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Objectives: Vocal fold leukoplakia (VFL) is a precancerous lesion of laryngeal cancer, and its endoscopic diagnosis poses challenges. We aim to develop an artificial intelligence (AI) model using white light imaging (WLI) and narrow-band imaging (NBI) to distinguish benign from malignant VFL., Methods: A total of 7057 images from 426 patients were used for model development and internal validation. Additionally, 1617 images from two other hospitals were used for model external validation. Modeling learning based on WLI and NBI modalities was conducted using deep learning combined with a multi-instance learning approach (MIL). Furthermore, 50 prospectively collected videos were used to evaluate real-time model performance. A human-machine comparison involving 100 patients and 12 laryngologists assessed the real-world effectiveness of the model., Results: The model achieved the highest area under the receiver operating characteristic curve (AUC) values of 0.868 and 0.884 in the internal and external validation sets, respectively. AUC in the video validation set was 0.825 (95% CI: 0.704-0.946). In the human-machine comparison, AI significantly improved AUC and accuracy for all laryngologists (p < 0.05). With the assistance of AI, the diagnostic abilities and consistency of all laryngologists improved., Conclusions: Our multicenter study developed an effective AI model using MIL and fusion of WLI and NBI images for VFL diagnosis, particularly aiding junior laryngologists. However, further optimization and validation are necessary to fully assess its potential impact in clinical settings., Level of Evidence: 3 Laryngoscope, 134:4321-4328, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL)., Methods: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance., Results: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists., Conclusions: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To propose a scoring system based on laryngoscopic characteristics for the differential diagnosis of benign and malignant vocal fold leukoplakia., Methods: Laryngoscopic images from 200 vocal fold leukoplakia cases were retrospectively analysed. The laryngoscopic signs of benign and malignant vocal fold leukoplakia were compared, and statistically significant features were assigned and accumulated to establish the leukoplakia finding score., Results: A total of five indicators associated with malignant vocal fold leukoplakia were included to construct the leukoplakia finding score, with a possible range of 0-10 points. A score of 6 points or more was indicative of a diagnosis of malignant vocal fold leukoplakia. The sensitivity, specificity and accuracy values of the leukoplakia finding score were 93.8 per cent, 83.6 per cent and 86.0 per cent, respectively. The consistency in the leukoplakia finding score obtained by different laryngologists was strong (kappa = 0.809)., Conclusion: This scoring system based on laryngoscopic characteristics has high diagnostic value for distinguishing benign and malignant vocal fold leukoplakia.

Objective: To evaluate the clinical value of high-definition intelligent endoscopy (iSCAN) combined with stroboscopy in identifying vocal cord leukoplakia. Methods: Seventy-nine patients with vocal cord leukoplakia who underwent CO 2 laser laryngeal microsurgery and diagnosed by histopathology were recruited between October 2020 to August 2021. The morphological features, microvascular morphology and mucosal waves were observed by stroboscope; SPSS 20.0 software was used for statistical analysis. Results: There were 79 patients with a total of 119 lesions (56 on left and 63 on right).Pathological examination showed that 51 sides of the vocal cords were malignant lesions (severe dysplasia, carcinoma in situ and invasive carcinoma), and 68 sides were benign lesions.Under stroboscopy, 69 sides of mucosal wave were normal or slightly decreased, and 50 sides were severely decreased or disappeared.The decrease degree of mucosal wave was positively correlated with malignant lesions ( ρ =0.687, P <0.001).Under iSCAN endoscopy, there was a positive correlation between the morphological changes of microvessels at the lesion site (vertical) and the malignant lesion ( ρ =0.687, P <0.001).Univariate analysis showed that lesion size, thickness, uneven color, granular elevation, peripheral erythema and asymmetry were positively correlated with malignant lesions ( ρ =0.530, 0.401, 0.538, 0.315, 0.497, 0.281, P <0.05).Logistic regression analysis showed that the risk of pathological malignancy with large lesions was 5.437 times higher than those of small lesions, the vertical vascular changes under iSCAN were 8.711 times higher than that of normal vascular morphology, and the severe reduction or disappearance of mucosal waves was 9.12 times higher than that of normal or mild reduction of mucosal waves. Conclusion: ISCAN can be combined with staphyloscopy to comprehensively observe and evaluate the changes of vocal cord morphology, submucosal microvessels and mucosal wave of vocal cord in patients with vocal cord leukoplosis, thus improving the ability to distinguish benign and malignant lesions.

Oral Precancerous lesions include leukoplakia, erythroplakia, and mucosa palate changes due to reverse smoking. Assessing the prevalence of these lesions in a cross-sectional study can be effective in the timely prevention and treatment of lesions, in any community. Hence, in the present study, evaluation of P53 gene expression was done by immunohistochemistry method to diagnosis oral precancerous lesions. For this purpose, 111 Chinese patients (54 women and 57 men) were selected for examination. The age range of these patients was 22 to 69 years, and their average age was 32.6 years. All patients were examined by one physician. Oral mucosa was used for immunohistochemical evaluations. All samples taken from patients' mucosa were evaluated by one pathologist under a light microscope. 80 cases of the 111 patients were smokers and 27 were non-smokers. Among the 80 smokers, 56.25% had leukoplakia, 3.75% had erythroplakia, and 40% had mucosa palate changes. Regarding non-smokers, 74.07% had leukoplakia and 25.93% had erythroplakia. None of the non-smokers had mucosa palate changes. In terms of the lesion location, in patients with leukoplakia 89.23%, and patients with erythroplakia 90% of the lesion was located in the cheek mucosa and buccal vestibule. Also, in patients with leukoplakia 9.23%, and patients with erythroplakia 10% of the lesion was located in the lips vestibular mucosa. Only 1.54% of leukoplakia had a lesion in the vermilion border, and none of the erythroplakia patients had a lesion on the vermilion border. 76 patients (68.46%) showed positive expression of the P53 gene. The expression level of the P53 gene did not show a significant relationship with age, and the genders did not have a statistically significant difference in terms of gene expression. The expression level of the P53 gene was 59.8% in leukoplakia, 70% in erythroplakia, and 40% in Mucosa palate changes. The present study showed that the evaluation of P53 gene expression was well able to detect oral precancerous lesions and their severity by increasing their expression rate.

