The Laryngoscope C 2014 The American Laryngological, V
Rhinological and Otological Society, Inc.
Gender and Age in Benign Vocal Fold Lesions Alisa Zhukhovitskaya, MD; Danielle Battaglia, BA; Sid M. Khosla, MD; Thomas Murry, PhD; Lucian Sulica, MD 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. Key Words: phonotrauma, age, gender, polyp, pseudocyst, nodule, contact lesion, benign vocal fold lesion. Level of Evidence: 4. Laryngoscope, 125:191–196, 2015
INTRODUCTION Benign mucosal lesions are a group of acquired structural abnormalities of the glottis, typically resulting from trauma or irritation. Most are manifestations of tissue injury from phonatory vibration, termed phonotrauma. Others are consequences of irritants such as cigarette smoke or laryngopharyngeal reflux. These factors are generally well-recognized and—appropriately— are routinely addressed in the management of these lesions. Clinical practice suggests that additional factors may influence the development of certain lesions beyond sources of trauma or irritation extrinsic to the larynx and have implications for treatment. For example, it is commonly observed that specific lesions such as nodules and pseudocysts are more prevalent in females, and others are more prominent in certain age groups.1–3
From the Department of Surgery, North Shore - Long Island Jewish Health System (A.Z.), Bronx; Sean Parker Institute for the Voice, Weill Cornell Medical College (T.M., L.S.), New York, New York; the Florida Atlantic University (D.B.), Boca Raton, Florida; and the Department of Otolaryngology–Head and Neck Surgery, University of Cincinnati College of Medicine (S.M.K.), Cincinnati, Ohio, U.S.A. Editor’s Note: This Manuscript was accepted for publication August 12, 2014. Presented at the American Laryngological Association Annual Meeting at the Combined Otolaryngological Spring Meetings (COSM), Las Vegas, Nevada, U.S.A, May 14, 2014. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Lucian Sulica, MD, Department of Otolaryngology–Head and Neck Surgery 1305 York Avenue, 5th Floor, New York, NY 10021. E-mail:
[email protected] DOI: 10.1002/lary.24911
Laryngoscope 125: January 2015
Although associations between lesions and demographic factors have been identified in the past, age and gender have not been systematically examined. The purpose of this investigation is to describe gender and age associations in a large, treatment-seeking population at a university voice center and to offer possible explanations for such associations.
MATERIALS AND METHODS This study was approved by the institutional review board of Weill Cornell Medical College, New York, NY. New adult ( 18 years old) patients who presented over a 5-year period (April 29, 2008–April 18, 2013) with a voice complaint and were diagnosed with a benign vocal fold lesion during their initial visit were identified from the senior author’s (L.S.) database. Diagnosis was assigned by a single fellowship-trained laryngologist following transnasal flexible or transoral rigid laryngeal videostroboscopy. Medical records were reviewed for patients’ age, primary and secondary diagnoses, date of visit, chief complaint, duration of complaint, inciting factors, previous diagnoses and treatments, Voice Handicap Index-10 score, 4 substance use history, relevant medical and surgical history, and relevant medications. Whether the patient was a professional performer was recorded as well. Patients were classified according to age, gender, and lesion type. Lesion definitions were broadly consistent with those in the current literature.5–7 A contact lesion was defined as a mucosal irregularity over the vocal process of thearytenoid cartilage and included both contact ulcer and granuloma. A contact ulcer was a superficial ulcerated area on the medial surface of thearytenoid. Granuloma was an exophytic mass arising from the vocal process of arytenoid cartilage. Midfold mass is a heterogeneous category that encompasses a broad spectrum of subepithelial
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Fig. 3. Vocal fold pseudocyst (left).
