Idiopathic Interstitial Lung Disease

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1 KATHOLIEKE UNIVERSITEIT LEUVEN Faculty of Medicine Idiopathic Interstitial Lung Disease JA Verschakelen, W De Wever Department of Radiology, University Hospitals Leuven, Belgium

2 Goals... To clarify the current classification and terminology of the IIPs To highlight the clinical, pathological and imaging characteristics To review the radiological differential diagnoses

3 Idiopathic interstitial pneumonias... are non neoplastic disorders damage the lung parenchyma by inflammation and fibrosis do effect the interstitium primary

4 Idiopathic Interstitial Pneumonias Diffuse Parenchymal Lung Disease Idiopathic interstitial pneumonias

5 Diffuse Parenchymal Lung Disease DPLD of known cause e.g. drugs Granulomatous DPLD e.g. sarcoidosis Other forms of DPLD e.g. LAM, histiocytosis X Idiopathic interstitial pneumonias

6 Diffuse Parenchymal Lung Disease DPLD of known cause e.g. drugs Granulomatous DPLD e.g. sarcoidosis Other forms of DPLD e.g. LAM, histiocytosis X Idiopathic interstitial pneumonias American Thoracic Society / European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias (2002)

7 Diffuse Parenchymal Lung Disease DPLD of known cause e.g. drugs Granulomatous DPLD e.g. sarcoidosis Other forms of DPLD e.g. LAM, histiocytosis X Idiopathic interstitial pneumonias American Thoracic Society / European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias (2002)

8 American Thoracic Society / European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias (2002) Histologic Pattern Clinical Diagnosis UIP Idiopathic pulmonary fibrosis NSIP NSIP DIP DIP Respiratory bronchiolitis RB-ILD Organizing pneumonia COP Diffuse alveolar damage AIP LIP LIP

9 Essentials Each histologic pattern is associated with a characteristic imaging pattern although this pattern may be variable in practice. The differential diagnosis of IIP always includes underlying collagen vascular disease and inhalation exposures. The role of the radiologist is to identify the macroscopic morphologic pattern and to work with the clinician and pathologist to generate an integrated clinical diagnosis.

10 Idiopathic Interstitial Pneumonias 1. idiopathic pulmonary fibrosis (IPF) 2. nonspecific interstitial pneumonia (NSIP) 3. cryptogenic organizing pneumonia (COP) 4. acute interstitial pneumonia (AIP) 5. respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) 6. desquamative interstitial pneumonia (DIP) 7. lymphoid interstitial pneumonia (LIP)

11 1. Idiopathic Pulmonary Fibrosis (IPF) Clinical-pathological features IPF: clinical syndrome associated with the histological pattern of UIP

12 1. Idiopathic Pulmonary Fibrosis (IPF) Clinical-pathological features IPF: clinical syndrome associated with the histological pattern of UIP

13 1. Idiopathic Pulmonary Fibrosis (IPF) Clinical-pathological features IPF: clinical syndrome associated with the histological pattern of UIP Histologic examination: temporal and spatially heterogeneity

14 1. Idiopathic Pulmonary Fibrosis (IPF) Clinical-pathological features IPF: clinical syndrome associated with the histological pattern of UIP Histologic examination: temporal and spatially heterogeneity

15 1. Idiopathic Pulmonary Fibrosis (IPF) Clinical-pathological features IPF: clinical syndrome associated with the histological pattern of UIP Histologic examination: temporal and spatially heterogeneity > 50 years progressive shortness of breath and nonproductive cough (>6 m) poor prognosis (3.5-year mean length of survival) IPF does not usually respond to steroid treatment candidate for LTX

16 Imaging features The extent of honeycombing of honeycombing is the most useful finding when differentiating UIP from NSIP (*) (*) Radiology 2006; 241:

17 Imaging features mid and lower subpleural zones Reticular opacities Traction bronchiolectasis Ground-glass opacity (-) Images: Radiographics 2007;27:

18 Establishing a diagnosis of IPF : Differential diagnosis of the UIP pattern Collagen vascular d. Chronic EAA Asbestosis IPF The positive predictive value of UIP with HRCT is about 90%. CT- diagnosis of UIP is difficult to make in patients who do not show all the typical features, particularly honeycombing Ground-glass opacity commonly progress to fibrosis with honeycombing Complications: 1. opportunistic infections 2. lung cancer 3. acute exacerbation

19 Idiopathic Interstitial Pneumonias 1. idiopathic pulmonary fibrosis (IPF) 2. nonspecific interstitial pneumonia (NSIP) 3. cryptogenic organizing pneumonia (COP) 4. acute interstitial pneumonia (AIP) 5. respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) 6. desquamative interstitial pneumonia (DIP) 7. lymphoid interstitial pneumonia (LIP)

20 2. Nonspecific Interstitial Pneumonia (NSIP) Clinical-pathological features NSIP: Wastepaper basket of unclassified cases (1994) Clinical features: similar to those of UIP except - female (+) - younger mean age