Objective: Vocal fold leukoplakia is clinically defined by the presence of white mucosal lesions. Benign and malignant lesions of vocal fold leukoplakia can be distinguished clinically based on pathological biopsy. This study compared the acoustic and aerodynamic parameters of vocal cord carcinoma and dysplasia (mild to severe)., Materials and Methods: From February 2014 to December 2018, 1,925 voice evaluation assessments were collected before laryngeal microsurgery (LMS). Of 147 patients clinically diagnosed with vocal cord leukoplakia before LMS, 112 male patients were selected for examination. The pathologic findings after LMS were divided into the carcinoma group (56 patients) and dysplasia group (56 patients). Only patients with carcinoma in situ and early glottis cancer were included in the carcinoma group. Analysis of covariance was used to calibrate the age between the two groups., Results: There was no difference in smoking duration between the two groups. F0 (P < 0.00), jitter (P < 0.00), and mean pitch (P = 0.010) were significantly higher, while the mean sound pressure level parameter (P = 0.024) was significantly lower, in the carcinoma group than in the noncarcinoma group., Conclusions: In patients with early glottis cancer, differences in voice analysis parameters may be used to differentiate between early glottic carcinoma and noncarcinoma., (Copyright © 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The objective is to reduce the rates of misdiagnosis and inappropriate treatment of laryngeal tuberculosis (LTB)., Study Design: Retrospective case series., Materials and Methods: Medical records of 3 histopathology-confirmed cases at a tertiary medical center from 2000 to 2018., Results: Seventeen patients with LTB included in this study. Of the 17 patients, 16 patients were male and 1 was female; 11 patients had a history of smoking. Odynophagia was the chief complaint in 6 cases, and 11 patients complained of hoarseness. The appearance of the affected larynx was ranged from diffuse swelling (n = 7, 41.2%), mucosa white lesion (n = 5,29.4%), and granulomatous tumors (n = 2, 11.76%), and these features presented together (n = 2, 11.76%). Seventeen patients with LTB were misdiagnosed as acute epiglottitis in 4 (23.5%) patients, acute laryngitis in 1 (5.9%) patient, leukoplakia in 5 (29.4%) patients, laryngopharyngeal reflux (LPR) in 6 (35.3%) patients, and laryngocarcinoma in 1 (5.9%) patient. Chest computed tomography reported old pulmonary tuberculosis in 2 (11.7%) patients, active pulmonary tuberculosis in 7 (41.2%) patients, and normal lung status in 8 (47.1%) patients. Histopathological examination reported Mycobacterium tuberculosis infection by revealing epithelioid cell granulomas with Langhans-type giant cells in 14 (82.4%) patients and epithelioid cell granulomas with caseous necrosis and Langhans-type giant cells in 3 (17.6%) patients., Conclusions: Laryngeal tuberculosis was easily misdiagnosed as acute epiglottitis or leukoplakia because of diffuse swelling of the epiglottis or white lesions over the true vocal cord, especially patients with increasing LTB were misdiagnosed as LPR with the enhancement of LPR awareness among otolaryngologist. Clinicians should be aware of the possibility of LTB for chronic intractable laryngitis with failure treatment of proton pump inhibitor and recurrent acute epiglottitis with foreign body injury.

Background: We aimed to investigate possible causes of leukoplakia and squamous cell carcinoma. We particularly sought to characterize the effect of smoking history because leukoplakia has been observed in nonsmokers., Methods: We retrospectively identified patients with a diagnosis of leukoplakia who were treated at Mayo Clinic (Jacksonville, Florida), in the Department of Otorhinolaryngology, from 1/1/2006 through 8/31/2019. Each patient was age- and sex-matched (1:2 ratio) to control patients without leukoplakia. Information about possible risk factors, chief symptoms, and social history with smoking and alcohol use was obtained from health records. Nine risk factors were analyzed independently with multivariate analysis. Continuous risk factors were compared between cases and controls with the Wilcoxon rank sum test; categorical variables were compared with the χ 2 test., Results: The final cohort consisted of 72 patients with leukoplakia (mean [SD] age, 66 [11] years; 61 men [85%]) and 144 age- and sex-matched controls. Compared with the control group, significantly more cases were current smokers (26% vs. 5%) and fewer were never-smokers. (17% vs. 51%) (P < 0.001). Cases also had a significantly longer duration of smoking history compared with controls (median, 30 vs. 0 years; P < 0.001). Alcohol consumption was not significantly different between cases and controls (53% vs. 54%; P > 0.99). When assessing never-smokers and those who had not smoked for more than 25 years, a history of smoking (P = 0.002) and the number of years smoked (P = 0.002) were significantly different for cases and controls., Conclusion: Most vocal fold leukoplakia lesions have a low risk of malignancy. It is important to evaluate the characteristics of the lesion and assess the patient's risk factors. Follow-up is a key factor in patient management, but for patients with recurrent leukoplakia, the duration and frequency of surveillance is still controversial and varies among medical centers. Future prospective studies with advanced analyses are warranted because they may strengthen the ability to identify clinical factors that influence the development of squamous cell carcinoma., (Published by Elsevier Inc.)

