Idiopathic Interstitial Pneumonias Carlos H. Previgliano MD Associate Professor Radiology Louisiana State University – Shreveport

Idiopathic Interstitial Pneumonias • Idiopathic interstitial pneumonias are a group of diffuse parenchymal lung diseases • Also known as interstitial lung disease • Heterogeneous group of nonneoplastic disorders resulting from damage by varying patterns of inflammation and fibrosis • Interstitium primary site of injury • Airspaces, peripheral airways and vessels

History Previous Classifications of IIP Liebow and Carrington (1969)

Katzenstein (1995)

Müller and Colby (1997)

Usual interstitial pneumonia

Usual interstitial pneumonia

Usual interstitial pneumonia

Desquamative interstitial pneumonia

DIP/RB-ILD

Desquamative interstitial pneumonia

Bronchiolitis obliterans interstitial pneumonia and DAD

Lymphoid interstitial pneumonia Giant cell interstitial pneumonia

BOOP

Acute interstitial pneumonia

Acute interstitial pneumonia

Nonspecific interstitial pneumonia

Nonspecific interstitial pneumonia

Idiopathic Interstitial Pneumonias • In 2002 American Thoracic Society (ATS) and European Respiratory Society (ERS) published a new classification of IIPs • Defines clinical-radiologic-pathologic patterns • In their idiopathic form, IIPs rare diseases • Classification is based on histologic criteria that is associated with a characteristic CT pattern

Diffuse Parenchymal Lung Disease DPLD known cause e.g. drugs, collagen vascular disease

Idiopathic Interstitial Pneumonias

Granulomatous DPLD e.g. sarcoidosis

Other forms DPLD e.g. LAM, HX, etc

Diffuse Parenchymal Lung Disease DPLD known cause e.g. drugs, collagen vascular disease

Idiopathic Interstitial Pneumonias

Idiopathic Pulmonary Fibrosis

Granulomatous DPLD e.g. sarcoidosis

IIP other than IPF

Desquamative Interstitial Pneumonia

Respiratory Bronchiolitis Interstitial Lung Disease

Acute Interstitial Pneumonia

Cryptogenic Organizing Pneumonia

Nonspecific Interstitial Pneumonia

Lymphocytic Interstitial Pneumonia

Other forms DPLD e.g. LAM, HX, etc

Idiopathic Pulmonary Fibrosis • Distinct type chronic fibrosing interstitial pneumonia of unknown cause • Associated with histologic pattern of UIP • To diagnose IPF: – exclusion other cause (drugs, exposure, CVD) – abnormal radiographs and HRCT – abnormal pulmonary function studies (restriction)

• Definite diagnosis requires sx lung biopsy

Idiopathic Pulmonary Fibrosis Clinical • • • • • •

Onset of symptoms is gradually Dyspnea is most prominent symptom Nonproductive cough usual and paroxysmal Age: 50 yr and slightly more common males Digital clubbing and velcro crackles bibasilar In late stages there are right heart failure and peripheral edema • Survival: 2.5-3.5 yr

Idiopathic Pulmonary Fibrosis BAL • Excess of neutrophils and eosinophils • When eosinophils >20% → eosinophilic lung disease • Lymphocytosis above 15% should alert to an alternative diagnosis (NSIP, COP, sarcoid, hypersensitivity pneumonitis or other granulomatous disease)

Idiopathic Pulmonary Fibrosis Histology • Architectural destruction, fibrosis with honeycombing, fibroblastic foci (patchy) • Alternate normal and abnormal areas • Interstitial inflammation consists of alveolar septal infiltrate of lymphocytes, plasma cells and histiocytes • Fibrotic zones show temporal heterogeneity • Honeycomb areas show cysts filled w mucin

Idiopathic Pulmonary Fibrosis Radiologic Features • Chest x-ray may be normal • Commonest abnormality peripheral reticular opacity in lung bases and honeycombing • CT: – subpleural reticular opacities, honeycombing – traction bronchiectasis and GGO – bibasilar and peripheral – often patchy distribution – temporal heterogeneity

2008

2009

Trio of Signs Apicobasal gradient Subpleural reticular opacities Macrocystic honeycombing with traction bronchiectasis

Trio of Signs Apicobasal gradient Subpleural reticular opacities Macrocystic honeycombing with traction bronchiectasis

ATS/ERS Criteria for Diagnosis in Absence of Surgical Lung Biopsy

Am. J. Resp. Crit. Care Med. 2002;165:277-304

Idiopathic Pulmonary Fibrosis Differential Diagnosis • CT pattern of IPF can be indistinguishable from UIP due to asbestosis and collagen vascular disease • Hypersensitivity pneumonitis should be considered if micronodules are seen or there is sparing of lung bases • Sarcoidosis should be suspected if cysts are large or peribronchovascular nodules are present

