Laryngoscopic Characteristics in Vocal Leukoplakia: Inter-rater Reliability and Correlation With Histology Grading

Transcription

1 The Laryngoscope VC 2014 The American Laryngological, Rhinological and Otological Society, Inc. Laryngoscopic Characteristics in Vocal Leukoplakia: Inter-rater Reliability and Correlation With Histology Grading Chi-Kuang Young, MD; Wan-Ni Lin, MD; Li-Yu Lee, MD; Li-Ang Lee, MD; Li-Jen Hsin, MD; Chun-Ta Liao, MD; Huesh-Yu Li, MD, FACS, FICS; I-How Chen, MD; Tuan-Jen Fang, MD, FICS Objectives/Hypothesis: Vocal cord leukoplakia is a clinical diagnosis that comprises a spectrum of benignities, premalignancies, and malignancies. Accurate recordings of the visual characteristics of the affected area are important for communication between physicians and are helpful in further management. The objective of this study was to determine the laryngoscopic characteristics among patients with vocal cord leukoplakia and the reliability of examinations between different raters. Study Design: Retrospective chart review conducted in a tertiary referral center in Taiwan. Methods: From January 2010 to April 2013, 107 consecutive patients with vocal leukoplakia who had accepted excisional biopsy were recruited and classified into two groups according to histologic findings. The patients without clear preoperative flexible laryngoscope images stored in the picture archiving and communication system were excluded. There were 68 patients who met the inclusion criteria, and the preoperative laryngoscope images were reviewed by two laryngologists. The inter-rater reliabilities of the recordings were assessed. Correlation between the variables and histologic classification was also performed. Results: The inter-rater reliability of the assessment was significant in the recordings of color, texture, size, hyperemia, thickness, and symmetry (j to 0.573, P <.05) but not in vocal cord edema. The laryngoscopic findings including color, texture, size, and hyperemia were associated with the grade of dysplasia (P <.05). Conclusions: The specific proposed laryngoscopic characteristics are consistent in the recordings between raters and can be potentially used for stratifying patients risk. Key Words: Vocal leukoplakia, laryngoscopy, predictor. Level of Evidence: 4. Laryngoscope, 125:E62 E66, 2015 INTRODUCTION Vocal cord leukoplakia, Greek for white plaque, is a clinical descriptor indicating the keratin over the mucous membrane of the vocal folds. 1,2 Lesions can be either exophytic or flat depending on the thickness of the keratin layer of the epithelium. As noted in previous reports, 2,3 approximately 50% of patients with clinical vocal leukoplakia had no dysplasia in histologic examination, but others had more aggressive findings. Moreover, from the histologic examination of the surrounding epithelium, the diagnosis of vocal cord leukoplakia may comprise a spectrum from benign, premalignant, to malignant. 4 From the Department of Otolaryngology Head and Neck Surgery (C.-K.Y., W.-N.L, L-A.L., L.-J.H., C.-T.L., H.-Y.L., I.-H.C., T.-J.F.) and the Department of Pathology (L.-Y.L.), Chang Gung Memorial Hospital, Linkou, Taiwan; School of Medicine (W.-N.L, L-A.L., L.-J.H., C.-T.L., H.-Y.L., I.-H.C., T.-J.F.), Chang Gung University, Taoyuan, Taiwan; Chang Gung Memorial Hospital, Linkou, Taiwan. Editor s Note: This Manuscript was accepted for publication July 23, The research was supported by a Chang Gung Medical Foundation Grant (CMRPG 3B1412). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Tuan-Jen Fang contributed equally as first author. Send correspondence to Tuan-Jen Fang, MD, 5, Fu-Shin Street, Kweishan, Taoyuan 333, Taiwan. fang3109@cgmh.org.tw DOI: /lary E62 Patients with vocal cord leukoplakia usually display voice issues similar to other vocal fold lesions. Restoring voice capabilities as well as completely removing the lesion are the treatment goals for most cases. However, the management of such dysphonia from vocal cord leukoplakia should also take histologic grades into consideration. For a case of vocal cord leukoplakia with high possibility of malignancy, eradicating the cancer cells in an early stage is more important, and deeper resection may be necessary. On the other hand, a conservative treatment or watch-and-wait policy benefits those with a low risk of malignancy. Thus, an accurate and delicate recording of the characteristics of vocal cord mucosa is helpful in further management. The mucosal appearance of the vocal leukoplakia can be classified into multiple factors such as the homogeneity of color and regularity of texture. Recording the findings in a standard form is helpful for medical communication and follow-up. Thus, it is important to establish a scoring system that is reliable and also has clinical significance. Although the surface appearance of the laryngeal mucosa was suggested to be unreliable in predicting the degree of dysplasia in the entire lesion, 5 with the development of the high-resolution flexible laryngoscope and quality digital imaging, it is possible to stratify the vocal cord leukoplakia by the morphologic characteristics in an office-based setting. The purpose of this study was to

