Leucoplaquias laríngeas: Análisis de las lesiones y resultados vocales en una unidad de voz terciaria / Analysis of laryngeal leukoplakia characteristics and voice outcomes in a tertiary voice unit

Introducción: Las leucoplaquias laríngeas (LL) pueden corresponder a lesiones precancerosas. La aproximación diagnóstica es endoscópica y en caso de persistir, se debe estudiar con biopsia. Objetivo: Describir las características biodemográficas, clínicas, endoscópicas, histológicas y evolutivas de pacientes diagnosticados con leucoplaquias glóticas. Material y Método: Estudio prospectivo no-concurrente de pacientes diagnosticados con leucoplaquias glóticas en la Unidad de Voz del Departamento de Otorrinolaringología de la Pontificia Universidad Católica de Chile, entre 2012 y 2019. Resultados: Se incluyeron 29 pacientes, 65,5% hombres, con edad promedio de 61 años y seguimiento promedio de 21,1 meses. El principal motivo de consulta fue disfonía, en un 86,2% de los casos. El 38% presentó compromiso del pliegue vocal (PV) izquierdo, 24,1% derecho, 24,1% bilateral y 13,8% bilateral incluyendo comisura anterior. El 41,4% de las lesiones comprometían más del 50% del PV y 68% presentaba una onda mucosa alterada en la estroboscopia. Un 89,7% requirió biopsia, identificando carcinoma en 26,9%, displasia en 34,6% y otro diagnóstico en 38,5%. El 25,9% presentó recurrencias, del cual 28,6% progresó a cáncer. Se identificó asociación significativa en un análisis bivariado entre la edad (p = 0,030) y compromiso mayor al 50% del PV (p = 0,016) con displasia de alto riesgo o cáncer. En el análisis multivariado, solo la edad mostró ser significativa (p = 0,038; OR 1,27; IC 95% 1,01-1,59). Conclusión: El estudio de las LL es esencial para el diagnóstico precoz de cáncer laríngeo. La edad y el compromiso mayor al 50% del PV en la estroboscopia podría predecir un riesgo mayor de displasia de alto riesgo o cáncer.

Introduction: Laryngeal leukoplakia (LL) may correspond to precancerous lesions. The diagnostic approach is endoscopic, and if LL persist, a biopsy should be performed. Aim: To describe the biodemographic, clinical, endoscopic, histological, and developmental characteristics of patients diagnosed with glottic leucoplakia. Material and Method: Prospective non-concurrent study of patients diagnosed with glottic leukoplakia in the Voice Unit at the Otolaryngology Department of the Pontificia Universidad Catolica de Chile, between 2012 and 2019. Results: Twenty-nine patients were included, 65.5% men, with an average age of 61.7 years, and average follow-up of 21.1 months. Dysphonia was the chief complaint, present in 86.2% of the cases. The left vocal fold (VF) was involved in 38.0%, right in 24.1%, bilateral in 24.1%, and bilateral including anterior commissure in 13.8%. Only 41.4% compromised over 50% of the VF and 68.0% presented an altered mucosal wave in the videostroboscopy. A biopsy was performed in 89.7%, identifying carcinoma in 26.9%, dysplasia in 34.6% and other diagnosis in 38.5%. During follow-up 25.9% recurred, of which 28.6% progressed to cancer. A significant association was found in the bivariate analysis between age (p = 0.030) and extension over 50% of the VF (p = 0.016) with high-risk dysplasia or cancer. In the multivariate analysis only, the age was found to be significative (p = 0.038; OR 1.27; CI 95% 1.01-1.59). Conclusions: A thorough evaluation is essential in LL, favoring an early diagnosis for laryngeal cancer. Age and an involvement greater than 50% of the VF in the videostroboscopy could predict an increased possibility for high-risk dysplasia or cancer.

A morphological classification for vocal fold leukoplakia / Classificação morfológica das leucoplasias de prega vocal

