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.

Amyloidosis is not a specific disease per se, but rather is the result of a number of unrelated disease processes leading to deposition of extracellular protein in tissues throughout the body. This disease frequently presents with head and neck manifestations.

Amyloidosis is typified by extracellular deposition of insoluble proteinaceous material which has typical staining properties and electron microscopic appearance. Its hallmark is an apple green birefringence under polarized microscopy. Under the electron microscope, amyloid appears as a mass of rigid, nonbranching fibrils. X-ray crystallography reveals that these fibrils have a regular, antiparallel, beta-pleated sheet configuration.

The classification systems of the past divided amyloidosis into primary or secondary disease (depending on whether a coexisting disease was felt to be responsible) and localized or systemic. Amyloid secondary to multiple myeloma and familial types were also described. The classification systems used today are based on the type of protein which makes up the amyloid fibril. In the case of multiple myeloma, primary systemic, and localized nodular disease, the fibrils are made up of light chain immunoglobulins produced by monoclonal plasmacytomas. In familial amyloidosis, these are strands of prealbumin. In secondary amyloidosis, a serum protein called serum amyloid A is produced. These excess strands then form relatively insoluble beta-pleated sheets which are deposited in various tissues. It is felt that phagocytic cells may help to process these proteins through lysosomal digestion into fragments capable of forming amyloid. These deposits then cause disease in various organs by interfering with their function.

Amyloidosis can affect virtually any organ or tissue in the body. The most common presenting symptoms are fatigue or weakness, weight loss, ankle edema, dyspnea, paresthesias, and light-headedness or syncope. The most common physical findings are hepatosplenomegaly, edema, macroglossia, orthostatic hypotension and purpura. A number of associated syndromes are frequently seen, including carpal tunnel syndrome, peripheral neuropathy, nephrotic syndrome, congestive heart failure and sprue. The most significantly involved organ systems are the kidneys and heart. Failure of these two systems also constitutes the two leading causes of death.

Macroglossia is the most common head and neck manifestation of amyloidosis, and appears in between 15 and 20 percent of patients with light chain disease. The tongue can grow to massive proportions and can be smooth or possess a variety of polypoid appendages which form as the tongue grows against gaps in the teeth. In addition to its large size, the tongue becomes adynamic, firm and friable and may cause problems with deglutition, speech, and breathing. It frequently causes sialorrhea, and tissue may break down and hemorrhage. In addition, the gross facial deformity may lead to social withdrawal.

Dermatologic lesions are the next most common head and neck manifestations. The most characteristic are waxy, purpuric lesions located around the upper eyelids in patients with systemic disease. Other skin findings include macular lesions, papular lesions, and a modular or tumefactive form.

The laryngotracheal system is the next most common site. Amyloidosis constitutes approximately one percent of all benign lesions of the larynx. It usually occurs as nodules or polypoid lesions and can be located anywhere in the larynx or trachea. Systemic involvement is very rare with laryngeal amyloidosis and some authors have proposed that in patients without obvious involvement of other organs, an aggressive workup for systemic disease is probably not warranted.

Other sites of involvement include the thyroid, the nose, paranasal sinuses, the nasopharynx, Waldeyer's ring, the major salivary glands, and temporal bone.

Accurate diagnosis is often delayed up to a year or more. Diagnosis is usually initiated by clinical suspicion but this must be confirmed by histologic examination of tissue. In some instances this may be obtained by biopsy of an obvious lesion. However, in the majority of cases, no easily accessible lesion is present. The gold standard for diagnosis of systemic amyloidosis in the past consisted of a rectal biopsy, which was felt to be positive in approximately 80 percent of patients. Recently, though, the preferred method has become simple needle biopsy of clinically uninvolved abdominal subcutaneous fat. This has the obvious advantage of being very safe and less uncomfortable to the patient. This method is positive in 95 percent of primary systemic, 66 percent of secondary systemic, and 86 percent of heredofamilial amyloidosis cases.

Therapy for systemic amyloidosis is relatively unsuccessful. Although a variety of chemotherapeutic drugs have been employed, none have consistently shown control of the disease or increased survival. The current therapy of choice is prednisone and melphalan, although improvement with this regimen has been only anecdotal. Currently, a trial of chemotherapy is felt to be warranted based on anecdotal evidence.

Since the vast majority of lesions of the head and neck, with the exception of macroglossia, represent localized disease, therapy consisting of surgical excision has been far more successful. In the larynx, a conservative approach has been recommended consisting of local excision using laser or microlaryngeal instruments with conservation of surrounding tissue. Recent literature has advocated CO2 laser as the treatment of choice. Recurrence is rare, and, if it occurs, can be treated with further conservative excision.

Partial glossectomy for macroglossia represents localized surgery for a systemic disease. Results of partial glossectomy have been mixed but are generally favorable. Goals are to restore speech and swallowing, decrease sialorrhea, and improve cosmetic appearance.

Prognosis in patients with systemic amyloidosis is poor. Almost all patients with light chain disease are dead within three years of diagnosis. The median survival after diagnosis is between four and 15 months. The most common causes of death are renal and cardiac failure.

Case Presentation

A 78-year-old black male originally presented seven years ago to the dermatology clinic complaining of the development of papular lesions on his fingertips and polypoid lesions of his lateral tongue. Biopsy of these lesions revealed amyloidosis. Subsequent serum protein electrophoresis showed a lambda monoclonal spike, bone marrow biopsy revealed an elevated number of plasma cells, and skeletal x-rays revealed "punched-out" lesions of the skull and vertebrae. A final diagnosis of light-chain amyloidosis secondary to multiple myeloma was made. He was placed on a regimen of intermittent melphalan and prednisone and followed for the next several years with very little change in condition. The otolaryngology service was consulted for progression in the patient's macroglossia. At the time, his large tongue was noted to be impeding his speech but did not interfere with his airway or with eating. The patient declined surgery and was followed at approximately three month intervals for the next three years, declining surgery each time it was offered to him. At the time of this admission, he was brought in by his family because his tongue had become ulcerated and he was no longer able to swallow. He was now interested in surgery. In addition to his enlarged tongue his examination was significant for periorbital purpuric lesions; large, fleshy hands; pitting pretibial edema; and, severe lower extremity weakness. Admission laboratory values suggested moderate dehydration and malnutrition. Preoperative evaluation by the medicine service, including echocardiogram, revealed occasional junctional arrhythmias, but no other evidence of cardiac or pulmonary involvement. He was taken to the operating room where tracheotomy and resection of the anterior and lateral aspects of the tongue were performed. Surgery was complicated by cardiac arrhythmias including bigeminy and heart block but he remained hemodynamically stable. The immediate postoperative period was complicated by arrhythmias and hypotension, which were controlled with intravenous fluids and lidocaine. Postoperative healing of the tongue was excellent and he was able to close his mouth and speak more intelligibly; however, he still had difficulty swallowing. A closely supervised swallowing therapy program was instituted. He was progressing satisfactorily, when, on his 14th postoperative day, he was discovered unresponsive and without a pulse. He was not able to be resuscitated. An autopsy was requested but the family declined.

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