Expression of heat shock protein (HSP70) in oral lichen planus and non-dysplastic oral leucoplakia

The purpose of this study was to investigate the expression of heat shock protein (HSP70) in oral non-dysplastic leucoplakia and in relation to the clinical and pathological features of oral lichen planus. The expression of HSP70 was assessed in the epithelial compartment of normal mucosa (n = 5), oral lichen planus (n = 28) and benign leucoplakia (n = 11) using an immunohistochemical method. The immunostaining intensity distribution (IID) index was used to quantify the positivity of the staining. There was no association between HSP70 overexpression and clinical presentation of oral lichen planus. Oral lichen planus patients showed no statistically significant differences in the depth of the inflammatory infiltrate when expression of HSP70 was considered (X(i)- X(j) = 42.30; 95% confidence interval (95% CI) = -120.87-205.48). No statistically significant differences were identified in terms of HSP70 expression between oral lichen planus and normal buccal mucosal specimens (X(i)- X(j) = 4.07; 95% CI = -0.53-8.67). The IID index score for HSP70 expression in leucoplakia specimens was significantly higher than the one of the oral lichen planus group (X(i) - X(j)= 5.11; 95% CI = 1.73-8.48). It is concluded that there are no statistically significant differences in HSP70 expression between oral lichen planus and normal buccal mucosal specimens, suggesting that HSP70 does not play an obvious part in the pathogenesis of oral lichen planus. The expression of HSP70 was significantly higher in oral leucoplakia than in oral lichen planus, possibly because of differences in cellular activity or cell proliferation.     

Expression of heat shock protein (HSP70) in oral lichen planus and non‐dysplastic oral leucoplakia

Expression of heat shock protein (HSP70) in oral lichen planus and non‐dysplastic oral leucoplakia The purpose of this study was to investigate the expression of heat shock protein (HSP70) in oral non‐dysplastic leucoplakia and in relation to the clinical and pathological features of oral lichen planus. The expression of HSP70 was assessed in the epithelial compartment of normal mucosa (n = 5), oral lichen planus (n = 28) and benign leucoplakia (n = 11) using an immunohistochemical method. The immunostaining intensity distribution (IID) index was used to quantify the positivity of the staining. There was no association between HSP70 overexpression and clinical presentation of oral lichen planus. Oral lichen planus patients showed no statistically significant differences in the depth of the inflammatory infiltrate when expression of HSP70 was considered ( X?_{i ? X?j = 42.30; 95% confidence interval (95% CI) = ?120.87–205.48). No statistically significant differences were identified in terms of HSP70 expression between oral lichen planus and normal buccal mucosal specimens ( X?i ? X?j = 4.07; 95% CI = ?0.53–8.67). The IID index score for HSP70 expression in leucoplakia specimens was significantly higher than the one of the oral lichen planus group ( X?i ? X?j} = 5.11; 95% CI = 1.73–8.48). It is concluded that there are no statistically significant differences in HSP70 expression between oral lichen planus and normal buccal mucosal specimens, suggesting that HSP70 does not play an obvious part in the pathogenesis of oral lichen planus. The expression of HSP70 was significantly higher in oral leucoplakia than in oral lichen planus, possibly because of differences in cellular activity or cell proliferation.     

Human papillomavirus in squamous cell carcinoma, leukoplakia, lichen planus, and clinically normal epithelium of the oral cavity

Tissue specimens of carcinoma, leukoplakia, and clinically normal epithelium obtained at sites separate from the lesions were examined for the presence of human papillomavirus (HPV). Twenty-two paraffinized specimens of previously diagnosed oral lichen planus were also studied. The carcinoma and leukoplakia specimens were examined by Southern transfer hybridization and reverse blot hybridization; specimens HPV-positive by Southern hybridization were additionally examined by in situ hybridization and an immunoperoxidase technique. The lichen planus specimens were examined by in situ hybridization and immunoperoxidase techniques only. The HPV identification rates were in the range reported in previous studies, and the detection rates were similar for carcinoma, leukoplakia, histologically normal epithelium, and lichen planus. The clinical significance of HPV presence in carcinoma, leukoplakia, and lichen planus was not evaluable because of the short duration of follow-up.     

