Total RNA sequencing reveals gene expression and microbial alterations shared by oral pre-malignant lesions and cancer.

Head and neck cancers are a complex malignancy comprising multiple anatomical sites, with cancer of the oral cavity ranking among the deadliest and the most disfiguring cancers globally. Oral cancer (OC) constitutes a subset of head and neck cancer cases, presenting primarily as tobacco- and alcohol-associated oral squamous cell carcinoma (OSCC), with a 5-year survival rate of ~ 65%, partly due to the lack of early detection and effective treatments. OSCC arises from premalignant lesions (PMLs) in the oral cavity through a multi-step series of clinical and histopathological stages, including varying degrees of epithelial dysplasia. To gain insights into the molecular mechanisms associated with the progression of PMLs to OSCC, we profiled the whole transcriptome of 66 human PMLs comprising leukoplakia with dysplasia and hyperkeratosis non-reactive (HkNR) pathologies, alongside healthy controls and OSCC. Our data revealed that PMLs were enriched in gene signatures associated with cellular plasticity, such as partial EMT (p-EMT) phenotypes, and with immune response. Integrated analyses of the host transcriptome and microbiome further highlighted a significant association between differential microbial abundance and PML pathway activity, suggesting a contribution of the oral microbiome toward PML evolution to OSCC. Collectively, this study reveals molecular processes associated with PML progression that may help early diagnosis and disease interception at an early stage.

Maxillary resection prosthesis fabricated from urethane dimethacrylate for a patient with polymethyl methacrylate allergy: A clinical report.

The surgical resection of malignant tumors often leads to severe bone and soft-tissue deficits that can result in difficulty swallowing, impaired speech, and facial disfigurement. Prosthetic rehabilitation of these patients becomes an integral part of the patient's recovery and allows for improvement in quality of life. This clinical report describes a patient who underwent an anterior maxillectomy secondary to squamous cell carcinoma. After the insertion of a polymethyl methacrylate (PMMA) interim resection prosthesis, the patient developed a severe allergic stomatitis reaction in the oral cavity and oropharynx. By using the patch test approach, true PMMA allergy was diagnosed along with a suitable PMMA replacement for the prosthesis. A subsequent prosthesis was fabricated from urethane dimethacrylate in place of the standard PMMA.

Oral soft tissue manifestation of multiple myeloma after kidney transplantation: a case report.

This report presents a case in which oral soft tissue lesions were the first signs of multiple myeloma (MM) following a solid-organ transplantation. A 75-year-old man presented with bilateral primary oral gingival masses in the posterior mandible approximately 2 months after tooth extractions. A panoramic radiograph appeared normal and did not reveal "punched-out" lytic lesions of the bone, a classic sign of MM. A biopsy of the gingival masses was performed, and the resulting diagnosis was a plasma cell neoplasm. After a hematologic screening, positron emission tomography/computed tomography, and bone marrow biopsy, the diagnosis of MM with extensive disease was confirmed. Oral manifestations of MM are common, making the patient's oral health history an integral part of diagnosis. Although the isolated gingival hypertrophy observed in the present case is an atypical oral presentation, an understanding of the maxillofacial manifestations of MM is important to ensure diagnosis in the early stages of disease.

Sentinel lymph node biopsy for management of the N0 neck in oral cavity squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: The management of the clinically N0 (cN0) neck is controversial for early stage squamous cell carcinoma of the oral cavity (OSCC). This paper represents a single institution series analyzing the efficacy of sentinel lymph node biopsy (SNB) for early stage oral cavity cancers. METHODS: From 2005 to 2017, 108 patients with cN0 OSCC were treated with primary resection and SNB. Patients with positive biopsy results proceeded to neck dissection with or without adjuvant chemoradiotherapy. Mean follow-up for the entire cohort was 50.8 months (range: 8-147 months). Clinically, 56 patients were T1N0, 49 patients were T2N0, and three patients were T3N0 or greater. RESULTS: Disease-specific survival was 93% within the entire cohort. Sentinel lymph nodes were identified in 95.4% of patients. Twenty one patients had a positive biopsy. There were seven false-negative biopsies. The overall rate of nodal disease was 26%. Accuracy of node biopsy was 93%, with sensitivity of 75%, and negative predictive value of 91%. Recurrence rate was 19% (20/108), with an overall survival of 60% in this subgroup. CONCLUSION: SNB is a safe, effective, and well tolerated method for staging cN0 OSCC.