Fig. 1. Bilateral midfold masses.
change. Typical features include subepithelial fibrous thickening at the midpoint of the membranous vocal fold, usually less welldefined than a polyp, which often extends anteriorly and posteriorly along the vibratory margin. A midfold mass can be bilateral and approximately symmetric or, more rarely, unilateral. Lesions elsewhere termed nodules fit within this category, as do midfold lesions that do not easily conform to another category. Cyst was defined as an encapsulated-appearing subepithelial mass. Polyp referred to a well-defined sessile or pedunculated subepithelial lesion at the midpoint of the membranous vocal fold, which could be hemorrhagic and/or fibrotic. A pseudocyst was defined as fusiform translucent lesion on the vibratory margin of the vocal fold. A sulcus was defined as a focal invagination of epithelium, caused by tighter than usual epithelial adhesion to the deep tissue of the vocal fold, appearing as a furrow or groove. Hemorrhage referred to subepithelial extravasation of blood without focal mass effect. Reinke’s edema was a proliferation of superficial lamina propria material over the entire length of one or both vocal folds. Leukoplakia referred to a white-appearing area of epithelial change; it does not imply anything about histology other than the presence of keratosis. Scar was a heterogeneous category of lesions characterized by permanent change to the lamina propria featuring hypodynamic areas of mucosa, typically without mass effect. A reactive lesion was defined as a unilateral focal thickening of the mucosa at the midpoint of the membranous vocal fold, which in judgment of the clinician resulted from trauma from a contralateral lesion. Lastly, bamboo lesions were subepithelial rheumatoid deposits with a characteristic linear appearance of the superior surface of the vocal fold. Journal limits preclude the inclusion of illustrations of all lesion types. The following figures show examples of the three lesion types that we
judged most likely to be used ambiguously in clinical practice: bilateral midfold masses (BMM) (Fig. 1), polyp (Fig. 2), and pseudocyst (Fig. 3). The stroboscopic examinations of 127 patients with lesions, the categorization of which was not clear on the review of the database, were re-reviewed blindly by the laryngologist. For no more than 15 patients, the first visit exam was not diagnostic (usually because of acute inflammation or edema), and a follow-up exam was used to categorize the lesion. Most of the re-reviewed lesions were categorized as BMM or unilateral midfold mass (UMM). Patients diagnosed with a malignancy in addition to a lesion of interest were excluded. In patients with two or more pathologies of interest, the lesions were analyzed separately. Because of the variation in the number of subjects in each diagnostic category, chi square analysis was performed with age and gender analyzed for each diagnostic category. The prevalence of various lesions was compared among male and female patients, as well as between the three age groups using chi-squared analysis. An alpha level of .05 was selected as a reference for statistical significance. A Dunn correction was performed for the multiple chi-square analyses, and the tables reflect the corrected values. The corrected alpha values were 0.029 for gender comparisons and 0.023 for age comparisons.
RESULTS Table I describes the demographic characteristics of the study population. Table II and Figure 4 represent the prevalence of lesions by gender. For purposes of analysis, patients were divided into three age groups:
TABLE I. Gender and Age Groups Studied. Total
602 patients 641 lesions
Gender (cohort)
372 female (61.8%)
Gender (lesion)
230 male (38.2%) 396 female (61.8%) 245 male (38.2%)
Age (cohort) Age group (lesion)
Mean 5 41.09 (18–87 years old) 349 (54.4%): 18–39 years old 187 (29.2%): 40–59 years old
Fig. 2. Vocal fold polyp (right).
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105 (16.4%): 601 years old
Zhukhovitskaya et al.: Benign VF Lesions: Gender and Age
TABLE II. Lesion Type, Gender, Chi Square Value, and Level Of Significance for Genders (Corrected Alpha: 0.029). Lesion Type (N)
BMM (95)
Male (%)
Female (%)
P Value (df 5 1)
v2
9 (9.5%)
86 (90.5%) 33.21
P < 0.0001
Contact (37)
29 (78.4%)
8 (21.6%) 25.3
P < 0.0001
Cyst (43) Polyp (147)
16 (37.2%) 81 (55.1%)
Pseudocyst (126)
16 (12.7%) 110 (87.3%) 34.71 9 (20%)
27 (62.6%) 0.018 P > 0.8 66 (44.9%) 17.79 P < 0.0001
Reinke’s Edema (45) Scar (26) Sulcus (52) UMM (23) Hemorrhage (17)
14 (60.9%) 6 (35.3%)
9 (39.1%) 11 (64.7%)
Leukoplakia (23)
19 (82.6%)
Bamboo (3) Reactive lesion (4) Total (641)
P < 0.0001
36 (80%)
6.314 P < 0.012
12 (46.2%)
14 (53.8%)
0.697 P > 0.4
33 (63.5%)
19 (36.5%) 14.06
0 (0%) 1 (25%)
P < 0.0002
5.01 P < 0.025 0.058 P > 0.8
4 (17.4%) 19.21 3 (100% 3 (75%)
P < 0.0001
1.85 P > 0.18 0.295 P > 0.3
245 (38.2%) 396 (61.8%)
BMM 5 bilateral midfold UMM 5 unilateral midfold mass.
