Scanning electron microscopy of different types of oral leukoplakia: Comparison with normal and malignant oral mucosa

The present study analysed surface architecture of normal, premalignant and malignant oral mucosa using scanning electron microscopy to evaluate its role in early diagnosis of potentially malignant oral lesions. The surface ultrastructure of the buccal mucosa in tobacco chewers showed variations from that of non-chewers. Homogenous leukoplakia demonstrated well-defined intercellular junctions and the microrugal surface pattern as seen in normal mucosa. In verrucous leukoplakia, the surface layer consisted of characteristically-shrunken desquamated hyperkeratotic cells. Erosive leukoplakia had a discontinuous superficial layer along with complete loss of intercellular ridges. Speckled leukoplakia also showed marked abnormalities such as thickened irregular protrusions and evidence of a villuslike pattern. These villus-like structures were comparatively prominent in leukoplakia showing dysplasia. Oral carcinoma showed marked altered surface ultrastructure and had a pattern similar to dysplastic lesions. The irregular swollen elongated protrusions with villous-like structures that were observed in carcinoma and dysplastic lesions can, therefore, be considered as surface markers for potentially malignant leukoplakia.     

Papillomaviruses: the current status in relation to oral disease

Human papillomaviruses of different types are associated with a variety of benign oral lesions and may be associated with some premalignant and malignant oral lesions. However, since it is now clear that a variant of human papillomavirus 16 is harbored by normal oral mucosa, as well as by premalignant and malignant lesions, such associations may not necessarily always be causal. The rapid progress of recent research in this field is reviewed, with particular reference to oral disease, and the current status is discussed.     

Detection of potentially malignant and malignant lesions of oral cavity using autofluorescence visualization device

Light-based oral cancer screening aids have been developed in identifying potentially malignant and malignant lesions of oral cavity at their earliest stage. The VELscope system is a simple hand-held device that facilitates the direct visualization of oral-cavity fluorescence for the detection of precancerous and cancerous lesions. Some published reports have shown that this system can assist in the detection of precancerous and cancerous lesions, but there is no evidence that it can distinguish between them. We studied whether objective discrimination criteria can be set for this system when observing oral mucosal lesions. We examined 74 cases with biopsy-confirmed oral mucosal lesions; 37 squamous cell carcinoma lesions, 14 moderate to severe epithelial dysplasia lesions, 13 mild epithelial dysplasia lesions and 10 lichen planus lesions. Lesions were examined macroscopically under the conventional overhead light, and then, examined by this device. Each examination was recorded with a digital camera. We contrasted findings with histopathological manifestation, and calculated the attenuation score. It is found that several conditions and sites, such as keratinization and the degree of inflammatory cell infiltration, were associated with detection sensitivity using this device. Based on the attenuation scores, a significant difference was seen between squamous cell carcinoma and epithelial dysplasia. It is suggested that this device might be a valuable adjunct in the early detection of potentially malignant and malignant lesions of the oral cavity.     

Update review on prevention and early diagnosis in oral cancer

Oral cancer is a major health problem in some parts of the world, especially in developing countries. Worldwide, the annual incidence exceeds 3,000,000 new cases. The main risk factors are tobacco and alcohol. However, dietary factors, viruses and possibly genetic predisposition have also been associated with oral cancer. Several oral lesions such as leukoplakia, erythroplakia and lichen planus carry an increased risk for malignant transformation in the oral cavity. Prognosis of oral cancer differs significantly between specific oral locations, with cancer of the lip for example having a much better prognosis than at the base of tongue or on the gingiva. Prognosis of intra-oral cancer is generally poor, with a five-year survival less than 50 percent. Local recurrences as well as lymph node metastases occur in a significant percentage of patients, while distant metastases are less frequent. Prognosis correlates mainly with the size of the lesion and the nodal status at the time of diagnosis, therefore early detection of small, stage-1 oral cancer can reduce mortality and morbidity. Oral lesions can be easily observed by direct visualization, however, knowledge of the differential diagnosis of oral lesions is mandatory for early diagnosis of malignant and pre-malignant lesions in the oral cavity. Use of screening and detection aids such as vital stains and Oral CDX can increase the number of cases diagnosed at an early stage, or even in the pre-malignant stage. Development of molecular markers can improve the early diagnosis and can help in predicting treatment response. New treatment modalities including tumor specific antibodies and gene therapy are emerging, giving more hope for patients with oral cancer. There is an important role for the dentist in both early diagnosis of pre-malignant and malignant lesions, and in prevention by educating the patients of the risks associated with tobacco, alcohol and dietary factors.     

