Immunoprofile of the adenomatoid odontogenic tumor.

This study was focused on the immunohistochemical profile of the adenomatoid odontogenic tumor. A Pub/Medline search revealed a number of immunohistochemical studies including cytokeratin profiles, extracellular matrix proteins, Integrins, ameloblast-associated proteins resorption regulators (RANK, RANKL), p53, PCNA, MDM2 protein, cyclin D1, Ki-67, Bcl-2 metallothionein, metalloproteinases, D56 hepatocyte growth factor, c-met, DNA methyltransferase, podoplanin, TGF-ßI, Smad-2/3, Smad-I-5/-8, Smad 4, beta- catenin, calretinin, and clonality. Careful interpretation of the findings indicates that the adenomatoid odontogenic tumor may be more of a hamartomatous than neoplastic nature.

End-of-life care in the head and neck cancer patient.

Past the point of no longer being able to control malignancies of the oral cavity and head and neck, the decision-making process must shift to one that essentially concerns itself with creating comfort for the patient. The role of family, physicians, and other caregivers becomes, in many ways, more directed as active neoplasia-related concerns become less relevant. Challenges remain significant in terms of continuing management of prior treatment-related side effects and functional impairments to providers concerning themselves with maintenance of dignity, honoring the wishes of the family, and creating full understanding of on the part of all parties concerned what the goals of treatment cessation and palliation are key as death approaches.

Neuralgia-inducing cavitational osteonecrosis: a status report.

Neuralgia-inducing cavitational osteonecrosis remains controversial several years following the initial description. Changing etiologic concepts have led to confusion as well as the significant departures from the concept first defined by Ratner which served as the basis for the explaining the pain syndrome with features of trigeminal neuralgia. Since the earliest publications on the subject by Bouquot and colleagues there have been many challenges and counterclaims to the concept introduced, with a discussion of these included. Finally, absence of any form of research design and approval by institutional review panels remains a weakness in terms of acceptance of the information provided in the literature said to support the stated etiology of this entity.

Oral cancer. The importance of early diagnosis and treatment.

Oral cancer is an important health issue. The WHO predicts a continuing worldwide increase in the number of patients with oral cancer, extending this trend well into the next several decades. In the US the projected number of new cases of oral and oropharyngeal cancer will exceed 31,000 per year. Mortality due to cancers in this region exceeds the annual death rate is the US caused by either cutaneous melanoma or cervical cancer. Significant agents involved in the etiology of oral cancer in Western countries include sunlight exposure, smoking and alcohol consumption. Use of the areca or betel nut in many cultures is a major etiological factor outside of the USA. Other etiologic factors associated with oral squamous cell carcinoma, but far less significant statistically, include syphilis and sideropenic dysphagia. Recently, strong evidence for an etiological relationship between human papilloma virus and a subset of head and neck cancers has been noted. It is generally accepted that most sporadic tumors are the result of a multi-step process of accumulated genetic alterations. These alterations affect epithelial cell behavior by way of loss of chromosomal heterozygosity which in turn leads to a series of events progressing to the ultimate stage of invasive squamous cell carcinoma. The corresponding genetic alterations are reflected in clinical and microscopic pathology from hyperplasia through invasiveness. A wide range of mucosal alternations fall within the rubric of leukoplakia. Proliferative verrucous leukoplakia represents a relatively new type of leukoplakia that is separate from the more common or less innocuous form of this condition. Erythroplakia is particularly relevant considering its almost certain relationship with dysplasia or invasive carcinoma. Squamous cell carcinoma will develop from antecedent dysplastic oral mucosal lesions if an early diagnosis has not been made and treatment given. Early diagnosis within stages I and II correspond to a vastly improved 5-year survival rate when compared with more advanced stage III and IV lesions. Surgical management of this disease remains the mainstay of treatment. Other therapies include radiation and chemotherapy options that may be used adjunctively and palliatively. Following treatment, it is important to understand the significant risks of second primary cancers developing within the upper aerodigestive tract as a result of field cancerization. The most important message is that early detection of the asymptomatic early stage oral cancer translates in general terms to satisfactory clinical outcome and cure in most patients.

A possible role of catenin dyslocalization in pemphigus vulgaris pathogenesis.

BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucosa due to the presence of autoantibodies against the components of desmosomes. To date, less is known about the expression levels of beta- and gamma-catenins in blistering diseases. The objective of this study was to evaluate the role of beta- and gamma-catenins in the pathogenesis of acantholysis in pemphigus vulgaris. METHODS: beta- and gamma-catenin expression was evaluated by immunohistochemistry in 30 cases of PV at various stages of the disease and, as controls, in 18 specimens of the skin/oral mucosa of healthy patients. RESULTS: Healthy skin and normal oral mucosa showed a strong beta- and gamma-catenin expression in basal and spinous layers with a prevalent cellular membrane distribution; the intensity of staining progressively decreased toward the superficial layers of epithelium. In PV patients, cytoplasmic expression of gamma-catenin was detected in 28/30 cases, and in 19/30 cases of PV for beta-catenin. Moreover, a progressive displacement of the signal toward the nucleus was found in 14/30 cases for beta-catenin, with dyslocalization toward the nucleus, particularly in areas with intense acantholysis, and in 22/30 cases of PV for gamma-catenin. CONCLUSIONS: Abnormal distribution of gamma-catenin, consequent to PV IgG, may be considered a direct consequence of Dg3 dissociation from catenin. gamma-catenin likely plays a direct role in PV pathogenesis through its dyslocalization toward the nucleus or indirectly through the beta-catenin dyslocalization toward the nucleus, which is thought to induce transcription of selected target genes, such as uPAR.

Oral spindle cell lipoma.

Lipoma is an uncommon benign, oral, soft-tissue neoplasm commonly found on the buccal mucosa. It is predominantly composed of mature fat with or without other mesenchymal tissue elements, showing a variety of histologic subtypes, one of which is the rare "spindle cell variant" with only nine previously reported cases in the English literature. In this report, we review clinical and histomorphologic data of 164 cases of oral lipomas retrieved from the files of Long Island Jewish Medical Center, Department of Dental Medicine (New Hyde Park, NY). Of these, only two cases were diagnosed as the spindle cell variant, further confirming the rarity of this histologic subtype. A review of oral lipoma with particular reference to the spindle cell variant is also presented.

Ductal papillomas of salivary gland origin: A report of 19 cases and a review of the literature.

The term ductal papilloma is used to identify a group of 3 rare benign papillary salivary gland tumors known as inverted ductal papilloma, sialadenoma papilliferum, and intraductal papilloma. They represent adenomas with unique papillary features and arise from the salivary gland duct system. We describe the clinical and microscopic features of 19 new cases of ductal papillomas and combine them with 116 cases previously published in the English-language medical literature. These 19 cases were composed of 13 inverted ductal papillomas, 3 sialadenoma papilliferums, and 3 intraductal papillomas. Collectively, these 19 ductal papillomas occurred most commonly in the sixth to eighth decade of life, with an average patient age of 54 years. Men predominated 1.37:1. The sialadenoma papilliferums presented as papillary lesions clinically with all 3 misinterpreted as squamous papillomas by the surgeons. The inverted ductal papillomas and intraductal papillomas appeared as submucosal nodules. The lip and the palate were the most common locations for inverted ductal papilloma and sialadenoma papilliferum, respectively. The sites for the 3 intraductal papillomas were the parotid papilla of the Stensen's duct, the upper lip, and the buccal mucosa. With light microscopy, inverted ductal papillomas appeared to arise from the excretory ducts near the mucosal surface, whereas intraductal papillomas appeared to arise from the excretory ducts at a deeper level. Sialadenoma papilliferum had a more complex histology, with a biphasic growth pattern of exophytic papillary and endophytic components. All 19 cases were treated by surgical excision. Follow-up information was available in only 2 cases, both inverted ductal papillomas. Neither case recurred during a 20-year period. Sialadenoma papilliferum, with a literature-derived recurrence rate of 10% to 15%, seems to assert a more significant biological behavior than inverted ductal papilloma and intraductal papilloma. Our findings justify the separation of these 3 entities based on clinical and histologic parameters. They are tumors of adulthood and, in addition, have in common their relationship to the excretory duct system, their anatomical distribution, and their general behavior.

Oral cancer and its detection. History-taking and the diagnostic phase of management.

