Search Results (120)

Background and Clinical Significance: Juvenile nasopharyngeal angiofibroma (JNA) is a benign but locally aggressive vascular tumor, classically affecting adolescent males. Diagnosis in adulthood is exceptionally uncommon and may mimic other vascular or malignant nasopharyngeal lesions. This patient also had chronic hypocalcemia with Fahr-like intracranial calcifications secondary to long-standing postoperative hypoparathyroidism after thyroid carcinoma treatment. To our knowledge, this coexistence has not been previously reported. Case Presentation: A 34-year-old Caucasian male with papillary thyroid carcinoma treated with total thyroidectomy developed postoperative hypoparathyroidism with chronic hypocalcemia and Fahr-like intracranial calcifications. During admission for acute respiratory insufficiency due to tracheostomy dysfunction, imaging revealed a 37 × 33 × 32 mm heterogeneous, hypervascular nasopharyngeal mass extending into the right pterygopalatine fossa (PPF) with bone remodeling and focal bony dehiscence. Digital subtraction angiography demonstrated a markedly hypervascular tumor, predominantly supplied by branches of the right internal maxillary artery (via the sphenopalatine artery). Endoscopic resection was performed, and histopathology confirmed JNA. Most JNA cases occur between 7 and 19 years of age; presentations in men older than 30 years are rare and often generate diagnostic uncertainty, particularly when differentiating from nasopharyngeal carcinoma or other lesions. In adults, magnetic resonance imaging/computed tomography for assessment of local extent and angiography for vascular mapping are key to minimizing hemorrhagic risk. The concurrent endocrine disorder emphasizes the need for multidisciplinary perioperative metabolic optimization, without implying a pathophysiological link. Conclusions: This report illustrates JNA diagnosed in adulthood in a male with Fahr-like intracranial calcifications secondary to chronic hypoparathyroidism. It highlights the necessity of considering JNA in the differential diagnosis of hypervascular nasopharyngeal masses in adults, especially in patients with complex comorbidities. Full article

Upper tract urothelial carcinoma (UTUC) is a rare and aggressive malignancy, accounting for only 5–10% of all urothelial carcinomas (UCs). Lung, bone, liver, and distant lymph nodes are common sites of metastasis, while gastrointestinal metastasis is extremely rare. We present a case of a 63-year-old female who developed a descending colon lesion 19 months after left radical nephroureterectomy for high-grade ureteral UC. The diagnosis was established by computed tomography (CT), magnetic resonance imaging (MRI), colonoscopy, and biopsy, which excluded primary colorectal malignancy. First-line therapy consisted of six 21-day cycles of gemcitabine plus cisplatin, followed by two cycles of tislelizumab maintenance immunotherapy. Restaging with contrast-enhanced CT and positron emission tomography/computed tomography (PET/CT) demonstrated disease progression. Despite switching to second-line nab-paclitaxel, the patient rapidly deteriorated from tumor cachexia and ultimately succumbed to septic shock secondary to severe pulmonary infection. This represents the first reported case of descending colon metastasis from primary ureteral UC. It highlights the colon as a potential metastatic site where biopsy is essential for definitive diagnosis. Notably, although the patient initially responded to platinum-based therapy, the subsequent rapid progression underscores the need for vigilant monitoring and timely adjustment of therapeutic strategies in managing such high-risk presentations. Full article

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with most cases arising from B-cell precursors expressing the CD19 marker. CD19 negativity in B-lineage ALL (B-ALL) is very rare de novo and poses diagnostic and therapeutic challenges. Sometimes, de novo CD19-negative B-ALL is associated with hypercalcemia, which is a potentially life-threatening metabolic disorder in children, rarely occurring in cancers. Most often it is reported in solid tumors, and few cases are reported in pediatric acute leukemia. CD19-negative B-ALL relapse is also an increasing dramatic event, secondary to immunotherapy. We describe a ten-month-old infant presenting with hypercalcemia, anemia, and osteolytic bone lesions. Bone marrow analysis revealed CD10-positive and CD19-negative B-ALL. The patient achieved complete remission but later experienced two relapses and died of respiratory failure after a second allogeneic hematopoietic stem cell transplantation (HSCT). Only nine cases of de novo CD19-negative B-ALL have been reported so far. Many are associated with hypercalcemia and osteolytic lesions. However, here we highlight the clinical impact of the more common secondary form of CD19-negative B-ALL as a relapse of CD19-positive ALL, right after the administration of targeted immunotherapy. Full article

