Endobronchial tumors
• Malignant
• Carcinoid tumors
• Hamartomas
Infectious and other endobronchial diseases
• Mycoplasma and viral
• Endobronchial tuberculosis
• Allergic bronchopulmonary aspergillosis
• Bronchocentric granulomatosis
• Sarcoidosis
Endobronchial Tumors
Endobronchial biopsies in adult patients are mostly done for the diagnosis of bronchogenic malignancies. Patients with bronchogenic malignancies come to biopsy with symptoms that are generally not specific, overlap with other airway diseases, and involve other organ systems as the disease progresses [5]. Wheezing, cough, and dyspnea are the most common symptoms in tumors of the airways and are shared with diseases that cause airflow obstruction, most notably chronic obstructive pulmonary disease and asthma. The classic paraneoplastic symptoms associated with some bronchogenic cancers that lend some diagnostic specificity are not common. Hypertrophic osteoarthropathy, a periosteal inflammatory condition of the long bones, and hypercalcemia can be found in squamous cell cancer of the lung. The Lambert–Eaton myasthenic syndrome with weakness and visual disturbance is seen in small cell lung cancer. Bronchorrhea is occasionally associated with adenocarcinoma in situ. Hemoptysis is occasionally the presenting symptom for bronchogenic cancer and portends more extensive involvement of the airway and poorer outcome [6]. Pneumonia, especially if it is recurrent in the same location, may indicate an obstructing lesion of the airway. Bronchoscopy may be a challenge in such cases because of the inflammation with swelling and purulence that make it difficult to biopsy the lesion. The clinician may elect to postpone the procedure until the pneumonia is treated and well into resolution.
Like their malignant counterparts, benign endobronchial tumors present with similar symptoms of airway obstruction with wheezing, cough, dyspnea, and sometimes with hemoptysis or post-obstructive pneumonia. Carcinoid tumors are derived from neuroendocrine tissues of the gastrointestinal (GI) and respiratory tracts. They are predominantly found in the GI tract, but up to 20 % occur in the airways [7, 8]. Compared to tumors in the GI tract, pulmonary carcinoids are less likely to produce the carcinoid syndromes of flushing, diarrhea, and heart failure. They can be found from the most proximal to the most distal conducting airways where neuroendocrine rests are found. On bronchoscopy, they have a very smooth, shiny, and sometimes very vascular surface in contrast to malignant tumors that have irregular lobulated borders with varying degrees of necrosis.
Hamartomas are the most common benign lung tumors, but only 10 % of those occur in the bronchi [9]. They usually come to attention in patients who present with post-obstructive symptoms or by chance in an abnormal chest film. On bronchoscopic inspection, they have no distinguishing features that separate them from malignant lesions. The histological diagnosis leads to a second therapeutic bronchoscopy with the removal of the tumor that is curative in most cases.
Infectious and Other Endobronchial Abnormalities
Diseases of the airways extend well beyond the malignant and benign tissue transformations described above. These diseases include infectious and noninfectious disorders that present with a broad constellation of symptoms that may extend beyond the respiratory system. The history and presentation of the individual is more complex with questions about immune status and lung function abnormalities at the forefront. Fever and metabolic abnormalities also become more prominent. The path to bronchoscopy usually takes longer and only after clinical, laboratory, and radiological evaluation has not yielded an answer.
Fever and weight loss will put infection at the top of the disease differential, so tissue sampling for both histological examination and culture and staining is prepared. On inspection, infections of the airways can take any form such as single or multiple nodules, ulcerated epithelium, discolored patches, or even only mild erythema and edema. Bronchial washings and brushings typically accompany tissue biopsies in these cases. Multiple samples for culture are taken first to avoid any possibility of contamination of the bronchoscope channel or forceps with fixative. While a positive culture of a non-commensal or opportunistic organism is sufficient to initiate specific therapy, demonstration of tissue invasion may be necessary in some circumstances.
Diffuse infections of the airways can cause them to become hyperresponsive and produce symptoms that are indistinguishable from asthma. Though asthma is very prevalent worldwide, individual cases sometimes present out of context with respect to risk factors, a history of atopy, exacerbating exposures, or response to therapy. The clinician may therefore elect to perform inspection and biopsy of the airways. Mycoplasma pneumoniae has been associated with and even implicated as the cause of asthma in some case series, the latter conclusion on the basis that the asthma was controlled after treating the infection [10]. Rhinovirus, respiratory syncytial virus, and influenza viruses have a strong relationship with asthma exacerbations and may be relevant in chronic uncontrolled asthma that may lead one to obtain bronchial tissues for examination [11]. The key point on reviewing bronchial biopsies of subjects with reactive airways is that, in addition to the anticipated inflammatory changes, awareness and detection of concurrent infection will aid the clinician with treatment.
Endobronchial tuberculosis is an uncommon manifestation of infection with Mycobacterium tuberculosis (MTB) [12, 13]. Cough, wheezing, fever, and dyspnea are nonspecific symptoms, and it is not usually detectable on plain chest radiography. Moreover, sputum cultures for MTB may be negative. On bronchoscopy, the lesions have no distinguishing features that would make the operator suspect MTB. The lesions may appear as endobronchial masses or ulcerations. They may obstruct airways or cause tracheal or bronchial stenosis. Expedient identification and medical treatment of endobronchial MTB are therefore essential to prevent fixed stenosis and need for surgical reconstruction.
