Amyloidosis is a generic term for heterogeneous disorders associated with the deposition of proteins in abnormal fibrillar form [1
]. Amyloidosis can be hereditary or acquired, localized or systemic and is potentially lethal. The deposits accumulate in the extracellular space, progressively disrupting tissue architecture, and can impair organ function. Solitary amyloid deposits in the tracheobronchial tree or pulmonary parenchyma are unusual manifestations of primary amyloidosis [3
Amyloid deposition may occur in association with inflammatory or neoplastic conditions or develop as part of an immunoglobulin (Ig) disorder.
Virchow first described amyloidosis involving the lungs in 1857 [3
]. The first case of amyloidosis confined to the lower respiratory tract was described by Lesser in 1857 based on an autopsy study [5
]. Amyloidosis may involve the lungs as part of a systemic process or may be confined solely to the lungs. Localized pulmonary amyloidosis may involve either lung parenchyma or the airways.
The most frequent types of protein amyloidosis are AL (primary) and AA (secondary) types. AL amyloidosis results from plasma cell dyscrasia that produces monoclonal light-chain Igs, whose fragments deposit as this protein. AA amyloidosis occurs in chronic diseases (for example, rheumatoid arthritis and chronic infection).
Localized AL amyloidosis is most often identified in the upper respiratory, urogenital and gastrointestinal tracts, the skin and the orbit [1
Tracheobronchial amyloidosis is among the localized variants of amyloidosis. Up until 2004, fewer than 150 cases were reported; about 86 cases were published in the literature as of 2009 in China. Most of the reports involved were a single case or small case series. Only a few were randomized control clinical studies. Tracheobronchial amyloidosis is characterized by the deposition of amyloid material as submucosal plaques and/or polypoid tumors in the airways [6
], which may be localized, diffuse or multifocal. The endobronchial form is not associated with systemic amyloidosis [7
The morbidity and mortality of tracheobronchial amyloidosis directly correspond to the quantity of amyloid infiltrating the airways. Death is a result of the progressive bronchial obstruction and respiratory failure. This condition can be completely asymptomatic or be revealed by dyspnea, wheezing, hemoptysis, recurrent pneumonia, cough and atelectasis [7
]. Proximal or upper tracheal disease presents with various degrees of obstruction; mid- or distal tracheal, main bronchial disease involves lobar collapse or recurrent parenchymal infections, severe obstruction of the main bronchi and respiratory failure. Distal airway disease presents with recurrent pneumonia, cough and bronchiectasis. However, the symptoms are usually nonspecific, mimicking common respiratory conditions such as bronchial asthma (Table ; [12
Symptoms of tracheobronchial amyloidosis in the literature.
The diagnosis of amyloidosis usually requires histological confirmation. Congo red staining that produces green birefringence under crossed light remains the gold standard [16
]. Positive histology results for amyloid must be followed-up by immunohistochemical analysis to determine the fibril type.
In amyloidosis of the respiratory tract, a complete evaluation must be done. It should include radiography, CT scanning, endoscopy and respiratory function tests. Evidence of systemic disease should be sought clinically, including examination and immunofixation of serum and urine for a monoclonal protein.
Treatment strategies are variable depending on the degree of obstruction (Table ). No treatment with simple monitoring is proposed in asymptomatic patients, whereas more aggressive local and/or systemic therapy is undertaken when the obstruction is significant and the patient symptomatic [11
]. Bronchoscopic debridement with forceps debulking remains the standard therapeutic approach to upper and mid-airway disease. Repeated debulking is commonly required [11
]. A silicone stent with local resection using a carbon dioxide laser or yttrium aluminum garnet laser have also been reported [21
]. Repeated bronchoscopic intervention is thought to be preferable and safer than open surgery [10
]. Isolated cases report the use of radiotherapy in the treatment of localized tracheobronchial amyloidosis [22
Endoscopic features and treatment.