Desmoglein-3 overexpression in oral squamous cell carcinoma is associated with metastasis formation and early recurrence: An immunohistochemical study.

The purpose of this study was to determine the expression patterns of specific desmosomal cadherins (desmogleins [DSG] 1/2/3) in oral squamous cell carcinoma (OSCC), and to examine possible associations with clinicopathological parameters and recurrence rates. Changes in desmosomal cadherin assembly may promote tumor metastasis formation. Patients with surgically treated OSCC with 36-60 months of follow-up (median 46 months) qualified for inclusion in this retrospective cohort study. Demographic, clinical and pathohistological data were collected. DSG-1/2/3 expression patterns were determined by an immunohistochemical approach on tissue microarrays. Descriptive and inferential statistics and survival analyses were computed (p ≤ 0.05). The study sample consisted of 88 patients (female: 38; male: 50; average age: 63.02 ± 17.5 years). DSG-3 overexpression was detected in 45 of 88 specimens. The expression rates for DSG-1 (28/88) and DSG-2 (14/88) were low and inconspicuous. DSG-3 overexpression was significantly associated with poor histologic differentiation (G3, p = 0.001), the presence of cervical node metastasis at primary diagnosis (N+ status, p = 0.001) and early recurrence (p = 0.001). Due to its possible relevance for lymph node metastasis formation and early OSCC recurrence, determination of DSG-3 expression in OSCC specimens may be a valuable tool for treatment planning and post-therapeutic risk assessment.

Is the oral cavity a reservoir for prolonged SARS-CoV-2 shedding?

Limited knowledge about the contagiosity and case fatality rate of COVID-19 as well as the still enigmatic route of transmission have led to strict limitations of non-emergency health care especially in head and neck medicine and dentistry. There are theories that the oral cavity provides a favorable environment for SARS-CoV-2 entry and persistence which may be a risk for prolonged virus shedding. However, intraoral innate immune mechanisms provide antiviral effects against a myriad of pathogenic viruses. Initial hints of their efficacy against SARS-CoV-2 are surfacing. It is hypothesized that intraoral immune system activity modulates the invasion pattern of SARS-CoV-2 into oral cells. Thus, the significance of intraoral tissues for SARS-CoV-2 transmission and persistence cannot be assessed. The underlying concept for this hypothesis was developed by the critical observation of a clinically asymptomatic COVID-19 patient. Despite a positive throat swab for SARS-CoV-2, molecular pathologic analysis of an oral perisulcular tissue specimen failed to detect SARS-CoV-2 RNA. More research effort is necessary to define the true origin of the contagiosity of asymptomatic COVID-19 patients.

First experience of chick chorioallantoic membrane (CAM) assay in the clinical work flow with oral squamous cell carcinoma patients.

INTRODUCTION: The oral squamous cell carcinoma (OSCC) is a leading cause of death in human malignancies. The aim of this study is to integrate the CAM Assay as a reliable and good working in vivo model for the evaluation of OSCC tumor samples and its growth into the clinical work flow. MATERIAL AND METHODS: Fresh human Tumor samples (OSCCs) 1×1 cm in size were cut into 350-450µm thick slices by a Vibratome and put on the prepared CAM model.After growth of the tumor tissue on the CAM, we started with topical induction of proinflammatory cytokines (TNFα) and growth factors (TGFß). After further growth of the tumor on the assay, we explanted the tumor tissue and first performed microscopic and then immunohistochemical examinations. E-cadherin and vimentin were used as Epithelial-to-mesenchymal transition (EMT) -makers and the histologic preparations were evaluated histomorphometrically. The results were correlated with clinical parameters of the patients. RESULTS: Under TNFα, the small tumors (T1 / T2) show higher E-cadherin expression than larger tumors (T3 / T4). The vimentin expression under TNFα behaved in the opposite direction, at T1 / T2 the expression decreased in T3 / T4 increased. Furthermore, an increased E-cadherin expression in N0 and diminished E-cadherin expression in N1 / N2b patients could be detected depending on the N-stage of the patients. Vimentin, on the other hand, was reduced in the N0 group and expressed more frequently in the N1 / N2b group. TGFß induction also led to increased expression of vimentin in the T3 / T4 tumors and N1 / N2b stages. CONCLUSION: By integrating a CAM assay into the clinical workflow, tumors with preserved tumor architecture can be cultured and subjected to histological and molecular biology studies. Effects on biological behavior are recognizable and demonstrable in this model. The key markers E-cadherin and vimentin alone are not sufficient to represent the complexity of the EMT in this model. Further molecular biology and signaling pathway analyzes are necessary.

