Portal de Periódicos da CAPES

Transbronchial Biopsy and Usual Interstitial Pneumonia

2006; Elsevier BV; Volume: 129; Issue: 5 Linguagem: Inglês

10.1378/chest.129.5.1117

1931-3543

Andrew Churg, Marvin I. Schwarz,

Pneumonia and Respiratory Infections

Usual interstitial pneumonia (UIP), the underlying histology of idiopathic pulmonary fibrosis (IPF), has a poor prognosis (median survival, 3 years), and to date there is no impressively effective therapy. Therefore, at least for prognosis, and in some cases for early transplant referral, it is important to confirm this diagnosis.Expert radiologists and clinicians can accomplish this in approximately 50% of cases of UIP with a high degree of specificity.1Flaherty KR King TE Raghu G et al.Idiopathic interstitial pneumonia: what is the effect of a multi-disciplinary approach to diagnosis?.Am J Respir Crit Care Med. 2004; 170: 907-910Crossref Scopus (468) Google Scholar When typical radiologic features are present and tissue acquisition is deemed unnecessary, most clinicians feel that the disease is already advanced. However, there are a number of patients without typical radiologic findings, and also younger subjects, in whom a histologic diagnosis is often necessary. In addition, a number of treatment trials are in motion for IPF and a tissue diagnosis is required for inclusion in these trials.Which type of biopsy is suitable for the diagnosis of UIP? In this issue of CHEST (see page 1126), Berbescu et al2Berbescu EA Katzenstein A-L Snow JL et al.Transbronchial biopsy in usual interstitial pneumonia.Chest. 2006; 129: 1126-1131Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar reviewed 22 patients with known UIP (21 cases diagnosed by surgical biopsy, 1 case diagnosed by clinical and radiologic features) and then retrospectively examined transbronchial biopsies (TBBs) from these patients. They concluded that a diagnosis of UIP was possible on the TBB in seven subjects, and in two others that the findings were consistent with UIP.As a rationale for the use of TBB, Berbescu et al2Berbescu EA Katzenstein A-L Snow JL et al.Transbronchial biopsy in usual interstitial pneumonia.Chest. 2006; 129: 1126-1131Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar cite a report3Utz JP Ryu JH Douglas WW et al.High short-term mortality following lung biopsy for usual interstitial pneumonia.Eur Respir J. 2001; 17: 175-179Crossref PubMed Scopus (213) Google Scholar in which there was 17% mortality within 30 days following surgical lung biopsy for UIP. However, this has not been the experience of many interstitial lung disease centers across the world. In most studies, the morbidity and mortality from surgical lung biopsy is < 3%. Thus, we would not view potential complications as a major factor in deciding what type of lung biopsy to perform.The question of which kind of biopsy should be performed to diagnose UIP has a long and controversial history. Surgical lung biopsy is accepted as the “gold standard,” but the role, if any, of TBB is contentious. The concept that TBB is useful for UIP and other forms of diffuse interstitial pneumonias was first addressed by Anderson.4Anderson HA Transbronchoscopic lung biopsy for diffuse pulmonary diseases.Chest. 1978; 73: 734-736PubMed Google Scholar Of 939 TBBs, 39% were read as “chronic interstitial pneumonitis and fibrosis,” an observation that lead many to view TBB as a useful tool in this setting.Subsequent reports challenged this idea. The most comprehensive is that of Wall et al,5Wall CP Gaensler EA Carrington CB et al.Comparison of transbronchial and open biopsies in chronic infiltrative lung diseases.Am Rev Respir Dis. 1981; 123: 280-285PubMed Google Scholar who compared TBB to open biopsy in the same patients with the TBB and open biopsies read, blinded, by an experienced pulmonary pathologist, the late Charles B. Carrington. Wall et al5Wall CP Gaensler EA Carrington CB et al.Comparison of transbronchial and open biopsies in chronic infiltrative lung diseases.Am Rev Respir Dis. 1981; 123: 280-285PubMed Google Scholar found that TBB findings read as normal or showing only a nonspecific pattern of interstitial inflammation and fibrosis missed cases of idiopathic interstitial pneumonias (mostly UIP) with a high frequency; conversely, TBB findings read as showing an idiopathic interstitial pneumonia were wrong in the vast majority of cases. Other reports, for example that of Wilson et al,6Wilson RK Fechner RE Greenberg SD et al.Clinical implications of a “nonspecific” transbronchial biopsy.Am J Med. 1978; 65: 252-256Abstract Full Text PDF PubMed Scopus (26) Google Scholar demonstrated that the morphologic findings of interstitial inflammation and fibrosis in TBB appeared to have little relevance to subsequent clinical course (for more detail see Chung7Churg A Transbronchial biopsy: nothing to fear.Am J Surg Pathol. 