Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Vocal Process Granuloma Vocal process granulomas are benign lesions of the posterior glottis that are commonly centered over the tips of the cartilaginous vocal processes of the arytenoids. Vocal process granulomas are rare lesions seen primarily in males with vocal professions: auctioneers, lawyers, ministers, and teachers. Post intubation granulomas, however, are more common in women. Patients with chronic cough, throat clearing, or gastroesophageal reflux disease are additional candidates. From a historical perspective, Elsberg first introduced the use of endotracheal intubation in 1910. Chevalier Jackson, shown here on the right, terms the laryngeal abnormality contact ulcer in 1928. The first report of post intubation granulomas were published in 1932 by Clawson. Jackson and Jackson described the mechanism of a hammer and anvil action in 1945 of the arytenoids. Cherry and Margolis, in 1967, first identified the association between reflux and granuloma formation. A quick review of the laryngeal anatomy shows us both the true vocal cord folds, and the false vocal folds as well as the cuneiform and corniculate tubercles on the arytenoid cartilages. It is this posterior glottic region which we will be concentrating on in our talk today. The vocal fold mucosa is a squamous epithelium with no mucous glands. It has a highly specialized lamina propria which separates the epithelium from the underlying muscle. There is a superficial layer also knows as Reinke space, an intermediate layer, and a deep layer also known as the vocal ligament. We see the vocalis muscle here as well. The posterior glottis is formed by two arytenoid cartilages and intervening mucosa. The arytenoids are the posterior attachments of both the true and false vocal folds and are responsible for opening and closing of the glottis. The arytenoid base articulates with the cricoid cartilage at a complex synovial joint allowing multi-axial rotation. The vocal process is an anterior and medial projection of the arytenoid and makes up the posterior segment of the vocal folds. This next slide shows a left arytenoid cartilage and the left true vocal fold and the anteromedial aspect of the cartilage which is the vocal process. Also we see the crico-arytenoid joint which, as stated before, is a synovial joint. The normal arytenoid is composed largely of hilum cartilage with a small amount of elastic cartilage at the apex. From early adulthood, the hilum laryngeal cartilage starts to calcify starting with the thyroid, then the cricoid, and finally the arytenoid cartilages. The body of the muscular processes of the arytenoids calcify but the vocal processes do not. This calcification usually occurs in a symmetric fashion. When working up a patient with possible vocal process granuloma, the otolaryngologist needs to concentrate on both the history and physical exam. Some key points to hit on while taking the history are onset and duration of vocal symptoms, common symptom complexes, the talkativeness of the patient, vocal commitments, caffeine, alcohol, and tobacco use, acid reflux symptoms, and a prior history of intubation. When focusing on the physical exam, the laryngeal examination, of course, is most important and can be accomplished either by a mirror, flexible endoscopy, or videostroboscopy exam. When definitive diagnosis is needed, a surgical biopsy is always possible. McFarren, et al, in 1994 reviewed 34 case records over a 10-year period and reported the following clinical presentations of his patients with vocal process granuloma. Hoarseness was at the top at 91%, sensation of lump in the throat or discomfort at 47%, dyspnea at 18%, cough at 12%, and hemoptysis at 6%. Vocal process granulomas range in color from pale gray to dark red. The size usually ranges from 2-15 mm. The character may be polypoid, nodular, fungating, or ulcerated. Clinical findings of proliferative tissue emanating from the vocal process is usually sufficient to make the diagnosis. The second half of this slide shows a true vocal fold on an intubated patient with a granuloma coming off of the vocal process. This is another endoscopic view of the larynx showing a vocal process granuloma. This patient had a prolonged surgery with intubation. Again, another view of a different vocal process granuloma and this granuloma, as you can see, has a more ulcerated character. The differential diagnosis for a vocal process granuloma includes a list of posterior glottic lesions that, with the exception of squamous cell carcinoma, are currently rare in the United