjuvant chemotherapy, along with wide intra-articular resection for local tumor control. Reconstruction was achieved using a novel, customized 3D-printed articulating cement spacer mold with plate osteosynthesis. Artificial elbow ligamentous reconstruction was performed using FiberTape and FiberWire sutures passed through drill holes, and the triceps tendon was reattached to the cement mold using an endobutton. This cost-effective and personalized surgical approach allowed successful joint reconstruction while maintaining elbow stability and function. Our case highlights a feasible reconstructive option for rare and anatomically challenging osteosarcoma presentations, contributing to the limited literature on proximal ulna giant cell-rich osteosarcoma. Full article

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: Liposarcoma (LPS) is a rare malignant tumor, but it is also one of the most common adult soft-tissue sarcomas. Myxoid liposarcoma (MLPS) accounts for 30% of all LPS cases. Diagnosis during pregnancy and the puerperium is very rarely reported, and only a few cases have been reported in the thigh. Case presentation: We report the case of a 36-year-old female patient on the 11th day of the puerperium after a cesarean section. The patient presented to the gynecology ward owing to the sudden appearance of a tumor in the medial part of her right thigh. The lesion was non-painful, mobile, soft, approximately 20 cm in diameter, and protruded above the level of the rest of the thigh surface. A suspicion of hematoma was raised. The final diagnosis was high-grade MLPS. Conclusions: An MLPS diagnosis is uncommon in female patients and even rarer during pregnancy. This case represents a novel occurrence, as the first instance in which symptoms manifested during the puerperium. Proper treatment and early detection could improve disease outcomes. Full article

Background: CIC-rearranged sarcoma is a rare and aggressive type of undifferentiated round cell tumor characterized by CIC gene fusion, most commonly CIC::DUX4. This study presents a series of eleven cases, highlighting their clinicopathological features. Methods: Pathology records (2019 to 2024) were searched using “sarcoma with CIC”, identifying eleven cases, of which seven referred cases were initially misdiagnosed. Pathological and clinical analysis was conducted. Treatment was dictated upon multidisciplinary panel discussion based on tumor stage. Follow-up data (1–25 months) was available for all patients. Results: The cohort included six males and five females, with a median age of 43 years (range;14–53), with nine in soft tissue and two in bone. Tumor size ranged from 3.5 cm to 20.0 cm (mean: 9.8 cm). Most cases showed sheets of undifferentiated round- to oval-shaped cells. Two cases showed an Ewing-like pattern, and one case showed spindle cells in a fibrotic stroma transitioning to epithelioid cells. Necrosis was present in nine cases, and mitotic count ranged from 2 to 38/ 10HPFs (mean = 14.2). CD99 was positive in (10/11) cases and WT-1 in (6/9). NKX2.2, S100, and MDM2 were positive in rare cases. CIC::DUX4 fusion was detected in four cases. FISH for CIC gene rearrangement was positive in seven cases, two of them confirmed by methylation analysis. Metastasis at diagnosis was common (n = 8), primarily in the lungs, with later metastasis to the brain and bone. At time of final analysis, eight patients died within a median of 10 months (range: 1–19 months), while three were alive, two with stable disease (for a period of 6 and 25 months) and one with progression after 10 months. Significant correlation was seen between overall survival and the presence of metastasis at diagnosis (p value = 0.03). Conclusions: CIC-rearranged sarcomas are rare, high-grade tumors with predilection for soft tissue. Misdiagnosis is frequent, necessitating molecular confirmation. These tumors are treatment-resistant, often present with lung metastasis, and carry a poor prognosis, especially with initial metastasis. Full article

Canine histiocytic sarcoma (HS) is a rare tumor with a poor prognosis. Rapid tumor growth often causes central hypoxia and starvation, impacting tumor progression. In the present study, HS cells were cultured under hypoxia and starvation for 1 and 3 days, simulating intermediate and central tumor zones, respectively. Cells were counted at each time point, followed by RNAseq analysis. Only hypoxia significantly reduced the cell number (p < 0.05). Short-term hypoxia altered 1645 differentially expressed genes (DEGs). Upregulated genes belonged to vasculature development, and downregulated genes to cell cycle processes. Short-term starvation affected 157 genes, mainly involving responses to stimuli. Prolonged hypoxia and starvation induced 1301 and 836 DEGs, respectively. Prolonged hypoxia upregulated genes mainly involved in immune responses, response to stimulus, adhesion, and angiogenesis. Prolonged starvation upregulated genes associated with signaling, adhesion, circulatory system development, and response to stimulus. Lipid metabolism and cell cycle pathways were downregulated under prolonged hypoxia and starvation, respectively. KEGG “pathways in cancer” were enriched under all conditions (adjusted p-values < 0.05). These findings indicate that hypoxia and starvation significantly alter the expression of genes involved in tumor progression. Further studies, namely post-translational analyses, are needed to elucidate the functional impact of these changes and identify potential therapeutic targets. Full article