Gingival and cutaneous angiosarcoma

Multiple oral and cutaneous nodular and papular reddish-blue lesions are described in the case of a 60-year-old woman. The duration of the lesions was more than 1 year, with the oral lesion preceding the skin lesions. Histopathological examination revealed malignant vascular tumour with changes consistent with angiosarcoma. Angiosarcoma is an extremely rare malignant tumour of the oral cavity, and the present case describes oral and skin lesions with a unique clinical behaviour.     

Dyskeratosis in human and experimental oral precancer and cancer. An immunohistochemical and ultrastructural study in men, mice and rats

Dyskeratotic cells were examined with light and electron microscopy in human oral leukoplakias and carcinomas and in chemically-induced oral premalignant and malignant lesions of mice and rats. Specific antisera against small and large keratins were used to analyse the distribution of keratin polypeptides. In normal oral mucosa, basal cells did not react with antibodies against large keratins in contrast to the suprabasal cells which did react. Small keratins were found in all epithelial cell layers. In human and experimental premalignant and malignant lesions, intensely labelled dyskeratotic cells were seen, which contained small and large keratins regardless of their position in the epithelium. At the ultrastructural level, these cells showed dense aggregates of tonofilaments. Dyskeratotic cells were often seen in advanced stages of degeneration of phagocytosis of these cells by macrophages and giant cells was frequent. The disturbance of the keratinization process in oral precancer and cancer is easily visualized using keratin antisera. Keratin analysis can give new insights in epithelial maturation and may be helpful for the classification of oral leukoplakia.     

Human papillomavirus infection in oral potentially malignant disorders and cancer

Human papillomavirus (HPV) infects keratinocytes in the mucosa or skin, and persistent infection with HPV may lead to premalignant lesions and invasive cancer, especially cervical cancer. It has also been hypothesized that HPV infection is an etiological factor of oral squamous cell carcinoma and oral precancerous disorders such as lichen planus, leukoplakia, and erythroplakia. A high percentage of HPV in oral lesions supports the possible viral contribution, but an association of HPV infection with these lesions remains to be established. The current paper will update the latest progress of HPV infection in several oral potentially malignant disorders and oral squamous cell carcinoma and discuss the impact of HPV infection on the progression of oral potentially malignant disorders.     

The role of the dental team in preventing and diagnosing cancer: 2. Oral cancer risk factors

Oral cancer is among the ten most common cancers world-wide, and is especially seen in disadvantaged older males. Cancer arises as a consequence of DNA mutations causing multiple molecular genetic events in many chromosomes and genes, leading to cell dysregulation. Tobacco and alcohol use are extremely important in oral mutagenesis. Environmental factors such as infective agents and genetic factors are implicated in a minority of patients. CLINICAL RELEVANCE: Dental staff can advise on lifestyle changes for the prevention of potentially malignant oral disease and thereby protect their patients, staff, colleagues, families and acquaintances, having the opportunity to make an impact on improving the survival rate and morbidity of oral cancer by detecting both potentially malignant and malignant oral lesions.     

Melanoma arising from the mucosal surfaces of the head and neck

Oral mucosal malignant melanoma is a rare disease. We reviewed 30 years of data from a tumor registry and identified 65 patients who had head and neck melanomas. Two thirds (43) of the 65 patients were identified as male, with the mean age in the sixth decade. Of the 65 patients, only 6 had melanoma that arose from the oropharyngeal mucosa. Of the lesions involving the oral mucosa, each lesion manifested itself as a mass or was associated with symptoms of discomfort; only one third (2) of the lesions were pigmented. The clinician must carefully examine the head, neck, and oral cavity, and any pigmented lesion that is not recognized as a specific entity, such as amalgam tattoo, should be biopsied. The more common presentation of amelanotic malignant melanoma requires a high index of suspicion for masses identified in the mouth and requires biopsy for definitive diagnosis. The prognosis for oral mucosal malignant melanoma is poor.     

Endocytoscopy for in situ real-time histology of oral mucosal lesions

This study investigated the utility of endocytoscopy, a novel emerging endoscopic system, for in situ real-time histology of oral mucosal lesions. Endocytoscopy involves the use of a contact light microscopy system with 380-fold magnification. With the development of endoscopic instruments, it has become possible to observe the abnormal microvascular and capillary patterns of tumour cells. The resolution of the endoscopic image is improved in situ, and a more detailed diagnosis is possible. In this study, endocytoscopy along with other diagnostic modalities was used in nine patients. Normal mucous membranes and oral malignant lesions were observed. Endocytoscopy enabled the pathological diagnosis of oral malignancies in situ and the observation of both structural and cytological atypia. In the future, it is expected that pathological diagnoses will be made in situ by direct viewing of living cells. This technique has the potential to allow an ‘optical biopsy’.     

