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CT-Histologic Correlation of the ATS/ERS 2002 Classification of Idiopathic Interstitial Pneumonias¹

¹ From the Departments of Radiology (C.W., T.C.M.) and Pathology (E.J.M.), Massachusetts General Hospital and Harvard Medical School, Founders Building 202, 55 Fruit St, Boston, MA 02114. Recipient of Certificate of Merit and Excellence in Design awards for an education exhibit at the 2002 RSNA scientific assembly. Received January 13, 2003; revision requested February 27 and received April 18; accepted April 21. Address correspondence to C.W. (e-mail: cwittram@partners.org).

View larger version (165K): [in a new window]   Figure 1a.  Idiopathic pulmonary fibrosis in a 47-year-old woman. (a) High-resolution CT scan demonstrates ground-glass attenuation in a peripheral distribution. There is interlobular septal thickening, irregularity of the fissures (arrowheads) and bronchiectasis (arrows) consistent with early usual interstitial pneumonia. (b) High-resolution CT scan acquired 22 months later shows progression of usual interstitial pneumonia, manifested as diffuse ground-glass attenuation, interlobular septal thickening (arrows), and a honeycomb pattern (arrowhead). (c) Photomicrograph (original magnification, x12.5; hematoxylin-eosin stain) reveals cystically dilated air spaces that constitute a honeycomb pattern (a) within dense fibrosis (b) beneath the pleura (c). Scar obliterates normal alveolar architecture. d = fibroblastic foci, e = smooth muscle hyperplasia. (d) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows active fibroblastic foci of myxoid connective tissue (d), which form nodules projecting into alveolar-sized air space. Pneumocytes are hyperplastic.

View larger version (136K): [in a new window]   Figure 1b.  Idiopathic pulmonary fibrosis in a 47-year-old woman. (a) High-resolution CT scan demonstrates ground-glass attenuation in a peripheral distribution. There is interlobular septal thickening, irregularity of the fissures (arrowheads) and bronchiectasis (arrows) consistent with early usual interstitial pneumonia. (b) High-resolution CT scan acquired 22 months later shows progression of usual interstitial pneumonia, manifested as diffuse ground-glass attenuation, interlobular septal thickening (arrows), and a honeycomb pattern (arrowhead). (c) Photomicrograph (original magnification, x12.5; hematoxylin-eosin stain) reveals cystically dilated air spaces that constitute a honeycomb pattern (a) within dense fibrosis (b) beneath the pleura (c). Scar obliterates normal alveolar architecture. d = fibroblastic foci, e = smooth muscle hyperplasia. (d) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows active fibroblastic foci of myxoid connective tissue (d), which form nodules projecting into alveolar-sized air space. Pneumocytes are hyperplastic.

View larger version (171K): [in a new window]   Figure 1c.  Idiopathic pulmonary fibrosis in a 47-year-old woman. (a) High-resolution CT scan demonstrates ground-glass attenuation in a peripheral distribution. There is interlobular septal thickening, irregularity of the fissures (arrowheads) and bronchiectasis (arrows) consistent with early usual interstitial pneumonia. (b) High-resolution CT scan acquired 22 months later shows progression of usual interstitial pneumonia, manifested as diffuse ground-glass attenuation, interlobular septal thickening (arrows), and a honeycomb pattern (arrowhead). (c) Photomicrograph (original magnification, x12.5; hematoxylin-eosin stain) reveals cystically dilated air spaces that constitute a honeycomb pattern (a) within dense fibrosis (b) beneath the pleura (c). Scar obliterates normal alveolar architecture. d = fibroblastic foci, e = smooth muscle hyperplasia. (d) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows active fibroblastic foci of myxoid connective tissue (d), which form nodules projecting into alveolar-sized air space. Pneumocytes are hyperplastic.