Acquired bullous diseases of the oral mucosa

Bullous diseases of the oral cavity cause painful erosion. They must be distinguished from aphthae and vesicles which may have a similar presentation. Acute, chronic and congenital conditions are recognized. Acute lesions may involve a polymorphous oral erhythema which has an polymorphous erythematous presentation or toxidermia (Stevens-Johnson syndrome, Lyell syndrome, fixed pigmented erythema). Examination of the skin and history taking are the keys to diagnosis. Patients with chronic bullous diseases may have a congenital condition (bullous epidermolysis or lymphangioma) suggested by the age at onset and the clinical presentation. Acquired chronic bullous diseases include lichen planus and autoimmune bullous diseases. Careful examination is essential to identify mucosal or cutaneous involvement and to obtain a biopsy for histological examination. Search for antibodies deposited in the perilesional mucosa is necessary. Chronic erosive gingivitis is a frequent presentation. Most of the patients have cicatricial pemphigoid, lichen planus, and more rarely pemphigus. The pinch sign is highly discriminative to differentiate the cause of this syndrome. Symptomatic treatment of bullous lesions of the oral cavity include adapted diet and correct and early use of antalgesics.     

Oral lichen planus and squamous carcinoma. Case report and update of the literature

A case of squamous cell carcinoma of the tongue arose in the plaque form of oral lichen planus. The literature on lichen planus is reviewed with emphasis on the issue of malignant transformation. Squamous carcinoma develops in 0.3% to 3% of patients with oral lichen planus (range, 0% to 10%). The average age of individuals with this complication is 50 to 55 years; 50% to 60% are men. Forty-four percent to 60% of patients have the erosive form of the disease, 28% to 34% plaque type, and 16% to 28% reticular. The mean interval from onset of the oral lesions to the development of cancer is nine to 12 years (range, three months to 40 years). Forty-six percent to 54% of the cancers occur on the buccal mucosa, 30% on the tongue, 16% on the lower lip, and 8% in miscellaneous sites. Twenty-four percent to 50% of the individuals also have cutaneous lichen planus.     

The clinical effectiveness of reflectance optical spectroscopy for the in vivo diagnosis of oral lesions

Optical spectroscopy devices are being developed and tested for the screening and diagnosis of oral precancer and cancer lesions. This study reports a device that uses white light for detection of suspicious lesions and green–amber light at 545 nm that detect tissue vascularity on patients with several suspicious oral lesions. The clinical grading of vascularity was compared to the histological grading of the biopsied lesions using specific biomarkers. Such a device, in the hands of dentists and other health professionals, could greatly increase the number of oral cancerous lesions detected in early phase. The purpose of this study is to correlate the clinical grading of tissue vascularity in several oral suspicious lesions using the IdentafiH system with the histological grading of the biopsied lesions using specific vascular markers. Twenty-one patients with various oral lesions were enrolled in the study. The lesions were visualized using IdentafiH device with white light illumination, followed by visualization of tissue autofluorescence and tissue reflectance. Tissue biopsied was obtained from the all lesions and both histopathological and immunohistochemical studies using a vascular endothelial biomarker（CD34） were performed on these tissue samples. The clinical vascular grading using the green–amber light at 545 nm and the expression pattern and intensity of staining for CD34 in the different biopsies varied depending on lesions, grading ranged from 1 to3. The increase in vascularity was observed in abnormal tissues when compared to normal mucosa, but this increase was not limited to carcinoma only as hyperkeratosis and other oral diseases, such as lichen planus, also showed increase in vascularity. Optical spectroscopy is a promising technology for the detection of oral mucosal abnormalities; however, further investigations with a larger population group is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant lesions.     

Malignant degeneration of oral lichen planus: our clinical experience and review of the literature

Lichen planus of the oral mucosa (OLP) is characterized by lymphocytic infiltrate in the epithelial layer and basal cells lysis. Some studies have suggested a high incidence of oral squamous cell carcinoma in patients with OLP that has been implicated as a premalignant lesion. We describe 19 cases of OLP, and the immunopathologic basis for OLP, its potential association with malignancy and the variable clinical pictures in patients with OLP are reviewed. Also, specific recommendations are given for treatment and follow-up of lesions.     

Expression of intermediate filament proteins in benign lesions of the oral mucosa

Immunohistochemistry with monospecific antibodies was used to study the expression patterns of cytokeratins (Cks) and vimentin in non-dysplastic lesions of the oral cavity, including lichen planus and fibromas. In hyperplastic lesions, Ck expression did not deviate significantly from the normal non-keratinizing squamous epithelium of the oral cavity. Hyperkeratotic lesions showed pronounced aberrations in their Ck profile. These lesions were characterized by extended expression of the keratinization marker Ck 10, the basal cell Ck 14 and the hyperproliferation-associated Ck 16 in the suprabasal compartment. The stratification markers Cks 4 and 13 showed a decreased expression. Coexpression of Cks and vimentin was found in lesions having accumulations of inflammatory cells in the subepithelial cell layer. These changes are felt to characterize benign mucosal lesions without dysplasia and might be helpful for distinguishing these lesions from potentially malignant ones. Received: 3 September 1998 / Accepted: 5 February 1999     

