Black Bronchoscopy

CHEST

Special Features

Special Features T he unusual fi nding of black pigmentation involving the airways from occupational exposure has been reported in the literature since the early 1940s. The term black bronchoscopy, describing the endobronchial appearance of malignant melanoma, was introduced in 2003. 1 However, a search of the literature reveals multiple etiologies that can cause a black discoloration of the airways ( Table 1 ). Bronchoscopic examination is being performed with increasing frequency in the modern era. Pulmonologists should be fully cognizant of the differential diagnosis of black bronchoscopy. The following is a review of the literature related to the conditions causing a black discoloration of the airways.

Congenital Cause

Melanosis

Tracheobronchial melanosis (TBM) is an uncommon fi nding reported in the literature. Previous series have quoted a prevalence of one in every 52 bronchoscopies performed. 2 The common sites affected are the sec-ondary and the tertiary carina. Men and women are equally affected. 2 Single or multiple areas of dark pigmentation are encountered incidentally on bronchoscopy performed for unrelated indications. No other mucosal abnormalities or distortions of the airways are noted ( Fig 1D ). Melanosis of the larynx and the oropharynx has been associated with occult malignancy, yet no such relationship has been reported with TBM. 3 In addition, an association between TBM and the melanosis involving other body organs or smoking has not been reported. With primary melanoma of the tracheobronchial tree being a rare entity, the clinical significance of TBM is not yet defi ned; however, it does need to be differentiated from other causes of black bronchoscopy.

Inborn Error of Metabolism

Alkaptonuria (Ochronosis)

Alkaptonuria is a rare inborn error of metabolism involving the degradation of the amino acids phenylalanine and tyrosine. It is a genetic disorder with an autosomal-recessive mode of inheritance. 4 It is caused by a defi ciency of the genes encoding for the homogentisate-1, 2-dioxygenase, which is an important A presence of black pigmentation involving the endobronchial tree is not uncommon. It was fi rst described in the literature in association with occupational exposure in the early 1940s. However, in 2003, Packham and Yeow formally used the term black bronchoscopy to describe endobronchial metastasis from a malignant melanoma. Hyperpigmentation of the airway, however, is associated with multiple etiologies such as congenital disease, inborn errors of metabolism, infections, environmental exposures, neoplasm, and iatrogenic causes. Although the majority of these conditions are benign, a proper diagnosis is important for optimal management. In this article, we review the etiology of black bronchoscopy and discuss its presentations and current management guidelines.

CHEST 2013; 144(5):1696-1706

however, long-term effi cacy and safety necessitate further evaluation. 4

Infection

Aspergillus niger

Tracheobronchial aspergillosis can present in various clinical forms, such as invasive, ulcerative, or pseudomembranous tracheobronchitis. 7 It predominantly affects the immunocompromised population. Endoscopic fi ndings vary depending on the Aspergillus species involved. One percent of all Aspergillus airway infections following lung transplantation are from the niger species. It is usually encountered in the nosocomial environment and in patients who are suffering from hypogammaglobulinemia and are on long-term itraconazole therapy. 8 In patients infected with Aspergillus niger , black pigmentation has been reported on FB. In addition to the black pigmentation, white masses of oxalate crystals are also seen; the fungus produces oxalic acid which binds to airway calcium ( Figs 1E-F ). 8 The treatment of endobronchial aspergillosis follows the treatment guidelines for invasive aspergillosis.

