Risk Factors For Malignant Transformation Research Articles

Direct Immunofluorescence in Clinically Diagnosed Oral Lichen Planus

Purpose: Oral lichen planus (OLP) is relatively common mucosal disease in clinical dentistry. OLP is intractable and regarded having malignant potential. Until now, there is some debate on how far OLP can be malignant, and which characteristics can be a risk factor for malignant transformation. Clinician need to know some differences between OLP and lesions similar to OLP to manage properly and suppose prognosis correctly. Therefore, the aim of this study was to divide clinical OLP into two groups and to compare the results of direct immunofluorescence (DIF) between two groups. Methods: This study was conducted on outpatients who visited at the department of Oral Medicine in Chonbuk National University Hospital from January 2007 to November 2015. Patients with DIF result were retrospectively reviewed. The selected patients were classified ‘clinical typical of OLP’ (CTO) or ‘clinical compatible with OLP’ (CCW) by modified World Health Organization diagnostic criteria of OLP and oral lichenoid lesion. Results: DIF were classified by deposition intensity or pattern of anti-human antibody and fibrinogen. The classification of fluorescence pattern in each specimen was graded as positive, possibly positive or negative. Conclusions: Both CTO and CCW had positive and possibly positive pattern. Prevalence of positive pattern was 68.8% in CTO and 52.6% in CCW and that of possibly positive pattern was 9.4% in CTO and 5.3% in CCW. Prevalence of negative was 21.8% in CTO and 42.1% in CCW.

Interlaboratory variability in the grading of dysplasia in a nationwide cohort of colorectal adenomas

Although high-grade dysplasia (HGD) is a risk factor for malignant transformation and the future development of adenomas/carcinomas, grade is not incorporated in the Dutch guidelines for colonoscopy surveillance, partly because of presumed interobserver variability. The aim of this study was to analyse, in a nationwide cohort of colorectal adenomas, the interlaboratory variability in the grading of dysplasia in daily practice. From the Dutch Pathology Registry, all synoptically reported classic adenomas in The Netherlands in 2013 were identified. The proportion of adenomas with HGD was determined for biopsies and polypectomies, and compared between 37 laboratories by the use of multivariable logistic regression analyses. In total, 21 030 colonoscopies of 20 270 patients were included. HGD was reported in 530 (3.6%) of 14 866 adenomas diagnosed on biopsies (range between laboratories: 0-13.6%) and in 983 (11.8%) of 8346 adenomas diagnosed on polypectomies (range: 3.1-42.9%). After adjustment for case mix, 13 (35%) laboratories reported a significantly lower or higher frequency of HGD than average. We observed considerable interlaboratory variation in the grading of dysplasia in colorectal adenomas, which could be only partly explained by differences in case mix. Therefore, better standardization of grading criteria is needed before grade of dysplasia can usefully be incorporated in colonoscopy surveillance guidelines.

Oral leukoplakia: A review and its update

Oral leukoplakia (OL) is the most common potentially malignant disorder of the oral mucosa. The etiological role of Candida in leukoplakia has been a subject of debate in recent years. Candida invasion has been suggested to be a significant risk factor for malignant transformation of OL and also it may be associated with certain clinical characteristics such as lesion type, size, and site, dysplasia, and tobacco use. Several studies showed that the greater risk of malignant change in women than men. Finally, the management of this common condition remains a variable and includes local, topical, and systemic therapies such as anti-oxidants, carotenoids, and antifungal therapies.

Marked variation in malignant transformation rates of oral leukoplakia.

