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Perceptual and acoustic characteristics of voice changes in reflux laryngitis patients.

The aim of the study was to outline the multidimensional perceptual, subjective, and instrumental acoustic voice changes in the group of reflux laryngitis (RL) patients. Data of multidimensional voice assessment of 108 RL patients and 90 healthy persons of the control group were subjected to comparative analysis. A slight hoarseness according to the GRB (G-grade, R- rough, B-breathy) scale was prevailing in the RL patients group. Statistically significant difference (P < 0.001) between RL patients group and the control group was found of all voice parameters measured, with the patients having worse results--increased mean jitter, shimmer, normalized noise energy, voice handicap index (VHI), and decreased parameters of phonetogram. The results of the study demonstrated that multidimensional voice assessment documented deteriorated voice quality and restricted phonation capabilities in the tested group of RL patients.

Adolescent↗

Phonatory impairment in Parkinson's disease: evidence from nonlinear dynamic analysis and perturbation analysis.

Many persons with Parkinson's disease (PD) will eventually experience vocal impairment as their condition advances. Using standard perturbation analyses (parameters like jitter and shimmer) to measure fluctuations in phonatory signal may inhibit researchers from recognizing severely disordered patterns that seem to be present in the voices of some PD patients. Nonlinear dynamic analysis can quantify these aperiodic patterns, which indicate severe pathology that is usually characterized perceptually by hoarseness. Here, sustained vowel phonations of a heterogeneous group of PD subjects (20 women and 21 men) were compared with those of a control group (22 women and 18 men) based on results of nonlinear dynamic analyses (D(2)) and perturbation analyses. Results showed PD subjects as a whole to have significantly higher D(2) values than control subjects (P = 0.016), which indicates increased signal complexity in PD vocal pathology. Differences in the comparison of these two groups were significant in jitter (P = 0.014) but nonsignificant in shimmer (P = 0.695). Furthermore, the performance on these three measures was affected by subject sex. Nonlinear dynamic analysis showed significantly higher D(2) in the female PD group than in the female control group (P = 0.001), but jitter and shimmer did not show such a difference. The male PD group had statistically higher jitter than the male control group (P = 0.036), but these groups did not differ in D(2) or shimmer. Overall, nonlinear dynamic analysis may be a valuable method for the diagnosis of Parkinsonian laryngeal pathology.

Female↗

Cytotoxic agents in the treatment of laryngeal sarcoidosis: a case report and review of the literature.

SUMMARY: Sarcoidosis is a multisystem disease with various clinical manifestations. It is characterized primarily on a histopathologic basis by the presence of noncaseating granulomata. Laryngeal involvement reportedly occurs in 3-5% of cases, and it is typically localized to the supraglottic region. Patients often present with hoarseness, dysphagia, stridor, or dyspnea. Laryngoscopy typically demonstrates a pale, edematous epiglottis studded with nodules. Tissue biopsy reveals the classic noncaseating granuloma; however, the finding is not diagnostic. Sarcoidosis remains a diagnosis of exclusion to be entertained once other verifiable etiologies for granulomatous disease of the larynx, such as TB, syphilis, fungal infection, berylliosis, or Wegener's granulomatosis, have been ruled out. Systemic corticosteroids remain the mainstay of treatment; however, new steroid-sparing therapies that target the inflammatory response of sarcoidosis are currently being investigated. The case history of a patient with laryngeal sarcoidosis who was managed with the immunosuppressant azathioprine (Imuran) is summarized along with a discussion of other treatment options.

Adult↗

Short-term effects of endotracheal intubation on voice.