Nonspecific Interstitial Pneumonia • Some pts with IID do not fit into any welldefined histologic patterns • Katzenstein & Fiorelli used this term in1994 • NSIP is divided into 2 subtypes: – cellular: interstitial inflammation – fibrosing: inflammation and fibrosis

Nonspecific Interstitial Pneumonia Clinical • • • • • • •

Better prognosis w almost complete recovery Age of onset 40 and 50 yr, M=F No association with smoking Duration symptoms 18-31 mo Breathlessness, cough, fatigue, weight loss Finger clubbing in 10%-35% Crackles initially basal, may be widespread

Nonspecific Interstitial Pneumonia BAL • Increase percentage of lymphocytes in about 50% of the cases • Increase neutrophils and eosinophils • Presence of lymphocytes strengthens the suspicion of NISP

Nonspecific Interstitial Pneumonia Histology • Histologic features do not fit the histologic pattern of UIP, OP, DAD, DIP, LIP • Varying degrees of alveolar inflammation or fibrosis • At cellular end there is mild/moderate interstitial chronic inflammation (L and PC) • At fibrosing end there is dense interstitial fibrosis and connective tissue is temporally homogeneous

Nonspecific Interstitial Pneumonia Radiologic Features • Plain: – bilateral pulmonary infiltrates lower lung zones – patchy parenchymal opacities – interstitial abnormalities

• CT: – GG bilateral, symmetrical, subpleural – reticular opacities with scattered micronodules – traction bronchiectasis – honeycombing and consolidation are infrequent

Nonspecific Interstitial Pneumonia Differential Diagnosis • • • •

Idiopathic interstitial fibrosis (IPF) Hypersensitivity pneumonitis Organizing pneumonia (OP) Desquamative interstitial pneumonia (DIP)

Cryptogenic Organizing Pneumonia • Described by Davison in 1983 • In 1985 Epler used the term BOOP • COP is preferred because conveys essential features and avoid confusion with BO (airway) • Features are organization within alveolar ducts and alveoli with or without organization within bronchioles • It is included in IIP because idiopathic nature

Cryptogenic Organizing Pneumonia Clinical • • • •

Equal sex distribution, mean age 55 y/o Nonsmokers outnumber smokers by 2:1 Illness of short duration (3 mo) Cough may be productive, dyspnea, sweats, chills, weight loss, fever • Crackles are localized or widespread • ↑ ESR, ↑ C reactive protein, neutrophilia • Patients recover on administration of steroids

Cryptogenic Organizing Pneumonia BAL • Increase lymphocytes up to 40% total cells • Increase neutrophils and eosinophils • If prominent increase of eosinophils should raise the consideration of eosinophilic pneumonia

Cryptogenic Organizing Pneumonia Histology • Organizing pneumonia involving alveolar ducts and alveoli with or without intrabronchial polyps • Majority of changes center on small airways • Associated interstitial inflammatory infiltrate and increase in alveolar macrophages • Relative preservation lung architecture

Cryptogenic Organizing Pneumonia Radiologic Features • Chest radiograph: – consolidation areas uni or bilateral, patchy – small nodular opacities 10%-50% – large nodular opacities (>1cm) 15% – normal lung volumes 75% – reduced lung volumes 25%

Cryptogenic Organizing Pneumonia Radiologic Features • CT: – airspace consolidation in 90% – subpleural or peribronchial in up to 50% – lower lung zones more frequent – GG attenuation 60% – multiple large nodules 15% – nodules irregular borders, air bronchogram – pleural effusion is rare

Cryptogenic Organizing Pneumonia Differential Diagnosis • Consolidation: alveolar cell Ca, lymphoma, sarcoidosis, infection, vasculitis • Subpleural consolidation: eosinophilic pneumonia • Multiple large masses: metastases, infection, lymphoma • Combination of GG and cysts should suggest either LIP or DIP

Acute Interstitial Pneumonia • • • •

Rapidly progressive Described as organizing form of DAD Indistinguishable from ARDS Also known as Hamman Rich

Acute Interstitial Pneumonia Clinical • No sex predominance, mean age 50 y/o • No association with smoking • Myalgias, arthralgias, fever, chills, malaise, dyspnea • Pulmonary function tests show restrictive pattern • Mortality rate 50% between 1 or 2 months of onset

Acute Interstitial Pneumonia BAL • • • •

Increased total cells Hemorrhage Neutrophils Occasionally lymphocytes

Acute Interstitial Pneumonia Histology • Exudative phase: edema, hyaline membrane, interstitial acute inflammation • Proliferative phase: type II pneumocyte hyperplasia • Organizing phase: loose organizing fibrosis within alveolar septa • May progress to end-stage fibrosis