Searches were carried out in the Medline, Embase and PubMed databases in July 2014 with a date range, 1960-2013. Observational cohort studies (either prospective or retrospective) were included. Studies following identical cohorts, case control studies, clinical trials, interventional studies, laboratory studies, experimental studies, studies with no follow-up data, studies of pre-leukoplakia or snuff-induced lesions were excluded. The databases were searched by one reviewer who also screened the studies and evaluated them against the inclusion criteria. Final decision on both inclusion and exclusion of the papers was agreed upon by both authors. A total of 24 studies were included in this review, involving 12,103 patients. Of the 24 studies included 14 were retrospective. Studies were analysed by subgroup, allowing the authors to identify the rate of malignant transformation as 14.9% with a range of 0.13% to 34%. Only 11 studies gave information on the site of malignant transformation; the most common site was the buccal mucosa. For buccal mucosa the malignant transformation was 3.53%, compared to 24.22% for the tongue. Homogenous oral leukoplakia (OL) was most common, however non-homogenous types showed a higher rate of transformation of 13.1%. There was an increased risk of malignant transformation with age. Most studies demonstrated that there is a higher risk of transformation in the female population. Malignant transformation rate of OL varies from 0.13 to 34% across the 24 studies reviewed here. The authors identified clear risk factors for malignant transformation of oral leukoplakia, including location (tongue), appearance (non-homogenous), increased age and female gender. There was little evidence that surgical intervention had any benefit in reducing the risk of transformation.

Squamous cell carcinomas in chronic venous leg ulcers. Data of the German Marjolin Registry and review.

Secondary squamous cell carcinoma (SCC) is a rare complication of chronic venous leg ulcers. So far, little is known about its pathophysiology and clinical behavior. Initiated by the working group "Wound Healing" (AGW) of the German Society of Dermatology (DDG), it is the objective of the current Marjolin registry to collect cases of SCC arising in venous ulcers, in order to evaluate diagnostic characteristics. All members of the AGW received questionnaires inquiring about basic patient data, ulcer characteristics, and therapy conducted. From 2010 to 2013, 30 patients (20 women, 10 men) from six tertiary wound care centers were registered. Mean age was 76.17 years. The average duration of venous leg ulcers prior to SCC diagnosis was 15.93 years. Suspicious wound characteristics primarily included: pain (n = 3), therapy resistance (n = 27), and fetor (n = 12) as well as clinical appearance (n = 10) with atypical morphology, nodular wound bed, and hypergranulation. Atypical morphology or changes in appearance as well as therapy resistance despite optimal care (6-12 weeks) should prompt physicians to take spindle-shaped, if necessary multiple and serial, biopsies. Primary risk factors for malignant transformation include patient age and ulcer duration.

Risk Factors for the Development of Hepatocellular Carcinoma in Thailand.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. The incidence of HCC is on the rise in Thailand, where it has become the most common malignancy in males and the third most common in females. Here, we review some of the risk factors that have contributed to this increase in HCC incidence in the Thai population. Hepatitis B virus (HBV) is the main etiologic risk factor for HCC, followed by hepatitis C virus (HCV). Patients with HBV genotype C have a higher positive rate of hepatitis B early antigen (HBeAg) and progress to cirrhosis and HCC earlier than genotype B. For HCV patients, 16% developed HCC associated cirrhosis by year 5 after diagnosis, and the cumulative risk for death from HCC at year 10 was 60%. Dietary exposure to the fungal hepatocarcinogen aflatoxin B1 has been shown to interact synergistically with HBV infection to increase the risk of early onset HCC. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. In recent years, obesity and metabolic syndrome have markedly increased the incidence of HCC and are important causes of HCC in some resource-rich regions.

Synergistic effects of betel quid chewing, tobacco use (in the form of cigarette smoking), and alcohol consumption on the risk of malignant transformation of oral submucous fibrosis (OSF): a case-control study in Hunan Province, China