The objective of this study was to examine the vocal symptoms and acoustic changes perceived in the short period after endotracheal intubation, and to find the association between these changes and the endotracheal tube parameters. A total of 35 subjects were included. They were examined preoperatively, and 2 and 24 hours postoperatively. The vocal symptoms of hoarseness, vocal fatigue, loss of voice, throat clearing, globus pharyngeus, throat pain, and the acoustic variables mainly average fundamental frequency, relative average perturbation, shimmer, noise to harmony ratio, voice turbulence index, habitual pitch, and maximum phonation time (MPT) were assessed as such and in relation to the following endotracheal tube parameters: duration of anesthesia, number of intubation attempts, size of the tube, cuff volume, cuff mean pressure, and the emergence. The association between anesthesia parameters with incidence of vocal complaints and changes in acoustic parameters were examined using logistic and linear regression. Vocal fatigue was associated significantly with the increase in cuff volume and the number of intubation attempts. Throat clearing was associated significantly with the increase in cuff mean pressure. Only the increase in habitual pitch was associated significantly with the increase in cuff volume. The acute short-term effect of endotracheal intubation on voice is significant. The most important endotracheal tube parameters that affect the vocal changes are the cuff mean pressure and volume. The laryngeal contribution to these vocal changes seems to be minimal. All vocal symptoms increased significantly except for globus pharyngeus at 2 hours postoperatively. The acoustic parameters did not change significantly except for a decrease in MPT. At 24 hours postoperatively, all vocal symptoms subsided with no significant difference to baseline value. The habitual pitch increased significantly, and the rest of the parameters remained comparable to baseline value.

Adolescent↗

Vocal problems among teachers: evaluation of a preventive voice program.

Vocal education programs for teachers may prevent the emergence of vocal disorders; however, only a few studies have tried to evaluate the effectiveness of these preventive programs, particularly in the long term. Two hundred and sixty-four subjects, mostly kindergarten and primary school female teachers, participated in a course on voice care, including a theoretical seminar (120 minutes) and a short voice group therapy (180 minutes, small groups of 20 subjects). For 3 months, they had to either attend the vocal ergonomics norms and, as psychological reinforcement, they had to make out a daily report of vocal abuse, or to follow the given exercises for a more efficient vocal technique, reporting on whether the time scheduled was respected or not. The effectiveness of the course was assessed in a group of 21 female teachers through a randomized controlled study. Evaluation comprehended stroboscopy, perceptual and electro-acoustical voice analysis, Voice Handicap Index, and a course benefit questionnaire. A group of 20 teachers matched for age, working years, hoarseness grade, and vocal demand served as a control group. At 3 months evaluation, participants demonstrated amelioration in the global dysphonia rates (P=0.0003), jitter (P=0.0001), shimmer (P=0.0001), MPT (P=0.0001), and VHI (P=0.0001). Twelve months after the course, the positive effects remained, although they were slightly reduced. In conclusion, a course inclusive of two lectures, a short group voice therapy, home-controlled voice exercises, and hygiene, represents a feasible and cost-effective primary prevention of voice disorders in a homogeneous and well-motivated population of teachers.

Adult↗

Voice problems of future speech-language pathologists.

Students training to be educators frequently exhibit voice disorders prior to employment. To date, there exist no similar studies of future speech-language pathologists (SLPs). The study is designed as a prospective, nonrandomized survey. The objective of this study is to determine the voice problems of first year graduate students training to be SLPs. Participants were 104 first year graduate students majoring in speech-language pathology at two universities. The Quick Screen for Voice was administered. Participants who failed completed a questionnaire regarding voice problems, medical history, daily habits, and voice use. When responses further indicated voice-related problems, endoscopic examination was completed. Fourteen percent (N=15) of the participants failed the screening by demonstrating two or more abnormal voice characteristics. These included persistent glottal fry (present in all who failed), low habitual pitch, juvenile resonance, hoarse, breathy, or strained phonation, abnormally low pitch on sustained vowels, and voice breaks during the frequency range. Twelve percent (N=12) failed both the screening and follow-up questionnaire. Responses included self-reported dysphonia, medical history with voice-related side effects, difficulty with excessive voice use, and voice problems occurring daily or weekly. Endoscopic evaluation showed one participant with bilateral vocal nodules. The results suggest that voice problems among future SLPs (12%) are more common than the 3-9% reported in the general population and similar to the 11% previously reported for teachers. However, future SLP voice problems are less frequent than those reported among education majors (21%) and all college students (17%). Faculty should identify students with voice problems and emphasize optimal voice use in classroom and clinical settings.

Adult↗

Dual intracordal unilateral vocal fold cysts: a perplexing diagnostic and therapeutic challenge.