Background: The diagnosis of vocal cord leukoplakia mainly relies on laryngoscopy. The morphology of vocal cord leukoplakia under laryngoscope is closely related to the pathological nature of leukoplakia. The specific manifestations associated with high-risk vocal cord leukoplakia remain to be explored., Objective: To investigate the characteristics of low-risk and high-risk vocal cord leukoplakia under conventional white light imaging (WLI) laryngoscopy and its correlations with narrow band imaging (NBI) laryngoscopy., Methods: One hundred and seventy-five cases of vocal cord leukoplakia were divided into low-risk and high-risk groups. The characteristics of low-risk and high-risk vocal cord leukoplakia under WLI laryngoscopy and its correlations with NBI laryngoscopy were analyzed., Results: Logistic regression analysis showed that thickness and hyperemia were independent factors ( p  < .05). Hyperemia had a strong consistency with the visualization of spots under NBI laryngoscopy (kappa = 0.758). The sign of hyperemia and the NBI classification had equivalent diagnostic efficacy for predicting the risk of cancerization of vocal cord leukoplakia., Conclusion: The sign of hyperemia under WLI laryngoscopy is significantly correlated with the visualized spots under NBI laryngoscopy. Hyperemia is an important feature for predicting malignant potential of vocal cord leukoplakia.

Objective: This state-of-the-art article reviews the epidemiology, diagnosis, and management of vocal fold leukoplakia, with focus on recent advances. It focuses on the clinical challenges that otolaryngologists face balancing both oncological efficacy and functional outcomes in leukoplakia and presents the current philosophies and techniques to consider when managing such patients., Data Sources: PubMed/MEDLINE., Review Methods: We conducted a detailed review of publications related to vocal cord and laryngeal leukoplakia, dysplasia, hyperkeratosis, leukoplakia endoscopy, and leukoplakia management focusing specifically on oncologic outcomes, voice preservation, current and emerging diagnosis, and management techniques., Conclusions: There has been a paradigm shift away from performing "vocal cord stripping" procedures that can cause irreversible hoarseness toward voice preservation surgery while achieving comparable oncologic control. Surgical technical and instrumental developments have been designed to maximally treat superficial disease while preserving underling vibratory mucosa. Recent improvements in histopathological grading systems and advances in biomarker classification may allow for improved oncologic risk stratification. Furthermore, improvements in endoscopic imaging capabilities and contact endoscopy are currently being studied for their potential diagnostic significance., Implications for Practice: To optimally manage vocal fold leukoplakia, the otolaryngologist should become familiar with the oncologic implications of the disease and the importance of obtaining pathologic diagnosis to rule out malignancy. In addition, the surgeon should maintain surgical techniques and knowledge of available instruments and lasers that can assist in surgical management while prioritizing the preservation of vibratory tissue and voice quality. Finally, the surgeon and the patient should understand the clinical importance of routine endoscopic surveillance.

Ichthyosis uterus is an uncommon condition in which the entire surface of the endometrium is replaced by stratified squamous epithelium. This condition most commonly develops secondary to longstanding cervical obstruction or chronic inflammation. It is considered a benign lesion, but its association with endometrial malignancy has been reported in the literature. We are reporting a case of ichthyosis uteri with dysplasia associated with cervical intraepithelial neoplasm (CIN III). The case is reported for its rarity and to aware about neoplastic potential of ichthyosis uteri., Competing Interests: None

Background: Mucosal diseases of the oral cavity are relatively common, and patients often seek initial assessment from their general practitioner., Objective: The aim of this article is to provide an overview of common oral mucosal diseases to help with formulating a differential diagnosis and stratifying the urgency of referral., Discussion: Pathological mucosal conditions of the oral cavity and jaws commonly present as a mucosal ulcer or a white, red or pigmented lesion. In this review, the authors outline the most common conditions organised according to their clinical presentation and describe their typical appearance and management.

Background: Current evidence on diagnostic value of aneuploidy with DNA image cytometry (ICM) using brushings for oral potentially malignant disorders (OPMD) is limited by sample size and inconsistent classification criteria of aneuploidy. This study aimed to explore the optimal cut-off values of DNA content and evaluate the diagnostic accuracy of DNA-ICM for detecting dysplasia and/or carcinoma in OPMD., Materials and Methods: A total of 401 consecutive patients with OPMD were enrolled in this prospective diagnostic study. Brushing and biopsy sample form each patient was processed by DNA-ICM and histological examination respectively., Results: When the optimal cut-off of at least one aneuploid cell with DNA index (DI) ≥2.3, the area under the curves (AUC) was 0.735 and positive predictive value was 92.7% for detecting dysplasia within OPMD. When the optimal cut-off of at least one aneuploid cell with DI ≥ 3.5, the AUC was 0.851 and negative predictive values was 96.8% for detecting carcinoma within OPMD. Importantly, multivariate analysis revealed that aneuploidy with DI ≥ 2.3 in OPMD was significantly associated with dysplasia risk (adjusted OR, 5.52; 95%CI, 2.90-10.51; P < .001), and aneuploidy with DI ≥ 3.5 in OPMD was strongly associated with malignant risk (adjusted OR, 21.05; 95%CI, 9.34-47.41; P < .001)., Conclusions: This largest-scale diagnostic study optimized the criteria of aneuploidy cytology for noninvasive detection of oral dysplasia and carcinoma within OPMD. DNA aneuploidy in OPMD was an independent marker that strongly associated with oral dysplasia/carcinoma. Our findings suggest that DNA-ICM may serve as a useful noninvasive adjunctive tool for oral cancer and OPMD screening., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: This retrospective study aims at comparing the variation of peripheral inflammatory markers in recurrent and cancerous vocal fold leukoplakia (VFL) and at exploring the potential connection with pathological outcomes., Methods: The patients undergoing carbon dioxide laser surgery with postoperative pathological diagnosis of recurrent vocal fold leukoplakia in the last 5 years were included. The clinical data were collected, and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocytes-to-lymphocyte ratio (MLR) before and after recurrence and canceration were calculated. Related comparison with two-grade pathological classification was made to evaluate their potential connection with postsurgical histopathology and clinical events., Results: The data of 193 patients were engaged into research, as 111 in the recurrence group (Group A) and 82 in canceration group (Group B). The NLR, PLR, and MLR were significantly increased in canceration event compared to the first ( P = 0.009, 0.004, 0.007, respectively) and penultimate ( P = 0.013, 0.041, 0.006, respectively) time when the previous pathologies were leukoplakia. When redividing the Group A according to the two-grade pathological classification, the high-risk groups showed statistically higher NLR and PLR values than low-risk groups in the subgroups with grade changing ( P = 0.016, 0.005, 0.007, 0.005, respectively) and subgroups without grade changing ( P = 0.020, 0.027, 0.030, 0.029, respectively)., Conclusions: NLR, PLR, and MLR are reliable biomarkers in the circulation system which show significantly interrelation with the pathological progression of vocal fold leukoplakia. Presurgical evaluation of NLR, PLR, and MLR may have potential values to indicate the following treatment in clinical practice., Competing Interests: There is no financial relationship and interest conflict among all authors., (Copyright © 2020 Yi Fang et al.)

