Bioengineering the ameloblastoma tumour to study its effect on bone nodule formation.

Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with its tumour stroma drives invasion and progression. We used stiff collagen matrices to engineer active bone forming stroma, to probe the interaction of ameloblastoma with its native tumour bone microenvironment. This bone-stroma was assessed by nano-CT, transmission electron microscopy (TEM), Raman spectroscopy and gene analysis. Furthermore, we investigated gene correlation between bone forming 3D bone stroma and ameloblastoma introduced 3D bone stroma. Ameloblastoma cells increased expression of MMP-2 and -9 and RANK temporally in 3D compared to 2D. Our 3D biomimetic model formed bone nodules of an average surface area of 0.1 mm2 and average height of 92.37 [Formula: see text] 7.96 µm over 21 days. We demonstrate a woven bone phenotype with distinct mineral and matrix components and increased expression of bone formation genes in our engineered bone. Introducing ameloblastoma to the bone stroma, completely inhibited bone formation, in a spatially specific manner. Multivariate gene analysis showed that ameloblastoma cells downregulate bone formation genes such as RUNX2. Through the development of a comprehensive bone stroma, we show that an ameloblastoma tumour mass prevents osteoblasts from forming new bone nodules and severely restricted the growth of existing bone nodules. We have identified potential pathways for this inhibition. More critically, we present novel findings on the interaction of stromal osteoblasts with ameloblastoma.

Effect of technetium-99 conjugated with methylene diphosphonate (99 Tc-MDP) on OPG/RANKL/RANK system in vitro.

BACKGROUND: RANKL and RANK play an important role in jaw resorption during the development of the ameloblastomas. Therefore, the aim of this study was to explore the effect of 99 Tc-MDP on OPG/RANKL/RANK system on RAW264.7 and MC3T3-E1 cell lines in vitro and provide the theoretical basis for the clinical treatment of the jaw ameloblastoma. METHODS: Different concentrations of 99 Tc-MDP were used to treat RAW264.7 and MC3T3-E1 cell lines. The cell proliferative inhibition rate was analyzed by CCK-8. Cell apoptosis and cell cycle were detected by flow cytometry. Western blot was used to detect the expression of OPG, RANKL, and RANK. RESULTS: Treatment of RAW264.7 cell lines with different concentrations of 99 Tc-MDP had inhibitory effects and decreased the expression of RANK protein. The cell proliferation of 99 Tc-MDP on MC3T3-E1 cell lines was stronger at 48 hours than at 24 hours except for 100 µg/mL concentration group. Compared with the concentration of 0.01 µg/mL, the treatment of MC3T3-E1 cells with 100 µg/mL 99 Tc-MDP showed that the cell proliferative effect decreased at 24 hours and 48 hours (P < 0.05). After treatment with 0.01 µg/mL 99 Tc-MDP, the expression of OPG in MC3T3-E1 cells was significantly increased (P < 0.05). Compared with 0.01 µg/mL, the expression of RANKL was decreased after treatment with 100 µg/mL 99 Tc-MDP (P < 0.05). CONCLUSION: 99 Tc-MDP can induce apoptosis of RAW264.7 cells and inhibit the expression of RANK protein. The effect of 0.01 µg/mL of low concentration of 99 Tc-MDP can promote the proliferation of MC3T3-E1 cells and increase the expression of OPG and RANKL protein. 99 Tc-MDP may have adjuvant therapeutic effects on the treatment of jaw ameloblastoma.

Expression profile of polycomb group proteins in odontogenic keratocyst and ameloblastoma.

