Accuracy of leukoplakia diagnoses: a retrospective study.

The objective of this study was to review the diagnostic accuracy of clinicians identifying leukoplakia and the diagnostic terminology used to indicate leukoplakic lesions at the University of Nebraska Medical Center (UNMC) oral biopsy service. Biopsy archives from the years 1983, 1995, 2005, and 2015 in the UNMC College of Dentistry were reviewed. Cases with a clinical diagnosis of leukoplakia (or white plaque), hyperkeratosis, dysplasia, and/or carcinoma were included in the study. Demographic and clinical information was recorded and descriptive statistics were utilized. Of 6113 cases, 517 lesions (8.46%) from 508 patients met the inclusion criteria. The mean age of the patients was 56.87 years, and the sample included 286 men and 222 women. Of these 517 lesions, 195 (37.72%) were clinically diagnosed as leukoplakia or white plaque. The records revealed that 133 (68.21%) of 195 clinical diagnoses were correct, with lesions histologically exhibiting hyperkeratosis (75 cases), dysplasia (52 cases), or carcinoma (6 cases). The remaining 62 lesions (31.79%) were found to have other histologic diagnoses. Hyperkeratosis made up the largest portion of the correct diagnoses. In general, the ability of clinicians to successfully identify leukoplakia improved over the years (46.15%, 73.68%, 64.29%, and 76.00% in 1983, 1995, 2005, and 2015, respectively). However, clinicians continue to misclassify identifiable pathoses such as lichen planus, lichenoid mucositis, and fibroma as leukoplakia. Hyperkeratosis and dysplasia, both of which represent histologic diagnoses, appear to be popularly misused clinical terms.

Marginal linear gingival leukoplakia progressing to "ring around the collar"-An ominous sign of proliferative verrucous leukoplakia.

BACKGROUND: Potentially malignant lesions of the gingiva may frequently present as well-demarcated white lesions confined to the marginal gingiva. These lesions often become thick and verrucoid and spread along the marginal gingiva to encircle the tooth. Some cases of marginal gingival leukoplakia, over time, progress to extensively involve the gingiva fulfilling the criteria for proliferative verrucous leukoplakia (PVL). The objective of this study is to raise awareness of this pattern of leukoplakia by reporting a series of cases of marginal gingival leukoplakia. METHODS: An Institutional Review Board approved retrospective search of University of Florida and University of Nebraska Medical Center oral biopsy services was performed for all gingival biopsies. Inclusion criteria included cases exhibiting marginal gingival leukoplakia, and with accompanying clinical images. RESULTS: A total of 30 cases of marginal gingival leukoplakia were included. All cases presented as well-demarcated leukoplakias, either on the buccal or lingual gingival margin, or circumferentially forming a "ring around the collar" of single or multiple teeth. Eight patients had recurrent lesions and 12 had multifocal involvement. Six of the 12 patients with multifocal involvement presented with a "ring around the collar." The histopathologic diagnoses were representative of benign lesions in seven cases, premalignant in 13, and malignant or suggestive of malignancy in 10 cases. Seven patients had carcinoma at the time of first biopsy, whereas 6 cases showed progression at time of follow-up. CONCLUSION: This study aims to raise awareness that marginal gingival leukoplakia may represent potentially malignant lesions, and if circumferential and/or thick, may be the first manifestation of PVL.

Early detection of cherubism with eventual bilateral progression: a literature review and case report.

Cherubism is a rare familial disease of childhood that commonly affects the bilateral mandible and maxilla and typically resolves in adulthood. It has been shown to have a male predilection and has been mapped to the SH3 BP2 gene. Only 2 cases of unilateral cherubism have been documented in the literature; in the first case, the contralateral side was eventually affected. Although rare, unilateral cherubism presents a diagnostic dilemma. This case report describes a unique presentation of unilateral cherubism that progressed to affect the contralateral side and describes some of the considerations in the diagnosis and treatment of unilateral benign giant cell lesions of the jaws.

Symmetric multiquadrant isolated dentin dysplasia (SMIDD), a unique presentation mimicking dentin dysplasia type 1b.

Dentin dysplasia (DD) is a rare developmental dentin disorder that causes root malformation. It is divided into radicular DD type 1 (DD-1) and coronal DD type 2 (DD-2). Recently, a new entity causing localized root malformation of permanent first molars that resembles DD-1b has been described as molar-incisor malformation (MIM). We report and compare 4 new cases that exhibit similar clinical, histologic, and radiographic features to the new entity, MIM. We believe MIM and our 4 cases to be the same entity, which is nonhereditary and, because of the isolated but bilaterally symmetric pattern of involvement, may be caused by a short-duration environmental insult that disrupts normal development/function of Hertwig's epithelial root sheath. We propose the name symmetrical multiquadrant isolated dentin dysplasia as the most appropriate descriptive designation for this unusual but highly distinctive anomaly.

A Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia, and Subjective Sialorrhea: A Systematic Review Sponsored by the World Workshop on Oral Medicine VI.

BACKGROUND: Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality of life. However, no evidence-based lists of the medications that cause these disorders exist. OBJECTIVE: Our objective was to compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea. DATA SOURCES: Electronic databases were searched for relevant articles published until June 2013. Of 3867 screened records, 269 had an acceptable degree of relevance, quality of methodology, and strength of evidence. We found 56 chemical substances with a higher level of evidence and 50 with a moderate level of evidence of causing the above-mentioned disorders. At the first level of the Anatomical Therapeutic Chemical (ATC) classification system, 9 of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous, and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices. LIMITATIONS: While xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when administered in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or was not detected in our search. CONCLUSIONS: We compiled a comprehensive list of medications with documented effects on salivary gland function or symptoms that may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful in helping practitioners anticipate adverse effects and consider alternative medications.

World Workshop on Oral Medicine VI: a systematic review of medication-induced salivary gland dysfunction: prevalence, diagnosis, and treatment.

OBJECTIVES: Medication-induced salivary gland dysfunction (MISGD) causes significant morbidity resulting in decreased quality of life. This systematic review assessed the literature on the prevalence, diagnosis, treatment, and prevention of MISGD. MATERIALS AND METHODS: Electronic databases were searched for articles related to MISGD through June 2013. Four independent reviewers extracted information regarding study design, study population, interventions, outcomes, and conclusions for each article. Only papers with acceptable degree of relevance, quality of methodology, and strength of evidence were retained for further analysis. RESULTS: There were limited data on the epidemiology of MISGD. Furthermore, various methods were used to assess salivary flow rate or xerostomia. Preventive and therapeutic strategies included substitution of medications, oral, or systemic therapy with sialogogues, use of saliva substitutes or of electro-stimulating devices. Although there are promising approaches to improve salivary gland function, most studies are characterized by small numbers and heterogeneous methods. CONCLUSIONS: Physicians and dentists should identify the medications associated with xerostomia and salivary gland dysfunction through a thorough medical history. Preferably, health care providers should measure the unstimulated and stimulated whole salivary flow rates of all their patients so that these values can be used as a baseline to rate the complaints of patients who subsequently claim to experience xerostomia or salivary gland dysfunction as well as the possibilities of effectively treating this condition. CLINICAL RELEVANCE: MISGD remains a major burden for the population. This systematic review provides a contemporary in-depth description of the diagnosis and treatment of MISGD.

World Workshop on Oral Medicine VI: clinical implications of medication-induced salivary gland dysfunction.

OBJECTIVE: This study aimed to systematically review the available literature on the clinical implications of medication-induced salivary gland dysfunction (MISGD). STUDY DESIGN: The systematic review was performed using PubMed, Embase, and Web of Science (through June 2013). Studies were assessed for degree of relevance and strength of evidence, based on whether clinical implications of MISGD were the primary study outcomes, as well as on the appropriateness of study design and sample size. RESULTS: For most purported xerogenic medications, xerostomia was the most frequent adverse effect. In the majority of the 129 reviewed papers, it was not documented whether xerostomia was accompanied by decreased salivary flow. Incidence and prevalence of medication-induced xerostomia varied widely and was often associated with number and dose of medications. Xerostomia was most frequently reported to be mild-to-moderate in severity. Its onset occurred usually in the first weeks of treatment. There was selected evidence that medication-induced xerostomia occurs more frequently in women and older adults and that MISGD may be associated with other clinical implications, such as caries or oral mucosal alterations. CONCLUSIONS: The systematic review showed that MISGD constitutes a significant burden in many patients and may be associated with important negative implications for oral health.

Gingival foreign body granuloma in conjunction with the use of a dental water jet: a case report.

Foreign body gingivitis has been described as an inflammatory reaction of marginal or attached gingival tissues due to foreign material in the connective tissue. This article presents the case of a 58-year-old woman with the chief complaint of periodic discomfort in her maxillary "gums" and redness in the facial gingival tissues of the maxillary anterior segment. A biopsy showed a granulomatous reaction in both the red and neutral areas. The patient revealed that she had been using a water jet device on a high pressure setting. She was advised to discontinue the water jet use, after which the gingival redness and inflammation began to subside, and appeared normal at 3- and 6-month follow-up visits.

Impact of local and systemic alendronate on simvastatin-induced new bone around periodontal defects.