BACKGROUND: Comprehensive patient evaluation begins with an accurate analysis of all factors of the patient's history before the physical examination is performed. Risk factor identification is particularly important in most cases of oral mucosal dysplasia and carcinoma, as it alerts the clinician to an increased susceptibility for such alterations. The armamentarium of the dentist, which ranges from noninvasive indicators to a scalpel biopsy, permits a thorough evaluation of any observed mucosal changes. Newer additions to this armamentarium have been developed and are emerging that aid in the process of characterizing lesions, thereby facilitating appropriate management. METHODS: The author presents methods of assessing and analyzing a patient's oral health status. He discusses carcinogens and cofactors, as well as dietary considerations, in the development of oral mucosal precancer and cancer. He also presents details of the clinical evaluation, which can lead the clinician to possible further evaluation and analysis by an expanding array of diagnostic tools. RESULTS: The article identifies the factors a clinician should consider when evaluating the dental patient, from initial presentation and risk factor identification to the use of traditional assessment parameters. New and evolving diagnostic tools, coupled with cell and tissue characterization by an oral and maxillofacial pathologist, remain critical in terms of patient management and in maintaining optimum standards of care. CONCLUSIONS AND CLINICAL IMPLICATIONS: A comprehensive oral examination must include integration of each patient's in-depth health history and the physical findings. Appreciation of subtle surface changes as a possible harbinger of pathology and the traditional process of observation combined with new and emerging tools now allow for earlier diagnosis that will translate into improved outcomes.

Oral precancer and cancer: etiology, clinical presentation, diagnosis, and management.

Oral and oropharyngeal cancers represent 3% of all cancers in the United States annually, with nearly 50% of people diagnosed with oral and oropharyngeal cancers dying as a result of the disease. Because the dental practitioner is in an ideal position for recognizing any abnormality of the oral mucosa, he or she is involved in the battle against oral cancer by helping establish the diagnosis at an early stage. This article presents the clinical appearance, explains the origins, and describes steps for the management of oral precancer and cancer.

Improving detection of precancerous and cancerous oral lesions. Computer-assisted analysis of the oral brush biopsy. U.S. Collaborative OralCDx Study Group.

BACKGROUND: A study group composed of researchers from across the United States undertook a study to evaluate the sensitivity and specificity of OralCDx (OralScan Laboratories Inc.), a computer-assisted method of analysis of the oral brush biopsy, in the detection of precancerous and cancerous lesions of the oral mucosa. METHODS: The study group conducted a multicenter double-blind study comparing results of OralCDx analysis with those of scalpel biopsy of suspicious oral lesions, as well as using OralCDx on oral lesions that appeared benign clinically. RESULTS: In 945 patients, OralCDx independently detected every case of histologically confirmed oral dysplasia and carcinoma (sensitivity = 100 percent, false-negative rate = 0 percent). Every OralCDx "positive" result was subsequently confirmed by histology as dysplasia or carcinoma. The specificity for the OralCDx "positive" result was 100 percent, while the specificity for the OralCDx "atypical" results was 92.9 percent. In 4.5 percent of clinically benign-appearing lesions that would not have received additional testing or attention other than clinical follow-up, OralCDx uncovered dysplasia or carcinoma (statistical sensitivity > 96 percent, P < .05, n = 131; statistical specificity for the OralCDx "positive" result > 97 percent and for the "atypical" result > 90 percent, P < .05, n = 196). CONCLUSIONS: The authors propose that this multicenter trial demonstrates that OralCDx is a highly accurate method of detecting oral precancerous and cancerous lesions. OralCDx can aid in confirming the nature of apparently benign oral lesions and, more significantly, revealing those that are precancerous and cancerous when they are not clinically suspected of being so. All OralCDx "atypical" and "positive" results should be referred for scalpel biopsy and histology to completely characterize the lesion. CLINICAL IMPLICATIONS: Given the difficulty in clinically differentiating premalignant and malignant lesions from benign lesions with a similar appearance, OralCDx appears to determine the significance of an oral lesion definitively and detect innocuous-appearing oral cancers at early, curable stages.

Heterotopic oral gastrointestinal cyst: report of 2 cases and review of the literature.

Oral heterotopic gastrointestinal cyst is a rare entity occurring in infants and children and showing a predilection for males. The cyst usually appears as an asymptomatic swelling in the floor of the mouth. Difficulty in feeding, swallowing, respiration, and speech have been reported in approximately 30% of those affected. The tongue-in particular, its anterior aspectis involved in up to 60% of reported cases. The clinical, radiographic, and histopathologic features of cases of heterotopic gastrointestinal cyst involving the anterior tongue in a 2-year-old girl and the anterior floor of the mouth in a 2-month-old boy are presented, and theories of pathogenesis are discussed.

Autoimmune aspects of pemphigus vulgaris and mucosal pemphigoid.