Abstract Introduction: There is still no general method for discriminating between benign and malignant leukoplakia and identifying vocal fold leukoplakia. Objective: To evaluate the reliability of a morphological classification and the correlation between morphological types and pathological grades of vocal fold leukoplakia. Methods: A total of 375 patients with vocal fold leukoplakia between 2009 and 2015 were retrospectively reviewed. Two observers divided the vocal fold leukoplakia into flat and smooth, elevated and smooth, and rough type on the basis of morphological appearance. The inter-observer reliability was evaluated and the results of classification from both observers were compared with final pathological grades. Clinical characteristics between low risk and high risk group were also analyzed. Results: The percentage inter-observer agreement of the morphological classification was 78.7% (κ = 0.615, p < 0.001). In the results from both observers, the morphological types were significantly correlated with the pathological grades (p1 < 0.001, p2 < 0.001, Kruskal-Wallis test; r1 = 0.646, p1 < 0.001, r2 = 0.539, p2 < 0.001, Spearman Correlation Analysis). Multivariate analysis showed patient's age (p = 0.018), the size of lesion (p < 0.001), and morphological type (p < 0.001) were significantly different between low risk group and high risk group. Combined receiver operating characteristic curve analysis of significant parameters revealed an area under the receiver operating characteristic curve of 0.863 (95% CI 0.823-0.903, p < 0.001). Conclusions: The proposed morphological classification of vocal fold leukoplakia was consistent between observers and morphological types correlated with pathological grades. Patient's age, the size of lesion, and morphological type might enable risk stratification and provide treatment guidelines for vocal fold leukoplakia.

Resumo Introdução: Ainda não há um método universal estabelecido para diferenciar entre a leucoplasia benigna e maligna ou identificar as leucoplasias das pregas vocais. Objetivo: Avaliar a confiabilidade de uma classificação morfológica e a correlação entre os tipos morfológicos e os graus histopatológicos das leucoplasias de pregas vocais. Método: Os registros de 375 pacientes com leucoplasia da prega vocal assistidos entre 2009 e 2015 foram revisados retrospectivamente. Dois observadores dividiram a leucoplasia da prega vocal entre tipo plano e liso, elevado e liso, e rugoso, com base na aparência morfológica. A confiabilidade interobservador foi avaliada e os resultados de classificação de ambos os observadores foram comparados com os graus histopatológicos finais. As características clínicas entre os grupos de baixo risco e alto risco também foram analisadas. Resultados: A porcentagem da concordância interobservador da classificação morfológica foi de 78,7% (κ = 0,615, p < 0,001). Nos resultados de ambos os observadores, os tipos morfológicos correlacionaram-se significativamente com os graus histopatológicos (p1 < 0,001, p2 < 0,001, teste de Kruskal-Wallis; r1 = 0,646, p1 < 0,001, r2 = 0,539, p2 < 0,001, análise de correlação de Spearman). A análise multivariada mostrou que a idade do paciente (p = 0,018), o tamanho da lesão (p < 0,001) e o tipo morfológico (p < 0,001) foram significativamente diferentes entre o grupo de baixo risco e o de alto risco. A análise da curva ROC (Receiver Operating Characteristic) combinada de parâmetros significativos revelou uma área sob a curva de 0,863 (IC 95%: 0,823 ± 0,903, p < 0,001). Conclusões: A classificação morfológica proposta para leucoplasia de prega vocal foi consistente entre observadores e os tipos morfológicos correlacionaram-se com os graus histopatológicos. A idade do paciente, o tamanho da lesão e o tipo morfológico podem permitir a estratificação de risco e fornecem diretrizes de tratamento para a leucoplasia da prega vocal.

A morphological classification for vocal fold leukoplakia.

INTRODUCTION: There is still no general method for discriminating between benign and malignant leukoplakia and identifying vocal fold leukoplakia. OBJECTIVE: To evaluate the reliability of a morphological classification and the correlation between morphological types and pathological grades of vocal fold leukoplakia. METHODS: A total of 375 patients with vocal fold leukoplakia between 2009 and 2015 were retrospectively reviewed. Two observers divided the vocal fold leukoplakia into flat and smooth, elevated and smooth, and rough type on the basis of morphological appearance. The inter-observer reliability was evaluated and the results of classification from both observers were compared with final pathological grades. Clinical characteristics between low risk and high risk group were also analyzed. RESULTS: The percentage inter-observer agreement of the morphological classification was 78.7% (κ=0.615, p<0.001). In the results from both observers, the morphological types were significantly correlated with the pathological grades (p1<0.001, p2<0.001, Kruskal-Wallis test; r1=0.646, p1<0.001, r2=0.539, p2<0.001, Spearman Correlation Analysis). Multivariate analysis showed patient's age (p=0.018), the size of lesion (p<0.001), and morphological type (p<0.001) were significantly different between low risk group and high risk group. Combined receiver operating characteristic curve analysis of significant parameters revealed an area under the receiver operating characteristic curve of 0.863 (95% CI 0.823-0.903, p<0.001). CONCLUSIONS: The proposed morphological classification of vocal fold leukoplakia was consistent between observers and morphological types correlated with pathological grades. Patient's age, the size of lesion, and morphological type might enable risk stratification and provide treatment guidelines for vocal fold leukoplakia.