States. This list includes tuberculosis, histoplasmosis, coccidioidomycosis, blastomycosis, Wegener granulomatosis, syphilis, leprosy, and Crohn’s disease. Fortunately for the otolaryngologist, these disorders commonly have additional organ system involvement, thus, making them distinguishable from the more isolated vocal process granulomas. Interpretation of the laryngeal examination in the context of clinical presentation is imperative for determining the need for biopsy. Histomorphologic evaluation consistently shows epithelial hyperplasia often with ulceration and proliferation of underlying granulation tissue. Inflammatory changes include a mixed inflammatory infiltrate of acute and chronic cells of varying severity. Marked capillary proliferation is commonly present beneath the surface and in sporadic cases you can find a giant cell reaction. This slide shows both the squamous epithelial hyperplasia as well as an ulcerated lesion. The ulceration is in the middle of the lesion. On a closer view, this is a different granuloma but it shows both the acute and chronic inflammatory cells as well as the vascular proliferation of the lesion. Lennig, et al reported 105 cases in 1990 that were confirmed vocal process granulomas at review at the AFIP. Specific misdiagnoses made included a full spectrum of both benign and malignant processes including hemangioma, pyogenic granuloma, angiofibroma, hemangioendothelioma, Kaposi sarcoma, vocal cord polyp, squamous cell carcinoma, and verrucous carcinoma. Vocal process granulomas evolve from repeat insult to the mucosal perichondrium overlying the cartilaginous posterior glottis. This insult can be mechanical, inflammatory, or both. This region is particularly susceptible to injury because of the fragile nature of the thin mucoperichondrium overlying the poorly vascularized cartilaginous vocal processes. Traumatic abrasion of the vocal process results in focal loss of epithelium. The subsequent inflammatory reaction leaves the initial ulceration followed by perichondritis and chondral necrosis. A granulomatosis reaction then occurs in response to either repeat mechanical insult or acid refluxing. Mechanical etiologies of the granulomas can either be vocal or non-vocal. Von Liden and Moore in 1960 identified that vigorous oscillations of the arytenoids at low vocal frequencies are associated with a clashing together that was not apparent at higher pitches. Himmen, et al in 1989 identified abnormally high vocal cord closure velocities and collision forces among patients with vocal process granuloma. Non-vocal mechanical etiologies include a habitual throat clearing and recurrent cough that instigate behavior that cause a clashing of the arytenoids as well as subsequent tissue injury. Intubation injury is also a proposed mechanical etiology. Donnelley in 1969 performed an autopsy study of 99 previously intubated patients and identified that ulceration of the posterior glottis was a function of duration of intubation. He found a pale mucosa overlying the vocal processes as early as three hours after intubation and vocal process perichondrium involvement with ulceration at 72 hours. Santos, et al in 1994 reports on the laryngeal examinations of 99 post intubations patient. Granulomas were identified in 44% of the patients with 57% becoming apparent at four weeks after extubation. There are several small series that report surgical traumas as possible mechanical etiologies as well. These have come after posterior laser cordotomy to improve the airway in patients with bilateral laryngeal paralysis. In one study, 7 out of 18 patients formed granuloma after the procedure requiring additional surgery. Inflammatory etiologies include, and are largely based on, gastroesophageal reflux disease. Cherry et al in 1968 successfully induced vocal process granulomas in dogs with atraumatic application of gastric juice to the arytenoids. Kaufmann, et al in 1994 demonstrated that acid sensitive supraglottic chemical receptors initiate laryngospasm in a canine model. These authors argue and propose that mucosal irritation to the arytenoid from the hyperactive reflux material coupled with the spasm lead to ulceration that forms granulomas. There are other inflammatory etiologies including bacterial, viral, and fungal infection of the oral cavity, lung, and sinonasal tract that have been implicated in promoting development of vocal process granuloma. Allergy and postnasal drainage are also mentioned in most publications as possible pre-disclosing factors. While most of the above may not be the primary cause, authors argue