Clinical and pathological characteristics of oral lichen planus in hepatitis C‐positive and ‐negative patients

Clinical and pathological characteristics of oral lichen planus in hepatitis C‐positive and ‐negative patients The reported prevalence rate of anti‐hepatitis C virus (HCV) antibodies in patients with oral lichen planus shows wide geographical variation and ranges from 0 to 65%. Certain characteristic clinical features have been attributed to oral lichen planus associated to HCV infection. The purpose of this investigation has been to assess hypothetical clinical differences, as well as differences in the intensity of the subepithelial inflammatory infiltrate between oral lichen planus‐HCV +ve patients and oral lichen planus‐HCV –ve patients. A total of sixty‐two patients entered the study. Their mean age was 63.5 ± 14.49 years, and 48.4% of them were men and 51.6% women. Patients were classified according to their serum HCV positivity. Age, sex, clinical presentation (reticular or atrophic‐erosive), extension of the lesions, location of the lesions, number of locations affected, intensity of the inflammatory infiltrate and Candida albicans colonization were recorded for each patient. Reticular lichen planus was the most frequent clinical presentation in both HCV +ve (57.1%) and HCV –ve patients (63.6%). C. albicans colonization ranged from 42.8% in HCV +ve and 41.7% in HCV –ve patients. HCV + ve patients showed certain oral locations more frequently affected than HCV –ve ones: lip mucosa, 28.6% versus 7.3%; tongue, 57.1% versus 29.1%; and gingiva, 71.4% versus 23.6%. The number of affected intraoral locations was higher in HCV +ve patients (71.4%) than among HCV –ve ones (20.4%; χ² = 8.34; P < 0.011). No statistically significant differences could be established in terms of density of subepithelial inflammatory infiltrate between the groups. Our results reinforce the need for liver examination in all patients with oral lichen planus, particularly those showing lesions on the gingiva with multiple intraoral locations affected, as no pathological differences could be identified between HCV + ve and HCV –ve patients.     

Clinical and pathological characteristics of oral lichen planus in hepatitis C-positive and -negative patients

The reported prevalence rate of anti-hepatitis C virus (HCV) antibodies in patients with oral lichen planus shows wide geographical variation and ranges from 0 to 65%. Certain characteristic clinical features have been attributed to oral lichen planus associated to HCV infection. The purpose of this investigation has been to assess hypothetical clinical differences, as well as differences in the intensity of the subepithelial inflammatory infiltrate between oral lichen planus-HCV +ve patients and oral lichen planus-HCV -ve patients. A total of sixty-two patients entered the study. Their mean age was 63.5 +/- 14.49 years, and 48.4% of them were men and 51.6% women. Patients were classified according to their serum HCV positivity. Age, sex, clinical presentation (reticular or atrophic-erosive), extension of the lesions, location of the lesions, number of locations affected, intensity of the inflammatory infiltrate and Candida albicans colonization were recorded for each patient. Reticular lichen planus was the most frequent clinical presentation in both HCV +ve (57.1%) and HCV -ve patients (63.6%). C. albicans colonization ranged from 42.8% in HCV +ve and 41.7% in HCV -ve patients. HCV + ve patients showed certain oral locations more frequently affected than HCV -ve ones: lip mucosa, 28.6% versus 7.3%; tongue, 57.1% versus 29.1%; and gingiva, 71.4% versus 23.6%. The number of affected intraoral locations was higher in HCV +ve patients (71.4%) than among HCV -ve ones (20.4%; chi2 = 8.34; P < 0.011). No statistically significant differences could be established in terms of density of subepithelial inflammatory infiltrate between the groups. Our results reinforce the need for liver examination in all patients with oral lichen planus, particularly those showing lesions on the gingiva with multiple intraoral locations affected, as no pathological differences could be identified between HCV + ve and HCV -ve patients.     

Vulvovaginogingival syndrome. New characteristic grouping of plurimucous erosive lichen planus

The triple association of a chronic painful erosive vulvitis, an erosive or desquamative vaginitis and an erosive vestibular gingivitis constitutes a hitherto unreported syndrome. The first 19 cases of this affection seen in the H?pital Tarnier over the last three years are presented and analyzed, the etiology of these erosive mucosal lesions, limited to three body regions, being lichen planus in each case. Detection of mucosal erosion at one of these three sites now requires clinical investigation of the other two, and biopsy of least one of them from the edge of an eroded zone, as well as search for other-possible mucocutaneous areas of lichen planus. Clinical onset is often asynchronous, one lesion appearing before the others, the simplest to recognize being gingival erosive lichen. In one case, however, peri-erosive lamellar detachments suggested chronic desquamative gingivitis of possible benign pemphigoid origin. Erosive lichen planus of vulva and vagina has not been reported previously. Knowledge of this syndrome allows correlation between lichen planus and certain cases of erosive gingivitis, erythroplastic vulvitis and desquamative vaginitis.     

