Morphological classification of oral leukoplakia (author's transl)

656 cases of oral leukoplakia were analysed according to macroscopic aspects, microscopic growth patterns and histologicalcytological differentiation, and the relationship to cancer of the oral cavity was studied. Homogeneous and speckled leukoplakia can be distinguished macroscopically, while flat (70%), papillary-endophytic (22%) and papillomatous-exophytic (8%) types can be distinguished by their growth pattern. Histological-cytological characteristics consist of epithelial hyperplasia (hyperkeratosis with ortho- or parakeratosis; akanthosis) and epithelial dysplasia (dyskeratosis, basal-cell hyperplasia, loss of polar arrangement of the basal cells, cell polymorphism, increased mitosis rate). No or little dysplasia was demonstrated in 74% of leukoplakias, moderate in 17% and marked in 6%. Carcinoma-in-situ, defined as high-grade dysplasia with additional loss of epithelial layering, was found in 3%. Precancerous leukoplakia (in almost 10% of cases, counting high-grade dysplasias and carcinoma-in-situ) must be delineated as a special group. Numerous correlations were found between dysplastic leukoplakias and oral cavity cancer as regards localisation, age and sex distribution. In the various leukoplakia forms there was an increased incidence of marked stroma reactions and of Candida colonisation with increased degrees of dysplasia.     

Paired filtration dialysis--evaluation of effectiveness of the method]

The regeneration of the oral mucosa is zinc- and vitamin A-pathway dependent. Hyperkeratoses, a disturbed immune system and a higher incidence of oral malignancies have been reported in cases of deficiency. In this study, blood samples were taken from 97 patients with oral lichen planus, oral leukoplakia, oral squamous cell carcinoma (OSCC), and a control group. Besides routine blood analysis, serum levels of zinc (Zn), vitamin A (Vit A) and retinol binding protein (RBP) were identified. Mean values in lichen ruber planus were Zn 784 micrograms/l, RBP 5.26 mg/dl and Vit A 656 ng/ml; in leukoplakia Zn 696 micrograms/l, RBP 5.30 mg/dl and Vit A 652 ng/ml; and in OSCC Zn 659 micrograms/l, RBP 5.00 mg/dl and Vit A 617 ng/ml. Patients with lichen ruber planus showed no statistically significant differences, whereas in leukoplakia patients there were statistically lower values for Zn compared to the control group and the lichen ruber planus group (P < 0.05). Patients with oral malignancies showed lower serum levels for Zn, RBP and Vit A. Compared with the control group and the lichen ruber planus group, differences of the serum Zn levels proved to be statistically significant (P < 0.01). In patients with oral leukoplakia and patients with oral carcinoma and Zn deficiency, a substitutional therapy should be considered.     

A high prevalence of p53 mutations in pre-malignant oral erythroplakia

Oral squamous-cell carcinoma is thought to be preceded by a number of precursor stages which induce morphological changes in cells of the oral mucosa resulting in clinically detectable pre-malignant lesions such as erythroplakia or leukoplakia. To better understand the etiology of oral erythroplakia, we have examined the p53 tumor-suppressor gene (exons 5-9) for mutations in 24 oral erythroplakia lesions of varying dysplastic phenotypes by PCR/single-strand conformational polymorphism and direct DNA-sequencing analyses. A total of 12 p53 mutations were detected in 11 of 24 (46%) erythroplakia specimens (one specimen contained two different p53 mutations); 25% were single-base-pair deletions and 33% were either G:C-->T:A transversions or G:C-->A:T transitions. A high prevalence of p53 mutation was observed in all categories of erythroplakia lesions: 33% for mildly dysplastic lesions, 50% for lesions exhibiting moderate to severe dysplasia and 50% for lesions that were carcinoma in situ. Although the combined prevalence of p53 mutations observed in erythroplakia was significantly higher (p = 0.02) than that observed earlier for leukoplakia, the prevalence of p53 mutations was similar in erythroplakia and leukoplakia specimens from smokers. The prevalence and spectrum of p53 mutations observed in this series of erythroplakia lesions are similar to those observed for oral squamous-cell carcinoma. These results indicate that mutations of the p53 gene may be linked to the high malignant potential of erythroplakia and provide further evidence that p53 mutation may be an early event in the genesis of oral squamous-cell carcinoma.     