21 2. Nonspecific Interstitial Pneumonia (NSIP) Clinical-pathological features NSIP: Wastepaper basket of unclassified cases (1994) Histologic examination: interstitial inflammation and/or fibrosis ( homogeneity pattern ) Clinical features: similar to those of UIP except - female (+) - younger mean age Type-1 NSIP Inflammation +++ Fibrosis - Cellular NSIP Type-2 NSIP Inflammation + Fibrosis + Type-3 NSIP Inflammation - Fibrosis +++ Fibrotic NSIP

22 2. Nonspecific Interstitial Pneumonia (NSIP) Clinical-pathological features NSIP: Wastepaper basket of unclassified cases (1994) Histologic examination: interstitial inflammation and/or fibrosis ( homogeneity pattern ) Clinical features: similar to those of UIP except - female (+) - younger mean age Type-1 NSIP Inflammation +++ Fibrosis - Cellular NSIP Type-2 NSIP Inflammation + Fibrosis + Type-3 NSIP Inflammation - Fibrosis +++ Fibrotic NSIP Prognosis: more favorable than UIP Radiology 2005; 236:10-21

23 Imaging features Peribronchovascular and/or subpleural No gradient No typical UIP-pattern... More ground-glass attenuation Finer reticular pattern Radiology 2001; 221:

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26 macrocystic microcystic

27 Establishing a diagnosis of NSIP... Clinical conditions commonly associated with NSIP pattern...» collagen-vascular disease» hypersensitivity pneumonitis» drug-induced lung disease» If no detectable cause idiopathic NSIP The parenchymal abnormalities of NSIP may be reversible 1/2005 6/2005

28 Idiopathic Interstitial Pneumonias 1. idiopathic pulmonary fibrosis (IPF) 2. nonspecific interstitial pneumonia (NSIP) 3. cryptogenic organizing pneumonia (COP) 4. acute interstitial pneumonia (AIP) 5. respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) 6. desquamative interstitial pneumonia (DIP) 7. lymphoid interstitial pneumonia (LIP)

29 3. Cryptogenic organizing pneumonia (COP) Clinical-pathological features COP is a clinical syndrome associated with the histological pattern of organizing pneumonia

30 3. Cryptogenic organizing pneumonia (COP) Clinical-pathological features Histologically: Patchy areas of consolidation characterized by polypoid plugs of loose organizing connective tissue ( young granulation tissue ) with or without endobronchiolar intraluminal polyps COP is not primarily interstitial» idiopathic nature» overlap of appearance with other forms of IIP (cfr. Histol. features of septal infiltration) Clinical presentation: cough, dyspnea and no response to antibiotics R/ corticosteroids

31 Imaging features: (1) Classical Consolidation Centrilobular nodules Ground-glass opacities (+++) Lower zones Peripherally Peribronchovascular linear pattern large masses (+)

32 Imaging features: (2) Variants Focal lesion Multiple focal mass-like lesions Eur.Radiol (2002) 12: Organizing Pneumonia: the many morfological faces

33 Linear and band-like pattern Perilobular pattern Eur.Radiol (2002) 12: Organizing Pneumonia: the many morfological faces

34 15 months Eur.Radiol (2002) 12: Organizing Pneumonia: the many morfological faces

35 Establishing a diagnosis of COP... Differential diagnosis of COP organizing pneumonia (OP) pattern secondary to a known cause: RA, viral pneumonia, drug reaction,... If idiopathic: COP! Bronchoalveolar carcinoma Lymphoma Sarcoidosis Chronic eosinophilic pneumonia Infection (septic emboli) Clinical evaluation BAL Transbronchial biopsy

36 Idiopathic Interstitial Pneumonias 1. idiopathic pulmonary fibrosis (IPF) 2. nonspecific interstitial pneumonia (NSIP) 3. cryptogenic organizing pneumonia (COP) 4. acute interstitial pneumonia (AIP) 5. respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) 6. desquamative interstitial pneumonia (DIP) 7. lymphoid interstitial pneumonia (LIP)

37 4. Acute interstitial pneumonia (AIP) Clinical-pathological features AIP is a clinical syndrome associated with the histological pattern of diffuse alveolar damage

38 4. Acute interstitial pneumonia (AIP) Clinical-pathological features AIP can be regarded as an idiopathic form of ARDS (Synonyms: Hamman-Rich syndrome, traumatic wet lung, non-cardiogenic pulmonary edema) Clinical features: severe, progressive dyspnea Respiratory failure with mechanical ventilation

39 Pathological features and evolution Exudative phase - hyaline membrane formation (< proteinaceous exudate in airspaces) - interstitial edema Chronic fibrotic phase (cfr. classification of the disease as interstitial fibrosis) Prognosis: complete resolution fibrotic pulmonary damage

40 Imaging features: (1) exudative phase Day 1 Day 7 Patchy ( geographic appearance ) Dependent areas Ground-glass attenuation Consolidation

41 Imaging features: (1) exudative phase Patchy ( geographic appearance ) Dependent areas Ground-glass attenuation Consolidation

42 Imaging features: (2) fibrotic phase Nondependent areas +++ Architectural distortion Traction bronchiectasis Honeycombing