2 TABLE I. Definition of Morphologic Features of Vocal Cord Leukoplakia. Factors Categories Score Definitions of the Vocal Cord Leukoplakia Color Homogenous 0 The color is distributed evenly. Nonhomogenous 1 The color is not distributed evenly. Texture Regular 0 The surface is smooth and flat. Irregular 1 The surface showed granular appearance. Size Small 0 The sum of all vocal cord leukoplakia is less than half a length of one true vocal cord. Large 1 The sum of all vocal cord leukoplakia exceeds half a length of one true vocal cord. Hyperemia Absence 0 The vocal cord leukoplakia is without peripheral erythema or increased vascularity. Presence 1 The vocal cord leukoplakia is associated with peripheral erythema or increased vascularity. Thickness Thin 0 The lesion is thin, and blood vessels beneath the lesion are visible. Thick 1 The lesion is thick, and blood vessels beneath the lesion are invisible. Symmetry Symmetric 0 Lesions are distributed at similar sites of bilateral vocal cords. Asymmetric 1 Lesions are located at one or unopposed sites. Edema Exist 0 Existence of vocal edema. Absence 1 Absence of vocal edema. determine the clinical laryngoscopic characteristics and the consistence of recordings between the examiners. The second aim of the project was to search for the relationship between the laryngoscopic characteristics of leukoplakia and histology grading. MATERIALS AND METHODS The medical records from patients with a preoperative diagnosis of vocal cord leukoplakia who were treated with microlaryngeal surgery from January 2010 to April 2013 were reviewed. All patients enrolled had complete excisional biopsy and multisectional interpretation by an experienced pathologist. The figures for evaluation of vocal cord mucosa were captured by high-quality, digital, distal-chip laryngoscopes connected to a white light source and imaging system (Laryngoscope: ENF Type VT; Platform: EVIS Exera II; Olympus Optical Co, Ltd., Tokyo, Japan). All patients accepted into the study had at least one image from a laryngoscope examination within 4 weeks before excisional biopsy. Those with previous laryngeal surgery or a gross tumor mass on the vocal cord and a preoperative suspicion of laryngeal cancer were excluded in our study. Because ulceration in vocal cord leukoplakia has been reported to be closely related to malignancy, 6 patients presenting with a vocal cord ulcer were also excluded. The main outcomes measure was the grade of histologic differentiations of vocal lesions. The cohorts were stratified into two groups following their histologic examination. According to the World Health Organization grading system, the low-risk group included those with keratosis without dysplasia, and mild and moderate dysplasia, whereas the high-risk group included those with severe dysplasia, carcinoma in situ, and invasive carcinoma. 7 Laryngoscopic Scoring for Vocal Cord Leukoplakia The clinical morphological characteristics of the vocal cord leukoplakia evaluated by preoperative flexible laryngoscopy were classified and scored by seven common parameters: the homogeneity of color, regularity of texture, lesion size, symmetry, thickness, hyperemia, and edema. The definition and scoring are listed in Table I. Two laryngologists, blinded to the patients identity and pathological results, concurrently but independently scored each laryngoscope image of the patients according to the above criteria. The reliability and percent of agreement of recordings was checked between the reviewers. The result of each record was correlated with the risk of malignancy. Study Setting and Ethical Approval This study was conducted in a tertiary referral center, Chang Gung Memorial Hospital, in Taoyuan, Taiwan. This retrospective chart review study was approved by the institutional review board of the hospital prior to commencement of the study. Statistical Analysis Descriptive statistics were calculated for baseline subject characteristics, and the results are reported with mean 6 standard deviation. The parameters of the laryngoscopic scoring were calculated with the kappa statistic for paired proportions to determine consistency among the raters. A Spearman nonparametric correlation test and Yates corrected v 2 test were used to investigate the relationships between morphological parameters and risk groups. All calculations were performed with SPSS software (version 17.0; SPSS, Inc., Chicago, IL). Two-sided P values <.05 were considered statistically significant. RESULTS There were 66 males and 2 females enrolled. The mean age was years. According to the histologic differentiation, the number of patients with no dysplasia was 36; with mild, moderate, and severe dysplasia was 8, 6, and 1, respectively; with carcinoma in situ was 7; and with invasive carcinoma was 10. The patient demographics are listed in Table II. Inter-rater Reliabilities of Laryngoscope Recordings The inter-rater reliability test generated from the correlation between different raters over the individual scoring showed a range of 48% to 79% agreement (Table III). The color, texture, size, hyperemia, E63