Chronic conductive hearing loss in adults: effects on the auditory brainstem response and masking-level difference

Chronic desquamative gingivitis (DG) is a common condition often first recognized by periodontists. DG is characterized clinically by erythema with epithelial desquamation, ulceration, and/or the presence of vesiculobullous lesions of the free and attached gingiva. However, DG is actually a clinical manifestation of several different disease processes, particularly lichen planus and benign mucous membrane pemphigoid. Correct diagnosis in DG is critical since proper treatment and follow-up will depend on which disease is involved. However, the diseases that cause DG frequently present diagnostic problems because their lesions often resemble each other clinically and routine histological examination sometimes cannot differentiate between them. Thus, immunohistology, particularly immunofluorescence, is increasingly being used with routine histology to more accurately diagnose DG diseases. This article reviews our experience over the past 10 years in the diagnosis of 72 cases of DG using direct immunofluorescent (DIF) in conjunction with histology and clinical evaluation. Of the 72 DG cases in this study, 30 cases were diagnosed as erosive lichen planus or lichenoid mucositis; 29 cases were diagnosed as benign mucous membrane pemphigoid; 2 cases each of linear IgA disease and pemphigus vulgaris were diagnosed; there was 1 case of bullous pemphigoid; and 1 suspected case of paraneoplastic pemphigus. Even with DIF analysis, 7 cases could not be definitively assigned a particular cause. DIF analysis is not only proving very useful for differential diagnosis, but also adds insight into possible pathogenic mechanisms of DG.     

Oral lichen planus: parameters affecting accurate diagnosis and effective management

Oral lichen planus is one of the most common mucosal diseases that require management by the dental practitioner. The gingival presentation of this disease can be particularly problematic. Accurate diagnosis is of paramount importance for effective management, and tissue specimens are often required to distinguish this disease from other vesiculo-ulcerative diseases. The lichen planus patient can generally be managed with topical steroids. The use of antibiotics may be an important adjunctive consideration for patients with a concurrent significant periodontal condition. The possibility of carcinoma arising in lichen planus lesions is addressed. The learning objective of this article is to define specific parameters that contribute to the definitive diagnosis in order to promote objective, rather than empirical, treatment and to delineate specific points to address in patient education.     

Nursing care in renal transplant patients with infection problems]

OBJECTIVES: To identify, from amongst drugs reported as causing lichenoid drug eruptions, those affecting the oral mucous membranes and to review the clinical, histological and immunological features of such oral lichenoid drug eruptions in comparison to oral lichen planus, amalgam contact lesions and lichen planus-like eruption in graft-versus-host disease (GVHD). DATA SOURCES: Ovid Medline data searches on CD-Rom were carried out for the years 1966-1996 to identify reports of oral lichenoid drug eruptions and their clinical, histological and immunological features. Articles retrieved were examined for further appropriate references in the period 1940-1996. DATA EXTRACTION AND SYNTHESIS: Each paper was critically examined for evidence of a clinically verifiable lichenoid drug-eruption affecting the oral mucous membranes and the effects of subsequent drug withdrawal. Available clinical, histological and immunological features were recorded. The papers examined were too diverse in nature to permit a structured criticism. The extracted data have been tabulated where appropriate. CONCLUSIONS: The reports of oral lichenoid drug eruptions are considerably fewer than those of cutaneous eruptions and fewer drugs have been reported as causing oral rather than cutaneous lichenoid eruptions. Histology and immunology cannot be used reliably to differentiate lichenoid drug eruptions from idiopathic lichen planus, amalgam contact lesions and lichen planus-like eruption in GVHD. Lichenoid drug eruptions may also show some histological characteristics of oral discoid lupus erythematosus. An accepted protocol agreed by a number of international centres would permit the gathering of substantial information on LDE and could lead to a greater understanding of the mechanisms involved.     