Summary The appearances of vocal cord leukoplakia are largely identical in the macroscopic examination even though the pathological character may differ. This makes it difficult for physicians to evaluate the extent of dysplasia of vocal cord leukoplakia and detect the occurrence of canceration using the conventional laryngoscopy, which might result in overtreatment or undertreatment of vocal cord leukoplakia in different patients. Therefore, an accurate preoperative assessment of the pathological character of vocal cord leukoplakia shows clinical significance in the selection of an appropriate treatment plan and predicting the prognosis of a patient. Recent studies have found that narrow band imaging（NBI） endoscopy can facilitate the early and differential diagnosis of head and neck cancers by observing the intraepithelial papillary capillary loop（IPCL） patterns at the mucosal surfaces. In this paper, the recent progress of NBI endoscopy in the diagnosis of vocal cord leukoplakia is reviewed., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To analyse the application of a new narrow-band imaging (NBI) classification in the diagnosis of vocal cord leukoplakia by laryngologists with different levels of laryngoscopic experience and to explore the impact of NBI training programmes on laryngologists' identification of benign and malignant leukoplakia., Design: Prospective multicentre study., Setting: Tertiary hospitals., Participants: Sixteen laryngologists were divided into less-experienced and experienced groups and received NBI training course. Thirty cases of vocal cord leukoplakia were investigated., Main Outcome Measures: Diagnostic accuracy and interobserver agreement under white light imaging (WLI), before and after NBI training, were analysed among doctors with varying levels of experience., Results: The accuracy in the less-experienced group was significantly lower than that of experience group (0.59 vs 0.69) under WLI. There was no significant difference in the diagnostic accuracy between the less-experienced group and the experienced group before NBI training (0.75 vs 0.74) and after NBI training (0.79 vs 0.83). NBI training could improve the interobserver agreement from fair or moderate to good agreement., Conclusion: The new NBI diagnostic classification is helpful for identifying benign and malignant vocal cord leukoplakia. In addition, the NBI training programme can improve the diagnostic accuracy and interobserver agreement of less-experienced doctors to the level of experienced laryngologists., (© 2019 John Wiley & Sons Ltd.)

Laryngeal mucosal precursor lesions represent a challenging clinical entity. Updated classification systems allow for grade-based categorization. Multiple management options exist, with treatment decisions made jointly by physician and patient and focused on both appropriate lesion treatment and preservation of laryngeal structure and function. Traditional methods include cold steel and CO 2 laser excision, with newer modalities using angiolytic lasers for lesion ablation. Both operating room-based and office-based treatment options exist, and there are advantages and disadvantages to each approach. Research is ongoing to advance the understanding of lesion biology, and to optimize prevention and treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To investigate the association between the cytokeratin (CK)-1 single-nucleotide polymorphism (SNP), the protein level of CK-1 and the risk of vocal leukoplakia and laryngeal squamous cell carcinoma (LSCC)., Methods: In this case-control study, 155 patients with vocal leukoplakia, 323 patients with LSCC, and 266 healthy controls were genotyped for the CK-1 (SNP RS14024) gene using pyrosequencing. The protein expression level of CK-1 was analyzed in vocal leukoplakia, LSCC, and vocal polyp patients by immunohistochemistry (IHC)., Results: Of the CK-1 RS14024 polymorphism, the heterozygote AG and homozygote GG genotype exhibited a significantly increased risk of LSCC (AG: OR = 2.16, p = 0.014; GG: OR = 2.15, p = 0.018) compared to normal controls. A higher protein expression level of CK-1 was detected in patients with LSCC compared to vocal leukoplakia and polyps (both p < 0.001), and a significant increasing trend of CK-1 protein expression level from mild-moderate dysplasia to moderate-severe dysplasia in vocal leukoplakia patients was also observed (p = 0.006)., Conclusions: This study demonstrates that the CK-1 SNP and high protein expression levels are associated with vocal leukoplakia and LSCC and promote the transformation from vocal leukoplakia to LSCC in a Chinese Han population., (© 2019 S. Karger AG, Basel.)

Competing Interests: Competing interests: None declared.