What Factors Are Associated With Regional Recurrence After Operative Treatment of Oral Squamous Cell Carcinoma?

PURPOSE: A considerable proportion of oral squamous cell carcinoma (OSCC) recurrences involve the neck, which has a substantial impact on prognosis and is poorly understood. The purpose of this study was to analyze clinical and pathologic characteristics of regional recurrence of OSCC and identify possible risk factors. MATERIALS AND METHODS: A single-center retrospective cohort study was designed to address the study purpose. All patients who were treated surgically for primary OSCC with or without adjuvant therapy between 2010 and 2015 were considered for inclusion with respect to predefined criteria, and demographic, clinical, and pathologic variables were collected. The lymph node status after primary OSCC treatment (pN) was defined as the predictor variable, and the occurrence of regional recurrence served as the primary outcome variable. Further variables of special interest were the histologic differentiation (G status) of the primary OSCC and the values of the lymph node ratio and log odds of positive lymph nodes. Descriptive, inferential, and appropriate time-dependent (Kaplan-Meier analysis, Cox regression model) statistics were computed. The level of statistical significance was set at P ≤ .05. RESULTS: The study sample was composed of 171 patients (70 women and 101 men; average age, 62.4 years). Neck failure occurred in 18 patients (11%) either in combination with local recurrence (15 patients) or in isolation (3 patients). Poor histologic differentiation of the primary tumor was identified as an independent risk factor for regional recurrence. Most neck recurrences manifested in previously unaddressed levels (IV and V). CONCLUSIONS: Regional recurrence of OSCC might be associated with specific clinicopathologic parameters of the primary tumor. The importance of these parameters for OSCC prognosis assessment and recurrence prediction should be elucidated in further studies.

Accuracy of Navigation-Guided Dental Implant Placement with Screw Versus Hand Template Fixation in the Edentulous Mandible.

PURPOSE: Preoperative planning of the implant position as part of a coordinated prosthetic and surgical concept is becoming increasingly important regarding function and esthetics. The aim of this study was to investigate the transmission accuracy of template fixation during surgery in edentulous arches with hand fixation in comparison to intermediary screw fixation. MATERIALS AND METHODS: Preoperatively, 10 implant positions were planned using computed tomography (CT) with the system med3D for implant placement in four mandible models of the Goettingen study model, using a prosthetic diagnostic template. A total of 40 implant insertions were created. For every 20 insertions, the template was temporarily fixed with three screws and compared with the insertion using a hand-fixed template. The precision of the transmission was evaluated with and without screw fixation by re-evaluating the preimplant planning with additional CT scanning of the respective models. RESULTS: Compared with the hand-fixed procedure (HFG) in the model situation, there were no significant differences between the deviations of planned and final implant position in the screw-fixed group (FG). According to the study results, the fixed procedure leads to less depth deviation and lateral error of the implant base in relation to the HFG. Within both groups, there were significant differences between the radial deviation tendencies from the implant base to the implant apex (P = .033 for FG and P = .001 for HFG). CONCLUSION: The use of CT-based implant planning succeeds in fixed and hand-fixed surgical procedures with high precision in the atrophic, edentulous mandible model. According to the results of this study, in cases demanding high depth precision, screw-fixation of the template can be helpful.

Is There Evidence for the Presence and Relevance of the PD-1/PD-L1 Pathway in Oral Squamous Cell Carcinoma? Hints From an Immunohistochemical Study.