SUMMARY: A 52-year-old professional voice user, a director of international sales and marketing and sports coach, described a 40-year history of severe hoarseness, with recent progressive dysphonia. He could not be heard on a cell phone and was unable to raise the volume or intensity of his voice. Strobovideolaryngoscopy revealed a perplexing set of dual intracordal lesions in the left vocal fold and a posterior glottal gap. The amplitude and magnitude of the left vocal fold mucosal waves were barely perceptible and were severely decreased in the right. There was marked phase asymmetry and aperiodicity bilaterally. A computed tomography scan of the neck with contrast and multiplanar reformatted reconstructions and a magnetic resonance imaging (MRI) of the neck with and without contrast revealed the nodular appearing masses of the left vocal fold without any definite evidence of paraglottic or supraglottic extension and no cervical lymphadenopathy. He had a hyperfunctional larynx with laryngopharyngeal reflux and chronic reflux laryngitis. Voice restoration required antireflux therapy, voice therapy, and phonomicrosurgical excision of the lesions. One benign epidermoid malformation cyst was lined by squamous epithelium. The second was a retention cyst lined with cuboidal epithelium. Finally, after 40 years, he has a normal voice.

Cysts↗

Artificial neural network-based classification to screen for dysphonia using psychoacoustic scaling of acoustic voice features.

SUMMARY: For diagnosis and classification of dysphonia, voice specialists can choose from an array of diagnostic tools like perceptual tests or acoustic voice analysis. These methods have in common that they require a high level of specialized training and experience, and therefore are mostly reserved to specialized centers. We aimed at developing an acoustic voice analysis system that could be used as a screening device to monitor, document, and diagnose voice problems that are also encountered by non-voice specialists, such as anesthesiologists, head and neck surgeons, and general surgeons before surgery of the thyroid gland and the upper thoracic aperture. An acoustical feature extraction paradigm that focused on jitter, shimmer, standard deviation of fundamental frequency, and the glottal-to-noise excitation ratio was used to reanalyse 120 voice samples previously analyzed by Schönweiler et al (A Novel Approach to Acoustical Voice Analysis Using Artificial Neural Networks. JARO. 2000:1;270-282). An improved artificial neural network (ANN) was used for classification. Building on this preliminary work, we modified the mathematical algorithm to further improve classification accuracy. Eighty percent of all voice samples could be classified correctly as either healthy or hoarse (sensitivity: 63.0%; specificity: 93.9%; area under the curve: 0.854). The adaptation of the ANN-voice analysis system for mobile use may facilitate its use and acceptance by non-voice specialists for the discovery and documentation of preexisting voice disorders, and may thereby lead to a timely initiation of further diagnosis and therapy by voice specialists.

Diagnosis, Differential↗

An integrated tool for the diagnosis of voice disorders.

A PC-based integrated aid tool has been developed for the analysis and screening of pathological voices. With it the user can simultaneously record speech, electroglottographic (EGG), and videoendoscopic signals, and synchronously edit them to select the most significant segments. These multimedia data are stored on a relational database, together with a patient's personal information, anamnesis, diagnosis, visits, explorations and any other comment the specialist may wish to include. The speech and EGG waveforms are analysed by means of temporal representations and the quantitative measurements of parameters such as spectrograms, frequency and amplitude perturbation measurements, harmonic energy, noise, etc. are calculated using digital signal processing techniques, giving an idea of the degree of hoarseness and quality of the voice register. Within this framework, the system uses a standard protocol to evaluate and build complete databases of voice disorders. The target users of this system are speech and language therapists and ear nose and throat (ENT) clinicians. The application can be easily configured to cover the needs of both groups of professionals. The software has a user-friendly Windows style interface. The PC should be equipped with standard sound and video capture cards. Signals are captured using common transducers: a microphone, an electroglottograph and a fiberscope or telelaryngoscope. The clinical usefulness of the system is addressed in a comprehensive evaluation section.

Computer Graphics↗

Professional delay in head and neck cancer patients: analysis of the diagnostic pathway.

The aim of this study was to identify which factors are related to specialist delay and to determine the length of the diagnostic pathway in head and neck cancer patients. Three hundred and six patients with a carcinoma of the larynx, pharynx or oral cavity were included in the study. Logistic regression analysis was used to identify risk factors for specialist delay. Large (T3-T4) tumors showed significantly less specialist delay than small (T1-T2) tumors (p=0.045, odds ratio [OR]=0.6). Pharyngeal (p=0.00, OR=0.2) and oral carcinomas (p=0.00, OR=0.2) had less specialist delay than glottic carcinomas. Hoarseness was associated with prolonged specialist delay (p=0.00, OR=5.9). Heavy drinking in combination with smoking (p=0.005, OR=0.3), a sore throat (p=0.02, OR=0.4) or having a lesion (p=0.03, OR=0.2) showed a shorter diagnostic period. The duration of the diagnostic process in a general hospital ranged from 0 to 570 days, with a median of 14 days. Only a small group of patients met the ideal management standards in our head and neck clinic. Although prolonged delay was associated with small (glottic) tumors, the diagnostic process takes a fairly long time. The results indicate that continued educational programs for professionals are warranted.