Nonsquamous cell malignant tumours of the oral cavity: an overview

Many malignant tumours other than squamous cell carcinoma may present in the oral cavity. Melanomas of the oral cavity are usually pigmented, aggressive tumours associated with a poor prognosis. Neoplasms of the minor salivary glands have a greater tendency to be malignant than those of the major glands, and some exhibit a predilection for occurring in the mouth. Many types of connective tissue malignant tumours (sarcomas) may arise in the mouth, including soft-tissue cancers and lesions of hematologic cells such as lymphoma, whereas osteosarcoma is the most common malignancy of the hard tissues found in the mouth. Cancers from distant organs such as breast, lung and prostate may metastasize to the oral cavity. This paper presents a brief overview of nonsquamous cell oral cancers, with emphasis on those most likely to be encountered by the practising dentist.     

Soft-tissue lesions in children

This article reviews some of the benign and malignant oral soft-tissue swellings that occur in children, with an emphasis on their clinical presentation, etiology, histopathology, and treatment. These lesions include single and multiple nodules, reactive lesions, and benign and malignant neoplasms. Diseases discussed include reactive gingival swelling, generalized gingival fibromatosis, melanotic neuroectodermal tumor of infancy, fibromas, vascular lesions, salivary gland lesions, and infantile rhabdomyomas. Also covered are lesions that may present in multiples, such as neuromas, multiple endocrine neoplasia type 2b, neurofibromatosis, and human papilloma virus-related benign epithelial lesions. Benign but locally aggressive and malignant neoplasms are discussed, such as aggressive fibromatosis, myofibromatosis, fibrosarcoma, and rhabdomyosarcoma.     

Malignant melanoma of the oral cavity: a review of literature.

Oral malignant melanoma is a rare aggressive neoplasm of the middle age. This malignancy commonly affects male subjects and is more frequently seen at the level of the hard palate and gingiva. At present, the clinicopathological classification of oral melanoma is not yet clearly outlined; consequently, the skin form is often taken as a reference. In many cases (up to 30%), the diagnosis of melanoma is made on lesions, which have evolved from the pre-existing pigmented lesions. The poor prognosis of oral melanomas requires that pigmented lesions of undetermined origin be routinely biopsied. The surgical approach, combined with the chemotherapeutic one, is the first choice treatment. The purpose of this study is to review literature that has been published about malignant melanoma of the oral cavity. MATERIALS AND METHODS: Thirty-eight published articles and 8 textbooks related to oral malignant melanoma and been published in the last two decades are reviewed. CONCLUSION: The review of literature in the field of malignant melanoma of the oral cavity show that this malignancy might be different from cutaneous malignant melanomas, and new criteria for diagnosis and therapy should be considered for this disease. Physicians and dentists who treat problems of the oral cavity should be aware of the need for early diagnosis of oral melanomas and performing biopsies of doubtful pigmented lesions.     

Molecular pathways regulated by areca nut in the etiopathogenesis of oral submucous fibrosis

Many oral mucosal lesions are due to substance abuse, such as tobacco and areca nut, amongst others. There is considerable evidence that oral lesions/disorders such as some leukoplakias, most erythroplakias, and submucous fibrosis have malignant potential, with a conversion rate of 5%‐10% over a 10‐year period. There have been several reports on possible biomarkers that predict malignant conversion of the oral lesions associated with these disorders. Management of these is mostly surgical removal of the lesion followed by observation, and in some cases treatment by antioxidants and anti‐inflammatory agents. Oral submucous fibrosis is due to excessive deposition of extracellular matrix in the connective tissue plus, particularly, collagens. The deposition of collagen leads to stiffness of the affected regions and results in difficulty in mouth opening. Areca nut chewing is proposed as the most probable etiological factor in the manifestation of oral submucous fibrosis. Several studies suggest involvement of proinflammatory cytokines, dysregulated by areca nut, in the development of the disease. Amongst these, transforming growth factor‐β is in the forefront, which is also shown to be involved in fibrosis of other organs. This review addresses the molecular mechanisms involved in oral submucous fibrosis development and provides a model for the regulation of transforming growth factor‐β by areca nut. It provides an exemplar of the role of modern molecular techniques in the study of oral disease.     