Characterization of dendritic cells in lip and oral cavity squamous cell carcinoma.

BACKGROUND: There may be differences in the antitumor immunity induced by dendritic cells (DCs) during the development of squamous cell carcinoma (SCC) located in the lip rather than in the oral cavity. The aim of this study was to evaluate the number of immature and mature DCs in SCC and potentially malignant disorders of the oral cavity and lip. METHODS: Immunohistochemistry was used to identify the number (cells/mm(2) ) of immature (CD1a(+) ) or mature (CD83(+) ) DCs in samples of oral cavity SCC (OCSCC) (n = 39), lip SCC (LSCC) (n = 23), leukoplakia (LK) (n = 21), actinic cheilitis (AC) (n = 13), and normal mucosa of the oral cavity (OC control, n = 12) and the lip (lip control, n = 11). RESULTS: The number of CD1a(+) cells tended to be higher in the OC control samples compared with the LK (P = 0.04) and OCSCC (P = 0.21). Unlike, this cell population was lower in the lip control than in AC or LSCC (P < 0.05). The number of CD83(+) cells was increased in the LSCC samples compared with the AC and lip control (P = 0.0001) and in OCSCC compared with both the LK (P = 0.001) and OC control (P = 0.0001) samples. LSCC showed an elevated number of CD1a(+) and CD83(+) cells compared with OCSCC (P = 0.03). The population of mature DCs was lower than the population of immature DCs in all of the tested groups (P < 0.05). CONCLUSION: There were a greater number of both mature and immature DC populations in the LSCC samples than in the OCSCC, which could contribute to establishing a more effective immune antitumor response for this neoplasm.

Immunohistochemical expression of Bcl-2 and Ki-67 in oral lichen planus and leukoplakia with different degrees of dysplasia.

OBJECTIVES: Oral lichen planus (OLP) is a chronic inflammatory disease of unknown cause. Malignant transformation in OLP lesions may be favored by changes in the expression of proteins that regulate cell proliferation and apoptosis. This study aimed to investigate these issues by immunohistochemical staining for Bcl-2 and Ki-67 and by correlating histopathological findings in samples from lesions of OLP and leukoplakia with epithelial dysplasia. METHODS: Data for patients with OLP or leukoplakia with moderate or severe epithelial dysplasia recorded during 2006-2011 were retrospectively reviewed. The study samples represented 37 subjects with OLP (n = 14), leukoplakia with moderate (n = 8) or severe (n = 6) epithelial dysplasia, and normal buccal mucosa (controls, n = 9). New sections were subjected to histological examination and immunohistochemistry for Bcl-2 and Ki-67 in the basal layer, suprabasal layer, and inflammatory infiltrate, respectively. RESULTS: All basal layer sections stained either negative or positive in <10% of cells for Bcl-2 in OLP (92.9% and 7.1%, respectively) and control (77.8% and 22.2%, respectively) samples. In leukoplakia, 85.7% of sections indicated positivity in <10% of cells, and 14.3% indicated positivity in 10-26% of cells. Most OLP (42.9%) and leukoplakia (64.3%) sections stained positive for Ki-67 in >50% of cells. All suprabasal sections stained either negative or positive in <10% of cells for Bcl-2 in OLP (92.9% and 7.1%, respectively), leukoplakia (42.9% and 57.1%, respectively), and control (88.9% and 11.1%, respectively) samples. Suprabasal staining for Ki-67 was negative or positive in <10% of cells in OLP (14.3% and 85.7%, respectively), leukoplakia (7.1% and 92.9%, respectively), and controls (88.9% and 11.1%, respectively). Staining for Bcl-2 in inflammatory infiltrate in OLP was positive in 92.9% of sections. CONCLUSIONS: Expression of Bcl-2 may play a dual role in tumor development and progression. Increased cell proliferation in the epithelium may present a predisposition to cancer in OLP. The expression of Ki-67 can be considered as an adjunct marker for proliferative activity in lesions with malignant potential. The prognostic value of these immunomarkers in the evaluation of precancerous oral lesions requires further investigation.

Increased VEGFR2 and MMP9 protein levels are associated with epithelial dysplasia grading.