Adolescent↗

Severe hypertrophy of the base of the tongue in adults.

The lymphoid follicles at the base of the tongue can be detected when examining the pharynx of adults, but the presence of large follicles, denoted "severe" hypertrophy of the base of the tongue (HBT) is rare. The objective of the present study was to identify severe HBT cases and their symptoms and to correlate them with the presence of pharyngolaryngeal signs and esophageal symptoms of gastroesophageal reflux (GER) in patients seen at a laryngology clinic. Severe HBT was considered to be present when the follicles prevented the view of the epiglottis or were massively distributed through the pharynx and larynx. Five cases of severe HBT were detected among 306 patients submitted to videolaryngoscopy over a period of 2 years, corresponding to 1.6% (5/306) of the total sample studied. However, this index markedly increases to 4% (4/101) among patients with pharyngolaryngeal signs of GER and reached 7.5% (4/53) among patients presenting GER symptoms such as heartburn, regurgitation, retrosternal burning feeling, and dysphagia. The complaints due to severe HBT were noisy respiration, hoarseness, throat clearing, dry cough, globus pharyngeus, and nasal voice. We conclude that the frequency of hypertrophied follicles is increased in the presence of signs and symptoms of GER and those HBT symptoms are confused with those of GER, except for nasal voice and noisy respiration.

Adult↗

Neck mass due to thrombosis of the jugular vein in patients with cancer.

The hypothesis that jugular thrombosis (JT) may cause a mass in the cervical region is usually overlooked. The objective of the present study was to identify the characteristics of neck masses resulting from JT in cancer patients and to analyze the possible reasons for their formation. A retrospective study was conducted on 8 patients with JT affected by 3 types of neoplasia, ie, carcinomas (3 cases), adenocarcinomas (3 cases), and lymphomas (2 cases) located in the breast, digestive apparatus, lymphatic system (2 cases each), lung and an undetermined site (1 case each), diagnosed over the last 12 years. The most frequent symptom of JT was the presence of a mass in the supraclavicular space (62.5% of cases) deeply located on the anterior margin of the sternocleidomastoid muscle and diagnosed by computed tomography and ultrasound. The masses were slightly hardened, with a clearly defined upper limit and an imprecise lower limit and with an irregular surface. The patients also presented with cough, hoarseness, pain during movements, facial edema, and collateral circulation. In one of the patients with a lung cancer, JT symptoms preceded the symptoms of cancer by 2 months. Hypercoagulation, compression, and invasion of a vessel possibly explain the occurrence of JT in these patients.

Adolescent↗

Neurologic and developmental features of the Smith-Magenis syndrome (del 17p11.2).

The Smith-Magenis syndrome is a rare, complex multisystemic disorder featuring, mental retardation and multiple congenital anomalies caused by a heterozygous interstitial deletion of chromosome 17p11.2. The phenotype of Smith-Magenis syndrome is characterized by a distinct pattern of features including infantile hypotonia, generalized complacency and lethargy in infancy, minor skeletal (brachycephaly, brachydactyly) and craniofacial features, ocular abnormalities, middle ear and laryngeal abnormalities including hoarse voice, as well as marked early expressive speech and language delays, psychomotor and growth retardation, and a 24-hour sleep disturbance. A striking neurobehavioral pattern of stereotypies, hyperactivity, polyembolokoilamania, onychotillomania, maladaptive and self-injurious and aggressive behavior is observed with increasing age. The diagnosis of Smith-Magenis syndrome is based upon the clinical recognition of a constellation of physical, developmental, and behavioral features in combination with a sleep disorder characterized by inverted circadian rhythm of melatonin secretion. Many of the features of Smith-Magenis syndrome are subtle in infancy and early childhood, and become more recognizable with advancing age. Infants are described as looking "cherubic" with a Down syndrome-like appearance, whereas with age the facial appearance is that of relative prognathism. Early diagnosis requires awareness of the often subtle clinical and neurobehavioral phenotype of the infant period. Speech delay with or without hearing loss is common. Most children are diagnosed in mid-childhood when the features of the disorder are most recognizable and striking. While improvements in cytogenetic analysis help to bring cases to clinical recognition at an earlier age, this review seeks to increase clinical awareness about Smith-Magenis syndrome by presenting the salient features observed at different ages including descriptions of the neurologic and behavioral features. Detailed review of the circadian rhythm disturbance unique to Smith-Magenis syndrome is presented. Suggestions for management of the behavioral and sleep difficulties are discussed in the context of the authors' personal experience in the setting of an ongoing Smith-Magenis syndrome natural history study.