Evaluation of a community-based dental screening program prior to radiotherapy for head and neck cancer: a single-center experience.

PURPOSE: Oral toxicities following radiation therapy (RT) for head and neck (HN) cancer can be profound and are associated with poor health outcomes. The Division of Oral Medicine and Dentistry at Brigham and Women's Hospital and Dana-Farber Cancer Institute therefore implemented a dental evaluation program designed for community-based (CB) dentists to evaluate and treat patients scheduled for HN RT. The aim of this retrospective single-center cohort study was to assess the compliance of CB dentists with this pre-RT dental evaluation program. METHODS: A retrospective analysis of dental evaluations completed by CB dentists from December 2013 to December 2015 was performed. Descriptive statistics were used to determine compliance. RESULTS: A total of 186 dental evaluations were received. Compliance with completion of dental treatment was as follows: scaling and prophylaxis: 94.5% (172/182); dental restorations: 78.7% (48/61); endodontic therapy: 76.9% (10/13); and dental extractions: 76.9% (30/39). Compliance of CB dentists with all requested components of the pre-RT evaluation and treatment was 77.4% (144/186). The median distance traveled by patients to the CB dentist and to the hospital was 5.2 miles (range 0.03-66.0) and 46.5 miles (range 0.8-1457; p < 0.01), respectively. CONCLUSION: In this study, the majority of patients completed their necessary dental treatment in a timely manner by their CB dentist in collaboration with an oral medicine specialist. Given the high compliance of CB dentists, this program could serve as a model for other cancer centers to optimize oral and dental health prior to RT.

Oral keratosis of unknown significance shares genomic overlap with oral dysplasia.

OBJECTIVES: To identify molecular characteristics of keratosis of unknown significance and to nominate pathways of molecular progression to oral cancer. Our work could provide a rationale for monitoring and treating these lesions definitively. METHODS: Patients with oral leukoplakia were eligible for our prospective observational study. We correlated alterations in cancer-associated genes with clinical and histopathologic variables (keratosis of unknown significance vs. moderate-to-severe dysplasia) and compared these alterations to a previously molecularly characterized oral cancer population. RESULTS: Of 20 enrolled patients, 13 (65%) had evidence of keratosis of unknown significance, while seven (35%) had dysplasia. Nine patients (45%) developed oral cancer (4/13 with keratosis of unknown significance, 5/7 with dysplasia). At a median follow-up of 67 (range 22-144) months, median overall survival was significantly shorter for patients with dysplasia (hazard ratio 0.11, p = .02). KMT2C and TP53 alterations were most frequent (75% and 35%, respectively). There were molecular similarities between keratosis of unknown significance and dysplasia patients, with no significant differences in mutational frequency among genes with ≥15% rate of alteration. CONCLUSIONS: Among patients with leukoplakia, both patients with keratosis of unknown significance and patients with dysplasia developed oral cancer. Molecular alterations between these two groups were similar at this sample size.

Progression of gingival squamous cell carcinoma from early to late stage after invasive dental procedure.

Early presentation of gingival squamous cell carcinoma (GSCC) is at times misdiagnosed as a benign inflammatory or reactive oral condition. Some misdiagnosed patients undergo unnecessary, invasive dental procedures, resulting in delayed cancer diagnosis and an increased risk of accelerated disease progression due to disruption of the periosteum and cortical bone. The records of 58 patients with biopsy-proven GSCC were retrospectively reviewed. The sample included 32 patients who underwent an invasive dental procedure (IDP) prior to cancer diagnosis and 26 patients who did not undergo an IDP (non-case group). Patients from both groups initially presented with similar symptoms. The median duration of symptoms at initial clinical presentation was 6 months for the IDP group and 2 months for the non-case group. In IDP patients, symptoms worsened after the IDP was rendered, with 37.5% presenting with a severe-grade symptom. In both groups, the majority of lesions were found on the posterior mandible and had a histologic grading of moderately differentiated GSCC. The odds of the IDP group having late-stage disease were 2.94 times greater than the odds for the control group. Stage T3/T4 malignancy was diagnosed in 77.4% of the IDP patients versus 53.8% of non-case patients. Disease-specific mortality was comparable; however, surgical treatment was significantly more extensive in the IDP group than in the non-case group. The disruption of alveolar periosteum in undiagnosed oral cancer patients results in significant delay in diagnosis, necessitating more complicated treatment regimens because of local tumor progression.