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare type of soft tissue sarcoma associated with poor prognoses. The standard of care for non-resectable tumors consists of surgical excision followed by radiation and chemotherapy. MPNSTs are most common in patients with neurofibromatosis type 1 but can also occur sporadically. Regardless of origin, MPNSTs most often rely on signaling pathways that increase basal oxidative stress. This provides the basis for developing therapeutics with mechanisms that can potentiate oxidative stress to selectively eradicate tumor cells at doses that are tolerable for normal cells. Artemisinin derivatives are a mainstay of malaria therapy worldwide, with a well-established safety profile. Artemisinin’s antimalarial effects are due to an endoperoxide bridge in its chemical structure that induces oxidative stress. We found that artesunate (ARS) and metabolite dihydroartemisinin (DHA) are selectively cytotoxic to MPNST cells relative to normal Schwann cells with the endoperoxide bridge required for activity. Mechanistically, DHA induced oxidative stress, lipid peroxidation, and DHA-mediated cytotoxicity could be prevented with co-administration of the antioxidant N-acetyl-cysteine. Furthermore, we found that DHA was able to selectively remove MPNST from co-culture with normal Schwann cells. These data supports the further development of artemisinins for the clinical management of MPNST. Full article

Background: Sarcomas are a rare and biologically diverse group of malignant tumors that originate from mesenchymal tissues. They are characterized by a broad range of histopathological subtypes, varying clinical courses, and differing responses to treatment. This study seeks to clarify the clinicopathological and molecular predictors of recurrence in leiomyosarcomas, carcinosarcomas, and endometrial stromal sarcomas to enhance our understanding, thereby improving clinical knowledge, consultation practices, and the overall benefit for patients. Methods: A literature search was conducted utilizing PubMed/MEDLINE, Embase, Cochrane Library, and Scopus to execute a comprehensive structured narrative review of articles published up to 31 March 2025. Results: We summarize existing evidence on the clinical, histological, and molecular predictors of recurrence and poor prognosis for leiomyosarcomas, carcinosarcomas, and endometrial stromal sarcomas. While the stage, grade, tumor size, and novel molecular biomarkers are crucial high-risk parameters that have been associated with recurrence, existing data demonstrate contradictory results, indicating the need for further research. Conclusions: Recent advancements in next-generation sequencing have facilitated the identification of women at increased risk of recurrence, poor disease-free survival, and overall adverse prognosis. Stratifying this risk requires a comprehensive understanding of the clinical, histological, and molecular risk factors involved. Understanding these underlying factors is essential for effectively addressing the initial consultation, guiding management, and—considering the novel treatment modalities—individualizing the care provided to the affected women. Full article

(1) Background: Quality of life (QoL) assessment is a crucial aspect for patients diagnosed with cancer. Over the years, different tools have been developed to measure QoL, both generic and pathology specific, but the inclusion of quality of life among other indicators of efficacy in randomized controlled trials (RCTs) remains a controversial issue. In this review, we aim to review the frequency and modality of QoL assessment in RCTs, enrolling patients diagnosed with mesenchymal tumors. (2) Methods: An electronic literature search of bone and soft tissue sarcoma and GIST-related RCTs published between January 2000 and December 2023 was performed by two independent reviewers using PubMed. English-language phase II and III clinical trials enrolling at least more than 15 patients were included, regardless of the disease stage. Studies involving patients under the age of 18 years or for which the full text was not available were excluded. For each study, data regarding the journal and year of publication, the study design, the primary objective, and the evaluation of quality of life as an endpoint with any type of patient-reported outcomes used were extracted. (3) Results: Among the 742 publications screened, 171 resulted eligible. QoL assessment was listed among the endpoints in 35 trials and QoL results were reported in 29 primary publications. In these trials, 16 included patients with soft tissue sarcomas, 8 Kaposi sarcomas, 6 GIST, and 3 desmoid tumors. Among all the trials included, 10.4% on an adjuvant/neoadjuvant setting and 24.4% on a metastatic setting included QoL as an endpoint. The proportion of trials, including QoL, was variable over time, as follows: 16.9% of trials in 2000–2014 vs. 23.4% in 2015–2023. In 35 trials, including QoL endpoints, 27 had a superiority design and 25 reported a positive result. In the majority of trials (80%), the tools for QoL assessment were generic and those mostly used were the EORTC QLQ-C30, the EQ-5D questionnaire, and the modified Brief Pain Inventory–Short Form. (4) Conclusions: Quality of life has not been assessed or published in many phase II and III trials, despite an improvement over time. QoL evaluation in RCTs should be considered even more carefully in patients with rare tumors, where the low number of patients who can be enrolled makes it difficult to draw statistically significant conclusions on the effectiveness of treatments. Full article

