Department of Tuberculosis and Respiratory Disease, Mahatma Gandhi Institute of Medical Sciences, Maharashtra, India
Reprints: Sajal De, MD, FCCP, Qr No-8, Type III, Vivekananda Colony, MGIMS Campus, Sevagram, Maharashtra 442102, India (e-mail: email@example.com).
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the Journal's Web site (www.bronchology.com).
Received December 19, 2010
Accepted February 14, 2011
Tuberculosis involving the tracheobronchial tree is known as endobronchial tuberculosis (EBTB). EBTB may present with or without parenchymal involvement. The prevalence of EBTB among pulmonary tuberculosis varies widely, from 10% to 36.8%.1
On the basis of bronchoscopic appearance of endobronchial lesions, Chung and Lee2 have classified EBTB into 7 subtypes. Among these subtypes, tumorous EBTB is a relatively less common. In tumorous EBTB, the lesions partially or completely occlude the lumen and often mimic malignancy. Previous study2 has reported residual bronchial stenosis, even after the effective treatment of tumorous EBTB.
We prospectively evaluated tumorous EBTB, which was diagnosed during bronchoscopy at Bhopal Memorial Hospital & Research Centre from January 2007 to December 2009. Four hundred sixty bronchoscopies were performed during this period for various indications and tumorous EBTB was diagnosed in 4 cases (1.0%). Brief descriptions of the cases are described below.
A 30-year-old gentleman had a history of low-grade fever for 4 weeks and cough for 8 days. During evaluation of fever, x-ray of the chest was found normal but computed tomographic scan of the thorax showed multiple mediastinal lymphadenopathies. On bronchoscopy, a growth with black mucosa was found in the left lower lobe bronchus (Fig. 1A). Histopathologic examination of bronchial biopsy showed focal collection of lymphocytes with necrosis and the presence of acid fast bacilli (AFB). However, AFB were not observed in the bronchial aspirate. After completion of 6 months of antitubercular treatment (ATT), repeat bronchoscopy showed complete resolution of the growth with black pigmentation at the site of initial lesion (Fig. 1B).
A 26-year-old woman complained of left-side chest pain for 1 month and x-ray of the chest showed nonhomogeneous opacity on the left lower zone. On bronchoscopy, a vascular growth at the opening of lingular bronchus occluding the entire lumen was identified (Fig. 2A, video 1, Supplemental Digital Content 1, http://links.lww.com/LBR/A72). Histopathologic examination of endobronchial biopsy specimen showed well-defined caseating granuloma. Both biopsy and bronchial aspirate were negative for AFB. However, Mycobacterium tuberculosis was isolated from the culture of the bronchial aspirate. After completion of 6 months of ATT, the tumorous growth had regressed completely, with black pigmentation at that site (Fig. 2B, video 2, Supplemental Digital Content 2, http://links.lww.com/LBR/A73).
A 39-year-old woman suffered with fever for 3 months and dry cough for the past 1 month. Chest x-ray showed nonhomogeneous opacity on the right mid zone. On bronchoscopy, a tumorous growth was seen on the apical segment of the right lower lobe bronchus. Histopathologic examination of biopsy sample showed granuloma with occasional AFB. Repeat bronchoscopy after completion of 6 months of ATT showed complete resolution of the growth with no residual abnormality.
A 47-year-old woman presented to the neurosurgery department with a history of neck pain and cough of 6 months' duration. Magnetic resonance imaging of cervical and thoracic spine showed heterogeneously enhancing destructive lesion on the left side of atlas and fifth cervical vertebra along with consolidation on the left lingular region. Bronchoscopy showed distorted carina with possible subcarinal lymphadenopathy. A fistulous communication between subcarinal lymph node and left main bronchus was seen below the carina (Fig. 3A, video 3, Supplemental Digital Content 3, http://links.lww.com/LBR/A74). A black necrotic soft growth partially occluding the left lingular segment was also seen (Fig. 3B). Histopathologic examination of endobronchial biopsy sample showed ill-defined caseating granuloma with AFB. However, AFB was not identified on direct smear examination or culture of bronchial aspirate. Repeat bronchoscopy after 12 months of ATT showed healing of the fistula and the complete regression of the growth with residual black pigmentation at the site of the growth (Figs. 3C, D, video 4, Supplemental Digital Content 4, http://links.lww.com/LBR/A76).
EBTB usually develops by direct implantation of tuberculous bacilli in the tracheobronchial tree or by extension from the adjacent parenchymal lesion. The other mechanisms include direct infiltration from adjacent mediastinal nodes, and the least common cause is lymphatic or hematogenous spread. The first case of the present series had developed EBTB because of erosion and protrusion of tubercular lymph node through the bronchus. Occasionally, a fistula may also develop between the mediastinal lymph node and bronchus, and the extrusion of caseous material into bronchus leads to EBTB. This was a possible mechanism of pathogenesis in the fourth case of the present series.
EBTB in adults may occur as a primary infection or as a reactivation. The stages of pathogenesis of tumorous EBTB along with bronchoscopic changes are well described.2 The initial lesion starts as erythema and edema of the mucosa with lymphocytic infiltration of the submucosa. This is followed by formation of submucosal granuloma. The rupture of caseous necrosis on mucosal surfaces leads to ulcerative lesions. These ulcers may evolve into hyperplastic inflammatory polyp, which can give rise to tumorous EBTB.