BACKGROUND: Simvastatin has been shown to stimulate new bone growth on rat mandibles, but much of the bone is lost over time. The purpose of this study is to evaluate the impact of a locally or systemically applied antiresorptive agent (alendronate) on simvastatin-induced bone formation in and adjacent to a rat periodontal defect. METHODS: Fenestration defects were created over mandibular molar roots in 65 mature female Sprague-Dawley rats. Two weeks later, animals were divided into eight groups of eight to nine rats, and three weekly injections around the defect were applied: 1) 0.5 mg simvastatin in ethanol (SIM-EtOH); 2) 0.5 mg simvastatin in alendronate-cyclodextrin conjugate (SIM-ALN-CD); 3) EtOH alone; 4) ALN-CD alone; or 5) no injections. Twenty-four animals were evaluated for new bone width around the defect 21 days after the last injections (short-term) and 41 rats were followed for 48 days (long-term). Three SIM-EtOH groups of long-term rats also were subjected to 2 weeks of daily systemic ALN or saline either during or 3 to 4 weeks after SIM-EtOH injections. Decalcified, hematoxylin-and-eosin-stained cross-sections of the defect area were analyzed for new bone width and groups were compared using mixed-model analyses of variance. RESULTS: All groups showed nearly 100% bone fill, with no differences among the short-term groups. However, in the long-term animals, two-fold to three-fold more new bone width (≤ 0.004) was seen around the periphery of the defect with the use of systemic ALN after SIM-EtOH injections (0.93 ± 0.12 and 0.78 ± 0.11 mm with early and late systemic ALN, respectively) compared to local SIM/ALN-CD preparations (0.32 ± 0.10 mm) or short-term SIM-EtOH injections (0.35 ± 0.10 mm). No significant new cementum formation or ankylosis was noted. CONCLUSION: The use of a short course of systemic ALN during the healing period after bone anabolic SIM injections has the potential to enhance local bone augmentation.

Ameloblastic fibro-odontoma of the anterior mandible in a 22-month-old boy.

We report an ameloblastic fibro-odontoma (AFO) presenting in the anterior mandible as a "bump on his gums" in a 22-month-old boy. An occlusal radiograph revealed a well-circumscribed radiolucency with scattered radiopaque foci. The tumor was enucleated under general anesthesia. The histologic findings were characteristic of an AFO, a mixed odontogenic tumor most common in the posterior jaws, primarily affecting individuals with an average age of 10 years. The clinical presentation, microscopic findings, differential diagnoses, and treatment are discussed.

Oral ulceration due to chronic use of Nicorette gum: case report.

Oral ulceration is a common presentation in a dental clinic. These ulcers may be acute or chronic, based on the duration of symptoms. The etiology of oral ulceration can range from trauma to squamous cell carcinoma. It is the responsibility of the dentist to differentiate the various etiologies of oral ulceration for proper management. This case report is presented to remind dentists that the long-term use of Nicorette gum should be considered in the differential diagnosis of chronic oral ulcers.

Desmosomal component expression in normal, dysplastic, and oral squamous cell carcinoma.

Squamous cell carcinoma (oral SCC) is the most common oral cancer in the U.S., affecting nearly 30,000 Americans each year. Despite recent advances in detection and treatment, there has been little improvement in the five-year survival rate for this devastating disease. Oral cancer may be preceded by premalignant disease that appears histologically as dysplasia. Identification of molecular markers for cellular change would assist in determining the risk of dysplasia progressing to oral squamous cell carcinoma. The goal of this study was to determine if any correlation exists between histological diagnosed dysplasia and OSCC lesions and altered expression of desmosomal cell-cell adhesion molecules in the oral epithelium. Our data showed that oral SCC tissue samples showed decreased immunoreactivity of both desmoplakin and plakophilin-1 proteins compared to normal oral epithelium. Furthermore, significant decrease in desmoplakin immunoreactivity was observed in dysplastic tissue compared to normal oral epithelium. In contrast, the level of desmoglein-1 staining was unchanged between samples however desmoglein-1 was found localized to cell borders in oral SCC samples. These data suggest that changes in expression of desmoplakin and plakophilin-1 may prove to be a useful marker for changes in tissue morphology and provide a tool for identifying pre-neoplastic lesions of the oral cavity.

Oral histoplasmosis: an unusual presentation.