2001; 25: 820-822Crossref PubMed Scopus (21) Google Scholar). Studies of this sort lead to a quiet campaign to discourage pulmonologists from relying on TBB to confirm the diagnosis of UIP as well as other forms of idiopathic interstitial pneumonias, a campaign that culminated in recent consensus statements from the American Thoracic Society/European Respiratory Society, which explicitly state that TBB has no role in the diagnosis of UIP.8American Thoracic Society/European Respiratory Society. Idiopathic pulmonary fibrosis: diagnosis and treatment: international consensus statement.Am J Respir Crit Care Med. 2000; 161: 646-664Crossref PubMed Scopus (978) Google Scholar, 9American Thoracic Society/European Respiratory Society. International multidisciplinary consensus classification of the idiopathic interstitial pneumonias.Am J Respir Crit Care Med. 2002; 165: 277-304Crossref PubMed Scopus (3342) Google ScholarDoes the report of Berbescu et al2Berbescu EA Katzenstein A-L Snow JL et al.Transbronchial biopsy in usual interstitial pneumonia.Chest. 2006; 129: 1126-1131Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar overturn the current collective wisdom? To a pathologist, UIP is a diagnosis based to a great extent on low-power architecture because the individual features of UIP are not necessarily specific; rather, it is the repetitive combination of patchwork fibrosis, fibroblast foci, and microscopic honeycombing interspersed with unaffected lung and arranged in a peripheral and often perilobular distribution that leads to the diagnosis.TBB does not allow assessment of the distribution of fibrosis within the lobe and lobule, nor does it allow one to determine whether the process is diffuse. For these reasons, Berbescu et al2Berbescu EA Katzenstein A-L Snow JL et al.Transbronchial biopsy in usual interstitial pneumonia.Chest. 2006; 129: 1126-1131Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar used the combination of patchwork fibrosis, fibroblast foci, and microscopic honeycombing as criteria they considered diagnostic of UIP, and some of their illustrations do show fields that could be UIP. But as the authors acknowledge, none of these findings individually has diagnostic specificity, and even this combination could be the result of a variety of processes, including drug reactions, chronic hypersensitivity pneumonitis, connective tissue diseases, or asbestosis. Pathologically, one could also argue that the combination of only patchwork fibrosis and honeycombing (one of Berbescu's acceptable combinations for diagnosing UIP) in a small specimen has much lower specificity, and it is now recognized that fibroblast foci, often but not exclusively found in areas of dense fibrosis, occur in other interstitial lung diseases. As a further complication, cases of unequivocal UIP can have focal areas that look like nonspecific interstitial pneumonia10Katzenstein AL Zisman DA Litzky LA et al.Usual interstitial pneumonia: histologic study of biopsy and explant specimens.Am J Surg Pathol. 2002; 26: 1567-1577Crossref PubMed Scopus (180) Google Scholar; this problem is readily addressed in surgical lung biopsies but likely to cause tremendous confusion in TBB.The strength of the report by Berbescu et al2Berbescu EA Katzenstein A-L Snow JL et al.Transbronchial biopsy in usual interstitial pneumonia.Chest. 2006; 129: 1126-1131Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar is that they do provide detailed pathologic descriptions of what UIP might look like in TBBs, descriptions that are virtually nonexistent in the literature, and thus they offer a set of criteria that can be tested. As the authors2Berbescu EA Katzenstein A-L Snow JL et al.Transbronchial biopsy in usual interstitial pneumonia.Chest. 