FOLs of the craniomaxillofacial region are described as the replacement of bone by cellular fibrous tissue containing varied amount of mineralized tissue. The lesions share a similar histological appearance, thus clinical and radiological features must be correlated to determine a final diagnosis [7, 11]. FOLs usually present a favourable prognosis, but evidence suggests that some FOLs, especially fibrous dysplasia, may have a risk of spontaneous malignant transformation [11].

COD is the most common FOL and has a predilection for middle-aged women of African descent [3, 4, 9]. As the name suggests, it is limited to the tooth-bearing region; characterized by the replacement of bone with cementum-like material [3, 6, 7]. These lesions lack expansile growth, are asymptomatic and normally detected as incidental findings on routine radiographic examination [2].

COD is further divided into three categories: periapical cemental dysplasia (PCD), focal COD and florid COD. PCD is a localized variant affecting the apices of vital mandibular anterior teeth. The focal variant is a solitary lesion usually not associated with a tooth and florid COD involves two or more quadrants of the jaws [5, 9].

Radiologically, as COD matures it transforms between three stages depending on the degree of mineralization, namely: (1) lucent/early stage where normal bone is resorbed, (2) mixed stage followed by (3) the opaque/final phase. New bone is deposited in increasing amounts in the second and third stages [5, 9, 12].

The interpretation of COD can be made based on the radiologic features and clinical findings [13]. Since COD can be diagnosed radiologically, it does not always require histological confirmation [2]. Due to the decreased vascularity in COD, biopsies are controversial as they predisposes the patient to osteomyelitis [2, 3, 14, 15]. CODs usually do not require treatment, but due to the tendency for mature lesions to become secondarily infected or exposed in the oral cavity, surgical intervention is then required to avoid complications such as osteomyelitis or draining cutaneous fistula [13].

Turning to OS, which in contrast to COD, is a malignant tumor of bone with a sinister prognosis. Symptoms such as pain and swelling are characteristic [6]. The case reported by Schneider et al. was the first example of a sarcoma arising in association with florid osseous dysplasia [15]. The concurrence of COD and OS is rare and, therefore, sparsely reported in the literature. There are only six reported cases known to the authors. A review of these cases was conducted, and a comparison is summarized in Table 1 [2, 6, 15,16,17]. The concurrence of COD and OS, as noted in these cases, prompts a re-evaluation of potential pathophysiological links. Wagner et al. has suggested that certain fibro-osseous lesions may harbour malignant potential under specific conditions [11]. Furthermore, genetic studies have identified pathways that could be implicated in both COD and OS, suggesting a relationship that may extend beyond mere coincidence [10]. The cases outlined in Table 1 demonstrate a range of demographic profiles and clinical presentations, yet consistently show an association between COD and the subsequent development of OS in the mandible. For instance, Schneider et al. and Melrose and Handlers both reported cases from the USA where patients presented with clinical and radiographic features suggestive of both COD and OS in the mandible [15, 16]. Lopes et al., Olusanya et al. and Haefliger et al., noted similar findings in Brazil, Nigeria and Switzerland respectively, indicating that this association is observed across different populations and geographic locations [2, 6, 17]. Haefliger et al. presented a case of a patient with established COD who developed high-grade OS over a period of 9 years [2]. This longitudinal evidence supports the hypothesis that COD may, under certain conditions, undergo malignant transformation. The review of these literatures supports a hypothesis of related pathogenesis, warranting further molecular and epidemiological studies.

OS of the jaws is rare and clinically distinct from OS of the long bones [2, 18], with the latter being diagnosed amongst adolescents and the former presenting between the 4th–5th decades [9]. Males and females are said to be equally affected. Paraesthesia, pain, loosening of teeth, swelling and ulceration are the most common symptoms present. Previous radiation therapy, fibrous dysplasia, Paget's disease are known pre-disposing factors [9, 12].

OS presents radiographically as an osteolytic lesion. Mineralization of the tumor matrix is frequently seen and depending on the stage of mineralization, it can appear radiolucent, mixed, or radiopaque. Several periosteal reactions have been described in the literature. These include Codman’s triangle; seen at the periphery of elevated periosteum, and the characteristic “sunburst” appearance [4, 9, 12, 19]. These features are seen in mandibular tumors [9].

Many OS arise spontaneously, however, there may be an increased risk of developing secondary OS with prior radiotherapy, an underlying Paget’s disease of bone, pre-existing bone lesions, or genetic predispositions (e.g. Li-Fraumeni syndrome). Molecular alterations include TP53 gene and retinoblastoma gene pathway alterations, translocations and numerical alterations. Cell cycle regulators, including CDK4 and CDKN2A genes, may also be altered in some cases [20]. The jaw bones are more commonly affected in the head and neck than any other craniofacial bones The majority of OS in the gnathic bones occurs intramedullary, but cases of parosteal types have been reported [21].

Conventional OS is characterised by atypical cells producing neoplastic, lace-like osteoid. The cells may be polygonal or epithelioid in the osteoblastic variant, similar to the case described in this report. The matrix may demonstrate extensive variability, including heavy mineralised sclerotic bone. Higher-grade OS are more aggressive, resulting in extensive bone destruction. There are several histologic subtypes, classified according to the predominant matrix, including osteoblastic, chondroblastic and fibroblastic. Immunohistochemical staining to confirm osteoblastic differentiation includes SATB2, MDM2 and CDK4 [21].

To date, and to the authors’ best knowledge, six cases have been reported where patients with COD also developed OS [2, 6]. One of these patients was known with Li-Fraumeni Syndrome, which predisposes those affected to developing malignant tumors due to TP53 mutations [2]. The molecular pathogenesis of COD is not well known but is not considered a precursor lesion for OS [2].

Management of any FOLs suspected to have developed malignancy is an urgent incisional biopsy to confirm the diagnosis. Histopathological confirmed malignancies should be discussed in a multi-disciplinary tumor board to establish the best care for the patient. OS are predominantly managed with an initial period of chemotherapy followed by wide surgical resection unless the patient is deemed more suitable for palliation [18].

Wagner et al., performed a systematic review of the literature concerning all documented cases of malignant transformation of craniomaxillofacial fibro‐osseous lesions [11]. Their results revealed that fibrous dysplasia was the only FOL that seemed to have a significant risk of malignant transformation; with OS being the most common malignant tumor [11]. It is advised that the initial diagnosis of any FOL be substantiated by clinical, radiological, and histopathological evaluation since some cases can progress to OS or lead to a misdiagnosis [11].

The association of OS and COD raises the question of whether a collision tumor has resulted in the transformation of COD into OS or their simultaneous presence is a mere coincidence [6, 15]. There is no consensus in the literature about the potential for malignant transformation of COD. Based on the literature reviewed, and this individual case, we cannot conclusively establish causation, but the co-occurrence of these conditions suggests more than a coincidental relationship. It highlights a potential pathogenic link, warranting further investigation. Whilst this paucity exists in the literature and the risk of malignant transformation may be even less, it should not be considered negligible. Awareness of possible malignant transformation can guide healthcare professionals to establish more stringent follow-ups. This is especially true for lesions such as COD as it is rarely surgically treated.