PURPOSE: To examine oral squamous cell carcinoma (OSCC) specimens for programmed death ligand-1 (PD-L1) expression and presence of programmed death-1 (PD-1)-positive tumor-infiltrating lymphocytes (TILs) and to determine possible clinicopathologic implications. It was hypothesized that PD-L1 expression and PD-1-positive TIL presence in OSCC would have no clinical relevance. MATERIALS AND METHODS: The authors implemented a retrospective cohort study design. The study cohort was chosen in compliance with predefined inclusion criteria. Demographic, clinical, and histopathologic data were gathered. Tissue microarrays were obtained from paraffin-embedded OSCC specimens and analyzed immunohistochemically for PD-L1 expression and PD-1-positive TIL infiltration. PD-L1 positivity of OSCC specimens served as the predictor variable and neck node metastasis served as the primary outcome variable. Descriptive and inferential statistics were computed and the significance level was set at a P value less than or equal to .05. RESULTS: The study sample was composed of 88 patients (48 men, 40 women; mean age, 61.34 yr). Marked PD-L1 expression was detected in 29% of OSCC specimens (26 of 88) and 83% of specimens (73 of 88) exhibited a high rate of PD-1-positive TIL infiltration. PD-L1 positivity of OSCC samples was significantly associated with the anatomic origin of OSCC (P = .039), presence of cervical metastasis (P = .039), and high PD-L1-positive TIL infiltration (P = .033). CONCLUSION: A considerable proportion of OSCCs exhibited marked PD-L1 expression. This could be associated with clinical parameters. PD-L1 expression in OSCC might differ depending on its anatomic origin. PD-1-positive TILs could be detected in most OSCC specimens. These findings might indicate a potential role for the PD-1 and PD-L1 pathway in OSCC.

Osteoblast-like cells with different embryologic origins behave differently in increasing zoledronic acid concentrations: a pilot study in pigs.

OBJECTIVE: We compared the intraindividual effects of increasing zoledronic acid (ZA) concentrations on osteoblast-like cells with different embryologic origins. STUDY DESIGN: Cultured osteoblast-like cells from mandible and iliac crest bone samples of domestic pigs were exposed to increasing concentrations of ZA (0, 10-8, 10-6, and 10-4 M). Proliferation was assessed by cell counting. Receptor activator of nuclear factor kB ligand and osteoprotegerin (OPG) messenger RNA expression were assessed at 0, 1, 4, 7, and 10 days. RESULTS: The OPG expression level was higher in the iliac crest than in the mandible. Neither ZA concentration nor the cells' origin affected the expression of receptor activator of nuclear factor kB ligand. At 10-6 M, OPG expression from both locations reached the same level after 7 days of cultivation, as OPG expression increased to a greater extent in the mandible in comparison to the iliac crest. CONCLUSION: Cultured mandibular osteoblast-like cells reacted more sensitively to high ZA concentrations than did osteoblast-like cells from the iliac crest.

Clinical features of peri-implant medication-related osteonecrosis of the jaw: Is there an association to peri-implantitis?

The purpose of this study was to examine the behavior of dental implants in patients diagnosed with MRONJ and to analyze the characteristics of peri-implant MRONJ. It was hypothesized that peri-implant parameters are not associated with peri-implant MRONJ. A retrospective study design was selected to address the research purpose. Patients with confirmed MRONJ and the simultaneous presence of dental implants who presented between 2010 and 2016 served as the study cohort. Predefined inclusion and exclusion criteria were applied. Demographic, clinical and radiological data were collected and analyzed statistically with respect to the variable scale (significance level p ≤ 0.05). The study sample was composed of 34 patients (female: 16; male: 18; average age: 70.6 years) with a total of 117 dental implants the majority of whom had received antiresorptive drug therapy within oncologic treatment protocols. Peri-implant MRONJ occurred in 15 patients (44%). Signs of peri-implantitis (present around 46/117 implants; 39%) appeared to be associated with the occurrence of peri-implant MRONJ. Patients receiving antiresorptive drugs in high doses seem to be at risk of developing MRONJ in the vicinity of dental implants. Peri-implantitis may be associated with the etiology of peri-implant MRONJ.

Clinical efficacy of grafting materials in alveolar ridge augmentation: A systematic review.