Substance P nerve fibres in the canine larynx by PAP immunohistochemistry

The distribution of the Substance P (SP) immunoreactive nerve fibres in the canine larynx and laryngeal nerves was studied by PAP immunohistochemistry. Many individual SP immunoreactive nerve fibres with varicosities were observed within the epithelial layer and in the connective tissue below the epithelium of the laryngeal mucosa. Small numbers of SP immunoreactive nerve fibres were also found in the submucosal gland region and some of them appeared to terminate in glandular cells. These findings are consistent with the view that SP might be involved in the laryngeal sensory innervation system and the laryngeal glandular secretion. No SP immunoreactive nerve fibres were found in any intrinsic laryngeal muscles. The recurrent laryngeal nerve and the superior laryngeal nerve contained SP immunoreactive nerve fibres and were considered to lie in the pathway of the SP nerve fibres to the larynx.     

The association of chronic inflammatory disease in lichen planus with cancer of the oral cavity

Heavy cigarette smoking and alcohol consumption are the major contributing factors in the development of cancer of the upper aerodigestive tract. Other factors, such as chewing substances and chronic irritation, have been implicated. The purpose of this presentation is to draw attention to chronic inflammation as another likely etiologic factor in the pathogenesis of oral cavity cancer. During the past 4 years, we diagnosed squamous cell carcinoma of the oral cavity in six consecutive patients who had no history of cigarette smoking, alcohol intake, or substance abuse. Although this series is too small for significant analysis, it does suggest that chronic inflammatory processes such as lichen planus and chronic gingivitis can induce neoplastic metaplasia in the epithelium of the oral cavity.     

Diagnosis and management of long-standing benign oral ulceration.

The authors formed a Mouth Clinic at Sunnybrook Hospital in 1973 since when there have been 3025 patient visits. Those patients with chronic ulceration present a challenge, the diagnosis sometimes being difficult and therapy not rapidly effective. The differential diagnosis includes lichen planus, pemphigus vulgaris, benign mucous membrane pemphigoid, discoid lupus erythematosus, erythema multiforme, aphthous ulcers, Behcets disease, periadenitis mucosa necrotica recurrens, specific infections and iatrogenic causes. It is possible to reach a definite diagnosis in virtually every case by means of a good history and careful clinical examination supplemented by biopsies and in some cases direct and indirect immunofluorescent studies. Treatment emphasizes scrupulous attention to oral hygiene with baking soda mouthwashes and careful teeth cleaning to minimize the accumulation of dental plaque. Specific therapy includes topical steroids in lichen planus, intra muscular gold in benign mucous membrane pemphigoid, a previously unreported treatment which considerably improved seven out of ten patients, and tetracycline mouthwashes in aphthous ulcers.     

Precancerous lesions of the buccal mucosa

OBJECTIVES: We analyzed data in the literature in comparison with experience at the Department of Cancer and Oral pathology of the Stomatology and Maxillo-Facial Surgery division of la Salpêtrière Hospital on precancerous lesions of the oral mucosa, in order to establish definitions and describe epidemiological, clinical, histological findings as well as natural history and treatment outcome. MATERIAL AND METHODS: Three literature sources were analyzed: Medline and Current Contents searches, books and references listed in articles. The following key words were used and classed into three groups; 1) oral mucosa, epidemiology, precancerous lesions, malignant transformation, dysplasia, leucoplakia, oral lichen planus, erythroplasia, verrucous, cheilitis, candidosis, immunodepression, 2) oral mucosa, tumor markers, carcinogens, keratin, keratinocytes, gene, nuclear proteins, p53 protein, Ki-67 antigen, 3) oral mucosa, therapy, prevention, nutrients. The period chosen ran from 1980 to 1998. This automatic literature search was completed by systematic manual search of summaries in specialized journals published in 1997-1998. The lists of references in the identified articles were consulted and furnished the principal publications concerning precancerous lesions of the buccal mucosa. In all 383 references were selected and analyzed by level of scientific proof. Among these 135 are cited in the text. If data in the literature were insufficient, the physicians at the Department of Cancer and Oral pathology of the Stomatology and Maxillo-Facial Surgery division of La Salpêtrière Hospital were consulted to provide their experience-based recommendations. RESULTS AND DISCUSSION: Clear and practical definitions drawn from current knowledge were adopted. Precancerous lesions were distinguished from precancerous states. Precancerous lesions included chronic lesions of the oral cavity on which cancer of the oral cavity is known to develop. These were: leucoplakia, oral lichen planus, erythroplasia, papillomatous lesions, actinic cheilitis, submucosal fibrosis, keratotic candidosis, and tertiary syphilis. The precancerous states included cancers occasionally observed in the oral cavity: immunodepression and Plummer Vinson syndrome were analyzed. Epidemiological, clinical, histological, and evolutive data as well as therapeutic strategies were described. A decisional algorithm was elaborated for leucoplakia. The text was enriched with images available in the Department. CONCLUSION: Precancerous lesions of the oral mucosa offer a particularly interesting area of research for understanding the process of cancer formation and its prevention. The level of scientific proof available in the large majority of the published reports is low. Few recent publications provide relevant data. In practice, the experience in the management of cancer and precancerous lesions of the oral mucosa accumulated over the last 40 years at the Department of Cancer and Oral pathology of the Stomatology and Maxillo-Facial Surgery division of la Salpêtrière Hospital provides an invaluable source of information.     

