AFS represents a rare odontogenic tumor, with approximately 80% of cases originating in the mandible and a median onset age around 27 years [9–11]. In this study, an exceedingly infrequent case of AFS was reported, involving an elderly female patient, manifesting in the maxilla.
Similar to numerous instances of soft tissue sarcomas, the precise mechanisms underlying the development of AFS remain elusive. Emerging research indicated that AFS may be linked to genetic mutations, hereditary factors, inflammatory processes, traumatic events, and intricate epithelial-stromal interactions [12]. Prior research reported a correlation between AFS and loss of heterozygosity (LOH) in the short arms of chromosomes 3 and 9 [13]. Bcl-2 alteration may also participate in the pathogenesis of this neoplasm [14]. Comprehensive genomic testing in AFS patients revealed the presence of EGFR exon 20 insertions and MDM2 amplification, emerging as potential drivers of AFS development [9].
The diagnosis of AFS solely based on radiographic evidence is not highly reliable. Radiologically, AFS appears as a nebulous translucent mass, leading to occasional misdiagnoses as a cyst, as evidenced in the present case, wherein the initial CT scan led to an interpretation of a cyst in the patient[6]. However, further pathological confirmation could solidify the diagnosis of AFS.
Some studies have suggested that AFS can arise de novo or from preexisting benign lesions, such as AF, immature enamel cell fibroma, or odontoma [15]. While studies have mainly concentrated on differentiating AFS from AF[6], this case highlighted the importance of distinguishing AFS from AFOS. The nature and relationship between mixed odontogenic tumors and related lesions remain elusive. The main distinction between AFS and AFOS lies in the presence or absence of dental hard tissue components within the stroma [16]. In the current case, the primary consideration leaned towards AFS or AFOS, while subsequent pathological examination confirmed a higher likelihood of AFS due to the absence of dental hard tissue components within the stroma. Despite recommendations from experts that the presence or absence of dental hard tissue in the stroma does not impact treatment decisions, no strong inclination was found for external pathological consultation when the patient refused the recommendation[17, 18]. Furthermore, reflection on the diagnostic challenges encountered with AFS and AFOS, which could be attributed to the involvement of multiple stages in tooth development, including growth, calcification, and eruption[19]. Each stage encompasses different processes and introduces uncertainties under microscopic observations, posing challenges for accurate diagnosis. While some studies have reported that an abnormal CD34 expression level in the maxillary bone can assist in diagnosing AFS, in this particular case, CD34 expression level was negative, providing valuable information regarding the diagnosis and characteristics of this rare tumor[17]. AFS and AFOS typically exhibit positive immunostaining for Vimentin, indicating the presence of mesenchymal components.
Given the scarcity of data and the lack of comprehensive guidelines, there is currently no universally accepted treatment protocol for AFS. AFS is characterized by a low likelihood of distant metastasis, and it has exhibited a significant recurrence rate of up to 37% and a mortality rate of 19%[20]. For such cases, the preferred treatment strategy involves early and aggressive management utilizing surgical intervention accompanied by adjuvant radiotherapy. Administering high-dose radiation therapy directly to the tumor site has the potential to effectively lower the recurrence rate and inhibit tumor metastasis[21]. Nevertheless, when considering the use of radiation therapy in younger patients, it is crucial to strike a balance between the benefit of reducing local recurrence and the potential risk of long-term development of secondary malignancies [22]. A previous study reported that some pediatric patients with AFS have exhibited a favorable response to chemotherapy [23]. With the advancements in molecular targeted therapy, studies have also indicated that patients with BRAF or NTRK mutations may benefit from the use of targeted inhibitors, leading to the improved survival outcomes in some AFS patients [24, 25]. However, further research is essential to explore precision medicine approaches and enhance our understanding of the biological aspects of AFS.
In conclusion, a rare case of AFS in the mandible of an elderly patient was reported. The diagnostic process and treatment experience were discussed. This case not only contributes to enriching the AFS database, but also may provide insights for the future research on AFS treatment.