Oral Squamous Cell Carcinoma (OSCC) Imitates Denosumab-Induced Osteonecrosis of the Mandibular Alveolus: A Diagnostic Challenge

Abstract

Oral squamous cell carcinoma (OSCC) may arise in the the alveolar ridge (in a minority of cases). Smoking, chronic mucosal injuries, and poor oral hygiene are involved in its pathogenesis. It mostly occurs to men instead of women and affects the mandible on a 3:2 ratio to the maxilla. The objective of the current study is to present an interesting case of an OSCC of the alveolar ridge mimicking jaw osteonecrosis due to denosumab, resulting in differential diagnostic dilemmas. A 78-year-old female patient, edentulous and bearing total dentures, was referred with a persistent (four months), severely painful, ulcerative lesion in the anterior lateral (right) region of the residual alveolar ridge of the mandible. Medical history referred to a long-term systemic steroid use due to sarcoidosis as well as the subcutaneous use of denosumab for osteoporosis one/month for one year. Cone-beam CT (CBCT) examination was performed where bone resorption was detected and a differential diagnosis of osteonecrosis of the jaws (ONJs) from denosumab or neoplasia was made. A biopsy was carried out, and the histological examination showed that soft tissues and underlying bone were infiltrated by abnormal, confluent, compact islands of malignant squamous cells with intense atypia and numerous mitoses indicating a moderately differentiated OSCC. Denosumab inhibits the binding of receptor activator of nuclear factor ligand (RANKL) to receptor activator of nuclear factor-kappa (RANK); this decreases bone resorption and results in increased bone density. However, denosumab may induce ONJ. The area of exposed bone and abnormal soft tissue alterations may resemble both benign and malignant diseases. Osteonecrosis may mimic OSCC or may even provide the suitable substrate for the development of OSCC. Biopsy as well as bone imaging examination are required to accurately determine the possibility of neoplastic formation and its boundaries in cases of osteonecrosis especially in patients under treatment with denosumab or bisphosphonate-related ONJ (BRONJ).

Keywords: denosumab and cancer; jaw osteonecrosis; medication-related osteonecrosis of the jaw; oral cancers; oral cavity squamous cell carcinoma.

Figure 1. Ulcerative mucosal lesion with underlying osteonecrosis

Figure 2. Three-dimensional radiographical imaging of the osteolytic lesion in the fourth quadrant (yellow arrows indicate the radiolucent lesion)

Figure 3. Histological examination showing ulceration (Figure 3A, blue arrow), neoplastic cell islands manifesting severe atypia and numerous mitotic divisions invading gingival mucosa (Figure 3B, yellow arrow) and alveolar ridge of mandible (Figure 3C, yellow asterisk)