Vocal cord leukoplakia is a clinical diagnosis defined as a whitish patch or a plaque on a mucosal surface. Because of the diversity of histopathological types, the complexity and unpredictability risks for malignant transformation, there are still many controversies about its histopathological classification, diagnosis and treatment. The aim of this article is to review the epidemiology, etiology, pathological classification, diagnosis, treatment and prognosis of vocal cord leukoplakia.

Objective: To investigate the value of stroboscopy and narrow band imaging (NBI)endoscopy in the diagnosis of vocal cord leukoplakia. Methods: Two hundred and forty-six patients with vocal cord leukoplakia who underwent laryngeal microsurgery and diagnosed by histopathology were recruited between August 2014 and July 2016 in this retrospective study. The diagnostic accuracy of stroboscopy and narrow band imaging endoscopy in the diagnosis of vocal cord leukoplakia was compared. SPSS21.0 software was used to analyze the data. Results: A significantly positive correlation was found between the decrease grade of mucosal wave and the histopathological diagnosis( Spearman r =0.526, P <0.01). A significantly positive correlation was found between the lesion classified by detailed morphologic findings of epithelial microvessel and the histopathological diagnosis( Spearman r =0.480, P <0.01). The sensitivity of stroboscopy for detecting severe dysplasia, carcinoma and invasive carcinoma was 92.73%, higher than NBI endoscopy. The specificity of NBI endoscopy was 90.55%, higher than stroboscopy. The results of logistic regression analysis showed: the positive pathological type risk in the group with mucosal waves severely reduced and absent was 3.906 and 19.737 times higher than the group with mucosal waves slightly reduced. In the group with mucosal waves severely reduced and absent, significant difference was observed when combined use of NBI endoscopy( P <0.001, P =0.047). Conclusions: In the diagnosis of vocal cord leukoplakia, stroboscopy is useful for detecting severe dysplasia, carcinoma and invasive carcinoma with high sensitivity. In the group with mucosal waves severely reduced and absent, combined use of NBI endoscopy was able to improve the diagnostic accuracy.

Oral leukoplakia and erythroleukoplakia are common oral potentially malignant disorders diagnosed in the oral cavity. The specific outcome of these lesions remains to be elucidated, as their malignant transformation rate exhibits great variation. The ability to predict which of those potentially malignant lesions are likely to progress to cancer would be vital to guide their future clinical management. The present study reported two patients with tongue squamous cell carcinoma: Case study 1 was diagnosed with a simultaneous leukoplakia and case study 2 developed an erythroleukoplakia following the primary tumor treatment. Whole genome copy number alterations were analyzed using array comparative genomic hybridization. The present study determined more genomic imbalances in the tissues from leukoplakia and erythroleukoplakia compared with their respective tumors. The present study also identified in tumor and potentially malignant lesions common alterations of chromosomal regions and genes, including FBXL5, UGT2B15, UGT2B28, KANSL1, GSTT1 and DUSP22, being some of these typical aberrations described in oral cancer and others are linked to chemoradioresistance. Several putative genes associated with hallmarks of malignancy that may have an important role in predicting the progression of leukoplakia and erythroleukoplakia to squamous cell carcinoma, namely gains in BNIPL, MCL1, STAG2, CSPP1 and ZNRF3 genes were also identified.

This work aims to analyze the recurrence of vocal fold leukoplakia after carbon dioxide (CO 2 ) laser resection. In this retrospective study, all patients undergoing CO 2 laser resection of vocal fold leukoplakia were followed up for at least 2 years. Recurrence was diagnosed as any presence of leukoplakia in the vocal cord subsequent to previous successful complete resection. A total of 326 patients with complete resection of vocal fold leukoplakia and follow-up subsequent surveillance laryngoscopy were studied. The recurrence rate, the recurrence time, and risk factors were evaluated. Of these, 52 (16.0%) patients experienced recurrence with a mean follow-up time of 50.5 ± 15.4 months. The mean time to recurrence was 16.2 ± 14.1 months. Univariate analysis showed that the size of lesion (P < 0.001, Pearson χ 2 test; P < 0.001, log-rank test) and the pathological grade (P = 0.025, Pearson χ 2 test; P = 0.028, log-rank test) were significantly related to recurrence. The size of lesion was an independent prognostic factor for recurrence using multivariate analysis (P = 0.001, logistic regression; P = 0.001, Cox proportional hazards model). Considering the possible recurrence of vocal fold leukoplakia, long-term follow-up is required after CO 2 laser resection. In conclusion, the size of lesion combined with the pathological grade are important risk factors that predict vocal fold leukoplakia recurrence.

In planning a clinical trial for demonstrating the efficacy of pioglitazone to resolve leukoplakia and erythroplakia in Fanconi anemia patients we had to discuss the need for a randomized controlled trial particularly under sample-size restrictions as very promising results were available from a single-arm clinical trial. Unfortunately, at a later stage, we had to suffer from the fact that single-arm clinical trials may sometimes mislead. When revisiting our planning at a later stage of a grant application, results of a randomized controlled trial had become available which were less impressive, but may still be of clinical interest. However, these results were perceived as disappointing in the light of previously raised hopes based on the results of the single-arm trial. We highlight some major problems when research is based on single-arm trials compared to randomized controlled trials. After debunking common arguments for the conduct of single-arm trials in rare disease we conclude that particularly in rare disease research should be based on randomized building blocks simply because more robust evidence is generated. The plea for single-arm trials should be substituted by a plea for cooperation of all stakeholders to provide best evidence for decision making under sample-size restrictions.

