TERMINOLOGY

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  Interstitial lung disease (ILD)

  
  
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  Idiopathic interstitial lung pneumonia

  
  
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  Eosinophilic lung diseases

DEFINITIONS

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  Transbronchial biopsy: biopsies taken via the flexible fiberoptic bronchoscopy.

  
  
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  Surgical lung biopsy: biopsies obtained by surgical mean either by

  
  
  
  
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    Video-assisted thoracoscopic lung surgery (VATS)—biopsies taken surgically using the VATS approach.

    
    
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    Open lung biopsy—biopsies taken surgically using an open thoracotomy.

  
  

INTRODUCTION

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  Lung biopsy is frequently required to establish the diagnosis in a number of different lung conditions, including interstitial lung disease, infections, and malignancies.

  
  
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  The indications and methods for obtaining lung tissue, the patterns of pathology encountered, and a number of illustrative cases are presented.

  
  
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  The term diffuse lung disease covers infiltrative processes that involve the alveolar spaces or the interstitium of the lung.

INDICATIONS FOR LUNG BIOPSY

Lung biopsy is indicated for the following purposes:

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  To provide a specific diagnosis of underlying ILD, malignancy, or infection that may present as diffuse lung diseases. This is important in a patient with atypical features (fever, younger than age 50 years, weight loss, signs of vasculitis, hemoptysis); unexplained extrapulmonary manifestations; a progressive course; a normal, atypical, or rapidly changing chest radiology; or pulmonary vascular disease of unclear origin

  
  
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  To make a definitive diagnosis and predict prognosis before proceeding with therapies, which may have serious side effects

  
  
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  To assess disease activity

DIFFERENT TYPES OF LUNG BIOPSY

Different options are available in obtaining lung tissue specimens.

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  Transbronchial biopsy via bronchoscopy

  
  
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  Lung biopsy via VATS

  
  
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  Open thoracotomy.

  
  
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  Transbronchial lung biopsy is more subject to sampling error as a consequence of small sample size. Because processes may be patchy, it is important to take biopsies from multiple sites.

SPECIMEN COLLECTION AND HANDLING

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  Optimal handling is essential for the accurate interpretation of biopsies and cytological preparations.

  
  
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  Transbronchial biopsies

  
  
  
  
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    Are intended to represent alveolar lung parenchyma beyond the cartilaginous airways

    
    
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    Crocodile-type forceps (Machida) or cupped forceps are used to obtain the biopsy, ideally at end expiration, with forceps being advanced under fluoroscopic guidance. The biopsy appears finely ragged and usually measures between 2 and 3 mm in diameter.

    
    
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    The number of biopsies required is at least five to seven adequate samples containing predominantly alveolated tissue.

    
    
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    To assess for lung transplant rejection, at least five adequate samples are required.

    
    
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    The biopsy is removed from the forceps with a sterile needle, and the specimens are immediately placed into fixative solution (10% neutral buffered formalin) or sterile transport medium.

    
    
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    Once processed, the biopsies are serially sectioned for processing.

  
  
  
  
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  Surgical biopsy

  
  
  
  
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    The optimal number, size, and location of surgical wedge lung biopsies depend on the suspected diagnosis and the anatomic distribution of the disease process.

    
    
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    Before any biopsy is performed, consultation among the radiologist, pulmonologist, and thoracic surgeon is essential to ensure proper sampling and location of ideal biopsy locations. High-resolution CT (HRCT) scanning may further assist in selecting the best location or locations to biopsy.

    
    
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    Adequate samples are ideally greater than 30 mm in the greatest dimension and are ideally obtained from more than one lobe of the lung.

    
    
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    The surgeon should avoid sampling only subpleural tissue (especially if pleuritis is present) and should avoid the dependent segments of the right middle lobe and lingula, because nonspecific fibrosis may be present at these sites. Areas of severe disease tend to exhibit end-stage fibrosis (i.e., honeycomb lung) without suggesting an etiology and, therefore, are unlikely to yield useful results.

    
    
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    Intraoperative pathology consultation with immediate handling of the specimen is ideal, if the lung biopsy is to be divided for microbiologic, electron microscopy, immunofluorescence or molecular studies, these portions can be removed before routine processing.

    
    
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    The specimen is injected using a 22- to 25-gauge needle with 10% buffered formalin into the cut edge. Initially the specimen is shaken vigorously within a container of fixative.

    
    
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    One biopsy could be taken from an area of lung that appears grossly and radiographically normal and another from an area with mild to moderate disease.

    
    
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    Alternatively, both biopsies could be taken from diseased areas of varying severity. This approach provides the pathologist with the data needed to evaluate the extent and distribution of disease. It also increases diagnostic accuracy.

