Serrano-Fernández, Martha L. MD*; Álvarez-Maldonado, Pablo MD, FCCP*; Aristi-Urista, Gerardo MD†; Valero-Gómez, Alfredo MD†; Cicero-Sabido, Raúl MD, FCCP‡; Redondo, Carlos Núñez-Pérez MD*
*Servicio de Neumología y Cirugía de Tórax
†Servicio de Patología del Hospital General de México O.D
‡Facultad de Medicina UNAM, México D.F., México
Disclosure: There is no conflict of interest or other disclosures.
Reprints: Pablo Álvarez-Maldonado, MD, FCCP, Servicio de Neumología y Cirugía de Tórax, HGM, Balmis 148, México D.F. CP 06726, México (e-mail: firstname.lastname@example.org).
Received June 18, 2013
Accepted April 29, 2014
Primary tracheobronchial amyloidosis (TBA) is a rare disease characterized by extracellular focal or diffuse submucosal deposits of amyloid proteins. Various types of endobronchial lesions have been described in TBA when bronchoscopy is performed using white light. Narrow-band imaging bronchoscopy has been mainly employed for detecting preneoplastic and neoplastic endobronchial lesions as it provides more detailed images of the microvasculature reflective of an altered angiogenesis process. Here, we describe bronchoscopic findings with white light and narrow-band imaging in 2 patients presenting with central airway obstructive disease later confirmed as having primary TBA.
Primary tracheobronchial amyloidosis (TBA) is a rare form of localized amyloidosis that is characterized by submucosal deposits of amyloid proteins derived from immunoglobulin light chains.1,2 A variety of unspecific lesions have been reported in the literature in TBA when bronchoscopic airway examination is performed using white light. Mucosal irregularity, edema, and redness are some examples according to the standard nomenclature.3 Multiple submucosal plaques or solitary deposits of amyloid having a nodular or “tumor-like” appearance have also been reported.2,4,5 Diagnosis of TBA can be established only by tissue biopsy. Histologically, submucosal amyloid deposits are eosinophilic in hematoxylin and eosin stain, positive in Congo red stain, and show birefringence turning apple-green under polarized light. Narrow-band imaging (NBI) bronchoscopy has been mainly employed for detecting altered mucosal microvasculature suggestive of preneoplastic or neoplastic lesions, serving as a guide for biopsy sampling.6–8 There are no reports on NBI findings in TBA. Here, we describe bronchoscopic findings using white light and NBI bronchoscopy in 2 patients with primary TBA.
A 63-year-old woman was admitted to the hospital because of progressive dyspnea, cough, and weight loss of 4 kilograms in a 2-month period. She denied smoking or other relevant history. Spirometry showed a mild obstructive flow pattern. Wall thickening of the trachea and both main bronchi were evidenced by computed tomography of the thorax. Flexible bronchoscopy was performed showing multiple plaques throughout the subglottic space and upper third of the trachea affecting its lateral walls; also, multiple yellowish nodules were present at the lower third of the trachea and main carina (Fig. 1A). At this level, NBI examination showed complex vascular networks, capillary loops, and abrupt-ending vessels of large caliber (Figs. 1B, C). Biopsies of nodules were taken and histopathology confirmed amyloidosis, showing eosinophilic amorphous interstitial deposits (Fig. 2A), with positive Congo red stain (Fig. 2B) and birefringence under polarized light (Fig. 2C).
A 61-year-old woman with history of systemic arterial hypertension was admitted to the hospital presenting cough, intermittent hemoptysis, and progressive dyspnea of 1-year duration. Acid-fast bacilli were negative on sputum. Computed tomography of the thorax showed mild stenosis of the left main bronchi. Flexible bronchoscopy was performed showing a reddish and irregular mucosa at the lower third of the trachea, with blurred cartilages and tortuous submucosal vessels. At the left main bronchi the mucosa was edematous, reddish, irregular, and friable, occluding 20% of its lumen (Fig. 3A); NBI examination at this level showed complex vascular networks, capillary loops, and abrupt-ending vessels of large caliber (Fig. 3B). Biopsies were taken and histopathology confirmed amyloidosis, showing eosinophilic amorphous interstitial deposits (Fig. 4A), with positive Congo red stain (Fig. 4B) and birefringence under polarized light (Fig. 4C).