We report a 26-year-old male presenting with a chronic cough and hemoptysis. Imaging revealed a large hypermetabolic mass in the left lower lung with the invasion of adjacent great vessels. A biopsy confirmed sarcomatoid carcinoma, a rare and aggressive form of primary pulmonary sarcoma. Due to vascular involvement, the patient underwent preoperative bronchial artery embolization followed by left pneumonectomy with pulmonary arterioplasty via median sternotomy. Postoperative recovery was uneventful. A two-year follow-up CT showed no recurrence. Primary pulmonary sarcomas are extremely rare, accounting for only 0.013–0.4% of lung malignancies, and are often diagnosed late due to nonspecific symptoms. This case highlights the importance of timely imaging, multidisciplinary planning, and aggressive surgical management in achieving long-term disease control, even in cases with extensive vascular invasion. Full article

Background/Objectives: Sarcomas are a rare and heterogeneous group of malignant tumors, which makes early detection and grading particularly challenging. Diagnosis traditionally relies on expert visual interpretation of histopathological biopsies and radiological imaging, processes that can be time-consuming, subjective and susceptible to inter-observer variability. Methods: In this study, we aim to explore the potential of artificial intelligence (AI), specifically radiomics and machine learning (ML), to support sarcoma diagnosis and grading based on MRI scans. We extracted quantitative features from both raw and wavelet-transformed images, including first-order statistics and texture descriptors such as the gray-level co-occurrence matrix (GLCM), gray-level size-zone matrix (GLSZM), gray-level run-length matrix (GLRLM), and neighboring gray tone difference matrix (NGTDM). These features were used to train ML models for two tasks: binary classification of healthy vs. pathological tissue and prognostic grading of sarcomas based on the French FNCLCC system. Results: The binary classification achieved an accuracy of 76.02% using a combination of features from both raw and transformed images. FNCLCC grade classification reached an accuracy of 57.6% under the same conditions. Specifically, wavelet transforms of raw images boosted classification accuracy, hinting at the large potential that image transforms can add to these tasks. Conclusions: Our findings highlight the value of combining multiple radiomic features and demonstrate that wavelet transforms significantly enhance classification performance. By outlining the potential of AI-based approaches in sarcoma diagnostics, this work seeks to promote the development of decision support systems that could assist clinicians. Full article

Background: Interdigitating dendritic cell sarcoma (IDCS) is a very rare haematologic malignant tumour that arises from antigen-presenting cells. While it primarily affects the lymph nodes, extranodal manifestations have been observed, and there is a slight male predominance. Due to its rarity, diagnosing IDCS can be challenging, as illustrated in our case report of a 61-year-old woman. Methods: In this case presentation, the oncological management of a patient suspected of having malignant melanoma metastasis in the neck lymph nodes is discussed. This includes otorhinolaryngological examinations, fine needle aspiration biopsy, PET CT imaging, and histological analysis with immunohistochemistry. Results: The patient’s medical history included the excision of a pigmented lesion from the left ala of her nose, which was diagnosed as malignant melanoma. After surgical treatment, she experienced a tumour-free period of one year; however, during a follow-up ultrasonography three pathological lymph nodes were detected on the left side of her neck. Initially, a nodal metastasis of melanoma was suspected. Yet, fine needle aspiration cytology revealed myofibroblastic tumour invasion, and a re-biopsy showed no signs of malignancy. To further investigate, PET-CT scans were conducted, and a modified radical neck dissection was performed based on the findings. The histological analysis of the lymph nodes revealed an IDCS, a second independent tumour distinct from the initially diagnosed malignant melanoma, originating from the submandibular, upper jugular, and mid-jugular lymph nodes. Conclusions: This case highlights the diagnostic difficulties associated with IDCS. Initially, the clinical suspicion of malignant melanoma was considered, necessitating further examinations and a multidisciplinary approach to reach a final diagnosis and provide the patient with appropriate treatment. Full article