Polycomb group (PcG) proteins are repressive chromatin modifiers required for proliferation and development. PcG proteins form two large repressive complexes, namely, Polycomb Repressive Complex 1 and 2. These proteins have been shown to drive tumorigenesis by repressing cell-type specific sets of target genes. Using immunohistochemistry, we investigated the expression patterns of five human PcG proteins, including Bmi-1, Ring1b, Mel-18, Ezh2, and Suz12, in various cellular components of odontogenic keratocysts (OKCs), ameloblastomas and, pericoronal follicles (PFs). In OKCs, expression of PcG proteins were found in the majority of cases while the expression pattern was relatively different for each PcG proteins. All PcG proteins were strongly expressed in the basal cells while some proteins showed variable expression in the parabasal and luminal cell layer of OKCs. In ameloblastomas, almost all PcG proteins showed a similar expression pattern of moderate to strong staining in the peripheral ameloblast-like cells and metaplastic squamous cells. Some of the central stellate reticulum-like cells also showed positive reaction to most PcG proteins. In PFs, most PcG proteins were intensely expressed in odontogenic epithelium lining the follicles, except Mel-18 and Suz12. The present study provides the initial evidence regarding epigenetic involvement by PcG proteins in these odontogenic lesions. Although these proteins are known to be in the same repressive group proteins, differential expression patterns of these proteins in OKCs and ameloblastomas indicates that these proteins may play different roles in pathogenesis of these odontogenic lesions.

Ameloblastoma: a clinical review and trends in management.

Ameloblastoma is a rare odontogenic neoplasm of the mandible and maxilla, with multiple histologic variants, and high recurrence rates if improperly treated. The current mainstay of treatment is wide local excision with appropriate margins and immediate reconstruction. Here we review the ameloblastoma literature, using the available evidence to highlight the change in management over the past several decades. In addition, we explore the recent molecular characterization of these tumors which may point towards new potential avenues of personalized treatment.

Are podoplanin and ezrin involved in the invasion process of the ameloblastomas?

The association between podoplanin and ezrin in the process of odontogenic tumors invasion has been suggested, but was not studied yet. Our purpose was to investigate the relationship between podoplanin and ezrin expressions in the odontogenic epithelium of ameloblastomas. Forty-seven ameloblastomas were analyzed by immunohistochemistry using anti-podoplanin and anti-ezrin antibodies. The expressions of both proteins were evaluated using a score method and the comparison and association between these proteins were verified, respectively, by Wilcoxon Signed-Rank test and by Spearman's rank correlation coefficient, using a statistical significance level of 0.05. The majority of tumors (87.2%) exhibited strong membranous expression of podoplanin in the peripheral cells. Cytoplasmic expression of ezrin in the peripheral cells of ameloblastomas was stronger than its membranous expression. No statistically significant correlation was observed between podoplanin and ezrin. However, there was statistically significant difference between membranous podoplanin and membranous ezrin expressions, between cytoplasmic podoplanin and membranous ezrin expressions, and between cytoplasmic podoplanin and cytoplasmic ezrin expressions. There was no statistical difference between membranous podoplanin and cytoplasmic ezrin expressions. These results suggest a synergistic role of both proteins in the process of invasion of ameloblastomas.

Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma.

Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave interactively via these cytokines to create a microenvironment that leads to the extension of ameloblastomas.

Osteochondroma of the coronoid process (Jacob's disease): an unusual cause of restricted jaw motion.

Osteochondromas are the most common benign bone tumor, most commonly found in the ends of long bones; however, they rarely involve facial bones, particularly the mandible. Osteochondromas involving the coronoid process have rarely been reported in the literature but pose a diagnostic dilemma. When large enough, osteochondromas of the mandibular coronoid process can form a joint with the zygomatic arch (Jacob's disease). This pseudoarticulation results in restricted jaw motion, which can clinically be mistaken for temporomandibular joint dysfunction. We report a case of a 39-year-old man with chronic restricted jaw motion undiagnosed for several years.

Osteoprotegerin (OPG) binds with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL): suppression of TRAIL-induced apoptosis in ameloblastomas.