Background/Objectives: Virtual surgical planning (VSP) and CAD/CAM technologies have revolutionized complex maxillofacial reconstruction. While high-resolution imaging is critical for these workflows, the specific clinical impact of photon-counting computed tomography (PCCT) remains to be fully established. This prospective pilot study evaluates the feasibility and clinical utility of integrating PCCT into the preoperative planning and surgical workflow of complex maxillofacial reconstructive cases. Methods: This feasibility study included ten patients requiring complex maxillofacial reconstruction with microvascular free flaps. All underwent preoperative imaging with photon-counting CT. Primary endpoints included clinical assessment of osseous invasion, reliability of donor-site vascular mapping from a single acquisition, and compatibility of PCCT datasets with VSP/CAD-CAM platforms. Secondary endpoints included resection margin status, flap survival, and short-term oncologic outcomes. Results: PCCT provided high-resolution visualization of cortical and medullary bone, enabling detailed assessment of tumor-related osseous involvement. In selected cases, findings supported refinement of resection planning when prior imaging had been inconclusive. Spectral reconstructions reduced metal artifacts and facilitated precise segmentation for multi-segment osteotomies. Donor-site vascular anatomy was successfully evaluated within the same scan, supporting operative planning without additional imaging. PCCT datasets were fully compatible with the virtual surgical planning (VSP) software used in this study (CMX Portal, version 2.6.1158, Medartis AG, Basel, Switzerland; or ProPlan CMF, version 5.7.8.025, Materialise NV, Leuven, Belgium) in all cases (100%). Reconstruction was completed successfully in all patients, with 100% flap survival and R0 margins in all malignant cases. No technical failures occurred during imaging transfer or CAD/CAM fabrication. Conclusions: The integration of PCCT into the surgical workflow proved technically feasible and clinically impactful. This pilot data supports its potential to enhance surgical precision and preoperative planning in complex jaw reconstruction. Full article

Background and Clinical Significance: Bladder cancer is common, with urothelial carcinoma (UC) comprising most cases in Western countries. Metastases usually involve pelvic structures, lymph nodes, and organs such as the liver, lungs, bones, and adrenal glands. Identifying unusual metastatic sites is critical for accurate diagnosis and treatment planning. Case Presentation: A 65-year-old man with a history of high-grade (G3) UC and carcinoma in situ, previously treated with TURBT, second-look resection, and SWOG-protocol BCG, presented with a new bladder lesion (pT1). Staging CT revealed extravesical spread and a 1.5 cm pancreatic body nodule. EUS-guided biopsy confirmed metastatic UC with concordant immunohistochemistry (GATA3+), excluding primary pancreatic cancer. The patient was referred for systemic therapy with immune checkpoint inhibitors and Enfortumab Vedotin. Conclusions: This case demonstrates the rare occurrence of pancreatic metastasis from bladder UC. EUS-guided biopsy with immunohistochemistry is essential to distinguish secondary lesions from primary pancreatic tumors. Accurate diagnosis is crucial to guide systemic therapy, particularly with emerging immunotherapy and antibody–drug conjugates. Full article

Background/Objectives: An Aneurysmal Bone Cyst (ABC) is a rare benign osteolytic bone lesion with locally destroying growth. It occurs mostly in the first two decades of life, rarely in older patients, and commonly affects the metaphysis. Clinical presentation includes pain and pathologic fractures. While most ABCs occur as primary lesions, there is an entity of secondary (reactive) ABC following osseous lesions such as fractures. We report a rare case of a secondary aneurysmal bone cyst of the distal radius following a distal radius fracture 4 years prior, with subsequent treatment and reconstruction. Methods: A 67-year-old female patient presented with a pathologic distal forearm fracture with radiologically expansive lytic bone lesion of the metaphysis of the distal radius, suspicious of an ABC. A biopsy and primary fracture management with an external fixator were performed due to the unclear dignity of the lesion. The diagnosis of an ABC was confirmed in the biopsy. The tumor resection and reconstruction were performed with a vascularized free fibula graft (ipsilateral, double barrel), using patient-specific 3D-printed osteotomy templates. Results: Follow-up radiographs showed excellent bone union with progressive remodeling. The functional outcome was very good with almost the same range of motion and grip strength as the contralateral side. No limitation in everyday life and no donor site morbidity was reported. Conclusions: ABC is a rare benign bone tumor the treatment of which consists of complete resection and reconstruction. Reconstruction of the distal radius can be achieved with a fibula graft. In our case, an excellent result was achieved with patient-specific osteotomy templates. Only a few cases of ABC in the distal radius and at this age have been reported; nevertheless, it should be considered as a differential diagnosis for osteolytic bone lesions Full article

