Dear Colleagues,

The molecular advances in characterizing emerging maxillofacial lesions (e.g., ameloblastic fibrosarcoma and SWI/SNF-deficient head and neck carcinomas) have opened new venues for affecting new anti-angiogenic agents, tailored agents, and checkpoint inhibitors. Topographically, primary intraosseous rhabdomyosarcoma, gnathic ossifying fibroma, and adenosquamous carcinoma (ASC), among others, have evinced molecular peculiarities found only in the maxillofacial region. Interestingly, the detection of ghost cells in neoplastic lesions is no longer confined to dentinogenic ghost cell tumors and ghost cell odontogenic carcinoma. Nevertheless, ghost cells detected in a salivary-type neoplasm that is atypical of parenchymatous structures have resulted in the proposal of salivary ghost cell carcinoma. This lesion showed a specific molecular and immunohistochemical profile. Significantly, KMT2D-deficient adenoid cystic carcinoma (AdCC) in the maxillofacial region has not been studied. However, atypical cases of AdCC have been found in the sinonasal area and minor salivary glands but were not present in other organs. Low- and high-grade ASC cases have been identified in breast pathology, while only high-grade ASC cases have been found in the maxillofacial area. 

The presence of non-native cellular populations in maxillofacial neoplasms (such as Merkel cells, rhabdoid cells, ghost cells) and the detection of conspicuous unusual histologic features (such as mucinous differentiation, neuroendocrine differentiation, sebaceous differentiation, signet-ring cell differentiation, pseudo/glandular differentiation, cartilaginous differentiation, sclerosis, hyalinization, and tumor-associated lymphoid proliferation) have been acknowledged to affect the neoplasms’ clinical behavior more than their conventional counterparts. For example, pseudoglandular differentiation in ameloblastoma has been associated with aggressive clinical behavior and potentially malignant transformation. Rhabdoid cells with a less favorable prognosis than conventional phenotypes have been found in salivary-type intraductal and myoepithelial carcinomas. The molecular signature of such atypical features highlights specific genetic mutations with practical therapeutic and prognostic implications. Although breast, renal, lung, and pancreatic cancer research has considered such features, little is known about their counterparts in maxillofacial regions. 

Thus, several questions about the possibility of wiring particular molecular pathways specific to the maxillofacial regions have been raised: Do some maxillofacial neoplasms not intersect with their counterparts in other topographies? Are there histogenetically similar neoplasms that can indicate diverse prognoses at different sites in the maxillofacial area (e.g., minor salivary glands of the palate vs. minor salivary glands of the tongue)? Why is there no extra-gnathic mucoepidermoid carcinoma? 

Therefore, we confine the scope of this Special Issue to exploring oncogenic pathways in maxillofacial neoplasms that differ from other topographies and could directly impact the prognostication and therapeutic interventions. The following topics are highly solicited: 

• Molecular specificities in hybrid odontogenic tumors;
• KMT2D-deficient adenoid cystic carcinoma in the maxillofacial region;
• BAP1, PI3kCA and SOX2 detection in gnathic mucoepidermoid carcinoma;
• Sclerosing vs. non-sclerosing odontogenic tumors;
• Prognostic value of sebaceous differentiation and/or clear-cell differentiation in odontogenic and salivary-type neoplasms;
• Molecular profile of Pindborg tumor;
• KRAS mutations in ameloblastic fibrosarcoma, adenomatoid odontogenic tumor and adenoid ameloblastoma;
• Synchronous multifocal maxillofacial neoplasms. 

We encourage all contributors to place their relevant research articles in our forthcoming issue.

Dr. Bacem Khalele
Guest Editor

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