Oral keratosis of unknown significance shares genomic overlap with oral dysplasia
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Abstract Objectives To identify molecular characteristics of keratosis of unknown significance and to nominate pathways of molecular progression to oral cancer. Our work could provide a rationale for monitoring and treating these lesions definitively. Methods Patients with oral leukoplakia were eligible for our prospective observational study. We correlated alterations in cancer‐associated genes with clinical and histopathologic variables (keratosis of unknown significance vs. moderate‐to‐severe dysplasia) and compared these alterations to a previously molecularly characterized oral cancer population. Results Of 20 enrolled patients, 13 (65%) had evidence of keratosis of unknown significance, while seven (35%) had dysplasia. Nine patients (45%) developed oral cancer (4/13 with keratosis of unknown significance, 5/7 with dysplasia). At a median follow‐up of 67 (range 22–144) months, median overall survival was significantly shorter for patients with dysplasia (hazard ratio 0.11, p = .02). KMT2C and TP53 alterations were most frequent (75% and 35%, respectively). There were molecular similarities between keratosis of unknown significance and dysplasia patients, with no significant differences in mutational frequency among genes with ≥15% rate of alteration. Conclusions Among patients with leukoplakia, both patients with keratosis of unknown significance and patients with dysplasia developed oral cancer. Molecular alterations between these two groups were similar at this sample size.Keywords:
Actinic keratosis
Keratosis
Epithelial dysplasia
Clinical Significance
The significance of leucoplakia/hyperkeratosis in colposposcopy or hyperkeratotic cells in Pap smear, is not fully understood. It is considered that hyperkeratosis itself is a benign change, but it may mask other pathologies, including invasive carcinoma. We studied 123 woman with colposcopically identified hyperkeratosis and its' possible relationship with dysplastic lesions of uterine cervix, based on correlation with cytopathological and histopathological data. The results of our study showed that 1) cervical dysplastic lesions are identified 2 times less frequently in conventional Pap smears from patients with thick leukoplakia, than in patients with thin leukoplakia and 2) histopathologically identified cervical dysplasias are 1,5 times more common in patients with thick leukoplakia. Pathologists and gynecologists in practice should be aware of this difference.
Dyskeratosis
Carcinoma in situ
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Oral keratotic white lesions are a common problem that is encountered on routine clinical examination. Clinical appearance of the lesion may belie the true nature of the lesion. So a biopsy followed by histopathological diagnosis is the gold standard in evaluating these lesions for malignant potential or dysplasias. Objective: The aim of the present study is to evaluate the clinicopathologic findings of oral keratotic lesions. Materials and Methods: Oral biopsies of 61 cases of oral keratotic white lesions during the period from January 2006 to July 2009 were studied retrospectively at the Department of Pathology, Kasturba Medical College, Manipal by microscopy. Clinical details and records were obtained from the medical records department. Results: In 61 cases of oral keratotic white lesions the age distribution ranged from 29 to 86 years. 66% were males while 34% were females and most lesions occurred between 31 and 70 years. The buccal mucosa was the most common site of lesion in 35% patients. Only 15 cases had some personal habits and 8/15 cases (53%) showed dysplasia. 12/ 54 cases (22%) of homogenous leukoplakia displayed dysplasia, of which 11 cases (92%) showed mild dysplasia and 1 case (8%) showed moderate dysplasia. Of the 4 cases of speckled leukoplakia, 75% showed dysplasia- mild, moderate and severe. 2/3 cases (66%) of verrucous leukoplakia displayed dysplasia- moderate and severe. There were 41 cases consistent with leukoplakia (67%), of which 22% showed epithelial hyperplasia and hyperkeratosis, 12 cases showed mild dysplasia, 3 cases moderate dysplasia and 2 cases showed severe dysplasia. Benign keratosis formed the largest group (35%) among the 61 cases. Of the 61 cases 17 (27%) showed dysplasia of which 19% was mild dysplasia, 5% was moderate dysplasia and 3% was severe dysplasia. Most frequent histomorphological feature seen in this study was nuclear pleomorphism in 21/ 27 cases (78%). There were 12 cases (71%) of dysplasia in males and 5 cases (28%) of dysplasia in females. There was 1 case of Progressive verrucous leukoplakia in an 86 year old female patient. There were 3 cases (5%) each of oral lichen planus, lichenoid dysplasia and lichenoid keratosis in the present study. 6 cases (9%) of candidiasis was seen among the 61 biopsies. In the study there was 1 case (2%) each of verrucous carcinoma, squamous cell carcinoma and micro-invasive squamous cell carcinoma. Conclusions: Oral keratotic white lesions demonstrate a wide spectrum of histopathological features from benign lesions to dysplastic lesions to carcinoma in situ to invasive ones. Scientific World, Vol. 10, No. 10, July 2012 p70-76 DOI: http://dx.doi.org/10.3126/sw.v10i10.6866
Keratosis
Epithelial dysplasia
Oral mucosa
Dyskeratosis
