Search Results (244)

Background: Primary fibula tumours are rare, representing approximately 0.25% of all primary bone tumours. While benign lesions are often asymptomatic, malignant ones typically present with pain and functional impairment. Most tumours arise in the proximal third of the fibula, yet the literature regarding their epidemiology and clinicopathological features remains limited. This systematic review aims to synthesise current evidence on presentation, diagnosis, management, and prognosis of primary malignant tumours of the proximal fibula. Methods: A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, and the Cochrane Register were searched on 28 October 2025 for English-language case reports and case series on primary malignant tumors of the proximal fibula. Two reviewers independently performed study selection and data extraction, collecting information on demographics, tumor characteristics, diagnostic approaches, treatments, and outcomes, with disagreements resolved by a third reviewer. Results: Thirty-three papers involving 228 patients (78 females, 128 males, 22 unknown) were included. The mean age at diagnosis was 22.8 years (range 4–79). The most common symptoms were painful mass and neurological complaints. Osteosarcoma and Ewing’s sarcoma were predominant histological types. Limb-sparing surgeries were most common, although 16 patients underwent amputation. At mean follow-up of 48.9 months, local recurrence occurred in 44 cases, and 12 developed distant metastases, most commonly in the lungs. Overall, 38 patients died, 37 due to disease progression. Conclusions: Primary malignant tumours of the proximal fibula, while rare, pose significant therapeutic challenges. Accurate diagnosis, appropriate multimodal treatment, and careful surgical planning are crucial to optimise oncological control and functional outcomes. Full article

Background and Objectives: Lacrimal sac/nasolacrimal duct (LS/NLD) tumors may present as primary acquired nasolacrimal duct obstruction (PANDO), raising debate over routine versus selective dacryocystorhinostomy (DCR) biopsy. We systematically reviewed (i) biopsy yields in routine versus selective strategies, (ii) clinical/imaging red flags for neoplasia, and (iii) outcomes of malignant LS/NLD tumors. Materials and Methods: Following a preregistered PRISMA 2020-compliant protocol, we searched PubMed/MEDLINE, Web of Science, and Scopus (1970–2025) for adult cohorts reporting histopathology, imaging, or oncologic outcomes in PANDO/DCR or LS/NLD tumors. Eligible designs included comparative, cohort, cross-sectional, and diagnostic accuracy studies with histology as a reference. Results: Across 16 cohorts, routine DCR series reported “any specific pathology” in 0–7.91% of specimens and malignant yields generally ≤0.73%. In Anderson, 7.91% of 316 patients had significant pathology and 4.43% neoplasia, with 2.53% unsuspected pre-/intra-operatively. Selective biopsy or tumor-enriched cohorts showed higher malignant burdens; pooled modern data yielded ~72.8% squamous cell carcinoma and ~21.4% lymphoma among malignancies. Imaging red flags included bone erosion (50% malignant vs. 11% benign) and infiltrative patterns (63% vs. 0%), while sac masses were present in 88% of tumors in one recent series. In LSSCC-only cohorts, contemporary multimodal therapy achieved 5-year overall survival of 87.6% and progression-free survival of 76.3%. Conclusions: Malignancy is rare in unselected PANDO but clinically significant when present. A tiered strategy combining bedside red flags, targeted CT/MRI, and selective biopsy appears to balance oncologic safety with resource stewardship and supports histology-directed epithelial versus lymphoma care pathways. Full article

The C-X-C motif chemokine ligand 10 (CXCL10) is implicated in the progression of osteosarcoma (OS), the most aggressive pediatric bone malignancy. However, its role often presents a profound clinical paradox: although high circulating levels are strongly linked to poor prognosis, its canonical function is to recruit anti-tumor immune cells. This review unravels these contrasting roles by proposing a novel spatiotemporal model. We argue that in the early stages, immune-evading OS cells initiate the formation of a pre-metastatic niche (PMN) in the lungs, creating a localized inflammatory environment that becomes the primary source of elevated circulating CXCL10. As the disease progresses, elevated systemic levels of CXCL10 overwhelm the localized chemokine gradient at the primary tumor site, creating a potent immune decoy that diverts anti-tumor CXCR3+ T cells away from the tumor. The resulting immune desertification permits unchecked tumor growth and an increased metastatic burden. We also discuss the therapeutic implications of this model, proposing that disrupting the chemokine axis offers a roadmap for developing rational, stage-specific therapies to effectively combat metastatic OS. Full article