Objective: To assess the effectiveness and identify vocal fold leukoplakia types appropriate for nonsurgical treatment., Methods: The vocal fold leukoplakia in 178 patients was divided by gross appearance into three subtypes: flat and smooth, elevated and smooth, and rough. All patients received nonsurgical treatment including smoking and drinking cessation, voice rest, omeprazole, and Chinese medication therapy. The clinical response of three subtypes was assessed after a 6-month follow-up., Results: Vocal fold leukoplakia subtypes included flat and smooth ( n = 66; 37.1%), elevated and smooth ( n = 103; 57.9%), and rough ( n = 9; 5.0%). The rate of complete response was 80.3%, 66.0%, and 0.0% for the 3 lesion types, respectively (rough versus flat and smooth, P < 0.001; rough versus elevated and smooth, P < 0.001, Fisher's exact test). The incidence of carcinoma in rough leukoplakia was significantly higher than that in smooth leukoplakia (44.4% versus 2.4%, P = 0.002, Fisher's exact test). Clinical type was the only significant factor for clinical response of nonsurgical treatment ( P = 0.005, ordinal logistic regression)., Conclusions: The effectiveness of nonsurgical treatment for smooth vocal fold leukoplakia is better in comparison to rough vocal fold leukoplakia. Smooth leukoplakia could be managed with nonsurgical treatment; more aggressive treatments should be considered for rough leukoplakia.

Objectives: To evaluate the degree of agreement between the clinical and the pathological diagnosis in patients undergoing laryngeal microsurgery due to epithelial or edematous lesions of the vocal folds., Study Design: This is a retrospective study., Methods: The study was developed in the ear, nose, and throat clinic of a tertiary hospital, through chart review. We included all patients who underwent microsurgery of the larynx, whose videolaryngoscopic tests showed vocal fold lesions, from January 2003 to August 2014. During the study period, we identified 48 patients with epithelial and edematous lesions. The patients were divided into two groups. In group A, patients with edematous lesions with clinical diagnosis of polyps and Reinke edema were included. Group B comprised patients with epithelial lesions, as leukoplakic injuries. A correlation between histopathological findings and clinical hypothesis between these two groups of lesions was performed., Results: In group B, there was agreement in 88.9% of cases between the clinical and pathological diagnosis. In group A, compatibility occurred in only 46.4% of cases. We observed a statistically significant difference between the compatibility of the clinical and pathological diagnosis just in edematous lesions (P = 0.029)., Conclusions: The study showed the limitation of the pathological examination on edematous laryngeal lesions. On the other hand, on the epithelial lesions, there was more agreement between those diagnosis., (Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Vocal fold leukoplakia is a descriptive diagnosis, and can be divided into simple hyperplasia, precancerous lesions(with atypical hyperplasia) and invasive carcinoma according to pathological types. Because of a close relationship with the laryngeal carcinoma, knowing the risk factors and treatment methods of vocal fold leukoplakia has grate significance in preventing the malignant change and recurrence. This paper summarizes the recent progress in clinical diagnosis and treatment of vocal cord leukoplakia, mainly including risk factors, means of examination, treatment and prognosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objectives: To evaluate the expression of Galectins (Gal) 1, 3 and 9, Metalloproteinase 3 (MMP-3) and mast cell density in oral lesions of patients with potentially malignant disorders (PMD) and oral squamous cell carcinomas (OSCC) by comparison with the controls., Study Design: We selected 40 cases of PMD, 40 OSCC and 13 with normal histopathological profile. Immunohistochemistry was performed for Gal-1, Gal-3, Gal-9 and MMP-3., Results: Gal-9 was significantly higher in patients with OSCC than in others groups (p < 0.001). Gal-1 expression was significantly lower in patients with leukoplakia than those with OSCC and controls (p = 0.0001). Gal-3 was significantly lower in patients with OSCC than those with leukoplakia (p = 0.03). MMP-3 was lower in patients with leukoplakia in comparison with the lichen planus group (p = 0.013)., Conclusion: The increased expression of Gal-9 may be helpful to differentiate of OSCC from other oral cavity lesions., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Leukoplakia is a descriptive clinical term designating a white patch or plaque of the mucosa and must be complemented by histology, which can range from simple totally benign keratosis with or without atypia up to invasive carcinoma. The aim of this study is to evaluate the accuracy of videostroboscopy in preoperative differentiation of early invasive glottic carcinoma from intraepithelial atypia and dysplasia. 46 patients with a total of 60 leukoplakia lesions on the vocal folds were included in the study. Videostroboscopy was used to divide them into two groups based on preservation of the mucosal wave and this was correlated with the final pathology after treatment. The sensitivity and specificity of videostroboscopy in predicting invasive nature of the lesions based on absence or reduction of the mucosal wave were 96.8 and 92.8 %, respectively, with an overall accuracy of 95 %. We suggest that routine application of videostroboscopy can be an important, simple, non-invasive tool, to achieve, in a single procedure, proper and accurate evaluation of glottic leukoplakia.

Background: Tumor markers, designated as a broad group of substances produced by malignancies, could be in the form of biochemical substances, immunological substances, cell surface changes and genetic alterations. Cancer, a disorder of cellular behavior is characterized by alteration of serum glycoproteins. L-fucose, a hexose, which is the terminal sugar in most of the plasma glycoproteins, may be useful as a tumor marker for the detection, monitoring and prognostic assessment of malignancies. The aim of the study was to ascertain the role of serum fucose as a biomarker for early detection of oral cancer and to compare serum fucose levels in healthy controls, leukoplakia and oral cancer patients., Materials and Methods: The study included 60 (100.0%) subjects, who were grouped as 20 (33.3%) control subjects, 20 (33.3%) squamous cell carcinoma patients and 20 (33.3%) leukoplakia patients. Fucose estimation was done using UV-visible spectrophotometry based on the method as adopted by Winzler using cysteine reagent. The results were analyzed statistically using ANOVA with Bonferroni post hoc tests., Results: Results showed a high significance in serum fucose in oral squamous cell carcinoma (OSCC) and leukoplakia subjects compared to normal controls. There was a gradual increase in the values noted from control to leukoplakia and to squamous cell carcinoma., Conclusions: Estimation of serum fucose may be a reliable marker and can be used as an effective diagnostic biomarker in oral squamous cell carcinoma patients.