Ochroconis gallopava

Dematiaceous fungi (dark-pigmented fungi) are characterized by the presence of melanin or melanin-like pigments. 9 Infections caused by this group of fungi include mycetoma, chromoblastomycoses, and phaeohyphomycosis. There has been an increase in the incidence of infections caused by these fungi, particularly in solid-organ transplant recipients. 9 Of particular liver enzyme that degrades homogentisic acid (HGA), a metabolite in the phenylalanine and tyrosine degradation pathway. The term ochronosis describes the accumulation of homogentisic acid in collagenous tissues of the body, resulting in dark gray pigmentation of the connective tissue and the cartilages, involving multiple organ systems. A history of early-onset degenerative arthritis, multiple joint replacements, and valvular heart disease suggest alkaptonuria along with the dark-colored airways. 4 The severity of symptoms progressively increases beyond 30 years of age. The physical examination may reveal the darkening of sclera and ear cartilage. The involvement of the respiratory system with ochronosis is most frequently diagnosed during autopsy. However, a premortem case of alkaptonuria has been reported as diagnosed with fl exible bronchoscopy (FB). 5 The bronchoscopic examination reveals hyperpigmentation of the airways, including the epiglottis, larynx, bronchial cartilages, and mucosa. Hyperpigmentation of the bronchial mucosa extends distally from the trachea to the small bronchioles, and the involved bronchial mucosa is typically covered with dry black secretions ( Figs 1A-C ).

The diagnosis of alkaptonuria is based on gas chromatographic-mass spectrophotometric assays that measure urine and plasma HGA levels. 6 Effective management of alkaptonuria is not clearly described. Neither high-dose vitamin C nor protein restriction has effectively reduced urinary HGA excretion. Nitisinone, a triketone herbicide that reversibly inhibits 4-hydroxyphenylpyruvate-dioxygenase, has been shown to reduce urinary HGA excretion by . 80% in a murine model. It can also decrease HGA production in humans; 10 Common pulmonary presentations include nodules and nonresolving infi ltrates with upper and middle lung predominance. Cough may or may not be present. 11 Involvements of interest to the topic of discussion is the genus Ochroconis which include species gallopava , constricta , and humicola . O gallopava infections generally involve the lung with extrapulmonary involvement especially of CNS and skin. 10 Among solid-organ transplant recipi- airways could present with black pigmentation and growth similar to A niger ( Fig 2A ). Diagnosis is made by transbronchial biopsies and fungal culture. Antifungal therapy anecdotally has been decided based on sensitivities. Rarely, cases of O gallopava have been reported in the non-solid-organ transplant population as well. 12 Healed Endobronchial TB Healed endobronchial Mycobacterium tuberculosis (MTB) often leaves black pigmentation within the airways. Multiple areas of dense peribronchial fi brosis and the deposition of black pigment are observed during bronchoscopy. In addition, multiple calcifi ed intrathoracic lymph nodes on CT scan of the chest raise suspicion for a past history of MTB 13 ( Figs 2B-C ). The proposed pathophysiology of black pigmentation associated with MTB could be explained by possible intrabronchial perforation involving infected lymph nodes burdened with pigment-laden macrophages into the adjacent bronchial mucosa. After years of healing and fi broblastic proliferation, airway stenosis may develop. 14 We presume that the black pigments are the residue of the MTB organisms. Based on current data, an anti-TB regimen may resolve atelectasis and bronchial narrowing. However, hyperpigmentation is considered irreversible. 13