BACKGROUND: Histoplasmosis is a localized or systemic fungal infection which may present as an acute primary or "reactivation" infection in the setting of immunosuppression. Tumor necrosis factor alpha (TNF-alpha) antagonists, used in the management of rheumatoid arthritis and Crohn disease, have been linked to reactivation of quiescent histoplasmosis. Microscopically, granulomas are either not evident or are infrequent in histoplasmosis when associated with TNF antagonist therapy presumably due to the suppression of macrophage activity. METHODS AND RESULTS: This article describes an unusual presentation of oral histoplasmosis in a 75-year-old-woman patient on TNF-alpha antagonist, namely infliximab. Microscopically, cellular atypia resulted in a work-up to rule out lymphoma. Gomori's methenamine silver stain demonstrated Histoplasma capsulatum leading to a diagnosis of histoplasmosis. She was treated successfully with itraconozole. CONCLUSION: This is the first reported case, insofar as the authors are able to determine, of oral histoplasmosis, in a patient undergoing treatment with infliximab.

Oral focal mucinosis: review of the literature and seven additional cases.

Oral focal mucinosis (OFM) is a rare, asymptomatic, benign lesion of unknown etiology that usually involves the mandibular gingiva. This article reports on seven patients, six of whom had lesions that involved the gingiva and one that involved the palate. All cases demonstrated the classic lobular, myxomatous mesenchymal tissue with stellate cells. In all cases, immunohistochemical staining for S-100-protein expression was negative, thus excluding the principal differential diagnoses of myxoid neurofibroma and neurothekeoma (nerve sheath myxoma). This article seeks to bring OFM to the attention of clinicians and pathologists who must consider the differential diagnosis of gingival and palatal nodules.

Peripheral odontogenic keratocyst.

BACKGROUND: An odontogenic keratocyst can develop at virtually any site in the jaws and is of concern because of its aggressive clinical behavior. It represents 3% to 12% of all odontogenic cysts. This paper describes the rare peripheral presentation of an odontogenic keratocyst localized to the maxillary anterior gingiva and its differential diagnosis. METHODS: A patient presented with a round yellow nodule on the maxillary gingiva between the left canine and first premolar. Clinical examination ruled out periapical abscess, periodontal abscess, and lateral periodontal cyst. A differential diagnosis included a gingival cyst, neuroma, neurilemoma, and mesenchymoma. The cyst ruptured during excisional biopsy revealing contents typical of an odontogenic keratocyst (OKC). Histology confirmed the peripheral OKC diagnosis. A conservative surgical treatment was performed assuming a less aggressive clinical course for the peripheral odontogenic keratocyst. Close follow-up was planned. RESULTS: To our knowledge, only 13 cases of peripheral OKC have been reported in the literature. Presently it is unknown if the peripheral variant shares the aggressive clinical behavior and recurrence rate of intraosseous OKC. CONCLUSION: This paper may contribute to the limited clinical knowledge base for the peripheral odontogenic keratocyst and assist clinicians in the identification and management of such lesions.

Local simvastatin effects on mandibular bone growth and inflammation.

BACKGROUND: Simvastatin has been shown to increase bone growth when applied topically to murine bone; however, it causes considerable soft tissue inflammation at high doses (2.2 mg), making future clinical use problematic. This study evaluated the effect of lower simvastatin doses and cyclooxygenase (COX) synthase inhibitors on tissue inflammation and bone growth in rats and gene expression in mice. METHODS: Adult female rats were untreated or treated with a single dose of 0.1, 0.5, 1.0, 1.5, or 2.2 mg simvastatin in methylcellulose gel in a polylactic acid membrane (SIM) on the lateral aspect of the mandible. The contralateral mandible side was implanted with methylcellulose gel/polylactic acid membrane alone (GEL), and five rats in each dose pairing were evaluated histomorphometrically after 3, 7, and 24 days. Subsequent rats were similarly treated with 0.5 mg simvastatin (optimal dose) and daily intraperitoneal injections of COX-2 inhibitor (NS-398; 1 mg/kg x 7 days; N = 16), general COX inhibitor (indomethacin; 1 mg/kg x 7 days; N = 16), or no inhibitor (N = 10) and evaluated histomorphometrically after 7 or 24 days by analysis of variance (ANOVA). Gene arrays were also used to evaluate osteogenic gene expression from 0.5 mg simvastatin in murine calvaria (N = 12). RESULTS: There was a 45% increase in bone area with 0.5 mg simvastatin versus gel control (P <0.001; similar to the 2.2-mg dose), and clinical swelling was reduced compared to the high simvastatin dose (P <0.05). The 0.1-mg simvastatin dose failed to stimulate significant bone growth. NS-398 and indomethacin reduced inflammation and bone growth. Simvastatin significantly upregulated procollagen, fibronectin, and matrix metalloproteinase-13 genes. CONCLUSION: Reducing the simvastatin dose from 2.2 to 0.5 mg reduced inflammation to a more clinically acceptable level without sacrificing bone-growth potential, but COX-associated inflammation appears to be necessary for in vivo bone growth.