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The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference—held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)—after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SICMF and SIPMO), written on the inputs of the experts of the Italian Allied Committee on ONJ (IAC-ONJ). The conference focused on the topic of MRONJ, and in particular on the common practices at risk of inappropriateness in MRONJ diagnosis and therapy, as well as on MRONJ prevention and the dental management of patients at risk of MRONJ. It is a matter of cancer and osteometabolic patients that are at risk since being exposed to several drugs with antiresorptive (i.e., bisphosphonates and denosumab) or, more recently, antiangiogenic activities. At the same time, the Conference traced for dentists and oral surgeons some easy applicable indications and procedures to reduce MRONJ onset risk and to diagnose it early. Continuous updating on these issues, so important for the patient community, is recommended.

Assessing accuracy in CAD-CAM mandibular reconstruction poses significant challenges but is essential for ensuring reliable outcomes. Existing methods are often operator-dependent, lacking repeatability and reproducibility. This study introduces the Global Positioning Layout (GPL) method, an accuracy assessment technique integrated into the reconstruction protocol based on CAD-CAM and additive printing technology. We describe its methodology and present its implementation through an automated workflow. Key principles of accuracy assessment were identified and structured as Requirements, Data input, Data reference system, and Data output. The necessary 3D virtual models were defined: planned mandible, reference mandible, patient-specific implant (PSI), postoperative mandible, and postoperative PSI. A unique coordinate system (GPL-RS) was built on the reference mandible. Three Roto-Translational Matrices (RTMs) were applied to measure movements and deviations between the designed and postoperative models to assess reconstruction accuracy. Five clinical cases with different operational diseases and defects were analysed, comparing spatial deviations between manual and automated methods. The GPL method represents a promising advancement in assessing the accuracy of CAD-CAM reconstructions, providing valuable insights that can improve surgical outcomes.

The lack of a standardized methodology complicates accuracy assessment in computer-assisted mandibular reconstruction. Existing landmark-based methods are susceptible to operator variability, while surface-based comparisons can mask local deviations. This study validates a novel, automated protocol, the Global Positioning Layout (GPL), to quantify the 3D discrepancy between the virtual surgical plan and the postoperative outcome, by comparing its performance and reliability against Methods A and B. A retrospective cohort of 17 patients was analysed, with three operators performing all measurements on two occasions. The GPL method demonstrated complete reproducibility, with no inter- or intra-operator variability, providing a detailed, spatially-oriented assessment of deviations. In contrast, the landmark-based method showed poor reproducibility and systematic bias and was often inapplicable due to the absence of landmarks after resection. The surface-based method, while objective for its mean error metric, was operator-dependent for initial alignment and its non-directional output masked significant localized deviations. This study validates GPL as a robust and fully reproducible tool that overcomes the critical limitations of established techniques. The GPL method provides a strong foundation for a standardized protocol, essential for the reliable comparison of surgical outcomes, refinement of surgical techniques, and improvement of long-term patient outcomes.

Background Cancer treatment-induced bone loss (CTIBL) is the most common adverse event experienced by patients affected by breast cancer (BC) patients, without bone metastases. Bone modifying agents (BMAs) therapy is prescribed for the prevention of CTIBL, but it exposes patients to the risk of MRONJ. Methods This multicentre hospital-based retrospective study included consecutive non-metastatic BC patients affected by MRONJ related to exposure to low-dose BMAs for CTIBL prevention. Patients’ data were retrospectively collected from the clinical charts of seven recruiting Italian centres. Results MRONJ lesions were found in fifteen females (mean age 67.5 years), mainly in the mandible (73.3%). The mean duration of BMAs therapy at MRONJ presentation was 34.9 months. The more frequent BMAs was denosumab (53.3%). Ten patients (66.7%) showed the following local risk factors associated to MRONJ development: periodontal disease (PD) in three cases (20%) and the remaining six (40%) have undergone PD-related tooth extractions. One patient presented an implant presence-triggered MRONJ (6.7%). In five patients (33.3%) no local risk factors were observed. Conclusions This is the first case series that investigated BC patients under BMAs for CTIBL prevention suffering from MRONJ. These patients seem to have similar probabilities of developing MRONJ as osteo-metabolic ones. Breast cancer patients under BMAs for CTIBL prevention need a regular prevention program for MRONJ, since they may develop bone metastases and be treated with higher doses of BMAs, potentially leading to a high-risk of MRONJ.