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, accounting for approximately 75–80% of all renal carcinomas, and is often diagnosed incidentally on abdominal imaging, such as abdominal ultrasound or CT scan. Among other types of renal cancer, ccRCC is recognized to be highly aggressive due to its metastatic potential, which leads to a poor prognosis and an increased mortality rate. The most common sites of ccRCC metastasis are the lung, lymph nodes, bone, liver, and adrenal glands. Clear cell RCC is the most frequent primary tumor associated with secondary pancreatic involvement, while overall, pancreatic metastases represent only 2–5% of all malignant pancreatic lesions. These metastases often occur many years after nephrectomy and may present as solitary or oligometastatic disease, frequently displaying a paradoxically favorable prognosis compared with other metastatic sites. The present narrative review we conducted emerged from presentations of ccRCC with pancreatic distant metastases, potentially labeled as primary pancreatic tumors on imaging studies, mimicking pancreatic neuroendocrine tumors due to the hypervascular nature of ccRCC. Four patients were investigated in our clinic for suspicious pancreatic lesions identified on CT imaging, involving both the head and body of the pancreas. The definitive diagnosis was established by performing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or fine-needle biopsy (FNB) and histopathological analysis of the collected tissue samples. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has emerged as a pivotal tool for obtaining tissue diagnosis, particularly when cross-sectional imaging is inconclusive. Through a synthesis of clinical data and literature, this article underscores the essential diagnostic role of EUS-guided tissue acquisition and its impact on therapeutic decision-making. Full article

Background/Objectives: Type 1 gastric neuroendocrine tumors (gNET) arise in the setting of autoimmune chronic atrophic gastritis and secondary hypergastrinemia. Vitamin D deficiency (VDD) has been associated with bone impairment and adverse outcomes in patients with neuroendocrine tumor (NET); however, data specifically addressing gNET remain limited. This study aimed to evaluate vitamin D status, supplementation requirements, and bone involvement in patients with type 1 gNET compared with those with entero-pancreatic NET (EP-NET). Methods: This retrospective study included patients with type 1 gNET followed at a tertiary referral center between 2010 and 2025 and an age- and sex-matched EP-NET cohort. VDD prevalence, time and dose required for normalization, supplementation formulations, bone status, and dietary habits were analyzed. Results: Twenty-six patients were included (thirteen gNET and thirteen EP-NET). VDD was significantly more prevalent in the gNET group compared with the EP-NET group (92.3% vs. 46.2%, p = 0.03, OR: 14). gNET required significantly higher daily cholecalciferol doses (3198.9 ± 1629 vs. 1580 ± 1121 IU/day, p = 0.008) and more frequently required multiple supplementation formulations (38.5% vs. 0%, p = 0.04). Multivariable linear regression analysis restricted to VDD patients confirmed that gNET was independently associated with higher daily cholecalciferol dose requirements (p = 0.037). Bone impairment, defined as osteoporosis or osteopenia, was significantly more common in the gNET group (61.5% vs. 15.4%, p = 0.04, OR: 8.8). Dietary adherence did not differ between groups. Conclusions: Type 1 gNET show a higher burden of VDD, increased vitamin D supplementation requirements, and a higher prevalence of bone impairment compared with EP-NET, irrespective of dietary habits. These findings suggest disease-specific mechanisms and support the need for tailored management in these patients. Full article

Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment (TME) and often adopt an M2-like immunosuppressive phenotype that promotes tumor growth. Reprogramming TAMs toward an M1-like pro-inflammatory state is an attractive therapeutic strategy. Tumor Treating Fields (TTFields), an FDA-approved, electric-field–based therapy, has recently been suggested to modulate immune responses in addition to its established anti-mitotic activity. Here, we investigated the direct effects of TTFields on macrophage activation and function. Murine bone marrow–derived macrophages (BMDMs) were polarized toward a pro-inflammatory M1-like phenotype or an anti-inflammatory M2-like phenotype and exposed to TTFields. TTFields rapidly activated guanine nucleotide exchange factor-H1 (GEF-H1), and downstream nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1, via c-Jun N-terminal kinase [JNK]) signaling. Functionally, TTFields reprogrammed M2-like macrophages by increasing major histocompatibility complex class II (MHC-II) and cluster of differentiation 80 (CD80); reducing arginase-1 (Arg1); and elevating secretion of chemokine (C-X-C motif) ligand 1 (CXCL1), interleukin-6 (IL-6), IL-1β, and IL-12 subunit p70 (IL-12p70). In interferon gamma (IFN-γ)-primed macrophages, TTFields provided a secondary signal, driving myeloid differentiation primary response 88 (MyD88)-dependent expression of inducible nitric oxide synthase (iNOS). In vivo, TTFields reduced tumor burden in an orthotopic murine lung cancer model and increased iNOS expression in both M1-like and a subset of M2-like TAMs. These findings demonstrate that TTFields directly reprogram macrophages toward a pro-inflammatory phenotype, suggesting a novel immunomodulatory mechanism that may enhance anti-tumor immunity in the TME. 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