that they may indirectly implicate behavior leading to granuloma formation. McFarren, et al in 1994 reviewed five cases of increased radiological density of the arytenoid cartilage on the site of granuloma formation. Calcification also extended to the vocal process. The authors believed that the increased calcification on the affected side was pathological and that the perichondritis may be the cause and effect of the granulomas. There explanation accounts for the unique site of occurrence as well as the tendency of lesions to occur after excision due to persistent perichondritis. They argue that adjuvant treatments for granuloma remove the trigger but fail to treat the underlying cause of the granulomas which is the perichondritis. This is a CT scan from McFarren’s paper showing both a calcified vocal process as compared to the other side as well as the medial soft tissue mass which is the granuloma. Sader et al in 1984 offered a classification system based on the presumed cause. He divided it up into three areas: post intubation, contact hyperfunctional, and hyperesthetic. TREATMENT The treatment of vocal process granuloma is directed by the cause. Voice therapy, managing reflux disease, surgery, antibiotics, steroids, radiation, Botox type A, prevention, and observation are all proposed treatment modalities. There is a general agreement in the literature that voice therapy is useful in the management of vocal process granuloma. Disagreement does exist regarding how and when it should be used. It is generally agreed that voice therapy should target adequate breath control, elevation of pitch, and elimination of hard glottic attacks. Treating laryngopharyngeal reflux disease is another treatment modality. Testing with pH probe is probably warranted in the initial workup of vocal process granuloma. Others will argue that even though your patients present without specific symptoms of reflux disease, subclinical reflux events may be sufficient to delay the healing of a granuloma. Patients should limit consumption of reflux-inducing agents including chocolate, caffeine, alcohol, and tobacco. Medical management with a proton pump inhibitor coupled with anti-reflux behavior is well supported in the literature. This endoscopic view of the larynx shows a granuloma on a patient who has reflux disease. You can see some subglottic changes consistent with reflux. This is the same patient, after initiation of a proton pump inhibitor. You still see reflux changes but the granulomas are gone. Some literature supports non-surgical interventions as a primary management with surgical excision of the granuloma necessary once management fails. Additional indications for surgical treatment includes need to establish a histopathologic diagnosis, persistent hoarseness despite medical management, or airway obstruction from a ball valve phenomena of the granuloma. This next slide shows a granuloma with a ball valve phenomena causing significant airway obstruction. The recommended extent of surgery still remains controversial in the literature and you really see both spectrums including excision with leaving the underlying cartilage intact versus a deeper resection with removal of the underlying cartilage. There are no randomized clinical trials of cold versus laser excision with current choice of technique based on surgeon’s experience. Additional treatments include antibiotics and steroids. Indirect support for the use of antibiotics comes from studies that have identified bacteria in the granuloma and histopathologic review. Steroids may help decrease the inflammation and alleviate the pain associated with vocal process granuloma, but strong evidence supporting the use of antibiotics or steroids is still lacking. There are several case reports of using radiation for refractory disease. The authors specifically used 12 Gy in four daily fractions. These authors have only used this treatment modality on patients who have failed both medical management and have had several surgical excisions done with recurrence of the granuloma. Those who support this treatment consistently recommend that it be used only after alternatives have failed and that the risks of developmental carcinoma be discussed with the patient before it is instituted. There are also several case reports of using Botox type A by injecting it unilaterally into the arytenoid muscle as an affective modality and decreasing the forceful adduction of the arytenoids that perpetuate the granuloma. Again, this treatment modality has been said in the literature to only be used on patients who are refractory to