Denosumab has proved effective at low doses in increasing bone mineral density in osteoporosis patients. In contrast to high-doses antiresorptive therapy, denosumab has a transient effect on the inhibition of the bone remodeling process, suggesting that denosumab-related osteonecrosis is a self-limiting disease, with a high curative potential of surgery when performed after a proper duration of receptor activator of nuclear factor-kB ligand (RANKL) inhibitor suspension. We report the long-term clinical and radiological (Computed Tomography—CT scan) data of a patient affected by secondary osteoporosis (cancer treatment-induced bone loss—CTIBL for metastatic breast cancer) who underwent surgical treatment for stage II denosumab-related osteonecrosis of the upper maxilla 7 months after denosumab suspension. A minimally invasive approach was performed with the extraction of the first right upper molar and debridement of the surrounding alveolar bone. After surgery, the patient was followed up at three-month intervals up to 1 year, and clinical and radiological data (CT scan) were recorded at each follow-up for the early detection of signs of recurrent disease. The mucosal healing remained stable in the long term, with radiological signs of bone remodeling in the post-operative site since the 6-month follow-up. The presented case strengthens the hypothesis that denosumab induces temporary alterations of bone turnover with a predictable curative effect of minimal surgical procedures in cases of denosumab-related osteonecrosis of the jaw.

A female patient with non-small-cell lung cancer presented with a huge area of exposed bone in the mandible following spontaneous teeth loss. She was receiving multimodal chemotherapy containing bevacizumab. No previous treatment with bisphosphonates or comorbid conditions was reported. Pain medications and infection control were offered to the patient who was closely followed up. Initial imaging and histology of bone and surrounding mucosa (8 weeks after bevacizumab cessation) confirmed the clinical suspicion of avascular osteonecrosis of the mandible. Subsequent imaging and histology of bone and gingiva (12 weeks after bevacizumab cessation) revealed the initial sequestration of the mandible with a marked expansion of the mucosal vascular network. Spontaneous bone sequestration eventually occurred few months later, followed by stable and painless mucosal coverage of the mandibular bone. The patient remained disease-free up to 3 years of follow-up.

AimsAmeloblastoma is a rare odontogenic tumour with an aggressive local behaviour. Mutations in the mitogen-activated protein kinase pathway, namely BRAF V600E mutations, are a common finding. To date, there is no clear correlation between BRAF V600 mutation and clinical outcome.MethodsWe retrospectively reviewed the medical records of patients who underwent surgery for ameloblastoma between May 1998 and June 2018, at 11 participating Italian centres. BRAF mutational status was evaluated by quantitative PCR/pyrosequencing. The primary end points were to determine BRAF mutational status in primitive and recurrent ameloblastoma, and to assess the relapse-free interval (RFI); the secondary end point was to investigate the correlation of BRAF mutational status with the clinical features of the tumour and survival outcomes.ResultsOverall, 74 patients were included: 33 (44.5%) were BRAF wild type and 41 (55.4%) BRAF V600 mutated. BRAF V600 mutated ameloblastomas occurred more frequently in younger patients (p=0.0031), were located at the mandible (p=0.0009) and presented with unicystic variant. After a median follow-up of 60 months, 21 (28.3%) patients relapsed (30.3% and 26.8% in the BRAF wild type and BRAF mutated group, respectively). At univariable Cox models, none of the investigated variables, including microscopic margin involvement, was associated with RFI.ConclusionsLocal recurrence occurs in 30% of patients with ameloblastoma. BRAFV600 mutation is associated with younger age, mandibular localisation and with unicystic ameloblastoma. Neither BRAF mutation nor microscopically positive surgical margins were associated with RFI. Further studies are needed to elucidate outcomes of this rare disease according to clinical, histopathological and comprehensive molecular features.