Comments on the article "Studies of the mortality of atomic bomb survivors. Report 12, part I. Cancer: 1950-1990" by D. A. Pierce, Y. Shimizu. D. L. Preston, M. Vaeth and K. Mabuchi (Radiat. Res. 146, 1-27, 1996)

We report the case of an 82-year-old woman with a 6-year history of erosive palmoplantar lichen planus associated with eccrine syringofibroadenoma (ESFA). Examination revealed a well-demarcated patche writish of reticulated whitish papular lesions in skin of otherwise normal appearance at the border of erosive lichen planus plaques. These lesions had the histological appearance of ESFA. We suggest that these lesions are induced by the inflammatory remodelling associated with erosive lichen planus and propose to consider ESFA in the context of skin tissue remodelling as a new subtype of ESFA.     

The proliferative activity in oral epithelial dysplasia analyzed by proliferating cell nuclear antigen immunostaining and argyrophilic nucleolar organizer region staining

The proliferative activity of leukoplakia without dysplastic change (LP), epithelial dysplasia (ED), and squamous cell carcinoma (SCC) in the oral mucosa was examined by means of proliferating cell nuclear antigen (PCNA) immunostaining, silver-binding argyrophilic nucleolar organizer region (AgNOR) staining, and the frequency of mitotic figures. Significant differences in the labeling index of PCNA immunostaining (PI) and mitotic index (MI) were noted between LP and ED and between ED and SCC. The mean numbers of AgNORs (AI) significantly differed between ED and SCC. There was a significant positive correlation between PI and MI in samples of ED. However, there was no significant correlation between AI and other indexes. The number and the distribution of PCNA-positive cells in ED varied among samples. Five samples with higher PI and MI indexes than the mean values were selected from those of dysplasia based on the correlation between PI and MI. Their histological features symptomatic of oral ED as defined by the World Health Organization (WHO) Collaborating Centre in 1978, were investigated and compared with 10 samples with lower indexes. Histological findings, such as "loss of polarity of the basal cells," "an increased nuclear-cytoplasmic ratio," "cellular pleomorphism," and "enlarged nucleoli," were significant histological features of these five samples. This study showed that the four histological components described previously and the increased number of mitotic figures used as the index of proliferating activity were the main histological components related to severe ED of oral mucosa. They will provide a useful means of deciding the histopathological grade of oral ED.     

The bone marrow stromal environment is a major factor in myeloma cell resistance to dexamethasone

The expression of several markers of epithelial cell proliferation was analyzed to establish baseline data for future chemoprevention studies of oral premalignant lesions. Punch biopsies (n = 60) from three different sites of oral mucosa (bucca, lateral tongue, and the floor of the mouth) were obtained from 20 normal donors of both sexes. After formaldehyde fixation and paraffin embedding, immunohistochemistry was used to detect the proliferation markers Mib-1, cyclin D1, and centromere-associated protein CENP-F. Analysis of sections stained for the three markers showed similar patterns, i.e., a low labeling index (LI) in the basal layer and a high LI in the parabasal layer at all three intraoral sites. No proliferative activity was seen above the parabasal layer (superficial layer). All sites showed similar Mib-1 LI values for the proliferative markers. The tongue epithelium exhibited higher parabasal LIs of cyclin D1 and CENP-F than did the other two sites. No significant differences were detected between smokers and nonsmokers. The data from normal mucosa were compared with those from low (n = 30)- and high (n = 17)-grade dysplastic leukoplakias. The Mib-1 LI showed a very significant change, with a 9-fold increase in the basal layer LI in dysplastic leukoplakias. Cyclin D1 and CENP-F showed similar trends with increments of up to 7-fold in the basal layer of high-grade dysplasia. Although the proliferative activity of the parabasal layer was similar in normal and leukoplakic epithelia, the superficial layer showed a significant increment in proliferative activity mainly in high-grade leukoplakia. These studies suggest that proliferation markers in the basal and superficial cells of premalignant lesions may serve as surrogate end point biomarkers for chemoprevention trials.     