previous medical management or who are poor surgical candidates. In summary, the diagnosis of vocal process granuloma can usually be established through the characteristic clinical presentation coupled with the response to therapy. If the granuloma persists after treatment or if the accompanying clinical findings raise concern that the lesion may not be granuloma, further evaluation with surgical excision is warranted. The etiology is likely multifactorial including both repeat mechanical and inflammatory insult to the thin mucoperichondrium overlying the vocal process of the arytenoid cartilage. Management should be directed primarily towards removal of the chronic irritants causing the granuloma. Additional treatment strategies may be warranted in patients who do not respond to standard therapy or who are poor surgical candidates. Case Presentation: M.K. is a 45-year-old African-American male followed in the Ben Taub Otolaryngology Clinic for a two-month history of chronic hoarseness secondary to a left posterior glottic mass. Initial treatment included referral to Speech Pathology for voice therapy, as well as placement on a daily PPI. He returned to the clinic with continued complaints of hoarseness. He is a local disc jockey and is occupationally dependent on his voice. He has never smoked tobacco nor had surgery before. He has no other medical problems. On flexible endoscopy, a persistent pale, left posterior glottic pedunculated mass was present. No other masses or abnormalities were noted. The remainder of the head and neck exam was normal. He was offered surgical excision of the mass for definitive treatment and underwent a MSDL, with cold excision, without complications. Pathology of the mass revealed granulation tissue with chronic inflammation and ulceration. No carcinoma was identified. Three months post-operatively, he is doing well with complete resolution of symptoms. Bibliography: Bloch CS, Gould WJ, Hirano M. Effect of voice therapy on contact granuloma of the vocal fold. Ann Otol 1981;90:48-52. Cherry J, Margulies SI. Contact ulcer of the larynx. Laryngoscope 1968;78:1937-1940. Clausen RJ. Unusual sequelae of tracheal intubation. Proc R Soc Med (Anesthetic Section) 1932;25:1507. Delahunty JE, Cherry J. Experimentally produced vocal cord granulomas. Laryngoscope 1968;78:1941-1947. Donnelly WH. Histopathology of endotracheal intubation. Arch Pathol 1969;88:511-520. Elsberg CA . Clinical experiences within intratracheal insufflation (Meltzer) with remarks upon the value of the method for thoracic surgery. Ann Surg 1910;52:23-29. Emami AJ, Morrison M, Rammage L, Bosch D. Treatment of laryngeal contact ulcers and granulomas: a 12-year retrospective analysis. J Voice 1999;13:612-617. Feder RJ, Michell MJ. Hyperfunctional, hyperacidic, and intubation granuloma. Arch Otolaryngol 1984;110:582-584. Gould RB. Laryngeal granuloma following intratracheal intubation. BMJ 1935;2:499-500. Hillman RE, Holmberg EB, Perkell JS, Walsh M, Vaughan C. Objective assessment of vocal hyperfunction: an experimental framework and initial results. J Speech Hearing Res 1989;32:373-392. Hoffman HT, Overholt E, Karnell M, McCulloch TM. Vocal process granuloma. Head Neck 2001:23:1061-1074. Hynes B. Contact granuloma. J Otolaryngol 1998;27:310. Jackson C. Contact ulcer of the larynx. 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CO2 and KTP-532 laser cordectomy for bilateral vocal fold paralysis. J Laryngol Otol 1999;113:637-641. Mitchell G, Pearson CR, Henk JM, Rhys-Evans P. Excision and low-dose radiotherapy refractory laryngeal granuloma. J Laryngol Otol 1908;112:491-493. Santos PM, Afrassiabi A, Weymuller EA. Risk factors associated with prolonged intubation and laryngeal injury. Otolaryngol Head Neck Surg 1994;111:453-459. Svensson G, Schalen L, Rex S. Pathogenesis of idiopathic contact granuloma of the larynx: Results of a prospective clinical study. Acta Otolaryngol ( Stockholm) 1988;449:123-125. von Leden H, Moore P. Contact ulcer of the larynx. Arch Otolaryngol 1960;72:746-752. Ward PH, Zwtman D, Hanson D, Berci G. Contact ulcers and granulomas of the larynx: new insights into their etiology as a basis for more rational treatment. Otolaryngol Head Neck Surg 1980;88:262-269. Wenig BM, Heffner DK. Contact ulcers of the larynx: A reacquaintance with the pathology of an often under-diagnosed entity. Arch Pathol Lab Med 1990;114:825-828. Grand Rounds Archive | Department Home page BCM Public | BCM Intranet | Privacy Notices | Contact BCM | BCM Site Map | ©2001-2005 Baylor College of Medicine
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