Background/Objectives: Unstable intertrochanteric femur fractures (IFFs) in geriatric patients are associated with high rates of morbidity and mortality due to poor bone quality, multiple comorbidities, and limited functional capacity. This study aimed to compare the clinical outcomes of cementless bipolar hemiarthroplasty (BHA) performed via a transtrochanteric approach and proximal femoral nailing (PFN) in elderly patients with unstable IFFs. Methods: This retrospective comparative study included 131 patients aged ≥70 years who underwent surgery for AO/OTA 31-A2 and 31-A3 unstable fractures between January 2021 and July 2025 were retrospectively reviewed. 64 patients received cementless BHA and 67 underwent PFN. Eligible patients were ambulatory prior to fracture (independently or with a cane/walker); patients with pathological fractures/malignancy, alternative procedures (cemented or posterolateral BHA, total hip arthroplasty, tumor prosthesis, or other osteosynthesis methods), incomplete records, or <6 months of follow-up were excluded. Demographics, perioperative variables, mechanical complications, revision requirement, time to mobilization, and 1- and 6-month mortality rates were analyzed. Primary outcomes were mortality and perioperative clinical parameters. Results: The two groups were comparable in age, sex, ASA scores, and fracture patterns. Intraoperative blood loss and transfusion requirements were significantly higher in the BHA group (both p < 0.001). Mobilization was observed earlier in patients treated with BHA (1 [1,2] vs. 3 [2,3] days; p < 0.001). Mechanical complications were more frequently observed after PFN, which was associated with a higher revision requirement (17.9% vs. 4.7%; p = 0.018). Operative time, hospital stay, and 1- and 6-month mortality rates showed no significant differences between the groups. Conclusions: In geriatric patients with unstable IFFs, cementless BHA performed via a transtrochanteric approach may be considered a viable surgical option with appropriate patient selection, taking into account its association with earlier mobilization and the observed mechanical complication profile. PFN offers advantages of reduced blood loss and lower transfusion needs. Surgical decision-making should be individualized based on fracture morphology, bone quality, and the patient’s overall medical condition. Given the heterogeneity of unstable fractures within the AO/OTA classification and the retrospective nature of the present study, larger, multicenter prospective investigations incorporating functional outcomes are warranted to further clarify optimal treatment strategies. Full article

The chest wall represents a complex musculoskeletal structure that provides protection to intrathoracic organs, mechanical support for respiration, and mobility for the upper limbs. Neoplastic diseases of the chest wall encompass a heterogeneous group of benign and malignant lesions, which may be classified as primary—originating from bone, cartilage, muscle, or soft tissue—or secondary, resulting from direct invasion or metastatic spread, most commonly from breast or lung carcinomas. Approximately half of all chest wall tumors are malignant, and their management remains a significant diagnostic and therapeutic challenge. Surgical resection continues to represent the mainstay of curative treatment, with complete en bloc excision and adequate oncologic margins being critical to minimize local recurrence. Advances in reconstructive techniques, including the use of prosthetic materials, biological meshes, and myocutaneous flaps, have markedly improved postoperative stability, respiratory function, and aesthetic outcomes. Optimal management requires a multidisciplinary approach involving thoracic and plastic surgeons, oncologists, and radiotherapists to ensure individualized and comprehensive care. This review summarizes current evidence on the classification, diagnostic evaluation, surgical strategies, and reconstructive options for chest wall tumors, emphasizing recent innovations that have contributed to improved long-term survival and quality of life in affected patients. Full article

We report a rare case of squamous cell carcinoma (SCC) arising from an intraosseous epidermal cyst (EC) in the distal phalanx of the left thumb. A 76-year-old male presented with progressive thumb pain experienced over the previous six months. Radiography revealed a radiolucent lesion without marginal sclerosis, and magnetic resonance imaging showed peripheral contrast enhancement with no solid components. Surgery revealed a bone-originating mass without adhesion to the surrounding skin or nail bed, which histopathological findings determined contained both cystic epithelium with laminated keratin and invasive keratinizing tumor cells, confirming SCC arising from an intraosseous EC. No primary lesion or lymph node enlargement was identified by postoperative computed tomography. Although wide resection and chemotherapy were proposed, the patient declined further intervention beyond the curettage performed during surgery, opting for close observation only. No recurrence or metastasis has been observed in the five years since the surgery. Intraosseous ECs are extremely rare, with malignant transformation even more uncommon. Accurate diagnosis requires histopathological confirmation, as imaging alone is insufficient. This case highlights the importance of considering intraosseous EC in the differential diagnosis of bone lesions and underscores the need for further case accumulation to clarify optimal management strategies. Full article