Retrospective study of a pilot program focused on educating dental patients on human papillomavirus and vaccination in a hospital setting.

INTRODUCTION: Human papillomavirus (HPV) is an epidemic currently affecting 80 million people in the United States. The HPV virus can be passed from one person to another via sexual intercourse, oral sex, open mouth kissing and skin-to-skin contact. In some cases, the infection is not eliminated by the immune system and can cause cancer of the head and neck, cervix, anus, and genitals. There has been a rise in oropharyngeal cancer (OPC) associated with HPV, which can be missed on conventional dental screening examinations. Dentists should engage in promoting HPV vaccination as a primary measure for OPC prevention. The goal of this HPV pilot program was to educate and offer same day HPV vaccination to dental patients by using a multidisciplinary approach in a hospital setting. METHODS: Patients 18 through 26 years of age who presented to the Erie County Medical Center's dental clinic were approached and educated on HPV. Eligible patients received a direct recommendation for the HPV vaccine. Those interested in same day vaccination were referred to the division of infectious diseases' YOU Center for Wellness. A retrospective chart review was completed for patients who were HPV educated from March 5, 2020, through December 15, 2021. Charts were evaluated for age, sex, race, ethnicity, reason for visit, HPV vaccine referral, and HPV vaccine administration. RESULTS: 326 patients were included in the chart review. The prominent sex, race, and ethnicity were male, Black or African American, and non-Hispanic origin. The median age was 23. Most patients presented to the dental clinic for an emergency visit and were not previously vaccinated against HPV. 110 patients were unvaccinated, and 44 patients were referred to the division of infectious disease for same day vaccination. Of these 44, 24 patients initiated the vaccination process. Five patients received all three doses, three patients received two doses, and 16 patients received one dose. CONCLUSION: This pilot program successfully vaccinated 24 patients with at least a single dose of the HPV vaccine. This multidisciplinary model can be implemented in other health care settings.

Total RNA sequencing reveals gene expression and microbial alterations shared by oral pre-malignant lesions and cancer.

Head and neck cancers are a complex malignancy comprising multiple anatomical sites, with cancer of the oral cavity ranking among the deadliest and most disfiguring cancers globally. Oral cancer (OC) constitutes a subset of head and neck cancer cases, presenting primarily as tobacco-and alcohol-associated oral squamous cell carcinoma (OSCC), with a 5-year survival rate of ∻65%, partly due to the lack of early detection and effective treatments. OSCC arises from premalignant lesions (PMLs) in the oral cavity through a multi-step series of clinical and histopathological stages, including varying degrees of epithelial dysplasia. To gain insights into the molecular mechanisms associated with the progression of PMLs to OSCC, we profiled the whole transcriptome of 66 human PMLs comprising leukoplakia with dysplasia and hyperkeratosis non-reactive (HkNR) pathologies, alongside healthy controls and OSCC. Our data revealed that PMLs were enriched in gene signatures associated with cellular plasticity, such as partial EMT (p-EMT) phenotypes, and with immune response. Integrated analyses of the host transcriptome and microbiome further highlighted a significant association between differential microbial abundance and PML pathway activity, suggesting a contribution of the oral microbiome towards PML evolution to OSCC. Collectively, this study reveals molecular processes associated with PML progression that may help early diagnosis and disease interception at an early stage. AUTHOR SUMMARY: Patients harboring oral premalignant lesions (PMLs) have an increased risk of developing oral squamous cell carcinoma (OSCC), but the underlying mechanisms driving transformation of PMLs to OSCC remain poorly understood. In this study, Khan et al., analyzed a newly generated dataset of gene expression and microbial profiles of oral tissues from patients diagnosed with PMLs from differing histopathological groups, including hyperkeratosis not reactive ( HkNR ) and dysplasia, comparing these profiles with OSCC and normal oral mucosa. Significant similarities between PMLs and OSCC were observed, with PMLs manifesting several cancer hallmarks, including oncogenic and immune pathways. The study also demonstrates associations between the abundance of multiple microbial species and PML groups, suggesting a potential contribution of the oral microbiome to the early stages of OSCC development. The study offers insights into the nature of the molecular, cellular and microbial heterogeneity of oral PMLs and suggests that molecular and clinical refinement of PMLs may provide opportunities for early disease detection and interception.