View larger version (209K): [in a new window]   Figure 1d.  Idiopathic pulmonary fibrosis in a 47-year-old woman. (a) High-resolution CT scan demonstrates ground-glass attenuation in a peripheral distribution. There is interlobular septal thickening, irregularity of the fissures (arrowheads) and bronchiectasis (arrows) consistent with early usual interstitial pneumonia. (b) High-resolution CT scan acquired 22 months later shows progression of usual interstitial pneumonia, manifested as diffuse ground-glass attenuation, interlobular septal thickening (arrows), and a honeycomb pattern (arrowhead). (c) Photomicrograph (original magnification, x12.5; hematoxylin-eosin stain) reveals cystically dilated air spaces that constitute a honeycomb pattern (a) within dense fibrosis (b) beneath the pleura (c). Scar obliterates normal alveolar architecture. d = fibroblastic foci, e = smooth muscle hyperplasia. (d) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows active fibroblastic foci of myxoid connective tissue (d), which form nodules projecting into alveolar-sized air space. Pneumocytes are hyperplastic.

View larger version (174K): [in a new window]   Figure 2a.  Nonspecific interstitial pneumonia in a 74-year-old woman. (a) High-resolution CT scan demonstrates bilateral, subpleural ground-glass attenuation. There are irregular linear areas of high attenuation (arrowhead) and evidence of architectural lung distortion with distortion of the left fissure (arrow). Follow-up CT in 7 months demonstrated no interval change. (b) Photomicrograph (original magnification, x12.5; hematoxylin-eosin stain) reveals alveolar architecture that is altered by interstitial fibrosis (a), all of which is approximately the same age. (c) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows alveolar walls that are thickened by chronic inflammation (b) and fibrillar collagen (c).

View larger version (184K): [in a new window]   Figure 2b.  Nonspecific interstitial pneumonia in a 74-year-old woman. (a) High-resolution CT scan demonstrates bilateral, subpleural ground-glass attenuation. There are irregular linear areas of high attenuation (arrowhead) and evidence of architectural lung distortion with distortion of the left fissure (arrow). Follow-up CT in 7 months demonstrated no interval change. (b) Photomicrograph (original magnification, x12.5; hematoxylin-eosin stain) reveals alveolar architecture that is altered by interstitial fibrosis (a), all of which is approximately the same age. (c) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows alveolar walls that are thickened by chronic inflammation (b) and fibrillar collagen (c).

View larger version (213K): [in a new window]   Figure 2c.  Nonspecific interstitial pneumonia in a 74-year-old woman. (a) High-resolution CT scan demonstrates bilateral, subpleural ground-glass attenuation. There are irregular linear areas of high attenuation (arrowhead) and evidence of architectural lung distortion with distortion of the left fissure (arrow). Follow-up CT in 7 months demonstrated no interval change. (b) Photomicrograph (original magnification, x12.5; hematoxylin-eosin stain) reveals alveolar architecture that is altered by interstitial fibrosis (a), all of which is approximately the same age. (c) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows alveolar walls that are thickened by chronic inflammation (b) and fibrillar collagen (c).

View larger version (135K): [in a new window]   Figure 3a.  Lymphoid interstitial pneumonia in a 51-year-old woman. (a) Prone high-resolution CT scan obtained through the carina demonstrates peripheral ground-glass attenuation and interlobular septal thickening (arrows). (b) Prone high-resolution CT scan obtained through the lung bases shows bilateral subpleural ground-glass (black arrows) and denser nodular attenuation. There is a minor degree of nodular interlobular septal thickening (white arrow). (c) Photomicrograph (original magnification, x25; hematoxylin-eosin stain) shows alveolar septa that are widened by a lymphoid infiltrate (a). No scarring is present. (d) Photomicrograph (original magnification, x100; hematoxylin-eosin stain) demonstrates interstitial infiltrate that consists of mature lymphocytes (b), plasma cells (c), and macrophages (d). Epithelium lining of the bronchiole (e) is unremarkable.

View larger version (92K): [in a new window]   Figure 3b.  Lymphoid interstitial pneumonia in a 51-year-old woman. (a) Prone high-resolution CT scan obtained through the carina demonstrates peripheral ground-glass attenuation and interlobular septal thickening (arrows). (b) Prone high-resolution CT scan obtained through the lung bases shows bilateral subpleural ground-glass (black arrows) and denser nodular attenuation. There is a minor degree of nodular interlobular septal thickening (white arrow). (c) Photomicrograph (original magnification, x25; hematoxylin-eosin stain) shows alveolar septa that are widened by a lymphoid infiltrate (a). No scarring is present. (d) Photomicrograph (original magnification, x100; hematoxylin-eosin stain) demonstrates interstitial infiltrate that consists of mature lymphocytes (b), plasma cells (c), and macrophages (d). Epithelium lining of the bronchiole (e) is unremarkable.

