# Intraosseous Squamous Cell Carcinoma Associated with Denosumab-Induced Osteonecrosis of the Jaw
## 2 Case Presentation  
The patient was a 70-year-old woman suffering from type II diabetes mellitus, arterial hypertension, dyslipidemia anemia, vitamin B12 deficiency, and osteoporosis. The patient had been treated with denosumab, at a dose of 60 mg every 6 months for more than 2 years and was referred to the Oral and Maxillofacial Surgery Department for evaluation of suspected mandibular osteonecrosis after multiple tooth extractions that had been performed at another centre. Physical examination revealed a pathological mandibular fracture with an extensive area of intraoral bone exposure. External examination revealed a cervical skin fistula (Figure 1). Following the usual protocol with these patients, it was decided to randomly perform superficial and deep intraoral bone biopsies as well as intraoral (mucosa) and extraoral (skin) perilessional soft tissue biopsies. Imaging tests were requested. The anatomopathological result was bone necrosis and inflammatory granulation tissue (Figure 2). Orthopantomography and computed tomography (CT) showed (Figure 3) a diffuse lytic involvement which was compatible with mandibular necrosis that extended from the left to the right mandibular angles, and the presence of the pathological fracture described above. No pathological lymphatic neck nodes were described, and no distant lesions were diagnosed in a whole-body CT scan. Due to negative bone and soft tissue biopsies (a diagnosis of carcinoma could not be established) and with the CT scan findings suggesting osteonecrosis of the jaw, it was not considered necessary to request an MRI scan. This decision was made in agreement with the  
Figure 1: (**A**) Mandibular osteonecrosis. Intraoral view. (**B**) Extraoral cutaneous submental fistula. With the suspected diagnosis of drug-associated osteonecrosis of the jaw, further studies were performed to evaluate microsurgical bone reconstruction with a fibula free flap. AngioCT of supra-aortic and tibioperoneal vessels ruled out pathology or anatomical variants in both vascular axes without clearly identifying perforating vessels from the vascular pedicle to the skin of the legs. The jaw resection surgery and the reconstruction with the fibula flap were virtually planned in order to design bone cutting guides in the mandibular area and in the lower limb (Figure 4). Based on this information, a custom-made titanium implant was designed to fix the free flap to the remanent mandible (Figure 5). Figure 3: Axial and sagittal CT scan demonstrating mandibular necrosis and pathologic fracture. Figure 2: (**A**) Hematoxylyn-eosin-stained section showing necrotic bony trabeculae demonstrating empty osteocyte lacunae necrotic devoid of inflammatory cells (original magnification \(\times\)2.5). (**B**) A border of new bone formation is identified with a superficial reactive line where osteoblasts can be seen (stain, H&E; magnification, \(\times\)10). The patient underwent surgery by means of a tracheotomy, an external cervical approach, placement of the cutting guides, segmental angle-to-angle mathibulectomy, and immediate reconstruction with a fibula free flap (Figure 6). The recipient vessels for the microsurgical anastomoses were the external carotid artery and two veins (the thyrolinguofacial trunk and the external jugular vein). Internal fixation of the custom-made titanium implant was performed with 2.0 screws. Intraoral soft tissue closure was achieved with two buccinator myomucosal flaps. The final histopathological specimen revealed a highly mature intraosseous squamous cell carcinoma surrounded by necrotic tissue with single focal cortical bone involvement. This epithelial neoplasm was organized in solid nests or cords with medium-sized cells with large eosinophil cytoplasm and well-defined membrane, large and vesicular nuclei, and the presence of nucleolus. Keratin formation and some corneal pearls were observed. The bone margins were free of disease. A primary intraosseous squamous cell carcinoma  
Figure 4: Virtual surgical planning.