Abnormalities, Multiple↗

EPs 7630-solution--an effective therapeutic option in acute and exacerbating bronchitis.

Acute bronchitis is one of the most common diagnoses in ambulatory care medicine. Although the benefit of antibiotics for acute bronchitis, which is mostly virally induced, is disputed, they are often prescribed. A therapeutic option for respiratory tract infections that do not fall within the strict indication range for antibiotic administration is the liquid herbal drug preparation from the roots of Pelargonium sidoides, EPs 7630 (Umckaloabo), which has been tested against placebo in double-blind clinical trials. EPs 7630 has both antibacterial and immuno-modulating properties. The efficacy and tolerability of EPs 7630 was investigated in a prospective, open, multicentric outcomes study with 205 patients suffering from acute bronchitis or acute exacerbation of chronic bronchitis. The main outcome measure was the change in the total score of five symptoms typical for bronchitis (cough, expectoration, wheezing/whistling on expiration, chest pain during coughing, and dyspnoea), which were each rated using a 5-point scale (from 0=not present to 4=extremely pronounced). Further symptoms (hoarseness, headache, aching limbs and fatigue) were assessed using a four-point scale (from 0=not present to 3=very pronounced). The total score of the typical bronchitis symptoms amounted to 6.1+/-2.8 points on average at the start of treatment and decreased by 3.3+/-3.8 points to 2.8+/-2.6 points by the final examination on day 7. About 60.5% of the patients assessed their health condition at the end of the study as much improved or free from symptoms. The onset of action appeared after two days on average. Adverse events occurred in a total of 16 patients. There were no serious adverse events. Altogether, 78% of the patients were satisfied or very satisfied with the treatment.

Acute Disease↗

Short course palliative radiotherapy of 20 Gy in 5 fractions for advanced and incurable head and neck cancer: AIIMS study.

BACKGROUND AND PURPOSE: A proportion of advanced stage head and neck cancer patients are incurable and have a limited life expectancy of 100 days or less. The study aimed to offer a short course of palliative radiotherapy (PRT) and evaluate the symptom relief, disease response and duration of survival. PATIENTS AND METHODS: Between 1995 and 2001, 505 patients of stage IV squamous cell carcinoma received uniform dose of 20 Gy in 5 fractions over 1 week along with symptom relief drugs. Incurable status and decision for palliation was made conjointly. Distressing symptoms were assessed before PRT. Patients showing more than 50% objective regression (PR) at tumor and nodal sites received further RT (FRT) up to 70 Gy. RESULTS: The overall PR rate was 37% (189 patients), but 153 (30%) completed FRT, and rest 352 were followed up after PRT only. None of the patients died due to radiation toxicity, and the radiation morbidities were confined to dry desquamation and patchy mucositis, which healed over 1 month. Symptom relief for pain, dysphagia, hoarseness, cough and otalgia was obtained in 47%-59% of the patients following PRT. The overall survival ranged from 34 days to 2065 days and median survival to PRT and FRT were 200 days and 400 days, respectively. Only 10% were disease-free after FRT. CONCLUSIONS: Unfavourable advanced stage head and neck cancer can be identified for a suitable short course of palliative radiotherapy which will achieve growth restraint and symptom relief in sizeable proportions for an approximate period of 7 months.

Adult↗

Esophageal involvement in scleroderma: gastroesophageal reflux, the common problem.