Environmental Causes

Anthracosis and Anthracofi brosis

Anthracosis refers to the deposition of carbon particles in the airways and the lung parenchyma. It is found among those who smoke cigarettes or reside or work in areas heavily polluted with atmospheric soot. The deposition of carbon within the bronchial mucosa or lung parenchyma does not induce infl ammation or fi brosis. Most anthracotic particles are usually removed by mucociliary clearance; however, a small amount of carbon particles, phagocytosed by macrophages, remain within the bronchioles. 15 Anthracofi brosis and anthracostenosis are the terms which describe the fi ndings of bronchial obliteration, along with an anthracotic (black) pigmentation covering the bronchial mucosa, without an associated history of cigarette smoking 16,17 ( Figs 2D-F 18 ). The fi brotic aspect of anthracofi brosis is associated with occupational exposure to silica. Highrisk occupations include coal mining, masonry, and those with exposure to woodsmoke. [19][20][21] Anthracofi brosis related to chronic biomass or woodsmoke exposure is usually found in nonsmoking elderly women using natural fuels for indoor cooking. 19,22 Common manifestations of anthracofi brosis are chronic cough, dyspnea, wheezing, and rhonchi. 16,19,22 COPD of the chronic bronchitis type with a minimal response to bronchodilators is the usual manifestation in the majority of patients. 22 Characteristic CT scan fi ndings include peribronchial thickening and obliteration, leading to lobar atelectasis, predominantly involving the right upper and middle lobes, surrounded by enlarged and/or calcifi ed peribronchial, hilar, or mediastinal lymph nodes. 14 A high proportion of crystalline silica in hilar lymph nodes and lung parenchyma raises the possibility of lymph node perforation into the bronchial walls, preceding the chronic healing process. The mechanism is similar to that described in MTB-associated fi brosis. The gold standard for the diagnosis is based on mineralogic analyses by transmission electron microscopy showing high percentages of crystalline silica and nonfi brous silicates, such as mica and kaolin particles, in lung tissue and BAL fl uid. 20 Cases of bronchogenic carcinoma have been reported in association with anthracofi brosis 23 ; in addition, poorly differentiated adenocarcinomas have been found to develop in severely anthracotic lungs. 24 However, this occurrence seems to be coincidental rather than a cause-effect relationship.

It is not necessary to perform FB if patients are asymptomatic. However, if the history suggests a high probability for malignancy, the procedure should be considered. 20 No defi nitive treatment exists for anthracofi brosis. In a single case report, a partial resolution of bronchial narrowing following treatment with corticosteroids and tamoxifen was documented. 19,25,26 Despite treatment, however, the multiple patchy areas of black pigmentation remained unchanged. 19 Other measures, including antibiotics, bronchodilators, physiotherapy, and postural drainage, remain of limited value. 22

Soot Inhalation

Residential fi res are a major cause of inhalation injury affecting airways and lung parenchyma. In the past, in association with skin burns and the exposure to carbon monoxide and nitric oxide, systemic shock and wound sepsis were the major causes of death in these patients. Currently, inhalation injury is the most frequent cause of death in burn patients. 27 The mortality rate from soot inhalation alone is approximately 10%. A combination of smoke inhalation and skin burns increases this rate to 30% to 90%. 28 The diagnosis of inhalation injuries is based on appropriate history and medical fi ndings (eg, facial burns, nostril edema). 29 Laryngeal edema following the soot inhalation could rapidly progress to acute upper airway obstruction and may necessitate intubation and mechanical ventilation. 30 Presently, FB is the standard procedure for the diagnosis of smoke inhalation. 31 Bronchoscopic fi ndings are characterized by multiple, focal, large black-and-gray edematous plaques involving the tracheobronchial mucosa, extending distally to the small bronchioles 32 ( Fig 3A 33 ). The fi ndings are usually associated with atelectasis and pneumonia, as seen on chest radiographs, as a consequence of a marked decrease in surfactant production. 34 Histologic examination reveals disruption of the tracheobronchial mucosa with focal necrosis and the formation of a pseudomembrane composed way suction, and pharmacologic agents, such as bronchodilators, racemic epinephrine, and mucolytic agents. In addition, FB is very effective for secretion and cell debris removal. If left untreated, airways could become completely obstructed, subsequently causing lobar of mucus, cell debris, fi brinous exudate, neutrophils, and bacteria. 28 The fundamental concept in managing smoke inhalation is secretion clearance by means of therapeutic coughing, chest physiotherapy, early ambulation, air- atelectasis and postobstructive pneumonia. 34 The combination of inhalation injury and pneumonia results in a 60% increase in mortality from burns. 28 A retrospective study has revealed that patients with a 30% to 59% surface-area burn and pneumonia who underwent at least one bronchoscopy required shorter duration mechanical ventilation (21 days vs 28 days, P 5 .0001), ICU stay (35 vs 39 days, P 5 .04), as well as overall hospital stay (45 days vs 49 days, P 5 .009) than otherwise. In addition, the mortality rate was reduced by 18% in the bronchoscopy group. 27 A prospective study proposes a graded severity of soot inhalation according to the depth of mucosal injury. This classifi cation is based on FB being performed within the fi rst 24 h after the injury ( Tables 2 , 3 ). 35 FB helps predict outcomes and leads to the development of effective treatment guidelines. Histologic examination reveals that the deeper the mucosal damage, the higher the rate of acute lung injury and the mortality rate. 35 Thus, early bronchoscopy is highly desirable for patients with an inhalation injury. 35,36