View larger version (161K): [in a new window]   Figure 3c.  Lymphoid interstitial pneumonia in a 51-year-old woman. (a) Prone high-resolution CT scan obtained through the carina demonstrates peripheral ground-glass attenuation and interlobular septal thickening (arrows). (b) Prone high-resolution CT scan obtained through the lung bases shows bilateral subpleural ground-glass (black arrows) and denser nodular attenuation. There is a minor degree of nodular interlobular septal thickening (white arrow). (c) Photomicrograph (original magnification, x25; hematoxylin-eosin stain) shows alveolar septa that are widened by a lymphoid infiltrate (a). No scarring is present. (d) Photomicrograph (original magnification, x100; hematoxylin-eosin stain) demonstrates interstitial infiltrate that consists of mature lymphocytes (b), plasma cells (c), and macrophages (d). Epithelium lining of the bronchiole (e) is unremarkable.

View larger version (188K): [in a new window]   Figure 3d.  Lymphoid interstitial pneumonia in a 51-year-old woman. (a) Prone high-resolution CT scan obtained through the carina demonstrates peripheral ground-glass attenuation and interlobular septal thickening (arrows). (b) Prone high-resolution CT scan obtained through the lung bases shows bilateral subpleural ground-glass (black arrows) and denser nodular attenuation. There is a minor degree of nodular interlobular septal thickening (white arrow). (c) Photomicrograph (original magnification, x25; hematoxylin-eosin stain) shows alveolar septa that are widened by a lymphoid infiltrate (a). No scarring is present. (d) Photomicrograph (original magnification, x100; hematoxylin-eosin stain) demonstrates interstitial infiltrate that consists of mature lymphocytes (b), plasma cells (c), and macrophages (d). Epithelium lining of the bronchiole (e) is unremarkable.

View larger version (152K): [in a new window]   Figure 4a.  Respiratory bronchiolitis-associated interstitial lung disease in a 30-year-old woman. (a) High-resolution CT scan of the upper lobe demonstrates centrilobular ground-glass attenuation (arrows). (b) Photomicrograph (original magnification, x40; hematoxylin-eosin stain) shows a terminal bronchiole filled with pigmented macrophages (a). (c) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows the "tobacco pigment" in macrophages (a) within alveolar ducts and alveoli. Collagenous scarring involves interstitium between alveoli. b = mild bronchiolar fibrosis, c = chronic inflammation.

View larger version (191K): [in a new window]   Figure 4b.  Respiratory bronchiolitis-associated interstitial lung disease in a 30-year-old woman. (a) High-resolution CT scan of the upper lobe demonstrates centrilobular ground-glass attenuation (arrows). (b) Photomicrograph (original magnification, x40; hematoxylin-eosin stain) shows a terminal bronchiole filled with pigmented macrophages (a). (c) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows the "tobacco pigment" in macrophages (a) within alveolar ducts and alveoli. Collagenous scarring involves interstitium between alveoli. b = mild bronchiolar fibrosis, c = chronic inflammation.

View larger version (190K): [in a new window]   Figure 4c.  Respiratory bronchiolitis-associated interstitial lung disease in a 30-year-old woman. (a) High-resolution CT scan of the upper lobe demonstrates centrilobular ground-glass attenuation (arrows). (b) Photomicrograph (original magnification, x40; hematoxylin-eosin stain) shows a terminal bronchiole filled with pigmented macrophages (a). (c) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows the "tobacco pigment" in macrophages (a) within alveolar ducts and alveoli. Collagenous scarring involves interstitium between alveoli. b = mild bronchiolar fibrosis, c = chronic inflammation.