    
    
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    The extent and severity of inflammation or fibrosis can provide information regarding the staging of disease. Other histologic parameters (e.g., the extent of fibroblastic foci in usual interstitial pneumonitis) may provide prognostic data.

  
  

COMMUNICATION BETWEEN PATHOLOGIST AND CLINICIAN

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  Pathologic abnormalities alone are rarely specific. More often, the findings are characteristic or consistent with a specific diagnosis. They may also be nonspecific reaction patterns common to several diseases that cause inflammation and/or fibrosis in the lungs.

  
  
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  Small tissue samples and substantial interobserver variability among pathologists further complicate interpretation.

  
  
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  As a result, most cases require careful clinical and pathologic correlation to arrive at a final diagnosis. With such an approach, surgical lung biopsy produces a definitive diagnosis in more than 90% of cases of ILD occurring in immunocompetent hosts. The diagnostic yield is lower (35% to 75%) in immunodeficient patients with diffuse parenchymal lung disease.

  
  
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  Data provided to the pathologist by the clinician at the time of biopsy should include

  
  
  
  
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    Information regarding the duration of illness, age of patient, and any exposure to occupational or environmental agents

    
    
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    Immune status of the patient

    
    
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    Any history of medication or illicit drug use

    
    
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    Suspected clinical diagnosis, which will often lead to a more targeted search by the pathologist

    
    
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    Because a drug reaction is a diagnosis of exclusion, the drug history is more important than the histology in most instances.

    
    
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    Similarly, the histology may be diagnostic in several of the pneumoconioses (e.g., silicosis, asbestosis), but lung tissue examination is not commonly required to establish a diagnosis.

  
  

HISTOPATHOLOGIC PATTERNS OF DISEASES

There are six broad histologic lung biopsy patterns.

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  Acute lung injury pattern

  
  
  
  
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    The lung biopsy is diffusely involved by variable amounts of edema and fibrin accompanied by reactive type 2 pneumocyte hyperplasia.

    
    
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    The dominance of noncellular, protein-rich material imparts an overall red or pink appearance to the biopsy at scanning magnification in routine hematoxylin-eosin (H&E) staining.

    
    
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    Diseases to be considered include diffuse alveolar damage (DAD) from infection, drug toxicity, collagen vascular diseases, diffuse alveolar hemorrhage, irradiation injury, eosinophilic pneumonia and idiopathic acute interstitial pneumonia (AIP).

    
    
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    Other considerations are acute hypersensitivity pneumonitis, acute pneumoconiosis, and acute aspiration pneumonia.

  
  
  
  
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  Fibrosis pattern

  
  
  
  
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    The lung biopsy is involved by variable amounts of fibrosis. As in the acute lung injury pattern, the biopsy tends to be more pink than blue at scanning magnification of H&E stained preparations, as a result of collagen deposition.

    
    
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    Some fibrosis patterns are accompanied by chronic inflammation that may result in a blue tinge to the process, or dark blue lymphoid aggregates may be present.

    
    
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    Diseases to be considered include usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), chronic hypersensitivity pneumonitis (HSP), chronic drug toxicity, collagen vascular diseases, advanced sarcoidosis, chronic eosinophilic pneumonia, and pneumoconiosis.

  
  
  
  
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  Chronic cellular infiltrative pattern:

  
  
  
  
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    The lung biopsy is involved by variable amounts of chronic inflammation and reactive type 2 pneumocyte hyperplasia.

    
    
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    The dominance of mononuclear cell infiltrates may impart an overall blue appearance magnification of H&E-stained preparations.

    
    
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    Diseases to be considered include HSP, NSIP, collagen vascular diseases, chronic infections, drug toxicities, lymphocytic and lymphoid interstitial pneumonia, lymphomas and leukemias, and lymphangitic carcinomatosis.

  
  
  
  
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  Alveolar filling pattern:

  
  
  
  
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    The dominant finding in alveolar spaces filled with either cellular or noncellular elements.

    
    
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    Diseases to be considered include infections, organizing pneumonia, diffuse alveolar hemorrhage, desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated interstitial lung disease (RBILD), alveolar proteinosis, alveolar microlithiasis, mucostasis and mucinous tumors, and dendriform calcification.

  
  
  
  
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  Nodular pattern

  
  
  
  
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    Nodules with evidence of an interface between the nodule and more nodule are noted.

    
    
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    The nodules can be of various sizes.

    
    
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    Diseases to be considered include sacoidosis, Wegener’s granulomatosis, berylliosis, aspiration pneumonia, pulmonary Langerhans cell histiocytosis, and primary and metastatic neoplasms.

  
  
  
  
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  Near-normal biopsy pattern:

  
  
  
  
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    The lung biopsy has little or no disease evident at scanning magnification.

    
    
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    Diseases to be considered include chronic small airways disease, vasculopathic diseases, lymphangioleiomyomatosis (LAM).