Search Results (287)

Phyllodes tumors are rare fibroepithelial neoplasms of the breast, and their malignant forms present significant diagnostic and therapeutic challenges. This review summarizes current knowledge across the benign-to-malignant spectrum, focusing on diagnostic approaches, histopathological classification, molecular alterations, and treatment strategies. While recent molecular studies have revealed recurrent genetic mutations, their clinical implications remain under investigation. Surgical excision remains the cornerstone of treatment, and systemic therapies are generally adapted from soft tissue sarcoma protocols. Future efforts should focus on improving diagnostic accuracy, identifying molecular targets for therapy, and fostering international collaboration to advance clinical research in this rare tumor type. Full article

Introduction: Tumors of the lateral skull base, particularly those arising from the external auditory canal and peri-retroauricular regions, present considerable surgical and reconstructive difficulties due to their intricate anatomy and aggressive nature. The anterolateral thigh (ALT) free flap offers a viable reconstruction option, enhancing oncological radicality while minimizing morbidity. Materials and Methods: A retrospective analysis was conducted on five cases of malignant tumors involving the external auditory canal and adjacent soft tissues, treated at a tertiary center from March 2023 to March 2025. All patients underwent radical resection, which included lateral or subtotal temporal bone resection, along with parotidectomy and neck dissection when necessary. Reconstruction was performed using myocutaneous anterolateral thigh free flaps. The study evaluated clinical outcomes, complications, and esthetic results. Results: The ALT flap was used in all cases without major postoperative complications. Two patients received adjuvant radiotherapy; one did not start treatment due to early recurrence. At follow-up, three patients were disease-free, while two had died from unrelated causes. Esthetic and functional outcomes were satisfactory in all patients. Conclusions: The ALT free flap is a universal and reliable option for the reconstruction of complex lateral skull base defects, especially in patients following the radical removal of tumors of the external auditory canal and peri-retroauricular areas. It offers excellent tissue coverage, facilitates adjuvant treatment, and has a low complication rate. While our experience supports its use in aggressive oncological resection, larger studies are needed to confirm these findings. Level of evidence: 4. Full article

Background: Malignant solid tumors diagnosed during the first year of life represent a rare but clinically significant subgroup of pediatric cancers. Their biological behavior, treatment responses, and prognosis differ substantially from tumors diagnosed in older children due to developmental immaturity and age-related therapeutic limitations. Methods: We retrospectively analyzed 88 infants diagnosed with malignant solid tumors before 12 months of age at a single tertiary center between March 2011 and March 2023. Demographic, clinical, pathological, and treatment data were collected. Overall survival (OS) was estimated by Kaplan–Meier analysis, and prognostic factors were evaluated using univariate and multivariate Cox regression models. Results: Of the 98 initially screened patients, 88 were eligible for analysis. The median age at diagnosis was 7 months, with a median follow-up of 42 months. The most common tumor locations were intra-abdominal (64.7%), brain (20.5%), and bone/soft tissue (12.5%). Neuroblastoma was the leading diagnosis (30.7%), with spontaneous regression observed in 29.6% of cases. Atypical teratoid rhabdoid tumor (ATRT) was the most frequent brain tumor (9.1%). The 5-year OS for the entire cohort was 78.3%. Brain tumors were associated with significantly higher mortality (HR 4.32, p = 0.01), while intra-abdominal tumors predicted improved survival (HR 0.31, p = 0.02). Conclusions: Infantile malignant solid tumors display heterogeneous clinical behavior and outcomes. While favorable results can be achieved in neuroblastoma and soft tissue sarcomas, brain tumors, particularly ATRT, remain a therapeutic challenge. Age-specific, risk-adapted treatment strategies and earlier detection are critical to improving survival and reducing long-term sequelae in this vulnerable population. Full article

