Frank Tavassol

Intraosseous arteriovenous malformations (AVMs) of the mandible are rare but potentially life-threatening vascular anomalies in childhood. We report the case of a 7-year-old girl with an initially misdiagnosed (“keratocystic”) lesion who presented with recurrent intraoral bleeding, swelling, and tooth loosening of the right mandible. Magnetic resonance and angiographic imaging revealed an extensive intraosseous mandibular AVM extending into the peri-mandibular soft tissues, with arteriovenous shunts and a venous aneurysm. Following emergency hemostasis and blood transfusion, a total of five staged interventional radiological embolization procedures were performed between 2023 and 2024. Acute bleeding episodes could be controlled; however, sustained remission was not achieved. During the course of treatment, the patient developed a submandibular abscess and post-traumatic stress disorder (PTSD). Histopathological examination demonstrated a vascular malformation without evidence of malignancy. Molecular genetic testing identified a somatic KRAS (Kirsten rat sarcoma virus) mutation. Due to insufficient response to interventional therapy, systemic treatment with the MEK (mitogen-activated protein kinase) inhibitor trametinib was initiated to facilitate future surgical resection. Under this therapy, marked clinical and radiological improvement was observed with good tolerability. This case (3-year observation period) highlights the diagnostic risk of misinterpreting an osteolytic lesion, the importance of early diagnosis, the interdisciplinary staged and combined approach, the potential of molecular targeted therapy with an MEK inhibitor in treatment-refractory pediatric mandibular AVMs, and the continued relevance of surgical treatment strategies. These findings should be interpreted with appropriate caution and require validation in prospective studies.

Background: Neuroblastoma is a common extracranial solid malignant tumor of early childhood; however, mandibular involvement is rare and may mimic odontogenic or inflammatory disease. Case Presentation: We report an 8-month-old girl with left paramandibular swelling initially suspected to represent parotitis or odontogenic inflammation. Imaging revealed a destructive mandibular lesion with sunburst periosteal reaction, and histology confirmed undifferentiated neuroblastoma. Staging identified a left primary adrenal tumor with extensive bone marrow infiltration and MYCN proto-oncogene amplification. The patient received multimodal high-risk neuroblastoma therapy, including chemotherapy, surgery, autologous stem cell transplantation, proton therapy, antibody therapy, and Lorlatinib. Despite radiological remission, she developed severe pulmonary complications and died shortly before the age of five years. Methods: A focused literature review was conducted to identify published pediatric cases of metastatic neuroblastoma involving the mandible. Results: Through our review, we identified 31 published pediatric cases of mandibular metastatic neuroblastoma. Reported cases most commonly described mandibular swelling, pain, tooth mobility, and facial asymmetry. Most mandibular lesions represented metastatic disease from an adrenal or abdominal primary tumor. Conclusions: Mandibular involvement of neuroblastoma is rare but clinically important. In infants and young children, persistent or atypical (para-/peri)mandibular swelling should not be assumed to be odontogenic or inflammatory. Early imaging, biopsy, and interdisciplinary referral are essential for timely diagnosis and treatment.

Background: This longitudinal cohort study evaluated implant-associated bone remodeling and paranasal sinus (PNS) status after the insertion of patient-specific titanium orbital implants (PSIs) in adult trauma patients. Sixteen patients with various orbital fractures underwent CT-based reconstruction at the University Hospital Halle (Germany) and were followed up to 6.5 years (observation period February/2019–October/2025). Post-operative CT scans assessed orbital bone remodeling, patency of the ostiomeatal unit, and PSI/screw exposure. Findings: Bone apposition was observed in 16 cases; 13 showed a patent maxillary sinus outflow tract. The median Lund score for the injured sides was 1.0 vs. for the uninjured sides 0 (Wilcoxon test, p = 0.131). PSI or screw exposure occurred in isolated cases, and basal maxillary sinusitis was noted in four patients. Significant bone remodeling was detectable from 6 months post-operatively. No implant-associated complications required further intervention. Conclusions and Relevance: These findings highlight the safety and precision of PSIs, with low long-term complication rates and preserved sinus function in non-irradiated patients, supporting their use in complex orbital reconstructions.

Animal models are essential for studying tumor pathophysiology; however, most lack the capacity for repeated in vivo observation of tumor growth and vascularization over extended periods. This study aimed to establish a novel in vivo model using the mouse dorsal skinfold chamber. Tumor induction was performed using different membrane types (two polytetrafluoroethylene meshes and a polydioxanone plate), followed by monitoring of tumor vascularization via intravital fluorescence microscopy (IVM). Tumors developed successfully over six weeks, demonstrating sustained vascular supply and enabling, for the first time, the investigation of vascular networks in advanced tumors. Among the membranes tested, the polydioxanone membrane facilitated easier chamber preparation but may negatively affect angiogenesis and promote inflammation. IVM revealed persistent microcirculation in manifested tumors over six consecutive days, allowing detailed assessment of microvascular parameters, leukocyte–endothelial interactions, and functional capillary density. This model enables repetitive, high-resolution visualization of tumor microcirculation dynamics in vivo. In conclusion, this improved mouse dorsal skinfold chamber combined with IVM provides a powerful tool for investigating tumor angiogenesis and evaluating therapeutic interventions in advanced tumors.

The regulator of the canonical Wnt pathway, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is expressed in the stem cell compartment of several tissues and overexpressed in different human carcinomas. The isoform of the stem cell marker LGR5, named LGR5Δ5 and first described by our group, is associated with prognosis and metastasis in oral squamous cell carcinoma (OSCC) and soft tissue sarcoma (STS). In a proof-of-principle analysis, the function of LGR5Δ5 was investigated in HEK293T cells, a model cell line of the Wnt pathway, compared to full-length LGR5 (FL) expression. The CRISPR/CAS knockout of LGR5 and LGR4 (thereby avoiding the side effects of LGR4) resulted in a loss of Wnt activity that cannot be restored by LGR5Δ5 but by LGR5FL rescue. The ability to migrate was not affected by LGR5Δ5, but was reduced by LGR5FL overexpression. The CRISPR/CAS of LGR4 and 5 induced radiosensitization, which was enhanced by the overexpression of LGR5FL or LGR5Δ5. RNA sequencing analysis revealed a significant increase in the ligand R-spondin 1 (RSPO1) level by LGR5Δ5. Furthermore, LGR5Δ5 appears to be involved in the regulation of genes related to the cytoskeleton, extracellular matrix stiffness, and angiogenesis, while LGR5FL is associated with the regulation of collagens and histone proteins.