Psychologic factors and oral lichen planus. A psychometric evaluation of 100 cases

OBJECTIVE: The purpose of this study was to analyze the importance of psychologic factors in patients with oral lichen planus, and attempts were made to identify possible personality features characteristic of patients with oral lichen planus. STUDY DESIGN: The study involved 100 patients with oral lichen planus (group 1) and 50 control subjects (group 2). We applied the following psychometric tests to both groups: Spielberger State-Trait Anxiety Inventory, Cattell Personality Questionnaire 16PF, Hassanyeh Rating of Anxiety-Depression-Vulnerability, Beck Depression Inventory, Raskin Depression Screen, and Covi Anxiety Screen. RESULTS: The patients with oral lichen planus were found to exhibit greater anxiety, as reflected by statistically significant scores with the anxiety tests that were used (Spielberger State-Trait Anxiety Inventory, Cattell Personality Questionnaire 16PF, Hassanyeh Rating of Anxiety-Depression-Vulnerability, and Covi Anxiety Screen). The patients with oral lichen planus likewise exhibited greater depression than the controls in all 3 depression tests applied (Beck Depression Inventory, Hassanyeh Rating of Anxiety-Depression-Vulnerability, and Raskin Depression Screen) and were more vulnerable to psychic disorders on the basis of the PD subscales (vulnerability) of the Hassanyeh questionnaire. Three features (conformity to the group, astuteness, and rebelliousness) defined the personalities of our patients with oral lichen planus, according to the Cattell 16PF questionnaire. Finally, those patients with erosive lichen planus exhibited higher depression scores than patients with nonerosive lichen planus. CONCLUSIONS: Despite the higher anxiety scores observed in patients with oral lichen planus, it was not established that the observed psychologic alterations constitute a direct etiologic factor of oral lichen planus; nor was it established that such alterations are a consequence of oral lichen planus and its lesions.     

Lichen planus pemphigoides is a heterogeneous disease: a report of five cases studied by immunoelectron microscopy

Lichen planus pemphigoides (LPP) is a rare and controversial disease. It is characterized by bullae arising on lichen planus papules and on uninvolved skin, subepidermal bullae in histology, and linear deposits of IgG and C3 along the basal membrane zone on immunofluorescence of peribullous skin. Our goal was to identify the localization of the target antigen in cases of LPP. Five patients diagnosed with LPP on clinical, histological and immunofluorescence criteria were explored by immunoelectron microscopy and immunoblot. Our results show that the target antigen in LPP is not unique. The localization of the immune deposits was consistent with a diagnosis of bullous pemphigoid in two cases, of cicatricial pemphigoid in two cases and of epidermolysis bullosa acquisita in one case. Our study supports the view that LPP is a heterogeneous condition in which lichen planus may induce different subepidermal acquired bullous dermatoses.     

Telomerase activity in oral lichen planus

The purpose of this study was to determine the expression of telomerase in refractory oral lichen planus. Using a polymerase chain reaction-based telomerase activity assay, we investigated telomerase activity in 20 oral lichen planus specimens (erosive 9, atrophic 11). Telomerase activity was detected in 14 cases (erosive 7, atrophic 7). Furthermore, 13 cases of lichen planus with mild dysplasia proved telomerase-positive in eight specimens and six of seven cases devoid of dysplasia were also positive in the telomerase assay. The data indicate that, in general, telomerase activity might be frequently detectable in OLP. The data also suggest that telomerase activity might not be particularly associated with the premalignant phenotype in OLP.     