Background and Clinical Significance: Kaposi sarcoma (KS) is a rare angio-proliferative mesenchymal tumor that predominantly affects the skin and mucous membranes but may involve lymph nodes and visceral organs. Clinically, it manifests as red-purple-brown papules, nodules, or plaques, either painless or painful, often with disfiguring potential. The diagnosis is traditionally based on clinical and histopathological evaluation, although non-invasive imaging techniques are increasingly used to support diagnosis and treatment monitoring. We report a case of HHV-8-negative Kaposi sarcoma evaluated with multiple non-invasive imaging modalities to highlight their diagnostic utility. Case Presentation: An 83-year-old man presented with multiple painful, violaceous papulo-nodular lesions, some ulcerated, on the lateral aspect of his left foot. Dermoscopy revealed the characteristic rainbow pattern. Dynamic Optical Coherence Tomography (D-OCT) allowed real-time visualization of microvascular abnormalities, identifying large serpentine and branching vessels with clearly delineated capsules. Line-field Optical Coherence Tomography (LC-OCT) showed irregular dermal collagen, vascular lacunae, and the presence of spindle cells and slit-like vessels. Histological analysis confirmed the diagnosis of Kaposi sarcoma, revealing a proliferation of spindle-shaped endothelial cells forming angulated vascular spaces, with red blood cell extravasation and a mixed inflammatory infiltrate. Conclusions: Non-invasive imaging tools, including dermoscopy, D-OCT, and LC-OCT, have emerged as valuable adjuncts in the diagnosis and monitoring of KS. These techniques enable in vivo assessment of vascular architecture and tissue morphology, enhancing clinical decision-making while reducing the need for immediate biopsy. Dermoscopy reveals polychromatic vascular features, such as the rainbow pattern, while D-OCT and LC-OCT provide high-resolution insights into vascular proliferation, tissue heterogeneity, and cellular morphology. Dermoscopy, dynamic OCT, and LC-OCT represent promising non-invasive diagnostic tools for the assessment of Kaposi sarcoma. These technologies provide detailed morphological and vascular information, enabling earlier diagnosis and more personalized management. While histopathology remains the gold standard, non-invasive imaging offers a valuable complementary approach for diagnosis and follow-up, particularly in complex or atypical presentations. Ongoing research and technological refinement are essential to improve accessibility and clinical applicability. Full article

Background: Ifosfamide, an alkylating agent used for treating various cancers, can cause encephalopathy in 10–30% of adults and 8% of children. Methylene blue has been used to treat ifosfamide-induced encephalopathy (IIE). This study aimed to describe our institutional experience with IIE in children and young adults with cancer, including its clinical manifestations, treatment, and outcomes. Methods: We reviewed the clinical records of patients with cancer aged up to 30 years who developed IIE over 10 years. Results: Twenty-four patients (median age: 17.6 years, range: 4–30 years) were included; 54% were male, and 71% had bone/soft tissue sarcomas. Ifosfamide was administered alone or with other drugs (dose range: 1.5–3.3 g/m²/day). Twelve patients developed IIE after short intermittent infusions (1–3 h), and twelve developed it after continuous infusions (12–24 h). IIE occurred at a median cumulative ifosfamide dose of 18 g/m². Symptoms appeared within hours to five days and resolved within 24–120 h. An altered mental status was present in all except one patient. Twelve patients had grade 3 IIE (severe somnolence, agitation, and confusion), and five had grade 4 IIE (coma and seizures). Twenty patients (83%) received methylene blue, with symptom resolution in nineteen patients (83%). Imaging studies showed nonspecific findings. Ten patients were re-challenged with ifosfamide; five received prophylactic methylene blue treatment, of whom three had recurrence. Conclusions: IIE can occur with both short intermittent and continuous ifosfamide infusions and presents as an altered mental status, seizures, and, rarely, hemiparesis. Symptoms are transient, and methylene blue may help alleviate this neurotoxicity, but it does not completely prevent its recurrence. Full article