Amyloidosis

Abstract

Although localized laryngotracheobronchial amyloidosis is rare, the otolaryngologist-head and neck surgeon should be familiar with this condition. Its characteristic appearance can suggest its presence in a patient who has the typical initial symptoms. Biopsies during direct laryngoscopy and bronchoscopy can play both a diagnostic and therapeutic role. After an appropriate examination to rule out systemic involvement, the patient should be managed with conservative surgery, although the use of C[O.sub.2] laser might be more efficacious than conventional surgery. With appropriate diagnosis and treatment, patients should expect a favorable prognosis. In this article, we describe a new case of localized larngotracheobronchial amyloidosis in a 67-year-old woman, and we review the literature on this subject.

Introduction

Localized idiopathic amyloidosis of the respiratory tract is rare. It manifests clinically either in the upper respiratory tract (usually in the supraglottic larynx) or in the lower respiratory tract (usually with tracheobronchial involvement). The occurrence of localized amyloidosis that involves both the upper and lower respiratory tracts is very unusual.

We describe a new case of localized laryngotracheobronchial amyloidosis. To date, the literature contains only a few scattered case reports and a few cases mentioned in reviews of amyloidosis localized to either the upper or lower respiratory tract. A review of the world literature over the past 100 years identified a total of 29 previously reported cases (table 1). (1-8) We have reviewed these cases and we present our conclusions regarding the initial symptoms, diagnosis, and management of this unusual disorder.

From the Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston (Dr. Clark), and the Department of Otolaryngology-Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill (Dr. Weissler).

Reprint requests: J. Madison Clark, MD, Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, P.O. Box 250582, 150 Ashley Ave., Charleston, SC 29425. Phone: (843) 792-7165; fax (843) 792-0546; e-mail: clarkm@musc.edu

Case report

A white 67-year-old woman was referred to the University of North Carolina Hospitals for further evaluation and management of a subglottic mass that had been discovered by the referring otolaryngologist during diagnostic direct laryngoscopy. The patient had been seen in consultation with a pulmonologist, who had sought assistance in the management of recalcitrant asthma, for which the patient had been hospitalized for 1 month.

On arrival, the woman reported a several-year history of intermittent hoarseness and frequent wheezing with dyspnea, which had been poorly controlled by bronchodilator inhalation. She denied cough, stridor, and hemoptysis. Her medical history was significant for tobacco abuse (80 pack-years), emphysema, hypertension, eczema, and panic disorder. Her initial physical examination was significant for a coarse, raspy voice, an absence of stridor, normal findings on oral cavity and oropharyngeal examination, and an anteriorly based, sessile, mucosa-covered subglottic mass. Both the appearance of her vocal folds and their motion on flexible fiberoptic laryngoscopy were normal. The results of her blood, chemistry, liver function, and urine tests were normal, as was her acetylcholinesterase level. Assays for human immunodeficiency virus and antineutrophil cytoplasmic antibodies were negative. Her rapid plasma reagin was nonreactive. Computed tomography (CT) of the neck and chest detected emphysematous changes, but no laryngeal, tracheal, or bronchial lesions.

The patient was taken to the operating room, where direct laryngoscopy and bronchoscopy were performed. These investigations revealed the presence of a sessile, mucosa-covered mass with a submucosal yellowish waxy appearance in the left anterior subglottis (figure 1). The mass had caused a 30% stenosis at the level of the subglottis. Two similar but smaller lesions were identified in the cervical trachea, and the right lower lobe bronchus was partially occluded by yet another similarly appearing lesion. Multiple biopsies were taken without complication. A review of pathology confirmed the diagnosis of amyloidosis (figure 2). Specific immunohistochemical staining for the AL subtype of amyloid protein was found in the deposits.

Three years later, the patient has remained stable and has required no further hospitalization or bronchoscopic procedures.