Osteoprotegerin (OPG) is a useful receptor in inhibiting Receptor Activator of NFkappaB Ligand (RANKL) in inducing osteoclastogenesis. Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) is a potent apoptosis-inducing ligand in ameloblastomas. Since OPG has been reported to bind to TRAIL as well, the effect of OPG in TRAIL's function in inducing apoptosis should also be investigated. To investigate on the expression of OPG in ameloblastomas, immuhistochemistry, immunofluorescence and Western blot were performed. From the immunohistochemistry results, we found that OPG was expressed in ameloblastoma tissues. Expression of OPG was clearly seen in AM-1 cells by immunofluorescence as well. Additionally, Western blot analysis confirmed OPG expression in ameloblastoma tissues and AM-1 cells. To investigate on the potential of TNFalpha, TRAIL and RANKL in inducing apoptosis, we performed an apoptosis assay. From the apoptosis assay, we found that TRAIL had the highest potential in inducing apoptosis compared to TNFalpha and RANKL. To investigate the binding of OPG with RANKL and TRAIL, we performed a binding assay. We noticed that OPG preferably bind with RANKL than TRAIL. However, at low levels of RANKL, marked binding of OPG with TRAIL was seen. As we suspected that the binding of OPG and TRAIL might cause the effect of TRAIL in inducing apoptosis in ameloblastomas, we combined the treatment of OPG and TRAIL in AM-1 cells. From the apoptosis assay, we found that under treatment of OPG, TRAIL's function in inducing apoptosis was suppressed. These data suggest that by binding with TRAIL, OPG suppressed TRAIL's function in inducing apoptosis in ameloblastomas.

Inhibition of Akt and MAPK pathways elevated potential of TNFalpha in inducing apoptosis in ameloblastoma.

Tumor necrosis factor alpha (TNFalpha) can trigger both cell survival and apoptosis. In the present study, from the flow cytometry results, we found that the prolonged-treatment of TNFalpha until 24 h, resulted apoptosis in AM-1 cells (ameloblastoma cell line). These results were confirmed by DAPI staining, which showed nuclear fragmentation feature of AM-1 cells under treatment of TNFalpha. Our further investigation using specific caspase inhibitors showed that caspase-3 played a crucial role in mediating TNFalpha-induced apoptosis in AM-1 cells. In addition, significant elevation of TNFalpha potential in inducing apoptosis was seen by applying LY294002, phosphatidylinositol-3-OH kinase (PI3K) inhibitor, or U0126, mitogen-activated extracellular-regulated kinase (MEK1/2) inhibitor, prior to the treatment of TNFalpha in AM-1 cells. These results suggested that TNFalpha induced both cell survival and apoptosis pathways in ameloblastoma and potential of TNFalpha in inducing apoptosis can be improved by inhibiting TNFalpha-induced Akt and p44/42 mitogen-activated protein kinase (MAPK) cell survival pathways.

Ameloblastoma induces osteoclastogenesis: a possible role of ameloblastoma in expanding in the bone.

Ameloblastoma, a tumor located in bone, when neglected, can perforate the bone and, ultimately, spread into the soft tissues. To expand in the bone, ameloblastoma must have a mechanism of resorbing the surrounding bone. However, the mechanism for bone resorption is poorly understood. In the present study, we found that RANKL and TNFalpha were expressed and secreted by ameloblastoma cells, and was proven to induce osteoclastogenesis. Our present results also showed that phosphorylation of p38, SAPK, p44/42 and Akt were upregulated under treatment of 10xCM (concentrated conditioned media of AM-1 cells). We also noticed formation of resorption lacunae on dentin slice by 10xCM-induced osteoclast-like MNCs. These results suggested that ameloblastoma by secreting RANKL and TNFalpha could induce osteoclastogenesis.

Clinical observations of odontomas in Japanese children: 39 cases including one recurrent case.

Retrospective investigations of odontomas in Japanese children and one recurrent case were carried out. Thirty-nine cases of odontoma in 38 children were treated in the Paediatric Dentistry Clinic of Niigata University Dental Hospital between September 1979 and December 2002. The patients consisted of 23 males and 15 females and their ages ranged from 1 year 2 months to 14 years old. The chief complaints were delayed tooth eruption in 19 cases (five: primary teeth, 14: permanent teeth), retention of primary teeth in 11, incidentally found on the radiographic examination in eight cases, and swelling of the jaw in one case. Thirty-four cases (87%) were associated with tooth eruption disturbances. The most frequently affected region was the maxillary anterior region. Treatment consisted of surgical removal of odontomas in all cases, after which if the impacted teeth did not erupt, exposure of the crown and/or orthodontic traction was performed. Pathological diagnoses were compound odontoma in 30 cases, complex odontoma (n = 7), and compound and complex odontoma (n = 2). A retrospective study of the radiographs revealed the developing process of odontomas in four cases and odontoma disturbed tooth eruption since the early uncalcified developing stage. A recurrent case was a boy aged 6 years 5 months in whom the first surgical removal of odontoma was performed at the age of 1 year 8 months. Recurrence of an odontoma is very rare, but in very young children odontomas are in the early developing stages, containing uncalcified portions, so it is important to perform periodical observations until the succedaneous teeth erupt.