Osteosarcoma (OS) remains the most common primary malignant bone tumor in adolescents, with conventional treatments yielding only modest improvements in long-term survival. Immunotherapy has emerged as a promising strategy to overcome these limitations. B7-H3 (CD276) stands apart from other potential targets due to its high expression in tumors cells, as well as its strong association with tumor aggressiveness and poor prognosis. This review provides a comprehensive overview of B7-H3, covering its molecular structure, regulatory mechanisms, biological functions, and expression patterns in tumor tissues. We emphasize the dual roles of B7-H3—both immunoregulatory and non-immunoregulatory—in shaping the tumor microenvironment (TME) and facilitating immune evasion. Building on these insights, we summarize current immunotherapeutic strategies targeting B7-H3 in OS, including monoclonal antibodies (mAbs), chimeric antigen receptor T cells (CAR-T), antibody-drug conjugates (ADCs), and bispecific antibodies (bsAbs). These four strategies have their own advantages and deficiencies. Excitingly, rapid advances in nanoparticle-based systems offer promising solutions to overcome the limitations, especially to develop more effective drug delivery systems and to reshape the TME by targeting immune cells. Despite promising progress, significant challenges remain. These include the absence of an identified B7-H3 receptor, the immunosuppressive and heterogeneous nature of the OS TME, and the need for improved targeting specificity and safety. Addressing these challenges through optimization of delivery systems, combination strategies, and the integration of nanotechnology may unlock the full potential of B7-H3-based immunotherapy in the treatment of OS. Full article

Background: Osteosarcoma (OS) is the most common primary malignant bone tumor, mainly affecting adolescents and young adults. While lung metastases are common, visceral metastases in the hepatopancreatobiliary system are extremely rare and usually associated with a poor prognosis. The limited diagnostic and therapeutic options for such metastases make the treatment of affected patients difficult. The possibility of very late metastatic onset in high-grade OS highlights the potential need for extended follow-up (FU) beyond established intervals. Methods: This study combines a retrospective analysis of prospectively collected data from the Vienna Bone and Soft Tissue Tumor Registry with a review of the literature of patients with OS and metastases to the hepatopancreatobiliary system. A descriptive statistical analysis is presented for the entire cohort. In addition, publications from scientific databases (PubMed, Embase) were analyzed to evaluate the frequency, diagnosis, therapy, and prognosis of visceral metastasis from both conventional OS and primary extraskeletal osteosarcoma (ESOS). Results: A total of six male patients with conventional OS and metastases in the liver (5) and pancreas (1), with a mean lesion size of 38 mm (range, 10–120), were included. The median age at the time of visceral metastasis was 29 years (mean, 32 years; range, 20–62 years), and the mean interval since initial diagnosis was five years and ten months (range, 9 months–10 years and 9 months). Visceral metastases are very rare in general and usually occur in advanced stages of disease. We identified 51 cases of visceral metastases from conventional OS and 34 cases of ESOS in the hepatopancreatobiliary system in the literature. The metastasis interval was three years (range, 15 months before diagnosis–17 years) at a median age of 27 years (mean, 32 years; range, 10–69 years). Conclusions: Visceral metastases from OS are rare but represent a significant therapeutic challenge. Early, targeted imaging in combination with improved methods for diagnosis confirmation and interdisciplinary treatment strategies may potentially improve the results. This study underlines the importance of early diagnosis and highlights the need for individualized long-term surveillance strategies exceeding ten years, especially in high-grade OS, aiming at early detection of late-onset metastasis. Full article

Background: Adamantinoma is a very rare primary malignant bone tumor. A histopathological grading is still lacking, and as a result, metastatic risk stratification at diagnosis is challenging. Due to this, imaging could play a role in prognosis prediction and treatment strategy assessment. We aimed to evaluate baseline imaging features and their correlation with the development of metastatic disease. Methods: We retrospectively collected clinical (metastatic disease) and radiological data at baseline (Conventional Radiography, CT, MRI) of all consecutive patients with a histopathological diagnosis of adamantinoma at our sarcoma center between 2006 and 2022. Tumor location, dimensions, main radiological pattern (lytic, sclerotic, mixed), Lodwick–Madewell grading, periosteal reaction, multifocality, soft-tissue extraskeletal component, peritumoral edema, peritumoral enhancement, and vascular invasion were analyzed. Associations between the above-mentioned radiological features and metastatic disease at diagnosis or during follow-up were assessed. Results: Twenty-two patients were included (15 [68.2%] women, median age 27 years old, range 7–58 years old). Six out of twenty-two patients (27.3%) developed distant metastases (only two of them were dedifferentiated adamantinoma): two patients (9%) presented with metastatic disease at diagnosis, while four patients developed metastases during follow-up (18.2%). The following radiological features represent a significant risk for metastatic disease (p = 0.01): (i) presence of an extra-skeletal component (Odds Ratio [OR] = 75.40; 95% CI = 3.15–1802.71), (ii) vascular invasion (OR = 121.00; 95% CI = 4.28–3424.73), (iii) diffuse peritumoral edema (OR = 75.40; 95% CI = 3.15–1802.71), (iv) peritumoral enhancement (OR = 84.33; 95% CI = 2.93–2423.26). All other features analyzed were not significantly associated with the onset of distant metastases. Based on these above-mentioned MRI features, we built two risk models for metastatic disease (excluding peritumoral enhancement, which was not available in five patients, to be applicable on unenhanced MRIs): Model (A) = simultaneous presence of two of those three features (2/3) with a sensitivity of 100% (54.07–100%) and a specificity of 93.75% (69.67–99.84%). Model (B) = simultaneous presence of all three features (3/3) with a sensitivity of 83.33% (35.88–99.58%) and a specificity of 100% (74.1–100%). Conclusions: An accurate evaluation of baseline imaging studies (particularly MRI) in patients affected by adamantinoma may significantly aid in prognosis prediction and the selection of high-metastatic-risk patients. For these patients, strict follow-up controls and more aggressive treatments should be suggested after multidisciplinary discussions in sarcoma centers. Full article