Background: Malignant melanoma remains an oncological challenge, with advanced-stage five-year survival rates under 20%. Precise molecular imaging has become indispensable for accurate staging, selection of targeted or immunotherapies, treatment response assessment, and early detection of immune-related adverse events. This review examines the roles of PET/CT, PET/MRI, and SPECT/CT radiopharmaceuticals in melanoma management and highlights novel tracers and theranostic strategies poised to enhance precision nuclear medicine in this disease. Methods: We performed a review of English-language literature from January 2000 through June 2025, querying PubMed, Scopus, and clinical-trial registries for original research articles, meta-analyses, clinical guidelines, and illustrative case reports. Eligible studies investigated PET/CT, PET/MRI, or SPECT/CT applications in melanoma diagnosis, nodal and distant staging, therapy monitoring, irAE (immune-related adverse events) detection, and the development of emerging radiotracers or theranostic radiopharmaceutical pairs. Results:¹⁸F-FDG PET/CT demonstrated a high detection rate for distant metastases, outperforming conventional CT and MRI in advanced disease, despite limited resolution for infracentimetric nodal deposits. PET/MRI offers comparable diagnostic accuracy with superior soft-tissue contrast and improved brain lesion detection, while SPECT/CT enhanced sentinel lymph node localization prior to surgical biopsy. Also, FDG PET/CT identified visceral irAEs with great sensitivities, revealing asymptomatic toxicities in up to one-third of patients. Emerging radiotracers targeting melanin, fibroblast activation protein, PD-1 (programmed cell death protein 1)/PD-L1 (programmed cell death-ligand 1), and CD8⁺ T cells have demonstrated enhanced tumor specificity and are on their way to forming novel theranostic pairs. Conclusions: While ¹⁸F-FDG PET/CT remains the cornerstone of melanoma imaging, complementary advantages of PET/MRI and SPECT/CT imaging refine melanoma management. The advent of highly specific radiotracers and integrated theranostic approaches heralds a new era of tailored nuclear-medicine strategies, promising improved patient stratification, therapy guidance, and clinical outcomes in melanoma. Full article

Malignant bone and soft tissue tumors are often resistant to conventional treatment, and treatment options for unresectable and metastatic cases are limited. L-type amino acid transporter 1 (LAT1) is overexpressed in several malignancies, including sarcomas, making it an attractive target for targeted alpha therapy. In this study, we investigated the therapeutic efficacy of LAT1-targeted alpha therapy using a novel modified 3-astatin-211 Astato-α-methyl-L-tyrosine (²¹¹At-AAMT) for bone and soft tissue sarcomas. LAT1 expression and the specificity of LAT1-mediated uptake of ²¹¹At-AAMT were evaluated in bone and soft tissue sarcoma cell lines. Antiproliferative effects were assessed using cell viability and colony formation assays. DNA damage was assessed using immunostaining with phosphorylated histone γH2AX. In vivo efficacy of ²¹¹At-AAMT, determined using xenograft mouse models, was compared with that of doxorubicin. LAT1 was highly expressed in all cell lines, especially MP-CCS-SY and MG-63 cells. ²¹¹At-AAMT uptake was LAT1-dependent and significant in all cell lines. It inhibited cell proliferation in a dose-dependent manner, comparable to that of doxorubicin. In xenograft models, a single administration of ²¹¹At-AAMT significantly inhibited tumor growth without systemic toxicity, whereas doxorubicin caused weight loss. Histopathological analysis showed reduced cell density, inhibited proliferation, and extensive DNA damage in tumors treated with ²¹¹At-AAMT, whereas LAT1 expression was maintained in residual tumor tissues. LAT1-targeted alpha therapy with ²¹¹At-AAMT demonstrated antitumor efficacy comparable to that of first-line chemotherapy for osteosarcoma and soft tissue sarcoma. Sustained LAT1 expression suggests the potential for repeated or combination treatments, highlighting its promise as a novel therapy for advanced, treatment-resistant sarcomas. Full article