The present study aimed to compare levels of VEGFR2 and MMP-9 among control, epithelial dysplasia (ED) and oral squamous cell carcinoma (OSCC) groups. We analyzed 48 patients with oral leukoplakia (OL), 20 patients with OSCC and 21 patients without OL and OSCC. Immunohistochemistry of VEGFR2 and MMP9 were performed and compared among groups. Analysis of tissue immunolocalization of VEGFR2 and MMP-9 assumed non-parametrical distribution and comparison between groups was performed using the Mann-Whitney and Kruskal-Wallis statistical tests. VEGFR2 and MMP9 immunoexpression appeared to correlate with the degree of dysplasia and was observed to increase in lesions with more severe dysplasia as compared to those with lower degrees of dysplasia. Immunoreactivity of MMP-9 was lower in the OL samples compared to the OSCC samples (p = 0.004). We observed no difference in VEGFR2 protein levels between OL and OSCC samples. A positive correlation was found between VEGFR2 and MMP-9 in OL samples (r = +0.452, p = 0.001), however, no correlation was found in OSCC samples (r = -0.042, p = 0.861). In conclusion, the results of the current study suggest that expression of MMP9 and VEGFR2 is associated with ED grading and MMP9 levels are increased in OSCC.

Exposure to alcohol or tobacco affects the pattern of maturation in oral mucosal cells: a cytohistological study.

OBJECTIVE: To assess the maturation pattern of oral mucosal cells of patients exposed to tobacco and alcohol. METHODS: (i) Group without lesions. Smears obtained from the lower lip, border of the tongue and floor of the mouth of 31 control individuals (group I), 49 tobacco users (group II) and 27 tobacco/alcohol users (group III) were stained using the Papanicolaou method. The first 100 cells counted on each smear determined the maturation pattern and the keratinization index (KI). Analysis of variance (ANOVA) and the Tukey multiple comparison test were used for statistical analysis, at a 5% significance level. (ii) Group with lesions. Cytopathological and histopathological studies were conducted for 15 patients: eight with leucoplakia without epithelial dysplasia, two with epithelial dysplasia and five with squamous cell carcinoma. RESULTS: (i) Group without lesions. Statistical analysis revealed a smaller number of superficial cells with nuclei in all sites of the group of tobacco/alcohol users (group III) when compared to the control group (group I), and this difference was statistically significant (P<0.005). (ii) Group with lesions. The severity of histopathological findings increased with the increase in the number of cells of the deeper epithelial layers, with a statistically significant difference in the number of intermediate (P=0.013) and parabasal cells (P=0.049), which increased with the severity of the epithelial maturation disorder: leucoplakias with dysplasia had a greater number of intermediate and parabasal cells than leucoplakias without dysplasia; and the number in squamous cell carcinomas was greater than in leucoplakias with dysplasia. CONCLUSION: The maturation pattern of cells in the three anatomic sites showed changes that may be associated with the synergistic effect of tobacco and alcohol. Also, the severity of histopathological findings was associated with the increase in the number of cells in the deeper epithelial layers.

Thermally induced 'nicotine' stomatitis. A case report.

A palatal lesion resembling "nicotine" stomatitis was found in a woman who did not smoke. However, the patient frequently drank extremely hot beverages. After she was instructed to reduce the temperature of the beverages, the lesion almost completely resolved. This suggests that heat was the primary cause of this lesion and also implicates heat as the major cause of nicotine stomatitis.

HPV incidence in the Republic of Panama in 1985.

The Author presents the analysis of the diagnostic possibilities in HPV infection with three associated methodologies: colposcopy, cytology and histology. With this aim he examined during 1985, 754 patients and carried out 898 colposcopic exams, 883 colpocytological studies and 159 target biopsies. Among these patients he found 271 cases affected by HPV. Reviewing the most representative clinical pictures facing the final diagnosis of HPV, leukoplakia was presented in 33.6% of cases; the atypical transformation zone in 16.6% associated with the virus and slight dysplasia. The atypical reepithelization zone represented 33.2% of cases associated with typical virus and slight dysplasia. The author emphasizes the real importance of using colposcopy integrated with cytology and histology in the detection of cervical viral lesions.

[Postoperative anus stricture and leukoplakia lesions]. / Estrechez anal postoperatoria y lesiones leucoplásicas.

We present 35 cases postoperative anal stenosis of patients operated at the Sanatorio y Maternidad del Sur, Bahía Blanca, Argentina, in the last 9 years (1978-1986). In 9 cases (25.7% the pathologist reported leukoplasic lesions from the anus and anal channel. We remark the value of the pathology in these cases and we suggest to send to the pathologist all the tissues from anal surgery, because we believe this is the way to make the best prophylaxis of anal cancer.