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Histopathological examination
Epithelial dysplasia
Hard palate
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One hundred two patients (115 lesions) with oral leukoplakia were studied and followed up for an average period of 6 years 2 months. Of all cases, 38 showed an abnormal epithelium with no dysplasia and the 77 others showed some degree of epithelial dysplasia. The grade of epithelial dysplasia was thought to be related to the following changes in the WHO criteria (1978).·loss of polarity of the basal cells.·the presence of more than one layer of cells having a basaloid appearance.·dro P-shaped rate processes.·irregular epithelial stratification.·nuclear hyperchromatism.Epithelial dysplasia or high mean scores based on the new scoring system for dysplastic changes were found in the following types of patients: Site: tongue (lateral borders, inferior surface), floor of the mouth. Age: fourth and fifth decades of life. Clinical type: leukoplakia erosiva. Habits: drinkers or drinkers and smokers. Three patients subsequently developed squamous carcinomas in an average time of 5 years 9 months, and these patients originally had moderate to severe epithelial dysplasia.The cumulative frequency of oral carcinoma in cases of oral leukoplakia was 0 % by 1 and 3 years, 1.2 % by 5 years, and 6.6 % by 10 years. This study suggests that certain of the characteristics of oral leukoplakia described above are associated with greater risks of malignant transformation, and thereby warrant consideration for more aggressive management.
Epithelial dysplasia
Malignant Transformation
Oral leukoplakia
Basal (medicine)
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Fifty-six cases of leukoplakia of the lateral border of the tongue were examined histopathologically.Of 56 cases of leukoplakia, 22 cases (39.3%) showed epithelial dysplasia.The outline of rete process could be classified into the following three types; flattened type, elongating type and drop-shaped type. Epithelial dysplasia was rarely observed in the flattened type. However, 30% of elongating types and 92.9% of drop-shaped types revealed epithelial dysplasia.In addition, the thickness of epithelium in leukoplakia were also examined in relation to epithelial dysplasia. The atrophic epithelium showed epithelial dysplasia more frequently than in the thickened epithelium.
Epithelial dysplasia
Oral leukoplakia
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Epithelial dysplasia
Keratosis
Verrucous carcinoma
Oral Lichen Planus
Dyskeratosis
Precancerous condition
Epidermolytic hyperkeratosis
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Two hundred fifty-seven patients with oral leukoplakia were studied and followed for an average period of 7.2 years. All lesions were more than one cm in size and had been present and observed for a minimum of 6 months. Of the initial biopsies, 235 revealed a benign hyperkeratosis and 22 others contained some degree of epithelial dysplasia. Seventy-three percent of the patients used tobacco, with cigarette usage being the predominant form. Forty-five patients (17.5%) subsequently developed squamous carcinomas in the hyperkeratotic epithelial site in an average time of 8.1 years. Eight of these malignant transformations came from patients who originally had epithelial dysplasia. High risks for malignant transformation also included non-smoking patients, the clinical presence of erythroplasia (erythroleukoplakia), and a clinical verrucous-papillary hyperkeratotic pattern. Duration of the leukoplakia progressively increased the total number of malignant transformations, with the largest rate occurring in the second year. This study confirms that oral leukoplakia is a precancerous lesion and that certain characteristics indicate greater risks and warrant consideration of more aggressive management.
Malignant Transformation
Epithelial dysplasia
Oral leukoplakia
Keratosis
Precancerous lesion
Premalignant lesion
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Parakeratosis
Keratosis
Dyskeratosis
Acanthosis
Oral leukoplakia
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Keratosis
Acanthosis
Parakeratosis
Dyskeratosis
Epithelial dysplasia
Oral mucosa
Papillomatosis
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Epithelial dysplasia was examined clinico-pathologically in 196 cases of oral leukoplakia according to WHO's criteria. Fifty-seven cases (29.1%) were found to have epithelial dysplasia. The tongue was the most prevalent site at which epithelial dysplasia occurred, that is 31 of 66 case (47.0%). In 12 tems of WHO's criteria for epithelial dysplasia, the items 2, 1, 12 and 4 which were reported to be important to evaluate the potentiality of malignant transformation, were frequently seen in that order. Malignant transformation occurred in 14 cases (7.1%) of oral leukoplakia, in which the tongue was the most frequent site of malignant transformation (12 cases). Of the 14 cases, 7 showed epithelial dysplasia before malignant transformation. The cases whose grade of epithelial dysplasia had increased with time had a tendency to develop into cancer. Thus attention should be paid to the existence and grade of epithelial dysplasia in the treatment of oral leukoplakia.
Epithelial dysplasia
Malignant Transformation
Oral leukoplakia
Tongue Neoplasm
Premalignant lesion
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