Argyria and Argyrosis

Argyria is a term which describes chronic silver exposure which causes an irreversible, blue-gray discoloration of the skin (argyria) and sclera (argyrosis). 37,38 Cases of argyria associated with occupational exposure and drug consumption have been reported since the early 1940s. 39,40 The duration of exposure varies from months to years prior to the diagnosis. 39,40 Silver particles can enter the body via inhalation, ingestion, or a parenteral route. 38,41,42 The deposition of silver particles could be confi ned to one area through prolonged direct contact or be widespread in distribution, involving organs such as the trachea, skin, liver, kidneys, corneas, gingival, mucous membranes, nails, and spleen ( Fig 3B). 43 Argyria is proposed as a mechanism of detoxifying silver from the bloodstream by its excretion into the tissues in form of a harmless silver-protein complex. 44 Sparse data are available on the possible toxic effects of silver deposition in organ tissues. 38 Patients who report high levels of silver exposure and present Table 2

-Classifi cation of Endobronchial Burns According to the Depth of Mucosal Damage

Group Finding

Confi rmed positive by biopsy G 1 Mild mucosal edema and hyperemia, with or without carbon soot G 2 Severe mucosal edema and reddening, with or without carbon soot G 3 Ulcerations, necrosis, and absence of both cough refl ex and bronchial secretions G 5 group. Adapted with permission from Chou et al. 35 Adapted with permission from Chou et al. 35 ALI 5 acute lung injury. See Table 2 legend for expansion of other abbreviation.

with plasma silver levels above the normal range could develop neuropathy. 45 Histologic examination reveals tiny dark-brown particles of silver deposited in the affected areas, especially the internal elastic lamina of small vessels. 39 This fi nding is visually distinguishable from the typical coarse deposition of black pigment seen in anthracosis. 37,43 Chronic inhalation of silver vapors could result in the discoloration of bronchial mucosa and alveoli. 39 However, no reports of signifi cant clinical consequences, except for chronic cough, mild bronchitis, emphysematous change, and reduction in lung volumes, were found. 46 A single case report described an unusual bronchoscopic fi nding of a dark hyperpigmented area with a distinctive demarcation in a patient in prolonged contact with a silver tracheostomy tube. Histologic examination revealed dark fi ne pigments underneath the epithelium, without the involvement of blood vessels ( Fig 3C ). 43

Neoplasms

Endobronchial Melanoma

Several endobronchial neoplasms exhibit dark pigments. Primary melanoma of the lung is a rare tumor involving 0.01% of all lung tumors. 47 Metastatic melanoma is the more common endobronchial lesion than its primary counterpart. Endobronchial melanomas, when metastatic, usually present after the onset of the primary tumors. It is vital to rule out an occult primary tumor if melanoma of the lung is suspected on bronchoscopy. The pathogenesis of endobronchial melanomas has been revised by Kiryu et al 48 who have classifi ed endobronchial melanomas into four developmental modes: type 1, direct metastasis to the bronchus; type 2, bronchial invasion by a parenchymal metastatic lesion; type 3, bronchial invasion by mediastinal or hilar lymph node metastasis; and type 4, a peripheral lesion extending along the proximal bronchus.

