Lung Biopsy

Scott E. Kopec

Richard S. Irwin

Lung biopsy is indicated whenever it is necessary to obtain a definitive diagnosis of a localized or diffuse pulmonary disease, usually after noninvasive diagnostic modalities have been used unsuccessfully.

Multiple lung biopsy techniques are available that have been well characterized with regard to tissue yield, diagnostic yield, complications, contraindications, and mortality rate. The relative usefulness of a particular biopsy technique depends not only on the availability of local expertise but also on the clinical situation. Each of the commonly used biopsy procedures is briefly described, and an approach to the lung biopsy procedure in the critically ill patient that focuses on the following questions is outlined: (a) When should a lung biopsy be considered in the critically ill patient? (b) Which biopsy technique should be chosen? (c) How should the specimens be handled?

Biopsy Procedures

General Considerations

Lung biopsy procedures can be grouped into two broad categories: open (i.e., surgical) and closed (i.e., nonsurgical). The major distinction between the two is that closed procedures avoid major surgical intervention and general anesthesia at the expense of a lower likelihood of obtaining a definitive
diagnosis. Contraindications and relative contraindications for open and closed lung biopsy procedures are listed in Table 69.1 [1,2,3,4,5].

Table 69.1 Contraindications and Relative Contraindications to Lung Biopsy [1,2,3,4,5]

Open thoracotomy biopsy
   Contraindication
      Too ill to undergo general anesthesia
Thorascopic lung biopsy
   Contraindications
      Too ill to undergo general anesthesia
      Extensive pleural adhesions
      Uncorrectable coagulopathy
      Postpneumonectomy patient
      Severe pulmonary hypertension
   Relative contraindications
      Inability to place a double-lumen endotracheal tube
      Inability to tolerate single lung ventilation
Closed biopsy
   Contraindications
      Uncorrectable coagulopathy (including uremia)^a
      Unstable cardiovascular status
      Severe hypoxia likely to worsen during bronchoscopy
      Inadequately trained bronchoscopist
      Poor patient cooperation
   Relative Contraindications
      Recent myocardial infarction or unstable angina
      Adjacent vascular abnormalities
      Positive-pressure ventilation
      Cavitating lesions (especially with air-fluid levels or > 10 cm diameter)
      Severe pulmonary hypertension
      Adjacent emphysematous lung disease
      Suspected echinococcal disease
      Uncontrollable cough

^aBronchoalveolar lavage can be performed safely in patients with severe thrombocytopenia.

Open Biopsy Procedures

Open Thoracotomy Lung Biopsy

Because thoracotomy allows the surgeon to obtain relatively large specimens of lung tissue under direct observation, open lung biopsy is a consistently accurate lung biopsy technique. The procedure requires endotracheal intubation, general anesthesia, and pleural catheter drainage for at least 24 hours after the biopsy. A description of the technique used to perform an open lung biopsy can be found elsewhere [3,4]. The following interventions maximize diagnostic yield [4]. First, average, rather than normal or markedly abnormal, lung tissue should be preferentially sampled. Second, in cases of diffuse pulmonary disease, more than one site should be sampled, if possible. Third, areas corresponding to ground-glass appearance on high-resolution chest tomography should be biopsied, as they are more likely to reveal the inflammatory process [5]. Some authors believe that biopsies of the tip of the lingula or right middle lobe should be avoided because prior scarring, inflammation, and passive congestion of a nonspecific nature are likely to occur in these sites [6]. However, several studies refute this [4,7].

Thoracoscopic Lung Biopsy

Thoracoscopy is a percutaneous procedure that involves the endoscopic exploration and sampling of the contents of the thoracic cavity [1,8]. Unlike the other percutaneous procedures, thoracoscopic lung biopsy is considered a surgical procedure. Although there are a variety of potential uses for thoracoscopy, only lung biopsy is highlighted here. Thoracoscopic lung biopsy involves multiple small chest wall incisions and a controlled pneumothorax to collapse the lung. One incision allows the insertion of a sterile flexible endoscope to visualize the lung and pleural surfaces. A biopsy device is inserted through another incision and guided by direct endoscopic vision/video monitoring. Multiple points of entry may be necessary to determine the ideal endoscopic approach.