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

Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases like malignant bone tumors is limited by scarce annotated data. This study evaluates same-modality cross-domain transfer learning by comparing an AI model pretrained on chest radiographs with a model trained from scratch for detecting malignant bone tumors on knee radiographs. Methods: Two YOLOv5-based detectors differed only in initialization (transfer vs. scratch). Both were trained/validated on institutional data and tested on an independent external set of 743 radiographs (268 malignant, 475 normal). The primary outcome was AUC; prespecified operating points were high-sensitivity (≥0.90), high-specificity (≥0.90), and Youden-optimal. Secondary analyses included PR/F1, calibration (Brier, slope), and decision curve analysis (DCA). Results: AUC was similar (YOLO-TL 0.954 [95% CI 0.937–0.970] vs. YOLO-SC 0.961 [0.948–0.973]; DeLong p = 0.53). At the high-sensitivity point (both sensitivity = 0.903), YOLO-TL achieved higher specificity (0.903 vs. 0.867; McNemar p = 0.037) and PPV (0.840 vs. 0.793; bootstrap p = 0.030), reducing ~17 false positives among 475 negatives. At the high-specificity point (~0.902–0.903 for both), YOLO-TL showed higher sensitivity (0.798 vs. 0.764; p = 0.0077). At the Youden-optimal point, sensitivity favored YOLO-TL (0.914 vs. 0.892; p = 0.041) with a non-significant specificity difference. Conclusions: Transfer learning may not improve overall AUC but can enhance practical performance at clinically crucial thresholds. By maintaining high detection rates while reducing false positives, the transfer learning model offers superior clinical utility. Same-modality cross-domain transfer learning is an efficient strategy for developing robust AI systems for rare diseases, supporting tools more readily acceptable in real-world screening workflows. Full article

Background: The disialoganglioside GD2, located at the plasma membrane, is selectively overexpressed in various solid tumors, where it contributes to tumor growth and the development of an aggressive tumor phenotype. Thus, over the last two decades GD2 has been gaining importance both as a tumor marker and a therapy target. In neuroblastoma, anti-GD2 monoclonal antibodies and CAR T-cells have become an integral part of the multimodal treatment for relapsed or refractory high-risk cases, which continue to associate with poor prognosis. GD2 characterization in neuroblastoma is well established for bone marrow aspirates and biopsies, but remains challenging in tumoral tissue samples, mostly due to epitope loss upon fixation. Aims: The aim of our work was to assess a new protocol by staining GD2 in tissue specimens prior to fixation. Methods: Positive controls were tissue specimens from patients with histologically confirmed neuroblastoma and GD2 expression in bone marrow aspirate (n = 5). Nephroblastoma or Hodgkin lymphoma samples were considered as negative controls (n = 5). Tissue staining was performed prior to fixation with either anti-GD2 antibody or isotype control, followed by secondary antibody staining and subsequent paraffinization. To examine GD2 staining before and after paraffinization, fluorescence images were acquired using 3D and 2D immunofluorescence microscopy techniques respectively. Results: GD2 signal was detected in all positive controls, while absent in all negative controls. After fixation, paraffinization and slicing no relevant signal loss was observed. Nevertheless, sufficient staining of 3D specimens required long incubation times, which led to increased cytolysis of the unfixed tissue. Conclusions: We were able to establish and validate a novel protocol to reliably perform immunostaining of the membrane antigen GD2 in unfixed, primary neuroblastoma tissue. Although including few limitations, this staining workflow enables relatively quick assessment of GD2 status and thus, might represent a relevant diagnostic tool within the framework of tumor staging and precision medicine. Full article