and UMM were all associated with male gender. Cyst and scar showed no statistically significant association with gender. No lesion had a statistically significant association with age alone. Reactive lesion, hemorrhage, and bamboo lesion showed no statistically significant association with either age or gender; however, the number of patients with these diagnoses was small.
masses;
df 5 degrees
of
freedom;
young (18–39 years old), middle-aged (40–59 years old), and older (601 years old). Table III and Figure 5 show the prevalence of each lesion type in the three age groups. BMM were associated with female gender and young age. The diagnosis of pseudocyst had similar associations. Reinke’s edema was found to be associated with female gender and middle and older age groups. Leukoplakia was associated with both male gender and the oldest age group. Vocal polyps were associated with male gender. Certain lesions had statistically significant associations with gender only. Contact lesions, keratosis, sulcus,
DISCUSSION In this analysis, we focus on gender and age associations of benign vocal fold lesions, often noted in passing in other articles addressing specific lesion types. Whereas none of the data presented is likely to surprise seasoned clinicians, it suggests degrees of association between lesions and age and gender that may be inadequately described by current pathophysiologic concepts. Benign mucosal lesions are considered to result from tissue injury by factors extrinsic to the larynx, principally vocal behaviors and irritants such as cigarette smoke and gastric acid reflux. These are considered to be fairly homogenous factors. For example, phonotrauma, or the physical stress on the vocal fold during phonation, although certainly a product of the amount and intensity of voice use, is considered to exert its effects on laryngeal tissues with little variation from individual larynx to individual larynx. Yet this conception does not account for the heterogeneous array of phonotraumatic lesions found clinically. When we note clear predispositions to develop certain types of lesions by gender or age, it is reasonable to turn to these features to seek explanations for lesion differences.
Lesions in Women Females report a greater rate of voice disorders in general and are found to have a disproportionately higher rate of benign vocal fold pathologies.1,2 Female
TABLE III. Lesion Type, Age Groups, Chi Square Value, and Significance Lever for Each Age Group (Corrected Alpha: 0.023). Lesion Type (N)
18–39 Years Old (%)
40–59 Years Old (%)
601 Years Old (%)
v2
P Value (df 5 2)
P < 0.0001
BMM (95)
81 (85.3%)
11 (11.6%)
3 (3.2%)
36.89
Contact (37)
14 (37.8%)
14 (37.8%)
9 (24.3%)
4.23
P > 0.1
Cyst (43) Polyp (147)
12 (27.9%) 68 (46.3%)
20 (46.5%) 57 (38.8%)
11 (25.6%) 22 (15%)
12.17 6.59
P < 0.024 P < 0.038
100 (79.4%)
20 (15.9%)
6 (4.8%)
32.5
P < 0.0001
7 (15.6%) 8 (30.8%)
21 (46.7%) 10 (38.5%)
17 (37.8%) 8 (30.8%)
29.7 6.71
P < 0.0001 P < 0.036
Sulcus (52)
23 (44.2%)
15 (28.8%)
14 (26.9%)
4.50
P > 0.1
UMM (23) Hemorrhage (17)
17 (73.9%) 10 (58.8%)
4 (17.4%) 6 (35.3%)
2 (8.7%) 1 (5.9%)
3.54 1.42
P > 0.17 P > 0.49
Pseudocyst (126) Reinke’s Edema (45) Scar (26)
Leukoplakia (23)
4 (17.4%)
8 (34.8%)
11 (47.8%)
29.89
P < 0.0001
Bamboo (3) Reactive lesion (4)
0 (0%) 4 (100%)
2 (66.7%) 0 (0%)
1 (33.3%) 0 (0%)
3.6 3.35
P > 0.16 P > 0.18
349 (54.4%)
187 (29.2%)
105 (16.4%)
Total (641)
BMM 5 bilateral midfold masses; df 5 degrees of freedom; UMM 5 unilateral midfold mass.
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Fig. 4. Prevalence of lesions in males and females. Asterisk indicates statistically significant difference (P