3 TABLE II. Patient Demographics (n 5 68). Age, yr Gender (male/female) 66/2 Smoking (yes/no) 59/9 Histology Nondysplasia 36 Mild dysplasia 8 Moderate dysplasia 6 Severe dysplasia 1 Carcinoma in situ 7 Invasive carcinoma 10 thickness, and symmetry showed significance, but the vocal edema had a poor consistency between raters. Associations of Parameters of Laryngoscopic Scores and Pathological Grading In the results from both raters, four of the seven laryngoscopic characteristics including color, texture, size, and hyperemia were significantly correlated with the histology classification by both Spearmen correlation test and Yates corrected v 2 test (Table IV). The other three parameters including lesion thickness, symmetry, and edema did not correlate with the histology classification by both tests. DISCUSSION Leukoplakia is a nonspecific term to describe a white-colored mucosal patch. The presenting symptoms vary from the sites of existence. Because mucosal leukoplakia had been reported to have the potential for malignant transformation, it is suggested that the lesion be removed completely. However, in patients with vocal leukoplakia, most showed concern over having a rough and husky voice and wanted to restore their vocal capability as well as eradicating the lesions. The goals of the treatment should include removing the lesions and preserving the healthy mucosa as much as possible. According to the report from Bouquot and Gnepp, 8 the annual incidence of vocal cord leukoplakia in the United States is 10.2 and 2.1 lesions per 100,000 males and females, respectively. In our series, excluding cases with ulcers, there were 26.4% (18/68) patients noted to be malignancies (from severe dysplasia to invasive carcinoma). Stratifying the patients according to risk can assist in making a tailored management plan. The morphologic description of oral mucosa leukoplakia lesions has been discussed in previous reports. 9,10 We modified the scales of factors including color, surface texture, lesion size, hyperemia, thickness, symmetry, and edema and adapted them into the laryngeal lesions. For simplified grading, the scoring included only the existence or not of such characteristics (yes or no). Each image was recorded by two independent reviewers. We noted that most of the laryngoscopic characteristics noted (excluding vocal edema) were significantly consistent between the two reviewers. Thus, the interrater reliability is acceptable for rating of the above six parameters. We can conclude that these six laryngoscopic parameters are available for communication between physicians and useful for follow-up and further decision on management. In our report, the subjects were classified into two groups according to histologic findings. A high-risk group included those patients with severe dysplasia, carcinoma in situ, and invasive carcinoma, whereas the low-risk group included those without dysplasia and those with mild to moderate dysplasia. The malignant transformation rate and the aggressiveness of invasion were significantly different between the groups. 11,12 In the individual ratings from both reviewers, among the laryngoscopic characteristics, four of them (color, surface texture, lesion size, and hyperemia) had significant correlation with the histologic classification. Patients with lesions presented with lower scores had very high probability to be less aggressive (Fig. 1). The laryngologists were encouraged to manage such lesions conservatively. The management of vocal leukoplakia is a challenging topic in laryngology. In the patients lack of invasive carcinoma signs, a 1-month watchful-waiting trial is reasonable consisting cessation of tobacco and alcohol use, reduction of dehydrators, and elimination of vocal abuse activities. 5 For patients with good compliance for followup, small biopsies or conservative resection and close follow-up can be an alternative option. From Zeitels report, 6 random biopsy of the vocal leukoplakia is discouraged because the grade of dysplasia may be varied among the lesions. Excisional biopsy with very carefully preservation of uninvolved layers was suggested. 5 Although the lesion can be eradicated with that type of management, the voice outcomes may be deteriorated. However, the decision on how wide or deep the excision should be depends on the individual surgeon s experience. In a less-experienced laryngologist, a deep TABLE III. Inter-rater Reliability of Laryngoscopic Rater Recording. Score Rater 1 Rater 2 % Agreement j Value P Color Texture Size Hyperemia Thickness Symmetry Edema E64