FB exhibiting a black, sticky endobronchial lesion raises a possibility of either a primary or a metastatic melanoma 49 ( Fig 3D 50 ). The differential diagnosis, however, also includes melanocytic carcinoid, schwannoma, the infl ammatory response in the lungs. In an animal model, the direct instillation of activated charcoal into the lungs resulted in increased microvasculature permeability and pulmonary edema. The aspiration of charcoal can also present as a spiculated, PET-positive mass years after aspiration and can be confused with lung cancer. 58 If FB demonstrates charcoal in the endobronchial tree ( Figs 3E-F ), 55,59 washings are performed to mitigate the severity of complications. Overall management is supportive care with mechanical ventilation, inhaled bronchodilators, and repeated bronchoscopy to facilitate clearance. 60 The best method to prevent charcoal aspiration is to provide adequate airway protection with endotracheal intubation in patients with impaired mental status. 55 Amiodarone Amiodarone is an effective agent against various cardiac arrhythmias. However, its use is limited by pulmonary toxicity. Amiodarone and its metabolite accumulate in lung tissue at levels 100-to 500-fold higher than serum. 61 Pulmonary complications develop in 5% to 15% of patients on 500 mg or more daily and in 0.1% to 0.5% of patients on doses up to 200 mg daily. 62 There are two possible mechanisms of pulmonary toxicity: (1) a direct toxic effect and (2) an immunemediated hypersensitivity reaction. 63 Patients may present with: interstitial pneumonia, organizing pneumonia, ARDS, pulmonary nodules, alveolar hemorrhage, and pulmonary fi brosis. 64 Hyperpigmentation of the airway is reported in one case ( Fig 4A ). 65 The possible mechanism may be the chronic accumulation of amiodarone in the submucosal tissue from its longterm use. Discontinuation of the drug results in the resolution of bronchial pigmentation ( Fig 4B ). 65 However, drug toxicity may initially continue to progress due to the long half-life of amiodarone. Regardless, a rechallenge of amiodarone is not recommended due to the risk of pulmonary fi brosis.

Tricoptysis

The condition of tricoptysis can be iatrogenic in origin. In a single case report, the patient presented with a gradual onset of shortness of breath, hoarseness, wheezing, and coughing of hair. This patient had undergone reconstruction surgery for a benign laryngeal tumor, which used a mucosal fl ap. FB revealed an extensive meshwork of black hair fi laments, below the epiglottis, partially covering the vocal cords. Some hairs were covered by thick mucus ( Fig 4C ). Most patients with a laryngeal tumor who undergo flap reconstruction require postoperative radiation to minimize ectopic hair growth. However, this patient did not receive external beam radiation. Laser hair or paraganglioma. 47 The diagnosis mainly rests upon histologic identifi cation. Occasionally, the metastatic lesion may lose its pigmentary characteristic and be labeled as amelanotic melanoma. Because primary melanoma of the lung is exceedingly rare, strict diagnostic criteria have been established: junctional changes (ie, dropping off or nesting of melanoma cells just beneath the bronchial epithelium), the invasion of the bronchial epithelium by melanoma cells in an area where the bronchial epithelium is not ulcerated, and no demonstration of a tumor elsewhere at the time of diagnosis. 51 The prognosis is poor for both primary and metastatic melanomas of the lung. Median survival after the diagnosis of metastatic disease is approximately 15 months, as the endobronchial condition represents advanced stage disease. 52 Surgical resection followed by chemotherapy and immunotherapy has been reported in a few instances, but long-term prognosis is not yet defi ned.