Background and Clinical Significance: Rhabdomyosarcoma (RMS) is a rare and aggressive malignant soft-tissue sarcoma (STS) arising from skeletal connective tissues and is most commonly seen in the pediatric population. The pleomorphic subtype is mostly seen in adults in the sixth and seventh decades of life, representing 1% of all histological types of RMS and having a very poor prognosis. Case Presentation: This report presents the case of a 63-year-old male with a medical history of papillary thyroid cancer, who presented with an ulcer-hemorrhagic malignant tumor, namely, a poorly differentiated desmin-positive pleomorphic rhabdomyosarcoma (PRMS), with impressive dimensions located on the posterior thoracic wall. This tumor was surgically removed via a wide resection, followed by palliative chemotherapy and radiotherapy. However, the patient relapsed locally, with pulmonary, bone, and lymph node metastases. The peculiarity of this case is represented by the rapid growth, aggressive nature, and high metastatic potential of the adult RMS, as well as its poor response to treatment. Conclusions: The presented case underscores the need for early diagnosis, multidisciplinary management, and exploration of molecular profiling for therapeutic planning. Full article

Background: Vulvar leiomyosarcoma (VLMS) is a rare and aggressive soft tissue malignancy arising from smooth muscle cells, comprising less than 3% of vulvar cancers. Its clinical resemblance to benign vulvar lesions often leads to delayed diagnosis. Despite surgical resection and adjuvant therapy, VLMS is associated with high recurrence rates and a poor prognosis, and due to its rarity, there is no standardized management or surveillance protocol. Case Report: We present a case of high-grade VLMS in a postmenopausal woman, initially diagnosed in 2020 and managed with surgical excision and adjuvant radiotherapy. The primary tumor was a 10 cm solid, lobulated mass involving the mons pubis, with histology confirming high-grade leiomyosarcoma based on marked cellular atypia, high mitotic activity, and smooth muscle differentiation. Immunohistochemistry was positive for SMA, vimentin, and CD34, and negative for S100 and MyoD1. Five years later, the patient developed a local recurrence with an enlarged inguinal lymph node. She underwent complete tumor resection and bilateral inguinal lymphadenectomy. Histology of the recurrent lesion mirrored the initial findings, with no lymph node metastases. This case highlights the aggressive nature and potential for late recurrence in vulvar leiomyosarcoma, underscoring the importance of long-term surveillance. Conclusions: High-grade VLMS is a rare malignancy with a high recurrence risk. This case highlights the importance of early diagnosis, radical surgical treatment, and long-term surveillance. Although recurrence occurred five years after the initial treatment, timely surgical intervention led to a favorable postoperative course. Multidisciplinary management and individualized follow-up strategies remain key to improving outcomes in these rare gynecologic sarcomas. Full article

Background: Due to the scarcity of cases, adjustments for confounding factors in analyses of the effects of postoperative infections on limb function after surgery for malignant bone and soft tissue tumors were insufficient in previous studies. One solution is to use big data from a nationwide registry. Methods: Data from the Bone and Soft Tissue Tumor Registry in Japan were used to examine the impact of postoperative infections on limb function after surgery for malignant bone and soft tissue tumors in the lower extremities. Limb function was evaluated using the Musculoskeletal Tumor Society (MSTS) score. Results: A total of 1099 soft tissue tumors and 410 bone tumor cases were included. Propensity score matching (PSM) was performed using significant factors in the propensity score logistic regression. After PSM, only “function” and “emotional acceptance” scores worsened in infection cases in the bone tumor group, while total MSTS scores remained unaffected in both the bone and soft tissue tumor groups. No subcategory scores worsened in the soft tissue tumor group. Conclusions: Our findings suggest that postoperative infections might not affect function in cases of soft tissue tumors and have only a limited impact in cases of bone tumors. Full article

Background: While changes in clinical practice during the COVID-19 pandemic in Japan have been widely studied, data specific to bone and soft tissue tumor care remain limited. Methods: A nationwide web-based survey was conducted among hospitals specializing in musculoskeletal tumors. It assessed the occurrence of COVID-19-related events (patient infections, outbreak clusters, and staff infections), delays in referral and diagnosis, postponement or cancellation of specific treatments, and changes in institutional management strategies. Results: Seventy-eight hospitals (91.7% of all specialized centers) responded. Patient infections, outbreak clusters, and staff infections were reported by 28.2%, 48.7%, and 53.8% of hospitals, respectively. While radiological exams and biopsies were largely maintained, patient referrals decreased significantly. Surgical treatment was more affected than chemotherapy or radiotherapy. Strategy changes included surgery delays or cancellations (48.7%) and prolonged follow-up intervals (20.5%). Among COVID-19-related factors, only direct patient infections were significantly associated with institutional changes in treatment policy. Conclusions: The pandemic substantially disrupted outpatient services and surgical care in musculoskeletal oncology. Patient infection was the main driver of treatment strategy modifications. Full article