An advantage of thoracoscopy is that it can obtain a larger piece of lung tissue than bronchoscopy techniques, equal in size to that obtained at open lung biopsy. Where available, it is the open procedure of choice for patients in stable condition who are not requiring mechanical ventilation. Some authors caution that ventilator-dependent patients should not routinely undergo biopsy procedures by thoracoscopy because they typically cannot tolerate the change to a double-lumen endotracheal tube or the single-lung ventilation technique (see Table 69.1).

Although several studies of noncritically ill patients with interstitial lung disease demonstrated that thoracoscopy and open lung biopsy were identical in providing the diagnosis and complications [2], we are unaware of any study that compares open lung biopsy with thoracoscopic biopsy in critically ill patients. Due to the absolute and relative contraindications of thoracoscopic lung biopsy, critically ill patients on mechanical ventilation should preferentially undergo an open procedure.

Closed Biopsy Procedures

Percutaneous Transthoracic Needle Aspiration Biopsy

Percutaneous transthoracic needle aspiration biopsy involves the insertion, under guidance of fluoroscopy or computed tomography (CT), of a sterile needle through the chest wall into the area of the lung to be sampled [9]. Yields appear greatest if the procedure is performed under CT-guided fluoroscopy [10]. Needles of varying sizes (18-, 20-, 22-, and 24- to 25-gauge) can be used. In general, the thinner the needle, the fewer the complications [11]. A specimen is obtained by aspiration; it usually consists of cells (e.g., neoplastic, parenchymal, inflammatory), tissue fluids, or small tissue fragments. The major advantage of this procedure is that it can be easily performed with local anesthesia. The major disadvantages are that lung architectural integrity may not be maintained in the specimen, and the incidence of pneumothorax can be as high as 20% [12].

Bronchoscopic Procedures

A variety of techniques, including bronchial and transbronchial biopsy, bronchial brushing, transbronchial needle aspiration, and bronchoalveolar lavage (BAL), can be easily and safely performed with the flexible bronchoscope. A detailed discussion of flexible bronchoscopy is presented in Chapter 9.

Transbronchial Lung Biopsy

Transbronchial lung biopsy is performed by passing the bronchoscope to the segmental level, instilling a dilute solution of epinephrine, and then advancing flexible biopsy forceps into the radiographically abnormal area [13]. The forceps usually are advanced under fluoroscopic guidance. They are passed in the closed position until resistance is met or the patient signals that he or she has chest (pleural) pain. If pain is felt, the forceps are withdrawn in 1-cm
increments until pain is no longer perceived. If no pain is felt, the forceps are opened, pressure is gently applied, and the forceps are closed. If no chest pain is felt, the forceps are then removed. Some authors recommend wedging the bronchoscope into the airway from which the biopsy was taken to tamponade any potential bleeding and to prevent any blood from spilling out into other airways. However, a technique of applying continuous suction while moving the bronchoscope back and forth in the airway has been shown to be effective at controlling bleeding [14]. Synchronization of the biopsy to a phase of respiration has affected neither the amount of alveolar tissue obtained nor the integrity of the specimen [15]. Because specimens are small (not greater than 3.9 mm² on average [15]), multiple specimens should be obtained to maximize the yield of this technique.

Bronchial Brush Biopsy

Using a flexible wire brush, the operator performs a bronchial brush biopsy in a manner similar to forceps biopsy [16,17]. Usually under fluoroscopic guidance, the brush is passed into the radiographically abnormal area. The usefulness of this method is limited by the fact that only cellular material can be obtained and, in general, only endobronchial processes are sampled. A nodule not in communication with the bronchial tree cannot be entered with the brush, although the nodule can be sampled with a needle passed transthoracically.

Transbronchial Needle Aspiration

The transbronchial needle aspiration technique allows the clinician to pierce the walls of airways and aspirate cellular contents and tissue fluid or processes not in communication with the tracheobronchial tree. Specially designed catheters with attached needles are passed through the suction channel of the bronchoscope to the abnormal area [2]. As long as the vascularity of the area to be aspirated is appreciated or has been defined, transbronchial puncture with aspiration can be safely performed [18]. The use of endobronchial ultrasound to locate the exact location of lymph nodes and blood vessels improves yield while decreasing complications [19]. This procedure has a role in the diagnosis and staging of lung cancer and in the diagnosis of some benign mediastinal diseases, such as bronchogenic cysts and sarcoidosis [20]. When appropriately applied and with good cytopathologic support, this procedure can eliminate the need for surgical staging in a substantial number of patients with inoperable lung cancer [21].