Objective/hypothesis: Certain lesions appear to occur predominantly in one gender or in younger or older patients. We examined a large sample from a treatment-seeking population to describe gender and age associations of an array of benign vocal fold lesions., Study Design: Retrospective review., Methods: The medical records and evaluations of all adult patients presenting for care over a 5-year period were examined for demographic characteristics and lesion type. A total of 641 lesions in 602 patients were grouped into 13 broad categories, and prevalence was compared between male and female patients and three age groups., Results: Pseudocysts and bilateral midfold lesions occurred principally in young (18-39 years old) females (P < 0.0001). Reinke's edema was found in older (> 39 years old) women (P < 0.012). Polyps, contact lesions, leukoplakia (all P < 0.0001), and sulcus (P < 0.0002) were found predominantly in men., Conclusion: Certain benign mucosal lesions are strongly associated with age and especially with gender. These differences may be explained by intrinsic differences in laryngeal anatomy and phonatory physiology in these groups, including differences in phonatory frequency and air pressure, and in the ability of the membranous vocal fold to withstand phonotrauma. Such inherent differences have implications for treatment expectations and approaches., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Vocal fold leukoplakia is a premalignant precursor of squamous cell carcinoma. Although many efforts have been contributed to therapy of this disease, none exhibits a satisfactory result. The aims of this study were to investigate the effectiveness and feasibility of andrographolide therapy in vocal fold leukoplakia and to explore the preliminary mechanism underlying., Materials and Methods: Forty-one eligible patients were enrolled in the study. The patients were treated for 10-minute exposures of 5 ml (25mg/ml) andrographolide injection aerosols twice a day, and 2 weeks was considered as one treatment course. Electronic laryngoscope was used to observe the condition of vocal fold leukoplakia during the treatment. Every patient received one or two treatment courses, and the follow-up was carried out for 12 months. Toxic reactions of treatments were evaluated on the basis of the standards of the United States MD Anderson Cancer Center. Moreover, laryngeal carcinoma cell line Hep2 was applied to explore the mechanism of effect of andrographolide. Anti-proliferative effect on Hep2, cell nuclear morphology, express of mitogen-activated protein kinases (MAPK) and pro-apoptotic protein were detected after andrographolide treatment., Results: We found that andrographolide exhibited significant curative effects on treatments, which were accompanied by thinning of the lesion of leukoplakia, reduction in the whitish surface area, and return of pink or red epithelium. A complete response up to 85% was observed, and no toxic side effect events occurred during the study. No patient with a complete response had a recurrence in the follow-up. Moreover, cellular experiments in Hep2 indicated that andrographolide activated MAPK pathway and caspase cascade, and finally induced apoptosis in laryngeal carcinoma cell., Conclusions: The advantages of andrographolide are connected with minimally invasive and localized character of the treatment and no damage of collagenous tissue structures, which are more convenient and less painful for patients. These results suggest that andrographolide treatment is a viable strategy for curing vocal fold leukoplakia., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The role of oxygen free radicals in the initiation, promotion and progression of carcinogenesis and the protective role of antioxidants has been a subject of much speculation. There are few studies that report evaluation of serum albumin and only one study in which salivary albumin was found and only one study that reports of salivary albumin in oral Leukoplakia and Oral Squamous Cell Carcinoma (OSCC). We evaluated serum and salivary albumin levels in normal individuals, patients with oral pre-malignancy and patients with oral malignancy, and we compared serum and salivary albumin levels in patients with oral pre-malignancy and oral malignancy. Our study comprised 45 subjects separated into three groups of 15: normal healthy, oral pre-malignancy and oral malignancy patients. Venous blood was drawn and unstimulated saliva was collected early in the morning. Albumin levels were estimated using the bromocresol green method. Serum albumin levels decreased in oral pre-malignancy and oral malignancy cases compared to healthy individuals. Salivary albumin levels increased in oral pre-malignancy and oral malignancy cases compared to healthy individuals. Our results suggest that albumin may play a role in early diagnosis and prognosis of oral pre-malignant and oral malignant tissues.

Background: Oral cavity cancer ranks as the fourth leading cancer in men in Taiwan. The development of a serum biomarker panel for early detection and disease monitoring is, therefore, warranted., Methods: Nine inflammation-associated markers were investigated in 46 patients with leukoplakia, 151 patients with untreated oral cavity squamous cell carcinoma (OSCC), and 111 age- and gender-matched healthy controls using enzyme-linked immunosorbent assay. During a subsequent 28-month surveillance of OSCC patients, serum samples were prospectively collected at predetermined intervals following the completion of therapy., Results: Logistic regression analysis showed matrix metalloproteases (MMP)-2, MMP-9, C-reactive protein (CRP), transforming growth factor-β1 (TGF-β1), and E-selectin having the best discrimination power between groups and significant elevation trends of those five markers were noted from control to OSCC. By combining those five markers, a 0.888 and 0.938 area under curve by ROC curve analysis with 67.4% and 80% overall sensitivity and fixed 90% specificity for leukoplakia and OSCC groups were demonstrated. In the follow-up period, 25 OSCC patients developed recurring or secondary tumors. All examined markers had decreased in relapse-free patients following treatment. However, in patients with relapse, interleukin-6, CRP, and serum amyloid A remained at elevated levels. Statistical analysis showed that patients with CRP ≧2 mg/L and E-selectin ≧85 ng/mL at baseline had highest probability of relapse (odds ratio=3.029, p<0.05)., Conclusions: The results indicate that inflammation plays a crucial role in the pathogenesis process of OSCC. By examining the inflammation markers, physicians could potentially identify patients at risk of cancer transformation or relapse.