PURPOSE: To evaluate the efficacy of grafting materials in lateral and vertical ridge augmentations. MATERIALS AND METHODS: A systematic review of the literature on the clinical use of grafting materials of the years 1995 to April 2015 was conducted using electronic search of PubMed and Cochrane libraries and hand search of eight print journals. A total of 184 papers were included, comprising 6182 patients. Parameters evaluated were observation period [months], bone formation [histologic area%], defect fill [%], horizontal and vertical gain [mm], loss of augmented volume [mm], complication rate [%], and implant survival rate [%]. Results are expressed as weighted means ± SD. RESULTS: Results were obtained after a weighted mean observation period of 27.4 months (range 3-168 months). Bone formation in the augmented areas varied from 33.2 ± 14.9% for allogeneic grafts to 56.0 ± 25.6% for mixtures of autogenous and other grafting materials. Defect fill in dehiscence defects ranged from 51.0 ± 13.6% (synthetic) to 85.8 ± 13.4% (xenogeneic) for the different materials, with an overall weighted mean of 79.8 ± 18.7%. Weighted mean horizontal gain for all particulate grafting materials was 3.7 ± 1.2 mm, with variation between 2.2 ± 1.2 mm (synthetic) and 4.5 ± 1.0 mm (mixtures of autogenous bone with allogeneic/xenogeneic grafting material) without statistical significance. Weighted overall mean vertical gain was 3.7 ± 1.4 mm. Vertical gain was substantially higher when space-making barrier materials such as titanium meshes were used; however this was also associated with strong increase in complication rate. Block grafts achieved higher horizontal gain by approximately 1 mm. The use of block grafts achieved significantly increased vertical gain compared to particulate material only when autogenous block grafts from extraoral donor sites were used. CONCLUSION: Horizontal and vertical gain by 3.7 mm on average can be achieved using particulate materials. This can be increased by using titanium meshes. Substantial vertical gains beyond this dimension require the use of extraoral bone block grafts.

Are There Clinical or Pathological Parameters of Maxillary Oral Squamous Cell Carcinoma With an Influence on the Occurrence of Neck Node Metastasis? An Appraisal of 92 Patients.

PURPOSE: To determine the proportion of patients with cervical metastases caused by maxillary oral squamous cell carcinoma (OSCC) and to identify any clinical or pathologic parameters that might be associated with the occurrence of metastatic neck disease. MATERIALS AND METHODS: A retrospective cohort study of all patients managed with primary surgical resection of maxillary OSCC at the authors' institution from 2006 through 2013 was performed. Cervical lymph node dissection and adjuvant therapy were performed as warranted by preoperative staging examinations or histopathologic evaluation or as recommended after multidisciplinary consultation, and regular follow-up protocols were followed. In this analysis, each maxillary OSCC was assigned to an anterior or a posterior anatomic group based on the location of the primary lesion, with the anatomic tumor location serving as the predictor variable and the occurrence of cervical lymph node metastases as the outcome variable. Descriptive and inferential statistics were calculated with a significance level set at a P value less than .05 and post hoc power analyses were performed. RESULTS: The study sample was composed of 92 patients (38 women, 54 men; average age, 60.9 yr). Overall, 27 patients developed cervical metastases (29.3%). Neck disease was present in 15 patients (16.3%) at initial presentation. Delayed cervical metastases were diagnosed in 12 patients (13%) and manifested after an average period of 11.17 months. The anatomic location of the OSCC within the maxillary structures (anterior vs posterior) and the histologic grade greatly influenced the occurrence of metastatic neck disease. No associations were found for the variables tumor size and resection status. CONCLUSION: In this series, cervical lymph node metastases were frequent and to some degree predictable based on anatomic location and tumor grade.

Etiology and clinical characteristics of symptomatic unilateral maxillary sinusitis: A review of 174 cases.

The purpose of the study was to analyze the causative pathology associated with symptomatic unilateral maxillary sinusitis requiring surgical treatment. A retrospective review of all patients that have been treated surgically for unilateral symptomatic maxillary sinusitis between 2006 and 2013 at a single institution was performed. Demographic, anamnesis, clinical, radiological, microbiological and histological data were gathered and analyzed. The patients were allocated into groups depending on the underlying cause of the disease. Descriptive and inferential statistics were computed (level of significance: p ≤ 0.05). The study sample was composed of 174 patients (72 female; 102 male) with a mean age of 52.7 years (SD 16.9). Most cases (130; 75%) were triggered by odontogenic pathology following dentoalveolar surgical interventions (83/130 patients; 64%). Other etiological factors for odontogenic unilateral sinusitis were periapical (23/130 cases; 18%) and periodontal pathology (13/130 cases; 10%). Rhinogenic factors for sinusitis were detected in 13 patients (7.5%) and dental implant-associated unilateral maxillary sinusitis was diagnosed in nine patients (5.2%). Four patients (2.3%) had undergone previous sinus augmentation surgery. A leading cause for the sinus infection could not be identified in 18 patients (10%) who all had a history of midfacial surgery. Medication-related osteonecrosis of the jaw (8) and squamous cell carcinoma (2) were incidental findings. There were no differences in the clinical appearance of the disease with respect to its etiology. Odontogenic causes for maxillary sinusitis must be considered especially in unilateral cases. Maxillary dental implants may induce symptomatic unilateral maxillary sinusitis.