[FIGURES 1-2 OMITTED]

Discussion

The term amyloidosis covers a diverse collection of diseases that manifest by the extracellular deposition of fibrillar amyloid protein. Amyloid deposits occur in many tissues (e.g., the skin, kidneys, heart, and brain) as well as in a variety of locations in the head and neck, including the eye and the major and minor salivary glands. Moreover, submucosal deposits can appear in the nose, paranasal sinuses, nasopharynx, oral cavity, oropharynx, larynx, tracheobronchial tree, and lung.

The most common site of involvement in the upper respiratory tract is the larynx, and the most common sites within the larynx are the false vocal folds. (7) The larynx can also be the first site of involvement in systemic amyloidosis, although laryngeal involvement is less common in systemic amyloidosis than it is in localized disease.

Amyloidosis localized to the lower respiratory tract is classified according to its bronchoscopic appearance as either tracheobronchial or parenchymal. (9) The tracheobronchial pattern is further categorized as either diffuse (more common) or localized (tumor-like masses). The parenchymal pattern is subcategorized as either diffuse or nodular (more common). Although localized amyloid depositions in both the upper and lower respiratory tracts have been reported, this combination is very uncommon. (8)

Our review of the literature reveals that most patients with localized laryngotracheobronchial amyloidosis are Caucasian and that most of these cases occur beyond the age of 40 years (table 1). Initial symptoms typically include hoarseness, cough, and/or dyspnea. The usual upper respiratory (laryngeal) location is the supraglottis, while the usual lower respiratory tract pattern is tracheobronchial. Because examination of the subglottis and lower respiratory tract by flexible fiberoptic laryngoscopy is inadequate, most patients require direct laryngoscopy and bronchoscopy.

In the older literature particularly, amyloid lesions were occasionally confused with tuberculomas and syphilitic gummas; they have also been mistaken for vocal fold polyps and other benign and malignant tumors. However, most authors agree that these lesions have a fairly typical appearance; they generally appear as sessile, mucosacovered masses with a yellowish waxy surface, as was the case with our patient, (10) Given this characteristic appearance, it is reasonable for the surgeon who is considering this disease in the differential diagnosis to take liberal biopsies of these lesions in a therapeutic effort to decrease the resistance to flow in the airways. Of course, the initial endoscopy is primarily diagnostic, and tissue must be sent for pathologic interpretation. Light microscopy will demonstrate glassy eosinophilic material in the submucosa and the classic apple-green birefringence on Congo red staining under a polarizing lens.

The current classification system for the entire group of amyloid diseases is based on the determination of the subunit protein by immunohistochemical staining (table 2). To date, at least 18 different human amyloid fibril proteins have been identified. (11) Primary systemic amyloidosis and localized upper and lower respiratory amyloidosis are made up of AL-type polypeptide light chains of the kappa or lambda (more common) variety. (7)

Determining whether amyloid deposits represent: localized or systemic amyloidosis is crucial, because patients who have the systemic form have a markedly shorter life expectancy. (12) The 5-year survival rate for these patients is less than 20%; it is even lower among those who have cardiac or renal involvement. (13)

The examination to determine the presence of systemic amyloidosis is summarized in table 3. Once the determination is made that the lesion represents localized amyloidosis, certain management conclusions can be drawn from a review of the limited number of cases reported thus far in the literature (table 1).

Management of combined upper and lower respiratory tract amyloidosis is strictly surgical. Although one report described the use of steroids in combination with surgical treatment, (14) most authors agree that neither steroids nor radiation therapy should be used in the management of localized laryngotracheobronchial amyloidosis. (10, 15) In fact, treatments that compromise the immune response--steroids, immunosuppressive chemotherapeutic agents, and ionizing radiation--might even accelerate the process. (16)

The goal of treatment is to remove as much of the grossly visible amyloid as possible without sacrificing normal tissue. A complete "oncologic" resection is rarely achieved. Overzealous resection can result in perforation of a bronchus or severe hemoptysis. (17) Some reports on management of laryngotracheobronchial amyloidosis have suggested that there are clinical advantages to the use of C[O.sub.2] laser surgery. (18) Compared with conventional surgery, laser therapy might be more precise, might cause less inflammation and scarring, and might result in more rapid healing.

References

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