Background and clinical significance: Paget’s disease of bone involves anomalies of the bone metabolism; however, the presence of tumor-derivate abnormal parathyroid hormone (PTH) levels does not represent one of these disturbances. To our best knowledge, the association with normocalcemic variant of primary hyperparathyroidism has been limitedly reported, and here we introduce such an unusual overlap in a male suffering from osteoporosis. Case presentation: A 71-year-old, non-smoker man was hospitalized for mild, nonspecific dysphagia, asthenia, decreased appetite, and mild weight loss during the latest 2 months. His medical history included cardiovascular conditions and an abnormal PTH level with normal serum calcium under daily cholecalciferol supplements (tested twice during latest 12 months). The lab findings pointed out a normocalcemic primary hyperparathyroidism (PTH of maximum 163 pg/mL, and total calcium of 9.3 mg/dL) caused by a right parathyroid tumor of 1.2 cm, as confirmed by computed tomography (CT). Additionally, CT showed a left humerus lesion suggestive of Paget’s disease of bone, a confirmation that also came from the whole-body bone scintigraphy. The subject presented increased P1NP and osteocalcin, CrossLaps as bone formation, and resorption markers, with normal total alkaline phosphatase. CT scan also detected multiple vertebral fractures and small kidney stones. Zoledronate i.v. (3 mg, adjusted for creatinine clearance) was administered, taking into consideration all three bone ailments (Paget’s disease, high PTH/calcium, and osteoporosis) with further follow-up. Conclusions: This case highlights the following technical notes based on a real-life setting: 1. Despite the mentioned bone diseases, no bone pain was present. Loss of appetite, dysphagia, and asthenia may be a consequence of mineral metabolism disturbances. 2. The panel of blood bone turnover markers levels might be related to both hyperparathyroidism and Paget’s disease; notably, rare cases of Paget’s disease with normal alkaline phosphatase were prior reported. 3. A meticulous differentiation between secondary and primary hyperparathyroidism is required. In this instance, lack of hypocalcaemia and vitamin D deficiency was suggestive of the diagnosis of a primary variant. 4. Kidney stones, osteoporosis, and osteoporotic fractures may be correlated with both conditions, as well, while a dual perspective of the therapy, since the patient was not a parathyroid surgery candidate, included a first dose of zoledronate with consecutive long-term follow-up. To our best knowledge, the co-presence of normocalcemic variant of primary hyperparathyroidism represents an exceptional finding in a patient synchronously diagnosed with Pagetic lesions and osteoporosis complicated with vertebral fractures. Full article

Background/Objectives: Resection arthroplasty is well established in treating bone defects following tumor resection, with the distal femur and proximal tibia being its most common localizations. The aim of this study was to analyze the functional outcomes and quality of life following endoprosthetic reconstruction for malignant bone tumors of the knee joint. Methods: We retrospectively included all patients treated with an endoprosthetic reconstruction following resection of a malignant bone tumor of the knee at our institution. Functional outcomes (KOOS, OKS, MSTS, and KSS) and health-related quality of life scores [QoL] (SF-36, Karnofsky Index) were evaluated. Chi-square and Fisher’s exact test was used for categorical variables, T-test and Whitney U-Mann tests for continuous variables. Survival was calculated using the Kaplan–Meier curves. Results: 32 patients were included. A total of 12 patients had died at the time of follow-up. Among the remaining 20 patients (m:w 17:3), mean follow-up was 8.1 years (range, 8.12 ± 6.8). Mean age at the time of tumor diagnosis was 50 ± 23.3 (10–83) years. According to age, patients were divided into two groups (group C1: <29 years, group C2: >29 years). Group C1 showed significantly better results regarding functional outcome (p < 0.05). The anatomic location of the replacement and a revision surgery did not influence the functional outcome (p > 0.05). QoL showed no significant differences in subgroup analysis (p > 0.05). Primary bone tumors had a significantly better survival (primary tumor: 216.90 months [168.42–265.83]; secondary tumor: 37.03 months [11.71–62.35] p = 0.01). Furthermore, pathologic fractures were associated with significantly worse survival (pathologic fracture: 50.24 months [0.00–102.43]; pathologic fracture 190.63 moths [139.28–241.45]; p = 0.007). Conclusions: Knee resection arthroplasty can offer meaningful long-term functional outcomes and acceptable quality of life in selected patients with musculoskeletal tumors. While the rarity and heterogeneity of such cases remain a challenge, our findings contribute to the growing evidence supporting this complex but limb-sparing surgical option. Full article