Oral submucous fibrosis (OSF) is a potentially malignant disorder, wherein 7% to 13% of patients with OSF develop oral squamous cell carcinoma (OSCC) at clinically coincident sites established to have OSF. We aimed at investigating the lifestyle-related risk factors for malignant transformation of OSF. A case-control study was conducted among 80 cases with OSF-associated OSCC and 80 controls with OSF but without clinically or histopathologically evident OSCC, recruited from January 2012 to October 2014 in the Xiangya Hospital, Hunan Province, Mainland China. The odds ratios (OR) for OSCC were 13.3 (95% confidence interval [95% CI]: 3.1-56.4) and 45.1 (95% CI: 9.6-212.9) at the highest exposure of betel quid (BQ) chewing, by duration and frequency, respectively. Higher risks were also found to be associated with the consumption of cigarette (OR = 5.0, 95% CI: 1.7-14.8) and alcohol (OR = 3.1, 95% CI: 1.1-8.6). Adjusted ORs increased substantially among patients who consumed BQ and cigarette or alcohol simultaneously, which were 26.1 (95% CI: 4.0-172.6) and 55.-(95% CI: 1.8-1742.8) at the longest duration, and 160.3 (95% CI: 18.7-11371.2) and 58.1 (95% CI: 2.4-1434.9) at the highest dose, respectively. The use of BQ, cigarette, and alcohol were identified as risk factors for malignant transformation of OSF in the Hunan province, Mainland China. Synergistic effects between BQ chewing and cigarette or alcohol consumption were revealed.

Malignant transformation of oral leukoplakia with a focus on low-grade dysplasia

ObjectiveOral leukoplakia (OL) is classified as a precancerous lesion with potential for malignant transformation. No consensus has been reached regarding appropriate treatment for OL with low-grade dysplasia (LGD). We have often seen that OL with LGD that goes untreated or is excised with insufficient margins develops into squamous cell carcinoma. The aim of this study was to identify the rate of and clarify risk factors for malignant transformation of OL, with a focus on LGD. MethodsConsecutive patients with OL with LGD treated between 2000 and 2011 were selected from the medical records of the Department of Oral and Maxillofacial Surgery at Tokyo Dental College, Chiba Hospital, Japan. Differences between clinical characteristics (age, sex, lesion site, smoking habit, alcohol intake, clinical appearance, lesion color, lesion surface, degree of dysplasia and treatment) and malignant transformation were analyzed using Fisher's exact test. ResultsA total of 115 OL patients with LGD were evaluated. Four cases (3.5%) showed malignant transformation to squamous cell carcinoma. No clinical characteristics showed any significant correlation with malignant transformation. ConclusionsStrict follow-up is recommended for OL with LGD to detect oral cancer in the early stage. Biomarkers to identify malignant transformation of leukoplakia are needed to facilitate treatment of these patients and confirm the malignant transformation rate.

Age-associated inflammation connects RAS-induced senescence to stem cell dysfunction and epidermal malignancy.

Aging is the single biggest risk factor for malignant transformation. Among the most common age-associated malignancies are non-melanoma skin cancers, comprising the most common types of human cancer. Here we show that mutant H-Ras activation in mouse epidermis, a frequent event in cutaneous squamous cell carcinoma (SCC), elicits a differential outcome in aged versus young mice. Whereas H-Ras activation in the young skin results in hyperplasia that is mainly accompanied by rapid hair growth, H-Ras activation in the aged skin results in more dysplasia and gradual progression to in situ SCC. Progression is associated with increased inflammation, pronounced accumulation of immune cells including T cells, macrophages and mast cells as well as excessive cell senescence. We found not only an age-dependent increase in expression of several pro-inflammatory mediators, but also activation of a strong anti-inflammatory response involving enhanced IL4/IL10 expression and immune skewing toward a Th2 response. In addition, we observed an age-dependent increase in the expression of Pdl1, encoding an immune suppressive ligand that promotes cancer immune evasion. Moreover, upon switching off oncogenic H-Ras activity, young but not aged skin regenerates successfully, suggesting a failure of the aged epidermal stem cells to repair damaged tissue. Our findings support an age-dependent link between accumulation of senescent cells, immune infiltration and cancer progression, which may contribute to the increased cancer risk associated with old age.

Risk factors for malignant transformation of mature cystic teratoma.