2006; 129: 1126-1131Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar note, the real issue is not whether these criteria are accurate in patients with UIP established on surgical lung biopsy; but rather, do they work applied in a prospective and blinded fashion? To this we would add two crucial questions: Do these criteria apply to patients who do not have the expected clinical and radiologic picture of IPF, because this is the setting in which a biopsy is of most importance, and are the features proposed by expert pathologists with a tremendous experience in this area usable by pathologists in the general medical community? These issues are worth investigating. But until such studies are performed, we suggest that the collective wisdom be followed and that TBB not be used to diagnose IPF/UIP. Usual interstitial pneumonia (UIP), the underlying histology of idiopathic pulmonary fibrosis (IPF), has a poor prognosis (median survival, 3 years), and to date there is no impressively effective therapy. Therefore, at least for prognosis, and in some cases for early transplant referral, it is important to confirm this diagnosis. Expert radiologists and clinicians can accomplish this in approximately 50% of cases of UIP with a high degree of specificity.1Flaherty KR King TE Raghu G et al.Idiopathic interstitial pneumonia: what is the effect of a multi-disciplinary approach to diagnosis?.Am J Respir Crit Care Med. 2004; 170: 907-910Crossref Scopus (468) Google Scholar When typical radiologic features are present and tissue acquisition is deemed unnecessary, most clinicians feel that the disease is already advanced. However, there are a number of patients without typical radiologic findings, and also younger subjects, in whom a histologic diagnosis is often necessary. In addition, a number of treatment trials are in motion for IPF and a tissue diagnosis is required for inclusion in these trials. Which type of biopsy is suitable for the diagnosis of UIP? In this issue of CHEST (see page 1126), Berbescu et al2Berbescu EA Katzenstein A-L Snow JL et al.Transbronchial biopsy in usual interstitial pneumonia.Chest. 2006; 129: 1126-1131Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar reviewed 22 patients with known UIP (21 cases diagnosed by surgical biopsy, 1 case diagnosed by clinical and radiologic features) and then retrospectively examined transbronchial biopsies (TBBs) from these patients. They concluded that a diagnosis of UIP was possible on the TBB in seven subjects, and in two others that the findings were consistent with UIP. As a rationale for the use of TBB, Berbescu et al2Berbescu EA Katzenstein A-L Snow JL et al.Transbronchial biopsy in usual interstitial pneumonia.Chest. 2006; 129: 1126-1131Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar cite a report3Utz JP Ryu JH Douglas WW et al.High short-term mortality following lung biopsy for usual interstitial pneumonia.Eur Respir J. 2001; 17: 175-179Crossref PubMed Scopus (213) Google Scholar in which there was 17% mortality within 30 days following surgical lung biopsy for UIP. However, this has not been the experience of many interstitial lung disease centers across the world. In most studies, the morbidity and mortality from surgical lung biopsy is < 3%. Thus, we would not view potential complications as a major factor in deciding what type of lung biopsy to perform. The question of which kind of biopsy should be performed to diagnose UIP has a long and controversial history. Surgical lung biopsy is accepted as the “gold standard,” but the role, if any, of TBB is contentious. The concept that TBB is useful for UIP and other forms of diffuse interstitial pneumonias was first addressed by Anderson.4Anderson HA Transbronchoscopic lung biopsy for diffuse pulmonary diseases.Chest. 1978; 73: 734-736PubMed Google Scholar Of 939 TBBs, 39% were read as “chronic interstitial pneumonitis and fibrosis,” an observation that lead many to view TBB as a useful tool in this setting. Subsequent reports challenged this idea. The most comprehensive is that of Wall et al,5Wall CP Gaensler EA Carrington CB et al.Comparison of transbronchial and open biopsies in chronic infiltrative lung diseases.Am Rev Respir Dis. 1981; 123: 280-285PubMed Google Scholar who compared TBB to open biopsy in the same patients with the TBB and open biopsies read, blinded, by an experienced pulmonary pathologist, the late Charles B. Carrington. Wall et al5Wall CP Gaensler EA Carrington CB et al.Comparison of transbronchial and open biopsies in chronic infiltrative lung diseases.Am Rev Respir Dis. 1981; 123: 280-285PubMed Google Scholar found that TBB findings read as normal or showing only a nonspecific pattern of interstitial inflammation and fibrosis missed cases of idiopathic interstitial pneumonias (mostly UIP) with a high frequency; conversely, TBB findings read as showing an idiopathic interstitial pneumonia were wrong in the vast majority of cases. Other reports, for example that of Wilson et al,6Wilson RK Fechner RE Greenberg SD et al.Clinical implications of a “nonspecific” transbronchial biopsy.Am J Med. 1978; 65: 252-256Abstract Full Text PDF PubMed Scopus (26) Google Scholar demonstrated that the morphologic findings of interstitial inflammation and fibrosis in TBB appeared to have little relevance to subsequent clinical course (for more detail see Chung7Churg A Transbronchial biopsy: nothing to fear.Am J Surg Pathol. 