Vascular endothelial growth factor receptor isoforms: are they present in oral squamous cell carcinoma?

PURPOSE: Although the clinical importance of vascular endothelial growth factor (VEGF) overexpression in oral squamous cell carcinoma (OSCC) has been investigated, there are limited data about the overexpression of VEGF receptors (VEGF-Rs) and their clinical importance. VEGF-R isoforms have proven influence on proliferation rates, metastasis, and survival in different neoplasms. This study was conducted to investigate VEGF-R expression levels in OSCC samples and to identify any clinical relevance. MATERIALS AND METHODS: A retrospective cohort study design (n = 50) was used. Clinical data were gathered from patient charts. Validated immunohistochemical methods were applied to determine VEGF-R isoform expression by tumor cells. Descriptive and inferential statistics with respect to the variable scale were computed. The significance level was set at a P value less than or equal to .05. RESULTS: This study found overexpression of different VEGF-R isoforms in 88% of examined specimens. Statistically important associations were detected between overexpression of specific VEGF-Rs and tumor size, neck node metastasis, and tumor-associated death. Furthermore, a history of common OSCC risk factors (smoking and alcohol consumption) were found considerably more often in patients whose OSCC specimens displayed VEGF-R overexpression. CONCLUSION: These findings show that VEGF-R overexpression occurs frequently in OSCC and could have clinical implications.

A review of pathogenesis, diagnosis, treatment options, and differential diagnosis of odontogenic infections: a rather mundane pathology?

Odontogenic infections are common in the dental practice and their treatment should be a standard procedure for every dentist. For optimal management of septic intraoral problems, the practitioner must understand the underlying causes and etiologies of odontogenic infections. Therefore, the purpose of this article is to outline basic inflammatory processes involved in the development of odontogenic and intraoral infections including relevant pathogens, biochemical processes mediated by pro-inflammatory molecules, the basics of abscess formation, the host response, and the clinical appearance of intraoral septic processes. Furthermore, treatment modalities of odontogenic infections and associated lesions are discussed and a brief explanation of possible complications and their management is provided.

Conservative management of medication-related osteonecrosis of the maxilla with an obturator prosthesis.

Advanced maxillary medication-related osteonecrosis of the jaw can cause extensive hard and soft tissue destruction that results in long-term oroantral fistulae. The surgical treatment of medication-related osteonecrosis of the jaw may relieve acute symptoms and eliminate the signs of inflammation, but the primary and sustained plastic closure of these defects can challenge both the clinician and the patients. Although the use of obturator prostheses for maxillary defects after ablative oncologic surgery is well documented, studies about this treatment for similar medication-related osteonecrosis of the jaw-related defects are missing. This presentation of clinical situations describes the use of obturators as a conservative alternative to repetitive surgery for the rehabilitation of selected maxillary defects with oroantral communications.

A comparison of conservative and invasive dental approaches in the treatment of tension-type headache.

OBJECTIVE: To investigate the efficacy of conservative dental treatment (occlusal splint and pharmacologic therapy) and invasive therapy (prosthetic restorations) in the treatment of tension-type headache (TTH). METHOD AND MATERIALS: The study sample was composed of 70 patients who presented with symptomatic TTH and were assigned to three treatment groups according to their treatment needs. Group A (30 patients): a conservative treatment protocol with a combination of an occlusal splint and analgesic and muscle relaxant medication. Group B (10 patients): invasive prosthodontic procedures. Group C (30 patients): patients who refused any type of treatment but consented to the study served as a control group. Pain quality was measured with the Headache Impact Test (HIT-6). The statistical analysis was performed with the Wilcoxon rank test (P≤.05). RESULTS: Conservative treatment with splints and analgesic medication and invasive treatment by prosthetic rehabilitation relieved the TTH symptoms. The patients who received treatment experienced a significant reduction in their discomfort after 6 months (P≤.01), whereas the patients who refused therapy remained, on average, at the same pain level (P≤.117). In group A, the HIT-6 score was reduced for 26 patients, and in group B for 8 patients. In group C a reduction of HIT-6 scores was observed in 10 patients. CONCLUSION: Conservative or invasive occlusal adjustments may serve as a useful tool in the treatment of TTH.