ObjectiveThe aim of this study was to investigate the preoperative characteristics of benign mature cystic teratoma (MCT) and struma ovarii and their risk factors associated malignancies, and determine the appropriate treatment options for these tumors.MethodsThis was a retrospective study on 248 patients who were pathologically diagnosed with ovarian MCT, struma ovarii, or malignant transformations of these tumors at Inje University Haeundae Paik Hospital from March 2010 to January 2015. Routinely evaluated results of adnexal masses before surgery were compared.ResultsA total of six patients (2.4%) were confirmed to have malignant tumors. Of the struma ovarii patients, two out of five patients (40%) were confirmed to have malignancy. The mean age at the diagnosis of patients with malignant transformation of teratomas was 43.0 years (range, 27 to 67 years), which was higher than that of patients with benign teratomas (36.5 years). The mean diameter of the tumor before surgery in the malignant tumor group was 11.4 cm and larger than 6.5 cm of benign group (P=0.003). The mean CA-125 level in the malignant tumor group was higher than that in the benign tumor group (P=0.01).ConclusionRisk factors for malignant transformation of MCT include elevated CA-125 levels, older age, large tumor masses, and postmenopausal status.

Hepatocellular carcinoma: epidemiology and risk factors.

Hepatocellular carcinoma is one of the major malignant tumors in the world today. The number of new cases of the tumor increases year by year, and hepatocellular carcinoma almost always runs a fulminant course and carries an especially grave prognosis. It has a low resectability rate and a high recurrence rate after surgical intervention, and responds poorly to anticancer drugs and radiotherapy. Hepatocellular carcinoma does not have a uniform geographical distribution: rather, very high incidences occur in Eastern and Southeastern Asia and in sub-Saharan Black Africans. In these regions and populations, the tumor shows a distinct shift in age distribution toward the younger ages, seen to greatest extent in sub-Saharan Black Africans. In all populations, males are more commonly affected. The most common risk factors for hepatocellular carcinoma in resource-poor populations with a high incidence of the tumor are chronic hepatitis B virus infection and dietary exposure to the fungal hepatocarcinogen aflatoxin B1. These two causative agents act either singly or synergistically. Both the viral infection and exposure to the fungus occur from early childhood, and the tumor typically presents at an early age. Chronic hepatitis C virus infection is an important cause of hepatocellular carcinoma in resource-rich countries with a low incidence of the tumor. The infection is acquired in adulthood and hepatocellular carcinoma occurs later than it does with hepatitis B virus-induced tumors. In recent years, obesity and the metabolic syndrome have increased markedly in incidence and importance as a cause of hepatocellular carcinoma in some resource-rich regions. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. Excessive iron accumulation in hereditary hemochromatosis and dietary iron overload in the Black African population and membranous obstruction of the inferior cava cause the tumor in a few countries.

What are the surveillance recommendations following resection of sinonasal inverted papilloma?

What are the surveillance recommendations following resection of sinonasal inverted papilloma?

A Case Report: Cystic Clear Cell Tumor of Borderline Malignancy of the Ovary

Introduction: Ovarian borderline clear cell tumor is a very rare tumor accounting for less than 1% of borderline ovarian tumors. Currently, only 30 cases of borderline clear cell tumors have been reported. This borderline ovarian clear cell tumor often arises from endometriosis. But there are no definitive guidelines for the management of endometriosis with malignant transformation due to a lack of understanding of the mechanistic details that mediate the transformation of endometriosis into ovarian cancer. Case: A 52-year-old woman (G2 P2) who periodically underwent ultraso-nography over the course of 12 years in order to follow the endometrioma present in her left ovary. The diameter of the lesion was 46 mm and it remained largely unchanged. However, a solid region within the ovarian cyst was detected. After the surgery, the final pathological diagnosis was cystic clear cell tumor of borderline malignancy. Conclusion: It reported that risk factors of malignant transformation are older age, postmenopausal status, and larger tumor diameters were associated with a higher prevalence of cancer development. But it is recommended that patients with endometriosis, regardless of patient age or tumor size, undergo careful monitoring to detect changes in growth or the formation of solid regions for as long as the lesion is present.