4 TABLE IV. Laryngoscopic Findings and Histology Groups. Rater 1 Rater2 Rater 1 Rater 2 Color r value* v P value P Texture r value v P value P Size r value v P value P Hyperemia r value v P value P Thickness r value v P value P Symmetry r value v P value P Edema r value v P value P *Spearman nonparametric correlation test Yate s corrected v 2 test. excisional biopsy might be performed in a benign mucosal lesion, or an inadequate superficial biopsy on a high-risk lesion might be performed. From our results, we noted that there were four laryngoscopic characteristics that had good inter-rater reliability and diagnostic roles. By using the scale, the communication between physicians and comparison between intervals would be feasible, and a decision on management of a vocal leukoplakia lesion is likely to be made more objectively. More importantly, the present laryngoscopic scale is available in the clinic for patients prior to surgery. Thus, the probability of malignancy can be estimated before sending patients into operating rooms. There were several limitations in the present study. First, the sample size was not large enough, thus Fig. 1. (A) A case demonstrating right vocal cord leukoplakia (arrowhead) with homogenous color, regular in texture, with a large lesion but no hyperemia. (B) The final pathology reporting squamous hyperplasia (hematoxylin and eosin staining 3100). (C) A case demonstrating bilateral vocal cord leukoplakia (arrowhead) with nonhomogenous color, irregular in texture, with a large lesion but no hyperemia. (D) The final pathology reporting squamous cell carcinoma (hematoxylin and eosin staining, 3100). [Color figure can be viewed in the online issue, which is available at E65

5 limiting its level of evidence. Second, the recording of each variable still can have up to a 30% disagreement between raters. Although we were not able to identify the risk of lesions from each specific factor, by combining all four factors, for cases with few risky laryngoscopic characteristics, conservative managements are preferred. CONCLUSION The present laryngoscopic morphologic scoring scale is helpful in a comprehensive evaluation of vocal leukoplakia lesions. The simplified four-variable laryngoscopic scale has relatively good consistency between raters and is helpful for stratifying patients for further management. We conclude that this evaluation method has the potential to be a comprehensive system for predicting malignancy by using these four laryngoscopic variables. Acknowledgments The authors thank the members of the Linkou CGMH Head and Neck Oncologic team for their kind support of this trial and Ms. Chih-Chen Liu for data collection. BIBLIOGRAPHY 1. Dean CM, Spiegel JR, Sataloff RT. Premalignant Lesions of the Larynx. In: Rubin JS, Sataloff RT, Korovin GS, eds. Diagnosis and Treatment of Voice Disorders. 2nd ed. Albany, NY: Delmar Thomson Learning; 2002: Isenberg JS, Crozier DL. Dailey SH. Institutional and comprehensive review of laryngeal leukoplakia. Ann Otol Rhinol Laryngol 2008;117(1): Ricci Ricci G, Molini E, Faralli M, Simoncelli C. Retrospective study on precancerous laryngeal lesions: a clinicopathologic study with long-term follow-up. Acta Otorhinolaryngol Ital 2003;23: V. Kambic. Epithelial hyperplastic lesions a challenging topic in laryngology. Acta Otolaryngol Suppl 1997;527: Zeitels SM, Casiano RR, Gardner GM, et al. Management of common voice problems: committee report. Otolaryngol Head Neck Surg 2002;126(4): Zeitels SM. Premalignant epithelium and microinvasive cancer of the vocal fold: the evolution of phonomicrosurgical management. Laryngoscope 1995;105(3 pt 2): Lewis Roy Eversole. Dysplasia of the upper aerodigestive tract squamous epithelium. Head Neck Pathol 2009;3: Bouquot JE, Gnepp DR. Laryngeal precancer: a review of the literature, commentary, and comparison with oral leukoplakia. Head Neck 1991;13: Schepman KP, Van der Waal I. A proposal for a classification and staging system for oral leukoplakia: a preliminary study. Eur J Cancer B Oral Oncol 1995;31B: Van der Waal I, Schepman KP, Van der Meij EH. A modifed classification and staging system for oral leukoplakia. Oral Oncol 2000;36: Sllamniku B, Bauer W, Painter C, Sessions D. The transformation of laryngeal keratosis into invasive carcinoma. Am J Otolaryngol 1989;10: Blackwell KE, Calcaterra TC, Fu YS. Laryngeal dysplasia: epidemiology and treatment outcome. Ann Otol Rhinol Laryngol 1995;104: E66