Background: Pelvic resections represent some of the most challenging procedures in orthopedic oncology, often necessitating the sacrifice of large bone segments and, subsequently, the loss of nearby soft tissues. Our study aims to evaluate the impact of surgical resections of pelvic bone tumors on the performance of the pelvic floor and digestive, urinary, and genital systems. Methods: We evaluated all malignant or locally aggressive pelvic bone tumors treated with bone resection in our institution between January 2017 and January 2024. The reconstructive approaches were recorded. Pre- and post-operative MRI and CT scans were used to evaluate the grade of pelvic prolapse. The prolapse of the pelvic floor was assessed with the M-line, the H-line, and the anorectal angle. Hydronephrosis was also evaluated. Urinary and fecal incontinence were evaluated with the Pelvic Floor Impact Questionnaire (PFIQ7). Results: Thirty cases were included in our study. Nine cases were treated with custom-made prostheses, five had ice-cone prostheses, two massive allografts, and one composite allograft-prosthesis. The others had no bone reconstruction. Meshes were used to reconstruct the pelvic floor in 9 cases. Patients with discontinuity of the pelvic ring had a significantly higher grade of pelvic prolapse (M-line) and worse PFIQ7 scores. Conclusions: The resection of pelvic bone tumors represents one of the main challenges in orthopedic oncology. While planning surgical demolition and performing the subsequent reconstruction, surgeons should also consider the impact of the surgical treatment on the pelvic floor and surrounding organs. Intra-operative reconstructions and post-operative rehabilitation are advisable. Full article

MRI is a non-invasive imaging technique employed today in modern diagnostic medicine due to the fact it is capable of generating tissue architecture and function information with high image resolution without the use of ionizing radiation, unlike x-ray or CT scans. The advantages of MRI discussed in this review include better soft tissue contrast, the opportunity to perform imaging in different planes, and the ability to detect small changes in tissues, which helps to use MRI in many specialties, including cancer diagnosis and staging, as well as neurological and cardiovascular diseases. More particularly, this review aims to assess the contribution of MRI to the detection of liver cancer, especially HCC and ICC—the most frequent and aggressive types of pathology. Because of its high-resolution, MRI provides clear visualization of the small hepatic lesion and vascular mapping, which is crucial for early diagnosis and staging. It also reveals higher sensitivity and specificity than ultrasound and CT in identifying liver cancer dimensions and relations with system vasculature and a safer technique for patients who need many follow-up images. This is in addition to newer techniques that have been developed from MRI, which include the DWI, DCE-MRI, and MRE, all of which yield functional information concerning the perfusion of the tumor and the stiffness of the tissue, respectively, thus improving the diagnosis. Moreover, the application of artificial intelligence to MRI is improving lesion identification and cancer assessment, as well as patient outcome prediction, while relieving the burden of radiologists. Suggested improvements for future work include the combination of MRI with other diagnostic approaches, including circulating cell analysis and molecular imaging in managing liver cancer. Still, there is a limitation in MRI’s access globally, because scanners are expensive and unavailable in some parts of the world. Technological improvements and greater availability will extend MRI more as a valuable modality in the treatment of liver malignancies, more so for diagnosis and staging. Full article