Bronchoalveolar Lavage

BAL is a safe diagnostic extension of routine flexible bronchoscopy [22]. The tip of the bronchoscope is wedged into a segmental or smaller airway, and physiologic saline is instilled and withdrawn through the suction channel. Using this technique, it is possible to sample cellular and soluble components from the distal airways and alveoli. A detailed discussion of the use of BAL analysis in a variety of lung diseases can be found elsewhere [23]. The usefulness of BAL and bronchoscopy-protected brush-catheter cultures in diagnosing lung infections is reviewed in Chapters 9 and 68. Because BAL is not really a biopsy procedure and little or no associated bleeding occurs, it may be performed in patients with bleeding abnormalities and pulmonary hypertension.

Expected Results from Lung Biopsy

General Considerations

To determine what type of lung biopsy procedure should be performed and when, it is important to appreciate the expected results. The yield of positive diagnoses and the complications incurred depend on the procedure performed, the disease process, and the clinical stability of the patient. Table 69.2 lists the usefulness of several procedures with respect to specific disease processes [2,24].

Table 69.2 Potentially High Yielding Biopsy Procedures for A Variety of Underlying Disease Processes [2,24]

Bronchoalveolar lavage
   Infections (PCP, mycobacteria, endemic fungal)
   Alveolar proteinosis
   Alveolar hemorrhage
   Acute eosinophilic pneumonia
   Lung cancer
   Lymphoma
   Exogenous lipoid pneumonia
Transbronchial needle aspiration
   Lung cancer
   Lymphoma
   Infections (endemic fungi, mycobacteria, Nocardia)
Bronchial brush biopsy
   Lung cancer
   Metastatic cancers
Transbronchial lung biopsy
   Sarcoidosis
   Lymphangitic carcinomatosis
   Alveolar proteinosis
   Lung cancer
   Chronic eosinophilic pneumonia
   Amyloidosis
   Lymphocytic interstitial pneumonia
   Cryptogenic organizing pneumonitis
   Hypersensitivity pneumonitis
   Invasive aspergillosis
Open lung biopsy or video-assisted thoracoscopic biopsy
   Pulmonary capillaritis
   Diffuse alveolar damage
   Idiopathic pulmonary fibrosis
   Nonspecific interstitial pneumonitis
   Inorganic pneumoconiosis

Diffuse Parenchymal Disease in Clinically Stable Patients

To maximize the diagnostic yield, the ideal biopsy procedure is one that maintains the architectural lung integrity in the specimen. The procedures that best meet this requirement are (a) open lung biopsy, (b) thoracoscopic biopsy, and (c) transbronchoscopic lung biopsy. A number of reports on stable patients with diffuse lung disease have documented average rates of mortality, complications, and diagnostic yield for these procedures (Table 69.3) [1,2]. The highest tissue and diagnostic yields with low morbidity and very low mortality rates are obtained with open and thoracoscopic lung biopsies. Transbronchoscopic lung biopsy has lower diagnostic yields but carries the lowest morbidity and mortality rates of any of these biopsy procedures.

Although open and thoracoscopic lung biopsies more consistently yield adequate tissue and an increased likelihood of definitive diagnosis than transbronchoscopic forceps lung
biopsy, the latter may be preferred as an initial procedure to avoid the morbidity of general anesthesia, postoperative chest tube drainage, residual parenchymal and pleural scarring, postoperative pain, and increased length of hospital stay. The potential morbidity of empyema that may complicate an open or thoracoscopic lung biopsy procedure is also avoided with transbronchoscopic lung biopsy. This closed procedure is much less expensive and less painful and carries less mortality than open lung biopsy.

Table 69.3 Representative Results of Lung Biopsy Procedures in Diffuse Lung Disease

Procedure	Mortality (%)	Complications (%)	Diagnostic yield (%)
Open	0–4.7	5–7^a	94–95
Thoracoscopy	0–8	0–15^b	96–100
Transbronchial forceps	< 0.12	< 10^c	84
^aIncludes pneumothorax, empyema, and bleeding. ^bIncludes subcutaneous emphysema, infection, persistent air leak, and hemorrhage with need to convert to an open thoracotomy. ^cIncludes pneumothorax and hemorrhage.