View larger version (114K): [in a new window]   Figure 5a.  Desquamative interstitial pneumonia in a 42-year-old man. (a) High-resolution CT scan of the upper lobes demonstrates diffuse ground-glass attenuation, a minor degree of interlobular septal thickening (arrow), and paraseptal emphysema. (b) High-resolution CT scan demonstrates a mosaic pattern of lung attenuation; the abnormal regions are manifested as ground-glass attenuation (arrows). (c) Photomicrograph (original magnification, x12.5; hematoxylin-eosin stain) shows purple macrophages (a) filling the air spaces, interstitial fibrosis (b), and lymphoid aggregates (c). (d) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) reveals an alveolar duct that is filled and distended by pigmented macrophages with purple cytoplasm. Occasional eosinophils (d) and neutrophils are present amidst the macrophages. Interstitial fibrosis is present.

View larger version (134K): [in a new window]   Figure 5b.  Desquamative interstitial pneumonia in a 42-year-old man. (a) High-resolution CT scan of the upper lobes demonstrates diffuse ground-glass attenuation, a minor degree of interlobular septal thickening (arrow), and paraseptal emphysema. (b) High-resolution CT scan demonstrates a mosaic pattern of lung attenuation; the abnormal regions are manifested as ground-glass attenuation (arrows). (c) Photomicrograph (original magnification, x12.5; hematoxylin-eosin stain) shows purple macrophages (a) filling the air spaces, interstitial fibrosis (b), and lymphoid aggregates (c). (d) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) reveals an alveolar duct that is filled and distended by pigmented macrophages with purple cytoplasm. Occasional eosinophils (d) and neutrophils are present amidst the macrophages. Interstitial fibrosis is present.

View larger version (185K): [in a new window]   Figure 5c.  Desquamative interstitial pneumonia in a 42-year-old man. (a) High-resolution CT scan of the upper lobes demonstrates diffuse ground-glass attenuation, a minor degree of interlobular septal thickening (arrow), and paraseptal emphysema. (b) High-resolution CT scan demonstrates a mosaic pattern of lung attenuation; the abnormal regions are manifested as ground-glass attenuation (arrows). (c) Photomicrograph (original magnification, x12.5; hematoxylin-eosin stain) shows purple macrophages (a) filling the air spaces, interstitial fibrosis (b), and lymphoid aggregates (c). (d) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) reveals an alveolar duct that is filled and distended by pigmented macrophages with purple cytoplasm. Occasional eosinophils (d) and neutrophils are present amidst the macrophages. Interstitial fibrosis is present.

View larger version (182K): [in a new window]   Figure 5d.  Desquamative interstitial pneumonia in a 42-year-old man. (a) High-resolution CT scan of the upper lobes demonstrates diffuse ground-glass attenuation, a minor degree of interlobular septal thickening (arrow), and paraseptal emphysema. (b) High-resolution CT scan demonstrates a mosaic pattern of lung attenuation; the abnormal regions are manifested as ground-glass attenuation (arrows). (c) Photomicrograph (original magnification, x12.5; hematoxylin-eosin stain) shows purple macrophages (a) filling the air spaces, interstitial fibrosis (b), and lymphoid aggregates (c). (d) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) reveals an alveolar duct that is filled and distended by pigmented macrophages with purple cytoplasm. Occasional eosinophils (d) and neutrophils are present amidst the macrophages. Interstitial fibrosis is present.

View larger version (127K): [in a new window]   Figure 6a.  Late-phase cryptogenic organizing pneumonia in an 81-year-old woman. (a) High-resolution CT scan of the upper lobes shows peripheral consolidation (arrow). (b) High-resolution CT scan obtained at the level of the bronchus intermedius demonstrates bilateral peribronchovascular ground-glass attenuation (arrows) and left-sided subpleural consolidation. (c) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows a branching tuft of myxoid fibrous tissue (black lines) filling an alveolar duct. a = alveoli, b = interstitial fibrosis.

View larger version (181K): [in a new window]   Figure 6b.  Late-phase cryptogenic organizing pneumonia in an 81-year-old woman. (a) High-resolution CT scan of the upper lobes shows peripheral consolidation (arrow). (b) High-resolution CT scan obtained at the level of the bronchus intermedius demonstrates bilateral peribronchovascular ground-glass attenuation (arrows) and left-sided subpleural consolidation. (c) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows a branching tuft of myxoid fibrous tissue (black lines) filling an alveolar duct. a = alveoli, b = interstitial fibrosis.

