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.

Odontogenic myxoma is a rare and aggressive tumor. Identifying the tumor based on imaging characteristics can pose a challenge due to similarities in features with other tumors, such as ameloblastomas and aneurysmal bone cysts. We report a 33-year-old female who presented with a palpable, tender mass in the lower right jaw. A computed tomography scan revealed a multicystic tumor which was proved to be an odontogenic myxoma. The patient underwent partial surgical resection followed by CO2 laser-assisted evaporation. During 1-year follow-up, the patient showed satisfactory results and no signs of tumor growth. This case report highlights the diagnostic challenges associated with odontogenic myxoma, emphasizing age as a key diagnostic feature.

Brown tumors represent the terminal stage of bone remodeling processes in primary hyperparathyroidism. Currently they are rare, and typically affect long bones, pelvis and ribs. Brown tumors may be not included in the initial differential diagnosis of bone disease, especially when they are present in atypical localizations. We reported two cases of oral brown tumors as the initial presentation of primary hyperparathyroidism. In the first case, a 44-year-old woman presented a painful and sessile lesion of 4 × 3 cm over the central body of the mandible which progressively increased in 4-month. The second case involved a 23-year-old woman who was referred with a 3-month history of a painful and ulcerated mass of 2 cm arising from left maxilla, episodes of gingival hemorrhage and difficulty of breathing. Both cases were solitary tumors with no evidence of palpable cervical lymphadenopathy. Incisional biopsy of oral tumors resulted in giant cell and primary hyperparathyroidism was confirmed by laboratory tests. After parathyroidectomy, histology confirmed adenoma in both cases. Although this type of clinical presentation has almost disappeared in the recent decades, brown tumors should be considered in the differential diagnosis of bone oral masses.
Los tumores pardos son raros y, por lo general, afectan huesos largos, pelvis y costillas. Pueden no estar incluidos en el diagnóstico diferencial inicial como manifestación de enfermedad esquelética, especialmente cuando se presentan en localizaciones atípicas. Comunicamos dos casos de tumores pardos orales como presentación inicial de hiperparatiroidismo primario. En el primer caso, una mujer de 44 años presentó una lesión dolorosa y sésil de 4 × 3 cm sobre el cuerpo central de la mandíbula que aumentó de tamaño progresivamente en 4 meses. El segundo caso corresponde a una mujer de 23 años que acudió por presentar una masa dolorosa y ulcerada de 2 cm en maxilar izquierdo de 3 meses de evolución, episodios de hemorragia gingival y dificultad para respirar. Todos fueron tumores solitarios sin evidencia de linfadenopatía cervical palpable. La biopsia incisional de los tumores orales resultó en células gigantes, y las pruebas de laboratorio confirmaron el hiperparatiroidismo primario. Tras la paratiroidectomía, la histología confirmó adenoma en ambos casos. Los tumores pardos representan la etapa terminal de los procesos de remodelación ósea en el hiperparatiroidismo primario. Aunque este tipo de presentación clínica casi ha desaparecido en las últimas décadas, los tumores pardos deben ser considerados en el diagnóstico diferencial de las masas óseas orales.

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.

Primary hyperparathyroidism is a relatively common endocrine disorder, affecting 7 out of 1,000 adults. The median age at onset is the 6th decade of life. Our objective was to present a young patient with primary hyperparathyroidism who has a positive CDC73 mutation. A 23-year-old woman was evaluated for hypercalcemia that was found after surgery for bilateral ovarian cyst removal. Her family history included multiple family members with nephrolithiasis. The physical examination revealed a well-appearing Caucasian woman with no palpable neck mass. The laboratory results showed serum calcium at 11.7 mg/dL (ref. 8.4-10.2), ionized calcium at 1.44 mmol/L (ref. 1.12-1.32), and serum PTH at 192 pg/mL (ref. 11-65). A technetium-99 sestamibi scan revealed focal uptake inferior to the left thyroid lobe. Thyroid ultrasound showed a left parathyroid adenoma. The patient subsequently underwent left inferior parathyroidectomy, which confirmed parathyroid adenoma, with resultant normalization of serum calcium and PTH levels. Due to her young age at diagnosis, genetic testing was performed, which revealed a mutation of CDC73. Although penetrance and expression are variable, the CDC73 mutation is associated primarily with hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism, and sporadic parathyroid carcinoma. This patient currently has no evidence of jaw, uterine or renal tumors on screening imaging. Given the potential impact of inheritable neoplasia, all young patients with unexplained hyperparathyroidism should be considered for genetic screening.

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.

Tubulopapillary hidradenoma-like tumor of the mandible is extremely rare, with only 3 cases published in the English-language literature. The clinicopathological characteristics and histogenesis of this tumor are unclear. Few pathologists and perhaps fewer clinicians are familiar with this entity, and it is likely underrecognized and under-reported. Herein, we present two additional cases, both misdiagnosed as malignancies preoperatively and postoperatively by different unwary pathologists. Awareness and knowledge of this enigmatic entity and its clinical and radiographic features, together with careful morphological assessment should enable the correct diagnosis and prevent unnecessary treatment.

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.