A reason for the use of toluidine blue staining in the presurgical management of patients with oral squamous cell carcinomas

Verification of oral cancer relies on histopathological diagnosis of suspect or malignant lesions. There is evidence for further pre-surgical screening procedures to localize tumor borders and define other malignant lesions. Important methods are: visual examination, including pan-endoscopy, fluorescence imaging, and brush biopsy, as well as radiologic techniques such as conventional radiography, computed tomography, magnetic resonance imaging, scintigraphy, and ultrasonography, which may reduce the mortality rate associated with oral cancer. In addition, toluidine blue staining is a simple, inexpensive, and excellent diagnostic tool. Herein we show that the clinical use of in vivo staining is effective to define the superficial tumor borders and to detect malignant or pre-malignant cells in the surrounding area of the tumor following detection of a malignancy of the oral cavity. In our reported case, the main tumor mass was surrounded by layers of an intact mucosa, yet in a distance of more than 1 cm a group of malignant or pre-malignant cells in the surrounding area required a resection of the tumor in a size that would have been unaddressed during visual examination alone followed by clinical routine program of presurgical examinations after the detection of a malignancy of the oral cavity.     

p53 expression in oral precancer and cancer

Expression of the p53 tumour suppressor gene is a frequent finding in human malignancies, including oral cancer, and it has been detected in some potentially malignant lesions. The results of the present project showed that 35 of the 41 (85 per cent) oral mucosal lesions with histological evidence of epithelial dysplasia expressed p53, but the presence or absence of p53 staining could not be used to predict the outcome of potentially malignant oral mucosal lesions.     

Adult and infantile myofibromatosis: a report of three cases affecting the oral cavity

Myofibromatosis is a rare but well recognized entity which was originally thought to affect only neonates and infants. It is now apparent however that adults may also be affected. Solitary cases affecting the oral cavity appear to be rare and only two cases of solitary lesions in adults appear in the literature. This report documents three solitary cases; two typical lesions in infants and a lesion from the tongue of an adult. The lesions were composed of small polygonal cells and large elongated cells in a scant fibrous stroma. The elongated spindle cells were identified as myofibroblasts by immunocytochemistry and electron microscopy. The lesions showed characteristic features which enabled them to be distinguished from other fibrous lesions and from benign or malignant smooth muscle tumors with which they have frequently been confused.     

Oral manifestations in Cowden's syndrome. Report of four cases

Cowden's syndrome or multiple hamartoma and neoplasia syndrome is a hereditary disorder combining multiple hamartomas of many organs. These hamartomas are derived from ectodermal, mesodermal, and endodermal tissues and may undergo spontaneous malignant changes. Small papular cutaneous lesions and papillomatous outgrowth and papular lesions of the oral mucosa are the most predominant features of the syndrome. Since the orocutaneous lesions often precede the associated malignant degenerations, they may serve as a diagnostic signal for the probably developing neoplasia in other organs. The presence of extensive papillomatous and papular lesions in the oral mucosa combined with skin lesions should therefore alert the clinician to suspect the presence of Cowden's syndrome, the early diagnosis of which is important in order that the concomitant malignant changes might be discovered at the earliest possible moment. Four cases of Cowden's disease are presented, with emphasis on the oral manifestations of this syndrome.     

Tobacco-associated lesions of the oral cavity: Part II. Malignant lesions

Nonmalignant tobacco-associated lesions of the oral cavity were discussed in the first part of this two-part article. Here, we describe malignant lesions associated with tobacco use, basic biopsy principles for such lesions and intervention strategies that dental professionals may use to reduce the chances of their patients developing precancerous lesions or primary malignancies.     

Oral potentially malignant disorders: Is malignant transformation predictable and preventable?

Leukoplakia is the most common potentially malignant disorder of the oral mucosa. The prevalence is approximately 1% while the annual malignant transformation ranges from 2% to 3%. At present, there are no reliable clinicopathological or molecular predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented. Furthermore, follow-up programs are of questionable value in this respect. Cessation of smoking habits may result in regression or even disappearance of the leukoplakia and will diminish the risk of cancer development either at the site of the leukoplakia or elsewhere in the mouth or the upper aerodigestive tract. The debate on the allegedly potentially malignant character of oral lichen planus is going on already for several decades. At present, there is a tendency to accept its potentially malignant behaviour, the annual malignant transformation rate amounting less than 0.5%. As in leukoplakia, there are no reliable predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented either. Follow-up visits, e.g twice a year, may be of some value. It is probably beyond the scope of most dentists to manage patients with these lesions in their own office. Timely referral to a specialist seems most appropriate, indeed. Key words:Oral potentially malignant disorders, oral leukoplakia, oral lichen planus.