Dental management of a 26-year-old female with fibrodysplasia ossificans progressiva: A case report.

PURPOSE: The purpose of the report is to present a rare case of clinical management of a 26-year-old patient with fibrodysplasia ossificans progressiva (FOP), and discuss treatment options and possible outcomes. SUMMARY: FOP is a rare autosomal dominant genetic disorder of the connective tissue that affects one in two million people. It is characterized by multiple areas of progressive heterotopic endochondral ossifications. The symptoms typically begin with painful soft tissue swellings in the patient's first decade, which frequently occur after minor trauma, but may also happen spontaneously. The soft tissue swellings eventually form hard bony masses that cause joint limitations, growth defects, skeletal deformities, and chronic pain. The results are severely limiting to the activities of daily living and overall quality of life with the average life expectancy being 40 years of age. Medical and dental treatment, including the use of general anesthesia, may be complicated by increased risk of ossification of the soft tissues in the airway and lungs. The following case report focuses on a 26-year-old Caucasian female, with FOP. The patient presented to the Erie County Medical Center Dental clinic in Spring 2019 with generalized dental pain. She reported a history of multiple dental infections over many years which were periodically treated with antibiotics. A thorough intraoral exam and radiographs were not able to be completed upon initial presentation due to severe trismus and mobility limitations. The patient was a wheelchair user, verbal, and maintained a completely liquid diet by mouth. The patient also had a medical history significant for dysphagia and aspiration. After a substantial pre-operative optimization process, the patient was brought to the operating room for full mouth dental extractions. At the 2-week follow-up from surgery the patient showed excellent healing. CONCLUSION: While there are greater potential risks with placing a patient with FOP patient under general anesthesia, proper management of dental disease can relieve the patient from recurrent infections and discomfort.

Ensuring head and neck oncology patients receive recommended pretreatment dental evaluations.

PURPOSE: Head and neck (H&N) cancer therapy can have a detrimental effect on oral health by increasing the risk of dry mouth, dental caries, dental infection, and osteonecrosis of the jaw. Pretreatment dental evaluations are recommended for patients with H&N cancer before radiation therapy to minimize the risk of acute and long-term adverse effects. In an earlier effort to educate patients and community dentists about the importance of pretreatment dental evaluations, we created a dental instructional guide (DIG) that outlines the necessary components of the preradiation dental evaluation. Yet our program did not have a system for documenting which patients received the DIG. The aim of this project was to create a reliable system to ensure that patients are given the DIG before radiation therapy and that such patients are readily identifiable, allowing us to confirm that their dental evaluations are complete before starting treatment. METHODS: We implemented a tracking template within the H&N oncology program at the Dana-Farber Cancer Institute that documents the date, patient, and clinician who gave the DIG. We used the Model for Improvement methodology and performed plan-do-study-act (PDSA) cycles to test and monitor the results of the template implementation. RESULTS: We showed a significant improvement in the rate of DIG documentation from a baseline of 0% (range, 0% to 0%) to a mean of 53% (range, 0% to 100%) over 3 months (P < .01). CONCLUSION: This intervention was the first step in creating a sustainable system for ensuring timely preradiation dental evaluation, thereby decreasing the risk of dental complications from H&N cancer therapy.

Sentinel node biopsy in lieu of neck dissection for staging oral cancer.

IMPORTANCE: Neck dissection is the standard staging procedure to ascertain the pathologic status of cervical lymph nodes in patients with oral cavity squamous cell carcinoma (OSCC), but it results in multiple morbidities. OBJECTIVE: To examine outcomes of patients with OSCC who underwent sentinel node biopsy (SNB) as the sole neck staging procedure. DESIGN: Retrospective review of patients who underwent SNB during the period 2005 through 2011. SETTING: National Cancer Institute­designated comprehensive cancer center. PARTICIPANTS: Thirty-eight patients with clinically T1 or T2N0 OSCC. INTERVENTIONS: Preoperative lymphoscintigraphy with intraoperative gamma probe localization was used. Sentinel lymph nodes were serially sectioned, formalin fixed, and examined at 3 levels. All patients with positive SNB results underwent neck dissection, and the patients with negative SNB results were observed clinically. MAIN OUTCOMES AND MEASURES: Sensitivity and predictive value of SNB, recurrence rates, and disease-specific survival rates. RESULTS: There were 18 T1 and 20 T2 tumors. Five patients had positive SNB results, of whom 3 had additional positive nodes on subsequent neck dissection. Two of 33 patients with negative SNB results developed a regional recurrence. The sensitivity and negative predictive value for staging the neck with SNB alone were 71% (5 of 7) and 94% (31 of 33), respectively. Mean follow-up was 31 months. The mean disease-free survival duration for patients with positive and negative SNB results was 30 and 65 months, respectively (P = .08). The disease-specific survival rate for patients with positive and negative SNB results was 80% and 91%, respectively. There was no significant difference in disease-specific survival between patients with true-negative and false-negative SNB results (34 vs 44 months; P = .38). CONCLUSIONS AND RELEVANCE: The majority of patients with positive results on SNB had additional positive nodes on neck dissection. A low rate of isolated neck recurrence was found in patients with negative results on SNB. Individuals with negative results on SNB exhibited better overall and disease-specific survival than those with positive results.

