The aim of our study was to review current concepts in targeted therapies for benign tumors of the jaw. Benign odontogenic and maxillofacial bone tumors often require radical surgery, with consequent morbidity that impacts patients\' postsurgical quality of life. Currently, targeted therapies and novel nonsurgical therapeutics are being explored for management of non-resectable tumors, with the aim of avoiding surgery or minimizing surgical scope. However, data on clinical applications of targeted therapies for benign tumors of the jaw remain sparse. Therefore, a literature review was conducted, based on the PubMed database, which included in vivo human clinical studies describing clinical application of targeted therapy for benign tumor of the jaw. The review assessed the outcomes of BRAF and MEK inhibitors for treatment of ameloblastoma, RANKL monoclonal antibody for treatment of giant cell tumor, cherubism, aneurysmal bone cyst, and fibrous dysplasia, and tyrosine kinase inhibitor for treatment of odontogenic myxoma and cherubism. Targeted therapies decreased tumor size, slowed down tumor progression, and reduced bone pain. Surgery remains the gold standard, but targeted therapies are promising adjuvant or alternative treatment options for reducing tumor progression and morbidity of tumor surgery.

Ameloblastoma is a rare, benign, odontogenic tumor of epithelial origin, characterized by locally aggressive, expansive growth. Treatment is controversial due to the risk of relapse. The aim of this multicenter retrospective study was to evaluate the effectiveness of complete resection in cases of complex ameloblastoma, which is considered at a higher risk of recurrence. Patients who met at least one of these criteria were included: recurrence, soft-tissue involvement, complete erosion of internal/external cortical walls with involvement of the inferior margin of the mandible, and invasion of the maxillary sinus or nasal cavity. Demographic data, tumor site, type of surgery, histological features, and follow-up information were collected for each patient. The cohort included 55 patients with a mean follow-up of 108 ± 66 months. A multivariate logistic model was used to evaluate variables independently associated with relapse. There were six soft-tissue or maxillary sinus relapses, with a recurrence rate of 10.9%. Most of them arose in patients previously treated. The statistical analysis identified the maxillary location as a fundamental relapse risk factor. En bloc resection with large surgical safety margins seemed to be effective in preventing the relapses. However, complete resection was less effective in preventing recurrences in the soft tissues or maxillary sinus.

Primordial odontogenic tumor (POT) is a rare mixed odontogenic tumor composed of primitive ectomesenchyme similar to the dental papilla. The outer surface consists of columnar/cuboidal odontogenic epithelium similar to the inner enamel epithelium, and there is no hard tissue formation. Until now, 27 cases have been reported in the English literature. This article describes the clinicopathological characteristics of one case of POT, representing the oldest patient (aged 26 years) reported to date.

Mutation of the CDC73 gene, which encodes parafibromin, has been linked with parathyroid cancer. However, no correlation between genotypes of germline CDC73 mutations and the risk of parathyroid cancer has been known. In this study, subjects with germline CDC73 mutations were identified from the participants of two clinical protocols at National Institutes of Health (Discovery Cohort) and from the literature (Validation Cohort). The relative risk of developing parathyroid cancer was analyzed as a function of CDC73 genotype, and the impact of representative mutations on structure of parafibromin was compared between genotype groups. A total of 419 subjects, 68 in Discovery Cohort and 351 in Validation Cohort, were included. In both cohorts, percentages of CDC73 germline mutations that predicted significant conformational disruption or loss of expression of parafibromin (referred as \'high-impact mutations\') were significantly higher among the subjects with parathyroid cancers compared to all other subjects. The Kaplan-Meier analysis showed that high-impact mutations were associated with a 6.6-fold higher risk of parathyroid carcinoma compared to low-impact mutations, despite a similar risk of developing primary hyperparathyroidism between two groups. Disruption of the C-terminal domain (CTD) of parafibromin is directly involved in predisposition to parathyroid carcinoma, since only the mutations impacting this domain were associated with an increased risk of parathyroid carcinoma. Structural analysis revealed that a conserved surface structure in the CTD is universally disrupted by the mutations affecting this domain. In conclusion, high-impact germline CDC73 mutations were found to increase risk of parathyroid carcinoma by disrupting the CTD of parafibromin.

Ameloblastoma is the only odontogenic tumor that displays diversified histomorphological features with subtypes like follicular, plexiform, acanthomatous, granular cell, clear cell, desmoplastic etc. In this paper we presented an extremely unusual presentation of ameloblastoma, which is characterized by desmolysis or acantholysis of stellate reticulum-like cells caused due to keratinocyte dissociation. A 35-year-old male patient presented with a painless hard 3×3 cm swelling in the mandibular right posterior region in the past 4-5 months. Radiographic examination revealed a multilocular radiolucent lesion in the body of mandible with resorption of the roots. Histopathological examination revealed ameloblastic follicles with central cells showing keratinocyte dissociation leading to desmolysis/acantholysis. Desmolytic cells were seen as an isolated entity in the follicular space with round to polygonal shaped morphology. Future retrospective studies on archival samples of ameloblastoma are recommended to relook into identification of such rare phenomenon. This will help in better understanding of the incidence rate and biological behavior of this rare variant of ameloblastoma.