OBJECTIVES: Systemic sclerosis (SSc) is a multisystem disease characterized by abnormalities of small blood vessels, and fibrosis of the skin and internal organs including gastrointestinal tract. This article reviews the esophageal involvement in SSc, emphasizing the gastroesophageal reflux, which is a common problem in SSc patients. METHODS: We conducted a Medline search from 1966 to 2005. The keywords "systemic sclerosis," "esophageal involvement," "gastroesophageal reflux," "esophagitis," and "treatment" were used. RESULTS: The gastrointestinal tract is frequently affected in diffuse and limited disease. Although any part of the gastrointestinal tract can be involved, esophageal disease occurs in nearly all patients with SSc. Common esophageal manifestations in SSc include motility abnormalities and gastroesophageal reflux (GER), Barrett's esophagus, adenocarcinoma, infectious esophagitis, and drug-induced esophagitis. Common complications of GER include esophagitis with erosions and bleeding and stricture formation. Extraesophageal manifestations of GER include mouth ulcers, chronic cough, hoarse voice, sore throat, pharyngitis, laryngospasm, asthma, and recurrent pneumonia. Diagnostic procedures used in the investigation of esophageal involvement include barium esophagram, esophageal manometry, 24-hour ambulatory pH, and endoscopy. Treatment of GER in SSc includes behavioral modification and medical therapy, mainly with proton pump inhibitors. Surgical intervention has a limited role in the management of GER in selected SSc patients. CONCLUSIONS: Esophageal involvement is frequent in SSc patients. Gastroesophageal reflux may cause high morbidity. Careful examination of the patients reveals gastrointestinal abnormalities even in patients without symptoms. Appropriate treatment of esophageal involvement ameliorates symptoms and prevents complications.

Esophagitis↗

Efficacy of laparoscopic fundoplication in controlling pulmonary symptoms associated with gastroesophageal reflux disease.

BACKGROUND: Gastroesophageal reflux disease (GERD)-induced pulmonary symptoms (PS) can be difficult to control. The effectiveness of laparoscopic fundoplication (LF) in controlling PS among patients with medically recalcitrant GERD is poorly documented. We evaluated our results in controlling important PS in patients with GERD undergoing LF. METHODS: Seventy-four patients (28 men, 46 women) were identified with clinically important PS from a prospective cohort of 155 patients undergoing elective LF for recalcitrant GERD. Median age was 52.5 years (range, 29-84 years). Sixty-seven (91%) patients were taking proton pump inhibitors at the time of operation. Quality of life by using the SF36 physical (PCS) and mental (MCS) component summary scores (normal, 50) and heartburn severity by using the health-related quality of life (HRQOL) (best score, 0; worst score, 45) were measured. RESULTS: All 74 patients with PS survived operation, and minor morbidity occurred in 5 (7%) patients. Median hospital stay was 2 days (range, 1-6 days), and return to normal activity was seen at 2.2 weeks (range, 1-8 weeks). Median follow-up was 12 months. PS were improved significantly (P < .01) for hoarseness (62% to 17.6%), bronchospasm (60% to 9.5%), and aspiration (22% to 1.4%). Before LF, 11 (14.9%) patients required bronchodilators or oral steroids. Postoperatively such therapy was required in only 3 (4.2%) patients (P = .019), with no patient requiring oral steroids. Patients with poorer control of their GERD on the basis of high HRQOL scores had significantly more PS after operation. CONCLUSIONS: A significant number of patients with medically recalcitrant GERD (46% from our prospective database) have important PS. LF can improve PS, decrease requirement for pulmonary medications, as well as improve typical reflux symptoms and quality of life.

Adult↗

Dedifferentiated chondrosarcoma of the larynx.

Dedifferentiated chondrosarcoma is an uncommon malignant cartilaginous neoplasm of bone characterized by the presence of a malignant spindle cell neoplasm associated with a low- or medium-grade chondrosarcoma. Origin of this tumor in the cartilagenous framework of the larynx is very rare. A 60-year-old male with a 2-year history of hoarseness and dyspnea was examined while presenting in acute airway distress. Direct laryngoscopy revealed a mass of the right side of the larynx. Histopathologic examination revealed a malignant cartilaginous tumor with a malignant spindle cell component. We report a case of dedifferentiated chondrosarcoma arising in the thyroid cartilage. This, to our knowledge, is the eleventh fully documented case of this neoplasm arising in the larynx.

Chondrosarcoma↗