Malignant odontogenic tumors: a 22-year experience.

OBJECTIVES/HYPOTHESIS: Malignant odontogenic tumors are exceedingly rare and arise from odontogenic epithelial residues and odontogenic cysts in the jaw bones. Odontogenic malignancies have various origins. Some develop directly from the remnants of odontogenic epithelium left after completion of dental development; others may result from malignant transformation of a benign odontogenic cyst or ameloblastoma. These lesions are usually locally aggressive with radical surgery being the primary mode of treatment. Because of their rarity, much of the existing information about malignant odontogenic tumors with regard to their origin, clinicopathological features, biological behavior, and therapeutics is derived from case reports or small series. The study represents one of the largest series of malignant odontogenic tumors compiled in a single institution. STUDY DESIGN: Retrospective 22-year review from an Academic Medical Center. METHODS: Twenty cases of reported malignant odontogenic tumors were diagnosed in the authors' institution between 1981 and 2002. All pathological slides were reviewed to reconfirm diagnosis. Malignancy was confirmed based on the following criteria: histological findings of infiltrative growth, atypical cytological features, and focal necrosis or clear evidence of distant metastatic spread. Patient age, race, sex, treatment and outcome were recorded on chart review. RESULTS: Of the twenty reported cases, only nine were actually found to be malignant tumors on re-evaluation. These consisted of four cases of malignant ameloblastomas, two cases of ameloblastic carcinoma, one case of malignant Pindborg tumor (calcifying epithelial odontogenic tumor), one case of odontogenic ghost cell carcinoma, and one case of squamous cell carcinoma arising in an odontogenic keratocyst. The racial demographics were six Caucasian patients, one African American patient, and two Asian patients; seven men and two women represented the gender distribution. Tumors of six cases were located in the mandible, and of three cases, in the maxilla. All cases were treated with radical surgical excision. Two patients died of their disease, three patients were alive and free of disease, and four patients were lost to follow-up. CONCLUSION: Malignant odontogenic tumors are rare. They require a multidisciplinary team to determine proper treatment. Long-term surveillance is mandatory and is accomplished by routine physical examinations, along with serial radiographic imaging.

Quality of life of patients with maxillofacial defects after treatment for malignancy.

PURPOSE: The purpose of the study was to investigate how cancer patients with maxillofacial defects evaluate their quality of life after prosthodontic therapy, complemented by a retrospective interview for judging the various therapy steps. The results were compared with a nontumor control group (multiple tooth extractions) and with population-based norm data. MATERIALS AND METHODS: A total of 34 patients were included in the study, 17 in each group. Patients first filled in a questionnaire and then answered additional questions in a standardized interview. RESULTS: At the time of investigation, tumor patients did not significantly differ from nontumor patients regarding global quality of life. However, tumor patients had significantly less favorable values regarding role functioning, speech, mouth opening, and dry mouth, as well as pain and swallowing. In comparison with the reference data of the German population, tumor patients had considerable deficits (> 20 points) regarding role functioning, dyspnea, and financial difficulties. Other deficits (> 10 points) became apparent in global quality of life, fatigue, insomnia, and appetite. When reflecting the course of disease and recovery, tumor patients rated the diagnosis as the most stressful event and reported that the family was most instrumental in the recovery process. CONCLUSION: Patients with maxillofacial defects after treatment for malignancy suffer from numerous clearly definable quality of life-related symptoms and problems, even after prosthodontic treatment. These patients need psychologic care at the time of diagnosis to alleviate the burden of the cancer diagnosis and prepare for the demanding treatment. After completion of the prosthodontic treatment, therapy options for pain or speech problems should be offered.