Pulmonary amyloidosis occurs in 3 forms: tracheobronchial, parenchymal, and alveolar-septal.9 Primary TBA, although the most frequent among forms of pulmonary amyloidosis, is considered a rare disease. It is characterized by a slow and progressive deposition of amyloid material in the submucosa that could lead to airway obstruction, hemoptysis, chronic cough, and recurrent airway infections.4,5 Typically, it affects men more often than women and occurs in the fifth or sixth decade of life.1,2
Besides unspecific bronchoscopic findings while using white light as mucosal irregularity and redness,3 other lesions have been reported in TBA as “characteristics” including multiple submucosal plaques and solitary amyloid deposits having a nodular or tumor-like appearance suggestive of endobronchial neoplasms.2,4,10
Premalignant and malignant lesions can cause a variety of mucosal changes in the trachea and bronchi. Angiogenesis, a relatively early event during lung cancer pathogenesis, is often difficult to see with white light bronchoscopy. NBI bronchoscopy is useful enhancing fine superficial microvessel patterns of mucosal vascularity when incipient neoplastic processes occur in the airway.6–8 Also, NBI has shown utility for diagnosing benign diseases as hereditary hemorrhagic telangiectasia.11 A good sensitivity and specificity of NBI has been reported on early detection of lung cancer6,8,12 when 3 or more of the following criteria are present during bronchoscopic examination: capillary loops, dotted vessels, complex vascular networks of tortuous vessels, and abrupt-ending vessels. These findings, suspicious for intraepithelial neoplasm, are histologically correlated with the presence of moderate dysplasia, severe dysplasia, carcinoma in situ, and invasive carcinoma.12,13
Hui et al,14 with the help of NBI and magnifying endoscopy, described a greyish-green appearance of the nodules that infiltrate the mucosa in rectal amyloidosis without evidencing vascular changes that are present in colorectal cancer. This is probably related to amyloid deposits in the lamina propia. In the 2 cases presented, visualization of the mucosa with white light and high-resolution bronchoscopy allowed for the identification of changes already described in TBA, which are unspecific. Nodules, mucosal irregularity, and blurred cartilages presented in these cases could be considered suspicious of neoplasm when using white light.3,12
During NBI examination, 3 vascular patterns were observed in each case: capillary loops, complex vascular networks of tortuous vessels, and abrupt-ending vessels, leading to the suspicion of intraepithelial neoplasm. Interestingly, dotted vessels that were not found in these particular cases are associated with a major degree of angiogenesis and malignant invasion.13,15
Small septal and perivascular deposits of amyloid could be found by histopathology. Mucosal epithelium could remain intact or present changes of squamous metaplasia.16 Diffuse amyloid infiltration of the submucosa could involve glands and cartilage. It is probable that various degrees of epithelium metaplasia and vascular obstruction due to perivascular deposits of amyloid are responsible for the origin of collateral vessels and vascular patterns found in TBA.
Various changes in the tracheobronchial mucosa that are secondary to amyloidosis could suggest a neoplastic origin when the airway is exanimated using white light and NBI bronchoscopy. Indirect findings suggestive of neoplasm as mucosal irregularity, blurred cartilages, redness, and edema, as well as direct findings as endobronchial tumor could be evidenced during white light examination. We have found at least 3 vascular patterns suggestive of angiogenesis when performing NBI examination in TBA. Both white light and NBI bronchoscopic findings in TBA could mimic those findings suggestive of intraepithelial neoplasm. Definite diagnosis will be established only by histopathology analysis.
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