Adjuvant intraoperative photodynamic therapy in head and neck cancer.

IMPORTANCE: There is an immediate need to develop local intraoperative adjuvant treatment strategies to improve outcomes in patients with cancer who undergo head and neck surgery. OBJECTIVES: To determine the safety of photodynamic therapy with 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) in combination with surgery in patients with head and neck squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Nonrandomized, single-arm, single-site, phase 1 study at a comprehensive cancer center among 16 adult patients (median age, 65 years) with biopsy-proved primary or recurrent resectable head and neck squamous cell carcinoma. INTERVENTIONS: Intravenous injection of HPPH (4.0 mg/m2), followed by activation with 665-nm laser light in the surgical bed immediately after tumor resection. MAIN OUTCOMES AND MEASURES: Adverse events and highest laser light dose. RESULTS: Fifteen patients received the full course of treatment, and 1 patient received HPPH without intraoperative laser light because of an unrelated myocardial infarction. Disease sites included larynx (7 patients), oral cavity (6 patients), skin (1 patient), ear canal (1 patient), and oropharynx (1 patient, who received HPPH only). The most frequent adverse events related to photodynamic therapy were mild to moderate edema (9 patients) and pain (3 patients). One patient developed a grade 3 fistula after salvage laryngectomy, and another patient developed a grade 3 wound infection and mandibular fracture. Phototoxicity reactions included 1 moderate photophobia and 2 mild to moderate skin burns (2 due to operating room spotlights and 1 due to the pulse oximeter). The highest laser light dose was 75 J/cm2. CONCLUSIONS AND RELEVANCE: The adjuvant use of HPPH-photodynamic therapy and surgery for head and neck squamous cell carcinoma seems safe and deserves further study. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00470496.

Osteonecrosis of the jaw: dental outcomes in metastatic breast cancer patients treated with bisphosphonates with/without bevacizumab.

The etiology, optimal management, and outcome of osteonecrosis of the jaw (ONJ) are not well understood. Because healing after mucosal trauma requires revascularization, theoretically, the combination of bevacizumab (bev) and a bisphosphonate (BP) could affect the time to development of ONJ and/or the response to dental therapy. We reviewed all cases of ONJ in metastatic breast cancer patients treated at our institution with bev+BPs and BPs alone between October 2002 and April 2010. We identified 27 ONJ patients with a median age of 57 years (range, 40 to 68 years). Seven patients received bev+BPs; 20 patients received BPs alone. Patients received intravenous zolendronate (95%), pamidronate (20%), or both (15%). Patients were treated with antibiotics (93%), alveoplasty/debridement (67%), and chlorhexidine scrub (81%). There was no difference in dental treatment between the groups or by the year of diagnosis (before 2007 versus 2007-2010). Complete resolution (CR) was achieved in 24% of all patients; 33% treated with bev+BPs, and 21% treated with BPs alone. Rates of CR improved from 15% to 33% after 2007. The median time to response was 5.6 months (range, 1.3 to 67.5 months). The addition of bev to BPs did not appear to alter the time to development of ONJ (32.6 months versus 34.6 months, respectively). The number of BP treatments administered before the diagnosis of ONJ between bev+BPs and BPs (32 doses versus 36.5 doses) was similar. However, our sample size was too small to characterize the difference statistically. Because dental management of ONJ has not changed over time at our institute, early recognition and screening may account for the improvement in dental outcomes.

Human papillomavirus types 16 and 18 in epithelial dysplasia of oral cavity and oropharynx: a meta-analysis, 1985-2010.