Teratomas

The term tricoptysis refers to the expectoration of hairs in the sputum. Tricoptysis is seen in 15% of the cases of intrapulmonary teratoma. A mature teratoma may rupture and release its contents into airways, resulting in a recurrent cough, hemoptysis, and tricoptysis. 53 Involved airways exhibit dark black areas due to the presence of hair. Excision of the tumor is the treatment of choice for a mature teratoma even though the tumor is benign. A benign teratoma may potentially transform into a malignancy. 54

Iatrogenic Causes

Charcoal Aspiration

Activated charcoal is considered an effective GI decontaminant for acute intoxication with select drugs. Charcoal prevents absorption by binding directly to the toxic drug and creating a passive diffusion gradient from the bloodstream, across the GI lumen (GI dialysis). 55 Patients with an altered mental status are at high risk of aspiration of activated charcoal into the lungs, especially if the airway is not adequately protected. Aspiration is reported in 1.7% of patients who receive charcoal alone and 2.3% of those who also undergo gastric emptying. 56 The aspiration of gastric contents occurs concomitantly with charcoal aspiration, which frequently results in severe pulmonary complications.

Acute complications of charcoal aspiration include airway obstruction, bronchospasm, hypoxemia, and pneumonia. Late complications include ARDS, bronchiolitis obliterans, bronchopleural fi stula, and even death. 57 Although charcoal is an inert and nonabsorbable agent, it exerts a strong immunogenicity and activates tion (F io 2 ). 70 Strategies have been proposed to decrease the occurrence of endotracheal fi re during laser photoresection, as well as argon plasma coagulation. 68,[71][72][73][74][75] Endobronchial ignition, irrespective of the energy source, is an emergency. To avoid delay in the management, the operating room personnel should be trained to manage the circumstances promptly. A stepby-step protocol should be established. When a fl ash fi re is detected, all anesthetic agents should be immediately discontinued, followed by endotracheal tube removal and extinguishing the fi re with saline. The patient should receive pure oxygen ventilation by mask prior to reintubation. 69 The tracheobronchial tree should be reevaluated for the removal of any foreign particles. Daily FB should be performed to detect complications and delineate the extent of injury. 69 Steroids should be initiated with a gradual tapering as the patient improves. Daily tracheal cultures should be obtained for the early detection of changing microbiology. Prophylactic antibiotics, such as penicillin removal or fulguration techniques may be necessary to remove hairs permanently from this location. 66

Endobronchial Ignition

An endobronchial ignition during the thermal ablation of an airway lesion resulting in black discoloration has been reported on several occasions. Such complications can occur during the use of a laser, electrocautery, or argon plasma coagulation. Burned mucosa as a result of tracheal fi re exhibit black debris, based on the degree of injury ( Fig 4D ). 67,68 The black carbonaceous debris deposited in the airways, in addition to the toxic vapors from a burn, could produce chemical injury and chronic mucosal infl ammation. 69 Severe endobronchial burns can also lead to the perforation of the airways and fi stula formation with surrounding structures.

Major factors contributing to the endobronchial ignition include the types of endotracheal tube, bronchoscope and laser used, and high oxygen concentra- and cephalosporin, should be initiated and later adjusted, based on bacteriologic fi ndings. 69 In severe laryngopharyngeal injury, tracheostomy is necessary to prevent airway obstruction. A high-humidity nebulizer will facilitate the clearing of secretions because burned airways with impaired mucociliary function are prone to form mucus plugs, resulting in postobstructive pneumonia. 69

Conclusion

The presence of black pigmentation involving the bronchial mucosa is a relatively uncommon and, hence, underrecognized condition. In this article, we provide a comprehensive review on the etiology of black bronchoscopy. In most of the cases, diagnosis can be made by reviewing the history of exposure to hazardous substance and by performing endobronchial biopsies and cultures. In case these basic diagnostic tests are unable to reveal the etiology, special diagnostic tests may be needed such as microscopic examination under polarized light and measurement of urine and plasma HGA levels ( Table 1 ). Overall, it is important for a bronchoscopist to recognize the full range of possible etiologies of this rare entity for its optimal management.