Osteosarcoma (OSA) is an aggressive primary bone cancer mainly affecting the pediatric population. Despite intensive multimodal treatments, therapeutic progress has remained limited for decades, resulting in high recurrence rates, poor prognosis driven by metastatic progression, and severe chemotherapy-associated toxicities. To advance the development of more effective and safer therapeutic strategies, our recent studies identified Chondroitin Sulfate Proteoglycan (CSPG)4 as a relevant mediator of the malignant behavior of OSA cells. Targeting CSPG4 DNA-based vaccine demonstrated encouraging antitumor activity against OSA. Nevertheless, since single-agent immunotherapies are often constrained by tumor immune escape, the need for rational combinatorial strategies is of utmost importance. In this perspective, we broaden our analysis to include other potentially complementary targets beyond CSPG4, which may contribute to OSA pathogenesis. Among these, the cystine/glutamate antiporter xCT and Toll-like Receptor 2 (TLR2) emerge as particularly promising due to their established role in tumor progression, therapy resistance, and immune modulation. We discuss the contribution of all these molecules in major hallmarks of OSA—(1) proliferative and survival advantages, (2) metastasis and angiogenesis, and (3) immune evasion—and examine potential strategies for their combined targeting. By leveraging knowledge gained from other cancer models and integrating it with the distinct biological and clinical features of OSA, this perspective seeks to outline rational and innovative combinatorial strategies that may overcome current therapeutic limitations and ultimately improve patient outcomes. Full article

Osteosarcoma is the most common primary malignant bone tumor in adolescents and young adults; yet survival outcomes have remained stagnated for decades, underscoring the urgent need for new therapeutic strategies. Creatine kinase (CK)—comprising cytosolic CKB and mitochondrial CK—maintains malignant behaviors by supporting high-energy phosphate transfer through the phosphocreatine (pCr) shuttle. Here, we pharmacologically inhibited CK activity in osteosarcoma models and evaluated proliferation, cell death modalities, mitochondrial function, stemness, motility, and tumor behavior. CK blockade consistently suppressed growth and clonogenicity and induced apoptosis as the predominant mode of death. It impaired ATP buffering capacity and disturbed mitochondrial homeostasis, accompanied by reduced expression of stemness-associated markers and diminished migration and invasion. In mouse models, CK inhibition significantly restrained tumor progression and dissemination. These results indicate that disabling the CK-pCr energy-buffering system reprograms cellular energetics toward apoptosis and less aggressive phenotypes. Our findings support targeting the CK pathway as a tractable metabolic vulnerability and a rational partner for cytotoxic regimens, with pathway-specific signaling alterations representing downstream consequences of central energetic collapse. Full article