Allergic bronchopulmonary aspergillosis (ABPA) and bronchocentric granulomatosis (BCG) are entities that overlap with asthma in their clinical presentation [14, 15]. ABPA is mostly associated with Aspergillus fumigatus, but other fungi less commonly produce a similar syndrome. In addition to the symptoms and examination findings of asthma, the presence of mucus plugging or infiltrates may lead to bronchoscopic examination and biopsy of the involved airways. The hallmark demonstration of fungal hyphae in bronchial tissue, along with supportive findings of elevated IgE and cutaneous reactivity or precipitins to A. fumigatus, significantly impacts therapy. In ABPA, systemic steroids are required in addition to bronchodilator therapy. In recalcitrant cases, treatment with antifungals may be necessary.
BCG was first described in 1972 by Liebow as a focal bronchial and bronchiolar destructive granulomatous lesion [16, 17]. About one third of individuals with BCG have asthma, and three fourths of them will have A. fumigatus hyphae detected in their bronchial biopsies. Of the two thirds who do not have asthma, hyphae are present in only about one third. Radiographically, BCG may appear as a lung mass that will prompt the bronchoscopic examination. Steroid treatment is very effective, but the disease may recur so individuals must be monitored regularly.
Sarcoidosis is a multisystemic granulomatous disease of unknown etiology with a variety of clinical presentations depending on the organ involved [18]. Respiratory symptoms are nonspecific and include chest tightness, cough, and dyspnea on exertion. A high proportion of patients with pulmonary sarcoidosis will have some evidence of airflow obstruction suggesting endobronchial involvement with this disease [19]. On bronchoscopy, the bronchial mucosa may appear normal to erythematous with “cobblestoning” that indicates a heavy granuloma burden in the airways. The yield of random biopsies of the bronchial mucosa depends on the degree of involvement and in practice is a supplement to transbronchial biopsies and transbronchial needle aspiration of enlarged hilar, paratracheal, or other mediastinal nodes.
Parenchymal Diseases Diagnosed by Small Sample Lung Biopsies
New technologies have extended the reach and accuracy of small sample biopsies of solid and infiltrative diseases in the lung parenchyma. Table 1.2 lists parenchymal diseases categorized by radiological appearance. This categorization is useful for differential diagnosis and the selection of the biopsy technique and approach to diagnosis. Unlike endobronchial diseases, imaging using fluoroscopy and ultrasound assists in the localization and biopsy of lesions in the lung parenchyma. New tools for performing navigational bronchoscopy, linear and radial endobronchial ultrasonography, and cryobiopsy have extended the reach and accuracy of bronchoscopic biopsy of even the deepest pulmonary abnormalities.
Table 1.2
Parenchymal diseases diagnosed by small sample lung biopsies
Focal solid parenchymal lesions |
• Lung masses |
• Metastatic disease |
• Solitary pulmonary nodules |
Focal and diffuse infiltrative diseases |
• Granulomatous diseases |
– Sarcoidosis |
– Hypersensitivity pneumonitis |
• Non-granulomatous diseases |
– Idiopathic pulmonary fibrosis |
– Nonspecific interstitial pneumonitis |
– Smoking-related interstitial lung diseases |
– Organizing pneumonia |
Focal Solid Parenchymal Lesions
Standard flexible fiberoptic biopsy guided by fluoroscopy is the mainstay procedure for locating and sampling solid parenchymal lesions. Fluoroscopy is also used for safety purposes mainly to mitigate and assess for pneumothorax. Lung masses that are larger and centrally located are usually approached in this way. Lesions that are smaller and located peripherally are more accurately biopsied using navigational or ultrasound-guided bronchoscopy as described below [20, 21].
Lung masses by definition are discrete lesions greater than 3 cm in diameter by radiography [22]. A single mass in an adult is considered to be malignant until proven otherwise. Age, smoking history, and presence of chronic obstructive pulmonary disease all increase the pretest probability of primary lung cancer [23]. Therefore, it is imperative that the bronchoscopic sample demonstrates malignancy to avoid a more invasive biopsy approach. Radio- or chemotherapy is very rarely undertaken without a true-positive histological evidence of malignancy. The bronchoscopist maximizes diagnostic yield using fluoroscopy to locate the mass and take multiple transbronchial biopsies using a forceps “punched” into the lung parenchyma. Angling the tip of the bronchoscope slightly with each pass is done to sample different regions of the mass. Finally, ample tissue must be recovered for possible biomarker probing that may influence therapy.
Nonmalignant lung masses can sometimes be seen in chronic inflammatory and granulomatous diseases produced by infection, as pulmonary involvement in autoimmune diseases, or through environmental exposures. Though mostly presenting as lung nodules, fungal infections may sometimes present radiographically as lung masses [24]. Histoplasmosis or blastomycosis may present as a mass-like consolidations in immunocompetent patients, while cryptococcosis is found mainly in immunosuppressed individuals. Similar to malignant masses, the diagnostic approach is by transbronchial biopsy supplemented by bronchial washings with saline for culture.