Focal nodular hyperplasia and hepatocellular adenomas: What is new in 2013?

The history of benign liver cell tumors, namely, focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA), has recently progressed thanks to molecular biology and imaging studies that made it possible a new classification used in European, American and East countries. A review was performed of the numerous published articles, with focus on the management and clinical outcome of benign liver cell tumors is an attempt to promote more standardized guidelines. The discovery of genetic drivers of HCA has refined our knowledge of the life history of HCA from risk factors of malignant transformation. The clinical management of FNH and HCA have changed in the recent years. This will have an impact on the management of these lesions including surveillance.

Characteristics and Treatment Outcomes of Patients with Malignant Transformation Arising from Mature Cystic Teratoma of the Ovary: Experience at a Single Institution

Malignant transformation arising in mature cystic teratoma (MCT) is one of the most serious complications of MCT. Squamous cell carcinoma is the most common malignant change. Some clinical findings such as advanced age group and large tumor size are significant risk factors of malignant transformation. This study was conducted in order to evaluate characteristics, cell types, treatment and outcome of malignant transformation arising from dermoid cysts in our institution. A retrospective chart review was performed. General characteristics, operative data, procedure, operative finding and operative outcome were analyzed. Statistical assessment was performed with SPSS version 17.0, using mean, mode, median and percentage to describe those data. During the 10 years period, 11 cases of malignant transformation from a total of 753 cases (1.46% incidence) of MCT were reviewed. Mean age of the patients was 41.2 years (SD 4.34, range 24-70). The most common presenting symptom was a palpable mass (8 cases; 72.7%). Primary surgical staging was performed in 4 patients (36.4%). Re-staging was conducted in the other 4. Complete cytoreduction was obtained in 45.5% (5 cases) and optimal surgical resection was obtained in 36.4% (4 cases). Mean tumor size was 14.1 cm. (SD 1.55, range 6-20). Squamous cell carcinoma was found in 36.4% (4 cases) and mucinous cancer in the other 4. More than half of them were stage Ia (54.5%, 6 cases). All patients whose stage more than Ia received chemotherapy (45.5%). Mean disease free survival was 5.53 years (1.32, 0.3-10). According to our study, the incidence of malignant transformation was consistent with previous studies. The common malignant transformation histologic types are both squamous and mucinous carcinoma which differed from previous reports. Early detection for early stage disease and optimal surgery are important for long term survival.

IDH/MGMT-driven molecular classification of low-grade glioma is a strong predictor for long-term survival

Low-grade gliomas (LGGs) are rare brain neoplasms, with survival spanning up to a few decades. Thus, accurate evaluations on how biomarkers impact survival among patients with LGG require long-term studies on samples prospectively collected over a long period. The 210 adult LGGs collected in our databank were screened for IDH1 and IDH2 mutations (IDHmut), MGMT gene promoter methylation (MGMTmet), 1p/19q loss of heterozygosity (1p19qloh), and nuclear TP53 immunopositivity (TP53pos). Multivariate survival analyses with multiple imputation of missing data were performed using either histopathology or molecular markers. Both models were compared using Akaike's information criterion (AIC). The molecular model was reduced by stepwise model selection to filter out the most critical predictors. A third model was generated to assess for various marker combinations. Molecular parameters were better survival predictors than histology (ΔAIC = 12.5, P< .001). Forty-five percent of studied patients died. MGMTmet was positively associated with IDHmut (P< .001). In the molecular model with marker combinations, IDHmut/MGMTmet combined status had a favorable impact on overall survival, compared with IDHwt (hazard ratio [HR] = 0.33, P< .01), and even more so the triple combination, IDHmut/MGMTmet/1p19qloh (HR = 0.18, P< .001). Furthermore, IDHmut/MGMTmet/TP53pos triple combination was a significant risk factor for malignant transformation (HR = 2.75, P< .05). By integrating networks of activated molecular glioma pathways, the model based on genotype better predicts prognosis than histology and, therefore, provides a more reliable tool for standardizing future treatment strategies.