High-grade sarcomas often lack typical morphological features and exhibit no clear differentiation, often leading to a diagnosis of undifferentiated sarcoma (US). Pleomorphic leiomyosarcoma (PLMS) is a high-grade sarcoma consisting of a typical leiomyosarcoma (LMS) component alongside dedifferentiated high-grade areas. A few decades ago, PLMS was regarded as a subtype of high-grade sarcoma previously referred to as malignant fibrous histiocytoma; it is now classified as a variant of LMS. The mechanisms underlying myogenic differentiation and their relevance to the pathological diagnosis of high-grade sarcomas remain poorly understood. To investigate the gene expression networks associated with myogenic differentiation, we employed Cap Analysis of Gene Expression (CAGE) to distinguish PLMS from other high-grade sarcoma subtypes. We analyzed 27 frozen high-grade sarcoma samples, comprising 10 PLMSs, 11 high-grade myxofibrosarcomas, 3 dedifferentiated liposarcomas, 2 USs, and 1 high-grade sarcoma not otherwise specified, using CAGE profiling. Hierarchical clustering based on differentially expressed genes identified by CAGE separated 7 of the 10 PLMSs from other high-grade sarcomas, while the remaining 3 PLMSs clustered with a single US case. CAGE analysis also revealed that the myostatin (MSTN) promoter (false discovery rate [FDR] < 0.05) was more strongly activated in the high-grade sarcoma group lacking morphological and immunohistochemical smooth muscle differentiation than in the PLMS group, whereas the alpha smooth muscle actin (ACTA2) promoter (FDR < 0.05) was more prominently activated in the PLMS group. Immunohistochemical analysis showed reduced or absent myostatin expression in PLMSs, in contrast to diffuse myostatin expression in other high-grade sarcomas. Smooth muscle actin, encoded by ACTA2, was expressed in all 10 PLMS cases but only in 11 of 17 other high-grade sarcomas. Furthermore, both conventional immunohistochemistry and double immunostaining revealed that myostatin and myogenic markers exhibited largely mutually exclusive expression patterns within these tumors. A validation study was performed using 59 soft tissue sarcoma cases, including 27 PLMSs and 16 LMSs. Loss or reduction in myostatin expression was confirmed in both LMS and PLMS, and the ratio of myostatin loss was comparable (62.5% in LMS vs. 63% in PLMS). Collectively, these findings suggest that myostatin contributes to smooth muscle differentiation in high-grade sarcomas and has potential utility as a diagnostic marker. Full article

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor sampling, and bone/soft tissue) and used for MRI-based radiomics. These were then combined with clinical features to predict OS clinical outcomes. Results: The mean age of OS patients was 11.8 ± 3.5 years. Most tumors were located in the femur (65%). Osteoblastic subtype was the most common histological classification (79%). The majority of OS patients (79%) did not have evidence of metastasis at diagnosis. Progressive disease occurred in 27% of patients, 59% of patients showed adequate therapy response, 25% experienced relapse after therapy, and 30% died from OS. Classification models based on bone/soft tissue segmentation generally performed the best, with certain clinical features improving performance, especially for therapy response and mortality. The top performing classifier in each outcome achieved 0.94–1.0 validation ROC AUC and 0.63–1.0 testing ROC AUC, while those without radiomic features (RFs) generally performed suboptimally. Conclusions: This study demonstrates the strong predictive capabilities of MRI-based radiomics and multi-region segmentations for predicting clinical outcomes in pediatric OS. 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

We present a narrative review focusing on the therapeutic potential of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) in regenerating bone defects, particularly those resulting from surgical treatment of malignant bone and soft tissue tumors. These large bone defects pose significant challenges for reconstruction and functional recovery, highlighting the need for innovative regenerative strategies. Background: MSCs, which can differentiate into various cell types, are known for their immunosuppressive properties and ability to promote tissue repair. MSC-EVs, rich in bioactive molecules like microRNAs and proteins, play a crucial role in bone regeneration by mediating intercellular communication and modulating inflammation. Methods: This narrative review compiles data from various studies, including systematic reviews and individual research, focusing on the application of MSC-EVs in bone defect treatment. It examines the characteristics, mechanisms of action, and therapeutic effects of MSC-EVs, as well as the microRNAs involved in bone regeneration. Results: The findings indicate that MSC-EVs can enhance both osteogenesis and angiogenesis, highlighting their potential as promising candidates for clinical applications in bone defects. However, many mechanisms remain unclear; therefore, further investigation is needed. Conclusions: The review emphasizes the potential of MSC-EVs in improving patient outcomes for severe bone defects. It also highlights future challenges, including formulation, standardization, safety, and delivery methods, particularly in conjunction with biomaterials. Overall, MSC-EVs represent a significant advancement in regenerative medicine for bone defects. Full article