Mass-like lung densities may also be seen in autoimmune diseases like sarcoidosis, rheumatoid arthritis, and granulomatosis with polyangiitis. When lung masses are detected in the context of an autoimmune disease, the individual is often on immunosuppressive therapy. Opportunistic infection must be considered, and appropriate preparation to receive samples for Pneumocystis jirovecii, other fungi, and acid-fast organisms should be done. Often, bronchoalveolar lavage (BAL) supplements biopsy by accessing deep respiratory surfaces not obtained by simple washings. BAL involves wedging the bronchoscope into a fourth- to sixth-generation bronchus to produce a tight seal. Then, sterile saline is instilled in 30–50 mL. Aliquots are recovered by gentle suction. An acceptable BAL sample will demonstrate a “foamy” meniscus in the suction receptacle indicating recovery of pulmonary surfactant from alveolar surfaces and return few to no ciliated epithelial cells indicating little contamination from the conducting airways.
Occupational exposures to silica, coal dust, beryllium, and kaolin will produce one or more discrete lesions that must be differentiated from malignancy. The occupational history must be provided to the reviewing pathologist to prepare the appropriate microscopic assessment for the presence of particulates. Beryllium is indistinguishable from sarcoidosis histologically, but the lack of certain extrapulmonary manifestations found in sarcoidosis and the exposure history will increase the confidence that the noncaseating granulomas are the result of beryllium exposure [25].
Metastatic malignancies to the lungs may present as solitary or multiple lesions of varying size. Colorectal cancers occasionally present as solitary nodules. Identifying these lesions as originating from these organs is key since resection may improve survival [26]. In the setting of known cancer, patients with solitary metastases may go directly to surgery after risk assessment. However, if diagnosis is elected, then navigational bronchoscopy, described in more detail below, can accurately sample even peripheral metastases 1 cm in diameter or more.
Lymphangitic metastases are typically addressed with standard transbronchial biopsy with fluoroscopic guidance. Five to six passes in one selected lung lobe are done and yield an almost 70 % chance of diagnosis [27]. Although the risk of pneumothorax is low, the bronchoscopist never performs transbronchial biopsy in both lungs in the same procedure.
The approach to the diagnosis of solitary or multiple pulmonary nodules begins with a thorough interview of the patient emphasizing respiratory exposures and risk assessment. Then, the decision to observe over time, perform biopsy, or go directly to resection can be made. The advent of low-dose computerized tomography (LDCT) and comfort of practitioners to order this test have produced an upsurge of studies demonstrating pulmonary nodules. Indeed, in the National Lung Screening Trial in the United States in which over 53,000 individuals at risk for lung cancer underwent LDCT, a reduction in lung cancer mortality and discovery of earlier stage disease were demonstrated [28]. Still, the vast majority of nodules assessed were benign through observation over time or by diagnostic sampling or by resection. Biopsy and resection incur both cost and risks including mortality. The challenge is the decision to wait and watch biopsy or resect.
Solitary pulmonary nodules are by definition single nodular lesions of 3-cm diameter or less surrounded by normal lung tissue [22]. Location and size, along with risk factors for malignant potential, determine to a large degree how the nodule is to be approached. Sub-centimeter nodules may be observed by serial radiology and applying various algorithms based on risk, smoking history, and lung function [29]. Nodules that are one or more centimeters in diameter may be resected or sampled for diagnosis. Risk factors for malignancy, surgical risks, and patient desires determine the approach.
The advent of electromagnetic guidance has improved the diagnostic reach and accuracy of bronchoscopy in the assessment of pulmonary nodules by a technique called navigational bronchoscopy. Navigational bronchoscopy is a complicated procedure that matches the location of a subject’s lesion on computerized tomography to the anatomy of the subject who is enveloped in a magnetic field during the procedure [30]. A process called “registration” matches the image and magnetic field. Then, a probe with an extended working channel is inserted through the bronchoscope and guided to the lesion through a virtual image on screen. Once the lesion is located, the extended channel is locked in place. A biopsy forceps is inserted to sample the lesion under fluoroscopic guidance. The diagnostic yield of navigational bronchoscopy alone is about 60 %, and when combined with radial endobronchial ultrasound to confirm location, the yield approaches 90 % [31].
Focal and Diffuse Infiltrative Diseases
Infiltrative diseases of the lung prove challenging when diagnosis is attempted using small sample biopsy techniques. Routine transbronchial lung biopsy may be attempted in settings where there is clear expertise by both the clinical and pathological personnel involved in making the diagnosis. In general, granulomatous lung diseases like sarcoidosis and hypersensitivity pneumonitis are more likely to be diagnosed by transbronchial lung biopsy [32] than the non-granulomatous idiopathic interstitial pneumonias (IIPs) including idiopathic pulmonary fibrosis [33, 34]. Surgical lung biopsy is recommended for the latter despite the attendant risks of anesthesia and operation in patients who may already have significant pulmonary impairment.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