On the basis of bronchoscopic assessment of endobronchial lesions, Chung and Lee2 classified EBTB into 7 subtypes: actively caseating, edematous-hyperemic, fibrostenotic, tumorous, granular, ulcerative, and nonspecific bronchitic. Among different subtypes of EBTB, mucosal lesions are the most common.3,4 On bronchoscopy, tumorous EBTB appears as a vascular or ulcerative endobronchial mass partially or completely occluding the bronchus.
As all patients with tuberculosis do not undergo bronchoscopic evaluation, the actual incidence of EBTB among patients with tuberculosis is unknown. Chung and Lee2 reported the prevalence of EBTB as 5.9% among their patients with pulmonary tuberculosis, whereas Wang and Zhang3 observed the incidence of EBTB as 21.6% among 472 bronchoscopies. The incidence of tumorous lesions among the total EBTB varied from 10.5% to 62%.2,3,5
The symptoms of EBTB are insidious in onset and nonspecific. Tumorous EBTB often mimics asthma, pneumonia, foreign body aspiration, or malignancy.6 Physical examination and routine laboratory examination are rarely helpful in diagnosis. Similar to previous studies,2,4,6 higher prevalence of tumorous EBTB among female patients (75%) was also observed in the present series and all the patients were in their third or fourth decades of life.
Sputum positivity rate for AFB varies among different types of EBTB. EBTB with mucosal involvement and ulceration has higher sputum positivity, but the yield is low (10.5%) in tumorous EBTB.2 Absence of AFB in sputum samples of tumorous EBTB may be due to entrapment of distal secretion by the growth. Thus, patients may end up undergoing bronchoscopy, despite suspected tuberculosis. On bronchoscopy, tumorous EBTB mimics malignancy and as a result bronchial aspirates are either not collected or not sent for AFB staining in these cases. An erroneous diagnosis of carcinoma is possible in 30% of tumorous EBTB.1 All of the patients in the present series either were not producing sputum or had sputum samples that were negative for AFB.
Different bronchoscopic specimens provide variable diagnostic yields in the diagnosis of EBTB. Bronchial brushing samples have the highest diagnostic yield (86%) and bronchial biopsy may be positive in 11% to 84% of EBTB cases.3,5 There are no reports of diagnostic yield of bronchoscopic sample in tumorous EBTB. In the present series, the diagnostic yield of bronchial biopsy sample was 100% and AFB was identified in 3 biopsy samples (75%).
The natural history of EBTB is usually complicated, unpredictable, and often refractory to ATT.7 Any subtype of EBTB can transform into any subtype while on the treatment.2 Clinical outcome of EBTB depends on interaction between pathogenicity of mycobacteria, host immunity, and effective treatment. Chung and Lee2 reported poor outcome of tumorous EBTB and appearance of new tumorous lesions at different locations during treatment. Among 10 cases of tumorous EBTB in their series, complete resolution was achieved only in 1 case (10%). The rest of their patients developed residual stenosis of bronchus. All of our patients showed complete resolution of the growth with no residual bronchial stenosis.
In the present series, black pigmentation of mucosa was observed at the site of initial tumorous lesion after the treatment in 3 cases (75%). This black pigmentation is referred as “anthracosis” or “melenosis.”8 The black pigmentation of tracheobronchial mucosa occurs in active or old tuberculosis, especially among women, and is not related to smoking or exposure to environmental dust.8 In individuals with a history of environmental exposure, such pigmentations are due to sedimentation of silica, carbon, and asbestos particles in cytoplasm of mucosal and submucosal cells and macrophages.9 Sometimes, anthracotic dark materials trapped in the lymph node erode the bronchus and produce dark pigmentation, which occurred in the first case of this series. The presence of dark pigments was not mentioned in 2 previous large series of EBTB.3,6 It remains a matter of speculation that the dark endobronchial pigmentation after appropriate treatment in patients with tuberous EBTB is due to either local stimulation of melanocytes or release of pigments from the dead organisms. To my knowledge, the presence of environmental dust in such dark lesions has not been reported in patients with tuberous EBTB, before or after the treatment.
The optimal duration of therapy in EBTB is not well defined and patients were treated with 9 months of ATT by previous investigators2,4 All 4 patients received a daily regimen of ATT (isoniazid, rifampicin, ethambutol, and pyrizinamide for 2 months followed by isoniazid and rifampicin), and 3 patients received ATT for 6 months and 1 patient received it for 12 months because of involvement of cervical vertebra. No adverse reactions were observed during treatment. Serology for human immunodeficiency virus was negative in all cases.
The role of corticosteroid along with ATT in treatment of EBTB is controversial. Verhaeghe et al10 had shown rapid healing and complete resolution of EBTB by local injection of corticosteroids through the bronchoscope. None of the patients in the present series received steroids during treatment.
In conclusion, this study showed that the treatment outcomes of tumorous EBTB are favorable. The diagnostic yield of histopathologic examination of biopsy sample in tumorous EBTB is high. Short-course ATT without corticosteroid may be sufficient to prevent the residual bronchial stenosis.
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