Oral mucosal lesions of ulcerative, desquamative, and bullous character are major problems for clinicians and patients alike. Underlying such processes is the autoimmune reaction manifesting as specific subsets of immunopathology. Responsible for the maintenance of mucosal integrity within the oral cavity are numerous adhesion proteins which operate at the cell-to-cell and cell-to-connective-tissue-matrix level. Two of the better-understood conditions characterized by altered or disordered levels of adherence are the pemphigus and the pemphigoid groups of lesions. Autoantibodies in pemphigus vulgaris specifically attack normal proteins within the desmosomal structure. Cellular adhesion is affected by steric interference by antibodies directed against antigens residing within the intercellular space or the desmosome itself. Such alterations ultimately result in cell-to-cell separation, with production of the acantholytic element characteristic of pemphigus vulgaris. Mucous membrane pemphigoid is characterized by a separation at the junction of the epithelium and connective tissue at the level of the basement membrane complex. Histologically, a split occurs in the sub-basilar region, with antibodies directed to the 230-kDa protein component of the hemidesmosome. Minor antigens residing within the basement membrane area include a 180-kDa element as well as other less commonly found proteins near the membrane complex. Manifestations of these illnesses are often severe. Management strategies of pemphigus vulgaris have changed over the recent past, with new modalities supplementing the traditional corticosteroid approach. Both conditions are usually lifelong, with the implications of management a major consideration.

Opportunistic oral infections in the immunosuppressed patient: oral hairy leukoplakia and oral candidiasis.

Several opportunistic infections associated with immunosuppression are noted to occur secondary to an altered relationship between host and organism. In relation to diminished host immunologic defenses, associated commensal organisms may evolve to a pathogen state. Candidiasis, a common oral marker disease reflective of immunosuppression, results from dysfunction of complex cellular interactions keyed by depressed T-cell activity or function. Certain viral infections may also serve as probable markers of immunosuppression. One such infection is typified by the development of oral hairy leukoplakia, a condition highly correlated to HIV infection in most, but not all, patients. Detection of Epstein-Barr virus particles and subsequent molecular analytic verification of such and the absence of other potential viral candidates, such as papilloma and human immunodeficiency viruses, have led to a general acceptance of this virus as the cause of this condition.

Oral leukoplakia.

Leukoplakia has evolved as a clinico-pathologic concept over many years, with the current clinical designation being accepted worldwide. Reflective of the biology of leukoplakia is the concept of cellular atypia and epithelial dysplasia. Adding to a better understanding of leukoplakia in general has been the definition of relevant clinical subsets which, in some cases, includes etiology (snuff), while in other cases a verrucous clinical appearance will suggest a more aggressive anticipated behavior pattern. Tobacco usage, in many of its forms, remains the prime etiologic factor; however, other considerations also apply. More recently, the potential etiologic role of Candida albicans has been stressed, as well as its possible role in carcinogenesis. So-called oral hairy leukoplakia has been defined in relation to a possible Epstein-Barr viral infection, usually in the immunosuppressed patient. Other viruses, human papilloma virus in particular, have been implicated in leukoplakia, while genetic alterations involving tumor suppressor elements (p53) have also been investigated. Finally, the management of this common condition remains a variable and includes local, topical, and systemic therapies such as anti-oxidants, carotenoids, and retinoids.

Sjogren's syndrome: pathology, oral presentation, and dental management.

As one of the major autoimmune conditions involving the oral, head, and neck regions, Sjögren's syndrome has a significant level of dentally related pathology. As a result of salivary dysfunction, the teeth and mucosa may develop a wide array of changes. If these changes are not managed properly, major oral dysfunction can occur. An evaluation of salivary function, the management of xerostomia and its effects, dietary counseling, and an overall appreciation of the extraoral components of Sjögren's syndrome are presented. The dental component of comprehensive patient management is one of the most important aspects of this condition, with the dental practitioner being an essential part of the health-care team.

Terminal duct carcinoma. Recognition of a low-grade salivary adenocarcinoma.

We describe six cases of terminal duct carcinoma of the minor salivary glands. All were localized to the oral cavity, without regional nodal or distant metastases. Histologically, five were originally mistaken for adenoid cystic carcinoma; one was interpreted as monomorphic adenoma with areas of adenoid cystic carcinoma. Treatment consisted of wide resection with or without radiation therapy, with no incidence of recurrence or metastasis. The characteristics of this recently described pathologic entity are reviewed. The less aggressive behavior of this tumor compared with adenoid cystic carcinoma should call for less radical therapy, with a favorable prognosis in most cases. Recognition of this tumor as a distinct clinical and pathologic entity is therefore important.