English

Introduction Molecular changes in oral leukoplakia (OL) or in adjacent ‘clinically normal mucosa’ might influence the persistence/recurrence of OL, allowing an opportunity for transformation into squamous cell carcinoma. This paper discusses the surgical management of patients with OL. Short communication Clinicians must understand that available treatment options are limited in their capacity to prevent oral cancer. Surgical resection is still currently the best technique for management of OL. Patients with OL also need to adjust their lifestyle. Conclusion We call for further studies to improve our understanding. Introduction According to a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer, the term oral leukoplakia (OL) applies to ‘white plaques of questionable risk, having excluded (other) known diseases or disorders that carry no increased risk for cancer’1. OL typically presents as a white lesion of oral mucosa and is diagnosed when all other possible causes of white oral lesions are excluded1. A provisional diagnosis is made only when clinical examination is performed and any other clinical diagnosis is excluded1,2. Histological examination should support the diagnosis being mandatory for histological grading of epithelial dysplasia3. The extent or grade of dysplasia is currently the accepted reference method by which the malignant potential of OL is gauged to predict OL malignant transformation3. Key dysplastic features of stratified squamous epithelium include cellular atypia and loss of stratification4,5. Generally, dysplasia is classified by degree as mild, moderate or severe1,4,6. Despite being the gold standard method to predict malignant potential, there is little agreement between pathologists regarding epithelial dysplasia grading, and even nondysplastic lesions may transform. Subjectivity in the grading of OL, arbitrarily set grading thresholds, lack of calibration and limited knowledge of which criteria best predict malignant transformation may explain these disparities4,7,8. However, a meta-analysis has shown that the grade of dysplasia in OL and eventual malignant transformation correlate significantly9. Although excision may not eliminate this transformation, the likelihood is at least reduced9. Homogeneous OL lesions are flat, thin, uniformly white in colour and carry a low risk of malignant transformation1,2,10. On the other hand, mixed white and red lesions, with irregularly flat, nodular or verrucous areas, qualify as nonhomogeneous, and these are at high risk of progression to cancer2. The term oral verrucous leukoplakia signifies lesions with multifocal presentation that are resistant to treatment and are at a high risk of emergent cancer2. The primary risk factors for malignant transformation of OL are: (i) female gender, (ii) lesion chronicity, (iii) nonsmoker status, (iv) heterogeneous features, (v) tongue and floor of mouth sites, (vi) size >200 mm2, (vii) severity of dysplasia, (viii) aneuploidy and (xi) loss of heterozygosity2,11. Some molecular markers have shown promise in predicting the progression of premalignant oral lesions to squamous cell carcinoma, but none as yet are in routine clinical use12. Surgical techniques for managing patients with OL vary. However, randomized clinical trials have not addressed their efficacies in terms of preventing recurrent OL or its malignant transformation. This paper assesses the surgical treatment and what is achieved of patients with OL. Short Communication Treatment of OL At present, there is no scientific evidence that any manner of intervention prevents the development of squamous cell carcinoma in OL10. Recurrences may arise after surgical resection, based on mucosal field changes, which explains why widespread lesions pose a substantial threat of persistence/recurrence or malignant transformation. By definition, the concept of field cancerization denotes the presence of microscopic epithelial changes surrounding an oral cancer. Now we realize that even clinically normal mucosa, devoid of dysplasia at a microscopic level, might harbour molecular alterations predisposed to malignant transformation. Surgical excision is therefore ineffective in eradicating OL or preventing eventual malignancy. Instead, it is widely used for its potential as a diagnostic tool13. Of course, this benefit may be curtailed, if incisional biopsy is done rather than complete excision. * Corresponding author Email: rsgomez@ufmg.br 1 Department of Pathology, Biological Sciences Institute, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais – Brazil 2 Department of Oral Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais – Brazil

Amplification of Papillomavirus Oncogene Transcripts Assay for Bowenoid Papulosis