Cancer treatment-induced bone loss (CTIBL) is the most common adverse event experienced by patients affected by breast cancer (BC) patients, without bone metastases. Bone modifying agents (BMAs) therapy is prescribed for the prevention of CTIBL, but it exposes patients to the risk of MRONJ. This multicentre hospital-based retrospective study included consecutive non-metastatic BC patients affected by MRONJ related to exposure to low-dose BMAs for CTIBL prevention. Patients' data were retrospectively collected from the clinical charts of seven recruiting Italian centres. MRONJ lesions were found in fifteen females (mean age 67.5 years), mainly in the mandible (73.3%). The mean duration of BMAs therapy at MRONJ presentation was 34.9 months. The more frequent BMAs was denosumab (53.3%). Ten patients (66.7%) showed the following local risk factors associated to MRONJ development: periodontal disease (PD) in three cases (20%) and the remaining six (40%) have undergone PD-related tooth extractions. One patient presented an implant presence-triggered MRONJ (6.7%). In five patients (33.3%) no local risk factors were observed. This is the first case series that investigated BC patients under BMAs for CTIBL prevention suffering from MRONJ. These patients seem to have similar probabilities of developing MRONJ as osteo-metabolic ones. Breast cancer patients under BMAs for CTIBL prevention need a regular prevention program for MRONJ, since they may develop bone metastases and be treated with higher doses of BMAs, potentially leading to a high-risk of MRONJ.

Background Solitary fibrous tumour (SFT) is quite a rare neoplasm involving the eye and the orbit. It is described as showing benign behaviour in adults, but malignant cases are exceptionally reported in this location. This report describes four new cases of SFT/giant cell angiofibroma (GCA) of the eyelid and orbit, one in a 5-year-old child, and one with sarcomatous dedifferentiated transformation occurring 9 years after radiotherapy. Methods Four cases of ocular SFT/GCA were retrieved from the database of the Pathological Anatomy Unit, University of Padova; immunohistochemistry and RT-PCR were used to identify COL1A1—PDBGF fusion gene transcripts in all cases. Results In case 1, late relapse 9 years later was characterised by abrupt transition into a high-grade component, associated with a non-distinctive high-grade sarcomatous area. The latter component was CD34, CD99 and Bcl2 negative and smooth muscle actin positive. Molecular characterisation showed the absence of COL1A1-PDGFB fusion transcripts in cases 1, 3 and 4, excluded diagnosis of giant cell fibroblastoma in all cases. Analysis could not be performed in case 2. Conclusions An eyelid SFT/GCA in a 5-year-old child is the youngest case reported in the literature, indicating that the tumour is not exclusive to adults. The case with sarcomatous transformation, with dedifferentiated features occurring 9 years after radiotherapy, raises some questions about the choice of treatment for ocular SFT, in which excision is sometimes difficult without devastating surgery.

A female patient with non-small-cell lung cancer presented with a huge area of exposed bone in the mandible following spontaneous teeth loss. She was receiving multimodal chemotherapy containing bevacizumab. No previous treatment with bisphosphonates or comorbid conditions was reported. Pain medications and infection control were offered to the patient who was closely followed up. Initial imaging and histology of bone and surrounding mucosa (8 weeks after bevacizumab cessation) confirmed the clinical suspicion of avascular osteonecrosis of the mandible. Subsequent imaging and histology of bone and gingiva (12 weeks after bevacizumab cessation) revealed the initial sequestration of the mandible with a marked expansion of the mucosal vascular network. Spontaneous bone sequestration eventually occurred few months later, followed by stable and painless mucosal coverage of the mandibular bone. The patient remained disease-free up to 3 years of follow-up.