The natural history of malignant fibrous histiocytoma (MFH) is still heavily debated. It\'s anonymous natural history is precisely denoted by its new adapted terminology \'undifferentiated pleomorphic sarcoma (UPS)\'. Thus to diagnose a lesion as UPS, it is vital to correlate its histopathological features along with its immunohistochemical (IHC) expressions to confirm the tumor cell lineage. MFH is extremely rare in mandible with the literature search in PubMed database revealing only 13 case reports of MFH involving the mandible. Among these, only 7 case reports provide IHC details of the case. Without IHC data it is not possible to determine the accuracy of the diagnosis in the remaining 6 cases. Here we report an additional 8th case of MFH involving the ramus and angle of the mandible. Histopathology revealed proliferating malignant spindle cells interspersed with histiocyte-like cells. The tumor cells were strongly positive for vimentin and CD68 and were negative for S-100, epithelial membrane antigen (EMA) and cytokeratin (CK). The diagnosis was made by correlating the histopathological findings with the IHC profile. The report also provides the data (clinical, radiographic, histopathological, immunohistochemical features and treatment details) extracted from the 7 confirmed MFH case reports involving the mandible.

Introduction: Primordial odontogenic tumors are a rare recently described mixed odontogenic tumor composed histopathologically of dental papilla like tissue and enamel organ like tissue. Only nine cases have been documented worldwide and we are reporting the tenth case which is from Egypt. Clinical finding: A 2-year-old Egyptian boy that presented with an asymptomatic swelling of the mandible which appeared with multilocular radiolucency associated with an impacted developing tooth on a computerized tomography (CT) scan. Diagnoses, interventions, and outcomes: The lesion was excised and diagnosed as a primordial odontogenic tumor. The patient was followed up for two years with no recurrence. Conclusion: Differentiation of primordial odontogenic tumors from other odontogenic tumors, which resemble it histopathologically is crucial to avoid unnecessary aggressive treatment.

The aim of the present review was to systematically present the clinicopathological data of desmoplastic ameloblastoma (DA) from articles published in the literature. A comprehensive search of the databases (PubMed, Medline, SCOPUS, Web of Science, and Google Scholar) for published articles on DA was conducted. A total of 238 cases were identified and analyzed from 76 published papers. DA showed a slight male predilection (male: female=1.07:1) with a predominance in the fourth and fifth decades of life. Mandibular involvement (52.55%) was most commonly seen with a marked tendency for the anterior region (mandible: 40.9%, maxilla: 48.07%). The size of the lesion ranged from .5 cm to 20.4 cm, with the majority of cases measuring more than 3 cm in size (53.84%). Radiologically, most of the lesions presented mixed radiolucency and radiopacity (62%), and root resorption was observed in only seven cases. The majority of the lesions showed ill-defined margins upon radiographic examination (65.78%). Most of the cases were treated with resection (78.57%), and five of the 10 recurrent cases were treated by enucleation/curettage. DA is characterized by the unique presentation of clinicopathological parameters. It is not possible to comment on its aggressive/recurrent nature and best treatment modality due to inadequate follow-up data.

Inflammatory myofibroblastic tumors (IMTs) are rare. IMTs of the head and neck occur in all age groups, from neonates to old age, with the highest incidence occurring in childhood and early adulthood. An IMT has been defined as a histologically distinctive lesion of uncertain behavior. This article describes an unusual case of IMT mimicking apical periodontitis in the mandible of a 42-year-old man. At first presentation, the patient showed spontaneous pain and percussion pain at teeth #28 to 30, which continued after initial endodontic treatment. Panoramic radiography revealed a radiolucent lesion at the site. Cone-beam computed tomographic imaging showed osteolytic lesions, suggesting an aggressive neoplasm requiring incisional biopsy. Histopathological examination indicated an IMT. The lesion was removed en bloc under general anesthesia, and the patient manifested no clinical evidence of recurrence for 24 months. Lesions of nonendodontic origin should be included in the differential diagnosis of apical periodontitis. Every available diagnostic tool should be used to confirm the diagnosis. Cone-beam computed tomographic imaging is very helpful for differential diagnosis in IMTs mimicking apical periodontitis.

Cyst-like lesions in the mandible rarely develop into malignancies, and the reported incidence is between 0.3 and 2%. The present study describes a rare case of primary intraosseous squamous cell carcinoma of the mandible arising from an odontogenic cyst. A 59-year-old female was referred to Asahi University Murakami Memorial Hospital (Gifu, Japan), with acute pain in the right molars. An initial examination revealed buccal swelling and paresthesia of the mental nerve. Following an intraoral examination, the oral mucosa was confirmed to be normal, however, percussion pain was experienced between the lower right first premolar and second molar. Panoramic radiography revealed a retained lower right wisdom tooth and an irregular radiolucent area between the lower right molar and a mandibular angle with unclear margins. Computed tomography revealed diffuse bone resorption and an extensive loss of cortical bone on the buccal and lingual sides. A biopsy was performed and the pathological diagnosis was of a squamous cell carcinoma arising from the epithelial lining of the odontogenic cyst. Radical dissection was subsequently performed, however, histopathological examination of the resected specimen revealed neither invasion into the surrounding tissues penetrating the periosteum nor lymph node metastasis at the right submandibular lesion. Following the pathological diagnosis of primary intraosseous carcinoma (PIOC), the patient received 6,000 Gy radiation as post-operative radiotherapy and chemotherapy with oral administration of tegafur, gimeracil and oteracil potassium. The patient is currently undergoing follow-up examinations. Although PIOC arising from an odontogenic cyst is rare, it should be considered as a differential diagnosis for radiolucency of the jaw bone, particularly in older patients exhibiting a history of cystic lesions.