Background: Leukokeratosis of the vocal cords is a clinical descriptive diagnosis, which includes a group of squamous intraepithelial lesions of the vocal cord mucosa. We investigated the clinical classification and treatment efficacy of leukokeratosis of the vocal cords., Methods: We conducted a retrospective analysis of the medical history, laryngoscopic examinations, morphological features under a surgical microscope, and pathology results of 360 cases of leukokeratosis of the vocal cords to examine correlations among treatment modalities, therapeutic effects, and clinical features., Results: All cases were divided into four types based on symptoms, examination results, and treatment efficacies as follows: 21 patients had type I inflammatory leukoplakia and their vocal cord morphology and voice quality recovered after conservative therapies; 76 patients had type II frictional polyps and received CO2 laser submucosal cordectomy; 68 patients had type III sulcus vocalis and received mucosal slicing with dredging; and 195 cases had type IV simple leukokeratosis and received partial subligamental cordectomy with CO2 lasers or transmuscular cordectomy. Our treatment achieved a surgical cure rate of 90.9% (308/339), with a recurrence rate of 9.1% (31/339) and malignant transformation rate of 6.5% (22/339). All cancerous transformations occurred in type IV patients., Conclusion: Choosing conservative or CO2 laser surgery based on the morphological characteristics of squamous epithelial lesions of keratinized vocal cord mucosa can maximally protect voice quality, reduce complications, and improve the cure rate.

The case of a 73-year-old woman with a perforated corneal ulcer in the remaining eye with migrating endophthalmitis is presented. In addition, the affected eye had non-abradable whitish coating (leukoplakia) on the tarsal conjunctiva. The cause of leukoplakia was initially histologically diagnosed after an incisional biopsy as focal invasive sebaceous carcinoma with pagetoid growth. After exenteration of the orbit it was confirmed to be an early invasive, non-keratinizing squamous cell carcinoma (G2) of the conjunctiva, which had emerged from a spinocellular carcinoma in situ. The early histological differentiation of malignant lesions in the conjunctiva can be extremely difficult because the pathological changes in the tissue are very similar due to the cell metaplasia.

Objectives/hypothesis: Malignant transformation of laryngeal keratosis has been reported in a substantial subset of patients, yet reliable criteria for predicting patients most at risk have yet to be determined. Current methods for determining dysplasia ratings are susceptible to errors in biopsy sampling and interpretation. An understanding of the genetic underpinnings of the progression of vocal fold tumorigenesis may contribute to the creation of reliable and predictive diagnostic criteria. We hypothesized that genetic expression markers distinguish patients with keratotic noncancerous vocal fold lesions from invasive carcinoma., Study Design: Observational cross-sectional study., Methods: Real-time polymerase chain reaction (RT-PCR) was used to compare expression of 84 cancer pathway genes of patients following histologic diagnosis of nondysplastic keratotic epithelium (ND) (n = 7), dysplastic keratotic epithelium (DYS) (n = 3), and invasive carcinoma (CA) (n = 7). All patients had a clinical diagnosis of leukoplakia, and biopsies were obtained from true vocal fold tissue., Results: Four genes (IGF-1, EPDR1, MMP-2, S100A4) were significantly upregulated in DYS over the ND group. Seven genes were significantly upregulated in CA over the DYS group, and 31 genes were significantly upregulated in CA over the ND group (P < .02). The expression of matrix metalloproteinases (MMP-1, MMP-2, MMP-9) was found to statistically differentiate the groups (P < .02) and suggested disease progression associated with extracellular matrix degradation and angiogenesis promotion., Conclusions: With these preliminary array data, we demonstrate the feasibility of using RT-PCR to identify distinct genetic expression between diagnostic groups. Characterization of genetic changes marking the progression of vocal fold tumorigenesis may lead to robust diagnostic criteria in the future., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

The study included 32 patients (among them 20 patients with simple and 12 with verrucous leukoplakia) and presents both classic and advanced diagnostic methods for this disease: clinical examination, histological and immunohistochemical studies. The latter allows revealing neoplastic transformation of the oral mucosa.

Objective: Oral exfoliative cytology is a sensitive and reliable diagnostic tool for the early diagnosis of oral cancer. Traditional exfoliative cytology, though popular, has limitations which could be overcome using cytocentrifuge preparations. The purpose of this study was to compare the efficacy of cytocentrifuged specimens with that of conventionally prepared smears in the diagnosis of oral premalignancy and malignancy., Study Design: Exfoliative cytology was performed on 30 patients with oral premalignant and malignant lesions. The yield was smeared immediately onto a slide for conventional exfoliative cytology (group A). The lesion was then scraped again and the yield was suspended in a bottle containing a fixative solution for cytocentrifuge apparatus-assisted smearing (group B). Both smears were stained with rapid Papanicolaou stain and assessed for cellularity, cellular and nuclear morphology, evaluation of mitosis and background., Result: All the criteria assessed were statistically significant (p value of <0.001) in group B except for mitosis, which was significant in group A., Conclusion: Cytocentrifuge preparations can preserve the cellular details and reduce the overlapping of cells, enabling precise interpretation and thus aiding in the diagnosis of premalignant and malignant lesions of the oral cavity., (Copyright © 2012 S. Karger AG, Basel.)