Cytopathological analysis of sputum in patients with airflow obstruction and significant smoking histories

Advances in the understanding of lung cancer biology have led to observations that specific genetic changes occur in premalignant dysplasia. These observations have occurred predominantly in molecular studies of resected lung tumors and consequently, they may not be fully representative of those biological abnormalities characterizing premalignant lesions in individuals without overt lung cancer. Studies of premalignant epithelial cell biology and chemoprevention are needed in this patient subgroup. Such an initiative is now underway through the lung cancer Specialized Program of Research Excellence (SPORE) grant awarded to the University of Colorado Cancer Center (and affiliated institutions) by the National Cancer Institute. To identify participants for the early detection and chemoprevention trials of the Colorado SPORE, we initiated a sputum cytology screening program targeting persons with chronic obstructive pulmonary disease and smoking histories of 40 or more pack-years. During the first 26 months after activation of the screening program, sputum samples from 632 participants were evaluated. Of these, 533 (84%) of the subjects submitted specimens deemed adequate for cytopathological interpretation; 99 (16%) provided sputum samples unsuitable for cytodiagnosis. Of those participants who submitted adequate samples, 48% had cytodiagnoses of mild dysplasia, 26 % had moderate to severe dysplasia, and 2% presented with carcinoma in situ or invasive carcinoma. Logistic regression modeling was pursued to determine whether selected demographic and/or clinical status variables could be identified as statistically significant predictors of the specific cytological outcome to be expected (mild dysplasia, moderate dysplasia, and so forth). The only apparent associations found from both univariate and multivariate analyses were that the total number of pack-years of smoking history decreased with severity of cytodiagnosis and that those individuals with mild or moderate dysplasia were more likely to be ex-smokers than those with grades of regular metaplasia or lower. Based on the initial results of the Colorado SPORE sputum cytology screening program, we conclude that persons with chronic obstructive pulmonary disease and 40 or more pack-years of smoking history have a high prevalence of premalignant dysplasia detectable through sputum cytology and should be targeted for research programs focusing on lung cancer prevention, early detection, and exploratory biomarker studies.     

A clinico-laboratory validation of the combined therapy of lichen ruber planus of the oral mucosa

Fifty-two patients with lichen planus were examined over the course of disease using clinical, microbiological, and histological methods. Treatment protocols aimed at normalization of microbiocenosis have been developed, based on the detected microbiological and histological changes.     

Sexually transmitted diseases: laboratory diagnosis

Betel chewer's mucosa (BCM) was first described and defined in 1971. Its clinical appearance is characterised by a brownish-red discolouration of the oral mucosa with an irregular epithelial surface that has a tendency to desquamate or peel off. The buccal mucosa is most frequently affected. The prevalence of BCM varies between 0.2% and 60% in different studies from South and Southeast Asia. Women are more frequently affected than men. Betel chewer's mucosa may be found together with other oral mucosal lesions such as leukoedema, leukoplakia and ulceration. The histological features are characteristic. The epithelium is often hyperplastic, and brownish amorphous material derived from the betel quid may be demonstrated not only on the epithelial surface but also intra- and inter-cellularly. Ballooning of epithelial cells may occur. The etiology is traumatic and possibly chemical. Betel chewer's mucosa is most likely not precancerous. Differential diagnoses include cheek biting, with which it has a number of similarities, and other predominantly white lesions that may have taken up stains from tobacco and other substances. The natural history of BCM should be studied in more detail and its association with other oral mucosal diseases, particularly of a precancerous nature, should be the aim of further investigations.     

Effects of sympathetic efferent in diabetic hyperalgesia in rat]

Ensuring the validity and reliability of data collected in epidemiological surveys is an important consideration. The purpose of the present report is to describe a training and calibration programme for 16 examiners taking part in a national survey of oral mucosal lesions and to present an evaluation of the results. The programme included the distribution of a pictorial manual to participants and a series of lectures followed by three diagnostic sessions, two using slides and the last involving patients. At the final session, the trainees classified 88 per cent of 16 patients correctly in comparison with the definitive diagnoses of the trainer, and their sensitivity on recording oral carcinoma, leukoplakia and lichen planus was at least 0.88. However, correctly classifying submucous fibrosis on the basis of slides alone proved problematic. At the conclusion, the diagnostic accuracy of two examiners for all types of lesion remained appreciably lower than the majority. Training strategies for various types of study are discussed. The method reported is considered to represent a model approach to training and calibrating examiners for this type of survey work.     