43 Establishing a diagnosis of AIP... Radiologic differential diagnosis of AIP depends on the stage: acute chronic ARDS of a known cause Infection (PCP) Hydrostatic edema Pulmonary hemorrhage Acute hypersensitivity pneumonitis Diagnosis of AIP requires integration of biopsy results with clinical, laboratory and microbiologic findings

44 Idiopathic Interstitial Pneumonias 1. idiopathic pulmonary fibrosis (IPF) 2. nonspecific interstitial pneumonia (NSIP) 3. cryptogenic organizing pneumonia (COP) 4. acute interstitial pneumonia (AIP) 5. respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) 6. desquamative interstitial pneumonia (DIP) 7. lymphoid interstitial pneumonia (LIP)

45 Continuum of Smoking-related Lung Diseases Symptoms Microscopic features Ground-glass opacification Centrilobular nodules RB* uncommon bronchiolocentric small patches mild RB-ILD severe macrophages extend into peribronchiolar region DIP severe diffuse intraalveolar macrophages mild extensive extensive uncommon * respiratory bronchiolitis

46 Continuum of Smoking-related Lung Diseases Symptoms Microscopic features Ground-glass opacification Centrilobular nodules RB* uncommon bronchiolocentric small patches mild RB-ILD severe macrophages extend into peribronchiolar region DIP severe diffuse intraalveolar macrophages mild extensive extensive uncommon * respiratory bronchiolitis

47 Continuum of Smoking-related Lung Diseases Symptoms Microscopic features Ground-glass opacification Centrilobular nodules RB* uncommon bronchiolocentric small patches mild RB-ILD severe macrophages extend into peribronchiolar region DIP severe diffuse intraalveolar macrophages mild extensive extensive uncommon * respiratory bronchiolitis

48 Continuum of Smoking-related Lung Diseases Symptoms Microscopic features Ground-glass opacification Centrilobular nodules RB* uncommon bronchiolocentric small patches mild RB-ILD severe macrophages extend into peribronchiolar region DIP severe diffuse intraalveolar macrophages mild extensive extensive uncommon * respiratory bronchiolitis

49 5. Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) Clinical-pathological features Heavy smoker ( >30 pack-years ) Histological feature: pigmented intraluminal macrophages within the first-and second-order respiratory bronchiolus normal macrophage accumulation

50 Imaging features upper lobes diffuse centrilobular nodules ground-glass attenuation

51 6. Desquamative interstitial pneumonia (DIP) Clinical-pathological features DIP: cfr. desquamated alveolar cells (historical) Alveolar macrophage pneumonia (no consensus) Symptoms Pathologic features Ground-glass opacification Centrilobular nodules RB uncommon bronchiolocentric small patches mild RB-ILD severe macrophages extend into peribronchiolar region DIP severe diffuse intraalveolar macrophages mild extensive extensive uncommon

52 Imaging features Lower zone Peripheral Ground-glass opacification +++ Reticular pattern +

53 Establishing a diagnosis of RB-ILD or DIP... smoking Localization (predominance) Groundglass opacification Centrilobular nodules RB-ILD +++ upper lobes mild extensive DIP +++ lower lobes extensive uncommon EAA - no predelection centrilobular emphysema is NOT superimposed Differential diagnosis RB-ILD Hypersensitivity pneumonitis DIP

54 Idiopathic Interstitial Pneumonias 1. idiopathic pulmonary fibrosis (IPF) 2. nonspecific interstitial pneumonia (NSIP) 3. cryptogenic organizing pneumonia (COP) 4. acute interstitial pneumonia (AIP) 5. respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) 6. desquamative interstitial pneumonia (DIP) 7. lymphoid interstitial pneumonia (LIP)

55 7. Lymphoid interstitial pneumonia (LIP) Clinical-pathological features Patients: evidence of abnormal immune response Sjögren s disease AIDS idiopathic (rare) Routine histology: widespread interstitial lymphoid infiltration of the lung resembling low-grade lymphoma Clinical feature: cfr. underlying systemic disease

56 Imaging features Diffuse Perivascular Ground-glass opacity Lung cysts

57 Imaging features Diffuse Perivascular Ground-glass opacity Lung cysts

58 Establishing a diagnosis of IIP: key messages Characteristic HRCT findings can differentiate UIP and COP from other IIPs 2. IPF remains the commonest IIP and can be confidently diagnosed without biopsy in most cases 3. IPF is invariably fatal; there is no effective therapy 4. The standard treatment of COP is steroids: the response is impressive in most cases 5. When ground-glass opacification in the lower zones is present together with a no typical UIP-pattern, NSIP is the most likely cause

59 6. Cellular type 1 NSIP has a significant better prognosis when compared with fibrotic type 3 7. CT-features of RB, RB-ILD and DIP may represent a spectrum of small airway and parenchyma reaction to cigarette smoke 8. CT-features of AIP has a uniquely rapid onset similar to ARDS 9. An autoimmune disorder is likely in LIP 10. Clinical evaluation must prove that the interstitial pneumonia is idiopathic and exclude a recognizable cause (eg. collagen vascular disease, drug induced disease)

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