View larger version (197K): [in a new window]   Figure 6c.  Late-phase cryptogenic organizing pneumonia in an 81-year-old woman. (a) High-resolution CT scan of the upper lobes shows peripheral consolidation (arrow). (b) High-resolution CT scan obtained at the level of the bronchus intermedius demonstrates bilateral peribronchovascular ground-glass attenuation (arrows) and left-sided subpleural consolidation. (c) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows a branching tuft of myxoid fibrous tissue (black lines) filling an alveolar duct. a = alveoli, b = interstitial fibrosis.

View larger version (184K): [in a new window]   Figure 7.  Early-phase cryptogenic organizing pneumonia in a 51-year-old woman. Photomicrograph (original magnification, x25; hematoxylin-eosin stain) shows a localized lesion centering on a bronchiole (a) with involvement of alveolar ducts (b) and alveoli (c). d = mild interstitial chronic inflammation.

View larger version (166K): [in a new window]   Figure 8a.  Exudative phase of acute interstitial pneumonia in a 31-year-old woman. (a, b) High-resolution CT scans demonstrate diffuse ground-glass attenuation and minor interlobular septal thickening (arrows). (c) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows hyaline membranes (a) lining the alveolar ducts. b = acute interstitial inflammation.

View larger version (178K): [in a new window]   Figure 8b.  Exudative phase of acute interstitial pneumonia in a 31-year-old woman. (a, b) High-resolution CT scans demonstrate diffuse ground-glass attenuation and minor interlobular septal thickening (arrows). (c) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows hyaline membranes (a) lining the alveolar ducts. b = acute interstitial inflammation.

View larger version (194K): [in a new window]   Figure 8c.  Exudative phase of acute interstitial pneumonia in a 31-year-old woman. (a, b) High-resolution CT scans demonstrate diffuse ground-glass attenuation and minor interlobular septal thickening (arrows). (c) Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows hyaline membranes (a) lining the alveolar ducts. b = acute interstitial inflammation.

View larger version (169K): [in a new window]   Figure 9a.  Organizing phase of acute interstitial pneumonia in a 55-year-old man. (a) High-resolution CT scan demonstrates diffuse ground-glass attenuation, bronchiectasis, and bronchiolectasis (arrows). (b) High-resolution CT scan demonstrates diffuse ground-glass attenuation. A small amount of honeycomb lung affects the anterior part of the middle lobe (arrow). Small patches of consolidation affect the left lower lobe peripherally. (c) In the organizing phase, proliferative fibroblasts solidify the lung as they destroy alveolar architecture. Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows fibrin (a) filling a few residual alveoli (b). Pneumocytes are hyperplastic (c). d = alveolar septa.

View larger version (149K): [in a new window]   Figure 9b.  Organizing phase of acute interstitial pneumonia in a 55-year-old man. (a) High-resolution CT scan demonstrates diffuse ground-glass attenuation, bronchiectasis, and bronchiolectasis (arrows). (b) High-resolution CT scan demonstrates diffuse ground-glass attenuation. A small amount of honeycomb lung affects the anterior part of the middle lobe (arrow). Small patches of consolidation affect the left lower lobe peripherally. (c) In the organizing phase, proliferative fibroblasts solidify the lung as they destroy alveolar architecture. Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows fibrin (a) filling a few residual alveoli (b). Pneumocytes are hyperplastic (c). d = alveolar septa.

View larger version (226K): [in a new window]   Figure 9c.  Organizing phase of acute interstitial pneumonia in a 55-year-old man. (a) High-resolution CT scan demonstrates diffuse ground-glass attenuation, bronchiectasis, and bronchiolectasis (arrows). (b) High-resolution CT scan demonstrates diffuse ground-glass attenuation. A small amount of honeycomb lung affects the anterior part of the middle lobe (arrow). Small patches of consolidation affect the left lower lobe peripherally. (c) In the organizing phase, proliferative fibroblasts solidify the lung as they destroy alveolar architecture. Photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows fibrin (a) filling a few residual alveoli (b). Pneumocytes are hyperplastic (c). d = alveolar septa.