Human papillomavirus (HPV) types 16 and 18 are causally related to a sub-set of oral cavity and oropharyngeal squamous cell cancers. However, a clear estimate of the prevalence of HPV-16/18 in oral cavity and oropharyngeal dysplasia (OOPD) is not available. This literature review and meta-analysis was conducted to provide a prevalence estimate for HPV-16/18 in OOPD. Twenty-two studies that reported prevalence of HPV-16 and/or 18 in 458 OOPD lesions were analyzed. Meta-analysis was used to evaluate the prevalence of HPV-16/18 and logistic regression was used for stratified analysis by age, gender, and histological grade. The overall prevalence of HPV-16/18 in OOPD lesions was 24.5% [95% confidence interval (CI), 16.4-36.7%)]. The individual prevalence for HPV-16 alone was 24.4%. The prevalence of HPV-16/18 in oral cavity lesions alone was 25.3% (95% CI, 14.2-45.2%). The odds of detection of HPV-16/18 in dysplastic lesions in males were twice that of females [odds ratio (OR), 2.44]. HPV-16/18 were 3 times more common in dysplastic lesions (OR, 3.29; 95% CI, 1.95-5.53%) and invasive cancers (OR, 3.43; 95% CI, 2.07-5.69%), when compared to normal biopsies. There was no significant difference in HPV-16/18 rates between dysplastic lesions and cancers or between mild, moderate or severe dysplastic lesions. This meta-analysis provides a quantification of the prevalence of HPV types 16/18 in OOPD lesions. These results also support the assumption that HPV-16/18 infection occurs during the early phase of the oral cavity and oropharyngeal carcinogenesis.

Autofluorescence-guided surveillance for oral cancer.

Early detection of oral premalignant lesions (OPL) and oral cancers (OC) is critical for improved survival. We evaluated if the addition of autofluorescence visualization (AFV) to conventional white-light examination (WLE) improved the ability to detect OPLs/OCs. Sixty high-risk patients, with suspicious oral lesions or recently diagnosed untreated OPLs/OCs, underwent sequential surveillance with WLE and AFV. Biopsies were obtained from all suspicious areas identified on both examinations (n = 189) and one normal-looking control area per person (n = 60). Sensitivity, specificity, and predictive values were calculated for WLE, AFV, and WLE + AFV. Estimates were calculated separately for lesions classified by histopathologic grades as low-grade lesions, high-grade lesions (HGL), and OCs. Sequential surveillance with WLE + AFV provided a greater sensitivity than WLE in detecting low-grade lesions (75% versus 44%), HGLs (100% versus 71%), and OCs (100% versus 80%). The specificity in detecting OPLs/OCs decreased from 70% with WLE to 38% with WLE + AFV. Thirteen of the 76 additional biopsies (17%) obtained based on AFV findings were HGLs/OCs. Five patients (8%) were diagnosed with a HGL/OC only because of the addition of AFV to WLE. In seven patients, additional HGL/OC foci or wider OC margins were detected on AFV. Additionally, AFV aided in the detection of metachronous HGL/OC in 6 of 26 patients (23%) with a history of previously treated head and neck cancer. Overall, the addition of AFV to WLE improved the ability to detect HGLs/OCs. In spite of the lower specificity, AFV + WLE can be a highly sensitive first-line surveillance tool for detecting OPLs/OCs in high-risk patients.

Ewing sarcoma of the mandibular condyle: multidisciplinary management optimizes outcome.

BACKGROUND: Ewing sarcoma (ES) is a rare, primary malignancy of bone that occurs in childhood and early adolescence. Improved methods of diagnosis and treatment have dramatically increased survival over the last 20 years. Treatment mainstays are chemotherapy and surgical tumor resection. ES usually occurs in long bones of the axial skeleton; however, it may rarely arise in facial structures, particularly the mandible. In these cases, resection presents a challenging postsurgical reconstruction. METHODS AND RESULTS: We present the clinical findings and management of a case of ES that developed in the left mandibular condyle of a 15-year-old female. Chemotherapy and segmental mandibulectomy were used to achieve local control. An innovative temporomandibular joint reconstruction was successfully accomplished using a microvascular fibular free flap and conchal cartilage graft. CONCLUSION: Multidisciplinary management in diagnosis, treatment, and restoration of function produced an optimal result that eliminated disease and preserved aesthetics and quality of life.