[Radiologic features of desmoplastic ameloblastoma].

OBJECTIVE: To investigate the radiologic features of desmoplastic ameloblastoma. METHODS: The radiologic characteristics of 15 cases desmoplastic ameloblastoma which were diagnosed pathologically were analyzed retrospectively, and compared with solid or multicystic ameloblastoma. RESULTS: Desmoplastic ameloblastoma were mainly located in anterior and (or) premolar region of maxilla and mandible. There existed three features radiologically. 1. unilocular formation containing varying amounts of radiopaque islands or strands material. 2. multilocular destruction containing irregular or line-like radiopaque areas. 3. mixed destruction showing plxiform radiopaque material and unilocular change. Typical microscopic features were irregular and compressed epithelial islands or strands interspersed among dense fibrous connective tissue stroma. CONCLUSIONS: The desmopleatic ameloblastoma is a new type of ameloblastoma and exhibits some special characteristics radiologically and pathologically. It should be differentiated from osteofibroma and odontogenic myxoma.

Gnathodiaphyseal dysplasia: a syndrome of fibro-osseous lesions of jawbones, bone fragility, and long bone bowing.

We report an unusual generalized skeletal syndrome characterized by fibro-osseous lesions of the jawbones with a prominent psammomatoid body component, bone fragility, and bowing/sclerosis of tubular bones. The case fits with the emerging profile of a distinct syndrome with similarities to previously reported cases, some with an autosomal dominant inheritance and others sporadic. We suggest that the syndrome be named gnathodiaphyseal dysplasia. The patient had been diagnosed previously with polyostotic fibrous dysplasia (PFD) elsewhere, but further clinical evaluation, histopathological study, and mutation analysis excluded this diagnosis. In addition to providing a novel observation of an as yet poorly characterized syndrome, the case illustrates the need for stringent diagnostic criteria for FD. The jaw lesions showed fibro-osseous features with the histopathological characteristics of cemento-ossifying fibroma, psammomatoid variant. This case emphasizes that the boundaries between genuine GNAS1 mutation-positive FD and other fibro-osseous lesions occurring in the jawbones should be kept sharply defined, contrary to a prevailing tendency in the literature. A detailed pathological study revealed previously unreported features of cemento-ossifying fibroma, including the participation of myofibroblasts and the occurrence of psammomatoid bodies and aberrant mineralization, within the walls of blood vessels. Transplantation of stromal cells grown from the lesion into immunocompromised mice resulted in a close mimicry of the native lesion, including the sporadic formation of psammomatoid bodies, suggesting an intrinsic abnormality of bone-forming cells.

Effects of anatomical constraints on tumor growth.

Competition for available nutrients and the presence of anatomical barriers are major determinants of tumor growth in vivo. We extend a model recently proposed to simulate the growth of neoplasms in real tissues to include geometrical constraints mimicking pressure effects on the tumor surface induced by the presence of rigid or semirigid structures. Different tissues have different diffusivities for nutrients and cells. Despite the simplicity of the approach, based on a few inherently local mechanisms, the numerical results agree qualitatively with clinical data (computed tomography scans of neoplasms) for the larynx and the oral cavity.

Análise clínica e epidemiológica descritiva do carcinoma espinocelular do seio maxilar / Clinical Analysis and Descritive Epidemiologyc of the Squamous Cell Carcinoma of the Maxilla Sinus