Clinicopathologic features of oral squamous cell carcinoma: do they vary in different age groups?

PURPOSE: To analyze clinicopathologic parameters of oral squamous cell carcinoma (OSCC) in different age groups. We hypothesized that clinical and pathologic parameters of OSCCs will vary in different age groups. MATERIALS AND METHODS: A retrospective cohort study was performed. All patients who were treated for a primary manifestation of OSCC at a single institution from 2001 to 2012 were reviewed and allocated to predefined age groups (predictor variable) as follows: young (≤40 years), middle-aged (40-80 years), and very elderly (≥80 years). The following outcome variables were recorded: demographic parameters, classic risk factors, tumor location and size, neck node involvement, histopathologic and therapeutic details, and association with human papillomavirus (HPV). The descriptive statistics were computed. Parametric and nonparametric tests were used for additional analysis. The significance level was set at P < .05. RESULTS: We reviewed 739 patients and identified 11 (1.4%) young (mean age 34.2 ± 2.8 years) and 17 (2.3%) very elderly patients (mean age 83.1 ± 1.2 years). The predilection site for OSCC was the oral tongue (63%) in young patients, the floor of the mouth (52%) in middle-aged patients, and the alveolar process (60%) in very elderly patients. One patient in the young group (9%) and 8 patients in the very elderly group (47%) had been exposed to risk factors; however, all of the examined middle-aged patients had had such exposure. The association of OSCC with HPV was distributed equally among the age groups. No age-related differences in the histopathologic parameters of OSCC were found. CONCLUSIONS: The features of OSCC that vary at different ages are the anatomic predilection site and the association with classic risk factors. HPV was not an age-related independent risk factor for OSCC development in the present study.

Antibiotic concentrations in saliva: a systematic review of the literature, with clinical implications for the treatment of sialadenitis.

PURPOSE: The current recommendations for the treatment of bacterial salivary gland infections are mainly empirical. Therefore, an evidence-based literature review was conducted to identify antibiotics with favorable pharmacokinetics in saliva and to establish recommendations for the antibiotic treatment of sialadenitis. MATERIALS AND METHODS: The authors performed a systematic review of the pertinent literature published from 1985 to 2013. If the predefined inclusion criteria were met, the articles were screened for various variables: antibiotic type, mode of administration, type of examined saliva, peak salivary antibiotic concentrations, biochemical methodology, and minimal inhibitory concentrations of bacteria implicated in sialadenitis (Staphylococcus aureus, Viridans streptococci, various gram-negative strains, and anaerobes). RESULTS: The review included 18 studies. The systematic analysis of the reported results concurred that intravenously administered cephalosporins achieve the highest concentrations in saliva, followed by orally administered cephalosporins and fluoroquinolones. These concentrations exceed the minimal inhibitory concentrations of the bacteria of interest. Phenoxymethylpenicillin and tetracyclines are not secreted in the saliva at bactericidal levels. The antibiotic peak salivary levels depended on the type of saliva examined (parotid vs submandibular vs minor salivary gland) and the biochemical method of measurement (high-performance liquid chromatography vs bioassay). CONCLUSION: Cephalosporins and fluoroquinolones display superior pharmacokinetics in saliva and cover the spectrum of all bacteria implicated in sialadenitis. Within the limitations of this review, they can be recommended for the treatment of bacterial salivary gland infections.

Cutaneous mastocytosis as a rare differential diagnosis for unilateral chronic facial pain and erythema: a case report.

Cutaneous mastocytosis (CM) has been associated with urticaria, itching, and pain of the affected regions. Although the occurrence of CM in the facial skin is rare, it may be a cause of chronic facial pain, and pain characteristics may mistakenly be interpreted as trigeminal nerve pathology. However, the dermatological appearance of the different variants of cutaneous mastocytosis is distinct and should be considered as an uncommon differential diagnosis in an orofacial pain diagnostic algorithm. This article presents a case of telangiectasia macularis eruptiva perstans, a rare type of cutaneous mastocytosis, as the underlying cause of chronic facial pain, erythema, and swelling.