Background: Hypereosinophilia, defined as a peripheral blood eosinophil count greater than 1.5 × 10⁹/L, can arise from allergic, infectious, autoimmune, or malignant conditions. In solid tumors, it is rare and most often linked to mucin-secreting carcinomas, while on extremely rare occasions, it accompanies signet ring cell carcinoma, a highly aggressive form of adenocarcinoma. Case Presentation: A 64-year-old woman presented with dyspnea and hypereosinophilia (2.9 × 10⁹/L). She was admitted with suspected eosinophilic pneumonia, but extensive testing was inconclusive. After bone marrow biopsy, her condition deteriorated; histology revealed metastatic signet ring cell carcinoma. PET/CT showed skeletal metastases without apparent local recurrence, although colonoscopy could not be performed to definitively rule it out. Retrospective review uncovered a 2 mm rectal polyp with signet ring cell carcinoma (SRCC) removed two years earlier. Peripheral eosinophilia progressively increased from 0.16 × 10⁹/L ten months earlier to a peak of 4.29 × 10⁹/L one month prior to admission. She died four weeks after discharge. Conclusions: To the best of our knowledge, this case represents one of the smallest reported primary colorectal SRCC lesions (2 mm) presenting with disseminated disease and paraneoplastic hypereosinophilia as the first diagnostic clue. Monitoring peripheral blood eosinophil counts may provide additional insight into disease activity and prognosis in solid tumors. Full article

Primary spinal osseous tumors are relatively rare, comprising ~5–10% of spinal bone neoplasms, whereas metastases account for the vast majority of spinal lesions. Patients commonly present with insidious back pain, sometimes with a focal mass, and constitutional symptoms are uncommon early in the disease course. As clinical features are often nonspecific and may overlap with degenerative, infectious, and metastatic disease, imaging plays an important role in lesion identification, characterization, and treatment planning. Computed tomography helps to define osseous architecture and matrix characteristics. Magnetic resonance imaging can assess marrow involvement, soft tissue extension, neural compression and intra-canal disease, and tumor vascularity. Together, advanced imaging modalities guide further workup, optimize biopsy planning, inform prognostic assessment and therapeutic decision-making, and anticipate mechanical instability or neural compromise. This narrative pictorial review synthesizes radiographic, CT, and MRI appearances of primary spinal tumors across major histologic lineages (e.g., osteogenic, chondrogenic, notochordal, vascular), illustrated with representative cases. We correlate imaging with clinical presentation to distinguish typical from atypical variants and highlight mimics and pitfalls with implications for diagnostic interpretation and management. Full article

Iron metabolism has emerged as a critical regulator of cancer biology, with mounting evidence linking iron dysregulation to tumor initiation, progression, and resistance mechanisms. Osteosarcoma (OS) is the most common primary bone malignancy and a leading cause of cancer-related death in children and young adults; recent studies have identified profound alterations in iron homeostasis at both cellular and microenvironmental levels in OS. These include increased iron uptake, disrupted storage and export, and a reliance on iron-dependent metabolic pathways that promote proliferation, metastasis, and immune evasion. Despite advances in surgical and chemotherapeutic approaches, survival outcomes in OS have stagnated, underscoring the need for novel therapeutic strategies. Targeting iron metabolism represents a promising avenue, with strategies such as iron chelation, transferring receptor inhibition, ferroptosis induction, and modulation of ferritinophagy, showing preclinical efficacy. In this review, we provide an updated and integrated overview of the multifaceted role of iron in OS pathogenesis, dissect emerging therapeutic approaches aimed at disrupting iron regulatory networks, and highlight innovative delivery platforms including nanomedicine. By integrating current insights on iron metabolism with the molecular complexity of OS, we present a comprehensive perspective, while acknowledging that the limited clinical translatability of current findings still hinders progress toward clinical application. A deeper understanding of iron-driven mechanisms may guide future studies toward the development of safe and effective iron-targeted therapies for OS. Full article

Brown tumors (BTs) are rare osteolytic lesions that typically occur in association with primary or secondary hyperparathyroidism (PHP and SHP). Excessive secretion of parathyroid hormone induces increased bone resorption, resulting in lesions characterized by fibrosis, vascularization, and hemosiderin deposition. The most common sites include the jaws, ribs, pelvis, and long bones. Clinical manifestations may involve pain, swelling, or pathological fractures. We present the case of a mandibular BT in a 48-year-old female with chronic renal failure and secondary hyperparathyroidism. The patient exhibited progressive mandibular swelling with radiological features resembling an aggressive odontogenic or malignant lesion. Laboratory analysis confirmed markedly elevated parathyroid hormone levels, while scintigraphy demonstrated increased focal uptake in the mandible and ribs. Histopathological evaluation revealed multinucleated giant cells within a fibrous stroma, consistent with BT. Despite initiation of systemic endocrine therapy, the lesion continued to enlarge, necessitating complete surgical excision of the mandibular mass. This case underscores the diagnostic dilemmas of mandibular BT, which may closely mimic aggressive jaw pathologies. Importantly, while many BTs regress after systemic management of hyperparathyroidism, this case illustrates that surgical excision may be unavoidable in patients with unstable systemic status or progressive local disease. Comprehensive clinical, radiological, laboratory, and histopathological evaluation remains essential to ensure timely diagnosis and appropriate treatment. Full article