Entre as neoplasms malignas dos seios paranasais, o carcinoma espinocelular é o tipo histológico mais freqüente; e o seio maxilar, a estrutura anatômica mais afetada. Os sintomas são insidiosos e confundidos com processo inflamatório crônico, levando a um atraso no diagnóstico e um aumento nos casos avançados na primeira consulta. Objetivo: Avaliar as características clinicas dos pacientes e os fatores que retardam o diagnóstico, propondo medidas para um diagnóstico mais precoce. Material e método: Os autores apresentam um estudo retrospectivo com 60 pacientes examinados e tratados no Serviço de Cirurgia de Cabeça e Pescoço do Hospital Heliópolis, no período de 1977 a 1993, e analisados em tabelas e gráficos. Resultados: Em relação à profissão, 16,7% eram alfaiates e costureiros. Sinusite crônica era observada em 10%. As queixas mais comuns foram: inchaço na face (36,7%), obstrução nasal (23,3%) dor e/ou amolecimento dentário (21,7%).O tempo de queixa variou de dois a oito meses (81,7%) e o período entre diagnóstico e tratamento variou de duas a quatro semanas (20%) e até duas semanas (43,3(/o). Como causa do atraso, 61,7% não valorizaram os sintomas iniciais, e em 20% houve falta de orientação do dentista. Paciente com queixa de inchaço na fase levou até quatro meses para procurar o especialista (37,9%) e aqueles com obstrução nasal (29%), dor e/ou amolecimento dentário (25,8%) apresentaram um tempo superior a quatro meses. Conclusão: A incidência foi maior entre pessoas do sexo masculino e profissionais que manipulam tecidos. Obstrução nasal, dor e/ou amolecimento dentário foram as queixas que retardaram a procura ao médico especialista. O ensino da oncologia aos profissionais de saúde e a ampliação do serviços especializados contribuirá para diminuir o retardo no tratamento, levando ao melhor prognóstico.

From among malign neoplasms in paranasal sinus, the squamous cell carcinoma is the more frequent histological kind of carcinoma, and the maxillary sinus is the more affected anatômical structure. The symptoms are insidious and confused with chronic inflammatory process, leading to a delay of diagnosis and an increase in advanced cases in first attendance. Purpose: To evaluate the patients' clinical caracteristics, the factors that delay the diagnosis and to propose measures for and earlier diagnosis. Material and method: The authors present a retrospective study of 60 patients examined and treated in the Surgery of Head and Neck Center of the Heliópolis Hospital from 1977 to 1993 and analyze it in tables and charts. Results: In terms of their professions,16,7% were tailors and dressmakers. Chronic sinusites was observed in 10% of the patients. The most common complaints were: face swelling (36,7%), nasal obstruction (23,3%) dental weakening and/or pain (21,7%). The elapsed time of complaint varied from two to eight months (81,7%) and the period between diagnosis and treatment varied from two to four weeks (20%), and even two weeks (43,3%). As a reason for delay, 61,7% didn't took the initial symptoms into account and in 20% there was lack of dentist's orientation. Patients complaining about face swelling spent four months to see a specialist physician (37,9%) and those complaining about nasal obstruction (29%), dental weakening and/or pain (25,8%) reported more than four months. Conclusion: The incidence was wider among male and textile workers. Nasal obstruction, dental weakening and/or pain were the complaints which made the patients delay in seeing a physician. Oncology teaching to professionals of health and improvement of specialized health services will contribute to decrease the delay in treatment, leading to the best prognostic.

Tumors of the oral cavity and pharynx.

We have compiled all the reported cases of smooth muscle (stromal) tumors of the oral cavity and pharynx from 1884 through 1996. Our collective data included 139 leiomyomas (LM) and 68 leiomyosarcomas (LMS); but because we did not have sufficient information for 13 cases of LM, we report on only 126; and we report on only 66 of 68 cases of LMS. The peak age of incidence was 40 to 49 years for benign tumors and 50 to 59 years for malignant lesions, with the incidence in men slightly predominating over that in women. The most common sites of LM of the oral cavity and pharynx were the lips, tongue, and hard and soft palate. The most common sites of LMS included the maxilla and mandible. More than 40% of LMs presented as an intraoral mass, and more than half were known to be present for longer than 1 year. About 10% presented with pain, difficulty chewing or swallowing, swelling, toothache or loose teeth, or a combination of these symptoms. Patients with LMS were much more likely to have obvious symptoms of shorter duration, and one-third presented with pain or swelling (or both). Other relatively common symptoms of LMS included tenderness, interference with dentures, or an intraoral mass. In this review, there were almost twice as many LMs as LMSs, which was consistent with smooth muscle tumors found in other areas of the gastrointestinal tract.