2001; 25: 820-822Crossref PubMed Scopus (21) Google Scholar). Studies of this sort lead to a quiet campaign to discourage pulmonologists from relying on TBB to confirm the diagnosis of UIP as well as other forms of idiopathic interstitial pneumonias, a campaign that culminated in recent consensus statements from the American Thoracic Society/European Respiratory Society, which explicitly state that TBB has no role in the diagnosis of UIP.8American Thoracic Society/European Respiratory Society. Idiopathic pulmonary fibrosis: diagnosis and treatment: international consensus statement.Am J Respir Crit Care Med. 2000; 161: 646-664Crossref PubMed Scopus (978) Google Scholar, 9American Thoracic Society/European Respiratory Society. International multidisciplinary consensus classification of the idiopathic interstitial pneumonias.Am J Respir Crit Care Med. 2002; 165: 277-304Crossref PubMed Scopus (3342) Google Scholar Does the report of Berbescu et al2Berbescu EA Katzenstein A-L Snow JL et al.Transbronchial biopsy in usual interstitial pneumonia.Chest. 2006; 129: 1126-1131Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar overturn the current collective wisdom? To a pathologist, UIP is a diagnosis based to a great extent on low-power architecture because the individual features of UIP are not necessarily specific; rather, it is the repetitive combination of patchwork fibrosis, fibroblast foci, and microscopic honeycombing interspersed with unaffected lung and arranged in a peripheral and often perilobular distribution that leads to the diagnosis. TBB does not allow assessment of the distribution of fibrosis within the lobe and lobule, nor does it allow one to determine whether the process is diffuse. For these reasons, Berbescu et al2Berbescu EA Katzenstein A-L Snow JL et al.Transbronchial biopsy in usual interstitial pneumonia.Chest. 2006; 129: 1126-1131Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar used the combination of patchwork fibrosis, fibroblast foci, and microscopic honeycombing as criteria they considered diagnostic of UIP, and some of their illustrations do show fields that could be UIP. But as the authors acknowledge, none of these findings individually has diagnostic specificity, and even this combination could be the result of a variety of processes, including drug reactions, chronic hypersensitivity pneumonitis, connective tissue diseases, or asbestosis. Pathologically, one could also argue that the combination of only patchwork fibrosis and honeycombing (one of Berbescu's acceptable combinations for diagnosing UIP) in a small specimen has much lower specificity, and it is now recognized that fibroblast foci, often but not exclusively found in areas of dense fibrosis, occur in other interstitial lung diseases. As a further complication, cases of unequivocal UIP can have focal areas that look like nonspecific interstitial pneumonia10Katzenstein AL Zisman DA Litzky LA et al.Usual interstitial pneumonia: histologic study of biopsy and explant specimens.Am J Surg Pathol. 2002; 26: 1567-1577Crossref PubMed Scopus (180) Google Scholar; this problem is readily addressed in surgical lung biopsies but likely to cause tremendous confusion in TBB. The strength of the report by Berbescu et al2Berbescu EA Katzenstein A-L Snow JL et al.Transbronchial biopsy in usual interstitial pneumonia.Chest. 2006; 129: 1126-1131Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar is that they do provide detailed pathologic descriptions of what UIP might look like in TBBs, descriptions that are virtually nonexistent in the literature, and thus they offer a set of criteria that can be tested. As the authors2Berbescu EA Katzenstein A-L Snow JL et al.Transbronchial biopsy in usual interstitial pneumonia.Chest. 2006; 129: 1126-1131Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar note, the real issue is not whether these criteria are accurate in patients with UIP established on surgical lung biopsy; but rather, do they work applied in a prospective and blinded fashion? To this we would add two crucial questions: Do these criteria apply to patients who do not have the expected clinical and radiologic picture of IPF, because this is the setting in which a biopsy is of most importance, and are the features proposed by expert pathologists with a tremendous experience in this area usable by pathologists in the general medical community? These issues are worth investigating. But until such studies are performed, we suggest that the collective wisdom be followed and that TBB not be used to diagnose IPF/UIP.