Oral Lichen Planus and Its Association With Squamous Cell Carcinoma: An Update on Pathogenesis and Treatment Implications

Lichen planus of the oral mucosa (OLP) is characterized by lymphocytic mucositis, basal cell lysis, and lymphocyte transmigration into the epithelial compartment. Some reports have suggested a high incidence of oral squamous cell carcinoma (OSCCA) in OLP patients and have implicated OLP as a premalignant lesion. We describe five cases of OSCCA arising in patients with preexisting OLP. At our institution, the incidence of OSCCA in patients with OLP aproximates that reported in other series. The immunopathologic basis for OLP, its potential association with malignancy, and the variable clinical picture of OSCCA in patients with OLP are reviewed. Specific recommendations are given for treatment and follow-up of lesions, including the role of future testing with viral and oncogene markers.     

Malignant turn of oral planus in three new cases

The possible malignant potential of oral lichen planus (OLP) is still controversial. We present three new oral lichen planus (OLP) patients who developed oral squamous-cell carcinoma (OSCC). In all cases, were analyzed variables like sex, age, clinical type, localization, extension, follow-up study and treatment, moreover were considered the patient's habits, localization, stage and treatment of cancer. The average age was 59 years and both of them were non smoker or with no alcohol habits. The follow-up period was greater than two years and the malignant lesion developed after mean of nine years, after the diagnosis of OLP had been established. Oral squamous-cell carcinoma (OSCC) arose on lesions previously diagnosed clinically and histologically as atrophic and erosive oral lichen planus in two of our patients and on a plaque lesion LP in a patient. All of them had been using topical corticoids before the cancer was diagnosed. The appearance of new cases of OLP malignization framed inside the established approaches, suggests the realization of new researches in order to determine the factors involved in this process.     

Hypertrophic recurring lichen planus of the external auditory canal

Introduction

We report a case of unilateral progressive primary hypertrophic lichen planus of the external auditory canal requiring several surgical interventions to deal with constant pruritus, otorrhoea, stenosis and conductive hearing loss.

DNA content, Cyclooxygenase-2 expression and loss of E-cadherin expression do not predict risk of malignant transformation in oral lichen planus

Oral lichen planus (OLP) may be associated with a small risk of malignant transformation of the oral mucosa. Using cases which had transformed, and those which had not, this study aimed to evaluate the potential of DNA content, expression of Cyclooxygenase-2 (Cox-2) and of epithelial (E)-cadherin as risk markers in lesions of OLP. We investigated 78 archival biopsies from; (1) 26 OLP patients with at least two biopsies, of whom seven presented OLP with epithelial dysplasia, followed by oral squamous cell carcinoma (OSCC) in five of them, (2) 19 OLP patients with one biopsy taken. Image cytometry for measurement of DNA content and immunohistochemistry for visualisation of Cox-2 and E-cadherin expression were performed. All OLP biopsies investigated were classified as diploid, one OLP with epithelial dysplasia was tetraploid and all OSCC were diploid. Cox-2 was detected in the epithelium of all OLP specimens investigated, as well as in epithelial dysplasias and OSCC. Focal loss of E-cadherin expression was observed in basal keratinocytes in 88% of the OLP specimens investigated, in all epithelial dysplasias and OSCC. In conclusion, neither aneuploidy, Cox-2 expression, nor loss of E-cadherin expression, were significant reliable markers to select OLP lesions at risk for development of OSCC in the present patient material.