Malignant tumors of the oral cavity. Epidemiologic study of 294 cases observed during the decade 1984-1994

MATERIALS AND METHODS: The research has been carried out with the cooperation of Department of Otorhinolaryngology of the "Ospedale S.S. Trinita" in Cagliari, on 294 patients suffering from oral malignant tumours between 1984 and 1994. This kind of disease was studied in relation to age, sex, histological type, and afterwards the examination results were compared to other researchers' studies. All the 294 patients were recorded in the operating theatre's registers. Oral malignant tumours amount to about 45% of the neoplastic systemic pathology. Use and misuse of alcohol, smoking, repeated blows resulting in pre-cancerous lesions including leukoplakia, might be considered the main causes of the origin of oral tumours. RESULTS: Male patients (237) amount to 80.7% of the examined sample, while female ones (57) reach only 19.3%. The part most frequently involved is the tongue (97 cases, 33%), then the area of the lower lip (69 cases, 23.5%), and finally the lower part of the oral space (47 cases, 15.58%). CONCLUSIONS: From the histological point of view, the squamous carcinoma is found more often in the tongue, in the lower oral space and in the lips, while the basal carcinoma in the lower lip rather then in the upper one. A remarkable increase in the squamous carcinoma and a grow in the areas of the tongue has been observed.     

Flow cytometric analysis of DNA ploidy in colorectal adenoma

Flow cytometric measurement of nuclear DNA content in 159 colorectal adenomas was carried out to investigate the relationship between DNA ploidy and the histological findings. DNA aneuploidy was detected in 18 lesions (12.8%). The incidence of DNA aneuploidy was significantly higher in tubulovillous adenomas than in tubular adenomas (30.4% vs. 8.1%; p < 0.01). DNA aneuploidy was not found in any adenoma with mild dysplasia, but was noted in 19.1% of those with moderate dysplasia and in 33.3% of those with severe dysplasia. The mean size of the lesions was significantly larger in adenomas with aneuploidy than in those without aneuploidy (14.0 mm vs. 7.7 mm; p < 0.01). The DNA index values of 18 adenomas with aneuploidy were divided into two groups: one ranged from 1.07 to 1.23 and the other from 1.66 to 1.85. DNA index values correlated with the size of the lesions (p < 0.05), but not with the histologic type and degree of dysplasia.     

Isolated lichen planus of the lip successfully treated with chloroquine phosphate

Solitary lesions of lichen planus (LP) are often confused with other inflammatory or malignant epithelial lesions. We describe a 51-year-old woman who had had an LP of the lower lip for 11 years. She had undergone several oral and topical therapies with little improvement. The patient had an excellent response to chloroquine phosphate within 3 months. This report represents the third case of LP exclusively localized on the lower lip.     

The use of thrombomodulin to study epithelial cell differentiation in neoplastic and non-neoplastic oral lesions

Thrombomodulin (TM) is a glycoprotein originally isolated from rabbit lung vasculature and characterized as a natural endothelial anticoagulant. Thrombin binds to TM noncovalently with high affinity. Thrombin-TM complexes can activate protein C efficiently. Activated protein C inactivates factors Va and VIIIa and regulates the blood coagulation cascade. Thus TM converts thrombin from a procoagulant protease to an anticoagulant. TM is found on endothelial cells in veins, arteries and capillaries. Our previous study has shown that TM is also expressed on the cell surface of squamous epithelium. In the present study, we aimed to disclose differences in TM expression among normal, dysplastic, and malignant squamous epithelium in human oral mucosa by counting TM-positive cells in each lesion. TM was uniformly expressed in the spinous layer of normal human oral squamous epithelium. The number of TM-positive cells was not significantly different between normal epithelium, lichen planus and mild dysplasia. In contrast, in moderate and severe dysplasia and well-differentiated squamous cell carcinoma (SCC), there were significantly fewer positive cells compared with normal epithelium. In SCCs, the periphery and the central keratinized area of tumor islands were often negative. The proportion of TM-positive cells in poorly differentiated SCC was significantly lower than in well-differentiated SCC. These results indicate that TM may have diagnostic value in the histological examination of oral premalignant and malignant lesions.