Human papillomavirus (HPV) is an important causative agent of cervical carcinoma and some malignant cutaneous tumors. The integration of HPV DNA into the host genome is one of the most important risk factors for malignant transformation. Here, we report the case of a 53-year-old man with multiple, black-brown genital macules and nodules. Histological findings resembled those for Bowen’s disease, and we made a diagnosis of bowenoid papulosis. This condition is generally benign, but invasive squamous cell carcinoma (SCC) arising from bowenoid papulosis has been previously reported. Therefore, we took biopsy specimens from 10 lesions and tested them for the presence of HPV DNA. DNA sequencing identified HPV type 16 (HPV-16) DNA in all samples. Next, we excised 4 different relatively large lesions and performed an amplification of papillomavirus oncogene transcripts (APOT) assay. This assay showed that all samples had only episome-derived viral transcripts, indicating no integration of HPV DNA into the host genome. We have followed this case for 3 years, and no progression to Bowen’s disease or SCC has so far been observed. We conclude that the APOT assay is a feasible method for evaluating the malignant potential of bowenoid papulosis.

The clinical determinants of malignant transformation in oral epithelial dysplasia

While the size and clinical appearance are known risk factors for malignant transformation of potentially malignant oral the importance of site, grade of dysplasia and exposure to environmental carcinogens remains controversial. We aim to report the clinical determinants of malignant progression in a series of patients with histopathologically graded oral epithelial dysplasia (OED). We recruited patients with a histopathological diagnosis of OED to a longitudinal observational study in a tertiary oral dysplasia clinic. Clinical, histopathological and risk factor data were recorded at baseline. One of three clinical endpoints were determined: malignant transformation, progression of dysplasia grade, remission/stable dysplasia grade. Ninety-one patients meeting the criteria gave consent for inclusion to the cohort, with outcomes reported after a median follow up of 48 months. An estimated 22% (SE 6%) of patients underwent malignant transformation within 5 years, with significant predictors being: non-smoking status (χ(2)=15.1, p=0.001), site (χ(2)=15.3, p=0.002), non-homogeneous appearance (χ(2)=8.2, p=0.004), size of lesion >200 mm(2) (χ(2)=4.7, p=0.03) and, of borderline significance, high grade (χ(2)=5.8, p=0.06). Gender, age, number of lesions and alcohol history did not predict for malignant transformation. Although a number of these clinical determinants have previously been associated with higher malignant transformation in OED, the high-risk nature of lesions in non-smokers is of particular note and requires a greater emphasis and recognition amongst clinicians dealing with OED. It suggests that those non-smokers with OED, have an inherited or acquired predisposition and should be treated more aggressively; these should form the focus for further investigation.

Malignant transformation of oral epithelial dysplasia: clinicopathological risk factors and outcome analysis in a retrospective cohort of 138 cases

To explore the usefulness of a new binary system of grading dysplasia proposed by the World Health Organization and to identify significant risk factors for malignant transformation in a long-term follow-up cohort of patients with oral epithelial dysplasia. A total of 138 patients with histologically confirmed oral dysplasia between 1978 and 2008 were reviewed retrospectively in our department. The mean follow-up period was 5.1 years. Of these dysplasias, 37 (26.8%) developed into cancer, with a mean duration of 4.6 years. Cox regression analysis revealed that high-grade dysplasia was an independent risk factor for transition, but age, gender, lesion site, diet habit, smoking and alcohol intake were not risk factors. High-grade dysplasia was associated with a 2.78-fold (95% confidence interval 1.44-5.38; P = 0.002) increased risk of transition, as compared with low-grade dysplasia. Consistently, high-grade dysplasia had a significantly higher incidence of malignancy than low-grade dysplasia by Kaplan-Meier analysis (log-rank test, P = 0.001). The utilization of high-grade dysplasia as a significant indicator for evaluating malignant transformation risk in patients with potentially malignant lesions is suggested; this may be helpful to guide treatment selection in clinical practice.