Acute Interstitial Pneumonia Radiographic Features • Chest radiograph: – bilateral airspace opacification with air bronchograms – patchy with sparing costophrenic angles – as disease progresses lungs become more consolidated – volume near normal

Acute Interstitial Pneumonia Radiographic Features • CT: – GG attenuation, bronchial dilatation, architectural distorsion – in exudative phase GG bilateral, patchy, consolidation in dependent areas – in organizing phase distorsion bronchovascular bundles and traction bronchiectasis – cysts and lucent areas common in late stages of AIP

Acute Interstitial Pneumonia Differential Diagnosis • • • • • •

ARDS (asymmetric distribution) Infection (P jiroveci) Edema, hemorrhage Alveolar proteinosis Bronchioloalveolar cell carcinoma DIP

Respiratory Bronchiolitis-Associated Interstitial Lung Disease • Clinical manisfestation of ILD • Associated with pathologic lesion of respiratory bronchiolitis • RB is histopathologic lesion found in cigarette smokers characterized by intralumenal macrophages within respiratory bronchioles • Asymptomatic, rarely presents as ILD • Frequently associat centrilobular emphysema

Respiratory Bronchiolitis-Associated Interstitial Lung Disease Clinical • • • • •

Dyspnea, cough and hypoxemia 4th – 5th decades Smokers >30 pack-years M:F 2:1 Improve after cessation of smoking

Respiratory Bronchiolitis-Associated Interstitial Lung Disease BAL • Alveolar macrophages with golden, brown or black pigmented inclusion • Absence of these cells should alert to an alternative diagnosis • Modest increase in neutrophils may also be present

Respiratory Bronchiolitis-Associated Interstitial Lung Disease Histology • Changes are patchy and have bronchiolocentric distribution • Pigmented macrophages in respiratory bronchioles, alveolar ducts and peribronchial alveoli • Mild peribronchiolar fibrosis • Type II pneumocyte hyperplasia • Centrilobular emphysema

Respiratory Bronchiolitis-Associated Interstitial Lung Disease Radiographic Features • Chest radiograph: – thickening of walls central or peripheral bronchi (75%) – GG (60%) – chest x-ray normal in 14%

Respiratory Bronchiolitis-Associated Interstitial Lung Disease Radiographic Features • CT: – centrilobular nodules – GG – thickening walls central/peripheral airways – hypoattenuation areas represent air trapping

Respiratory Bronchiolitis-Associated Interstitial Lung Disease Differential Diagnosis • Hypersensitivity pneumonitis • DIP (GG more extensive, less poorly defined, centrilobular nodules are uncommon) • NSIP

Desquamative Interstitial Pneumonia

• Name originated from the belief that dominant histologic feature was desquamation • However now is recognized to be intra-alveolar macrophage accumulation • Condition may represent the end of a spectrum of RB-ILD (similar pathology) • Associated with cigarette smoke • Proper name alveolar macrophage pneumonia

Desquamative Interstitial Pneumonia Clinical • • • • • • •

Affects primarily cigarette smokers M:F 2:1 4th – 5th decades Patients improve with smoking cessation Survival rate 70% after 10 years Dyspnea and dry cough Decrease DLCO

Desquamative Interstitial Pneumonia BAL • Intra-alveolar macrophages with granules of “smokers pigment” • Also increase in neutrophils, eosinophils and lymphocytes

Desquamative Interstitial Pneumonia Histology • Diffuse involvement by macrophage accumulations within airspaces • Thickening alveolar septa by plasma cells and eosinophils • Intralumenal macrophages contain dusty brown pigment

Desquamative Interstitial Pneumonia Radiologic Features • Chest radiograph: – normal in 3%-22% – widespread GGO, peripheral, lower zones

• CT: – GG lower zones, peripheral, patchy – irregular linear opacities, reticular pattern – honeycombing (30%), limited in extent

Desquamative Interstitial Pneumonia Differential Diagnosis • Respiratory brochiolitis associated interstitial lung disease • Acute or subacute hypersensitivity pneumonitis • Sarcoidosis • Infections (P jiroveci)

Lymphoid Interstitial Pneumonia • Term introduced by Liebow and Carrington in 1969 • Considered as preneoplastic disease • Incidence of idiopathic LIP is low and its existence is doubted by some

Lymphoid Interstitial Pneumonia Clinical • • • • • • • •

Clinical presentation remains poorly defined More common in women Any age but most typically in 5th decade Cough, fever, weight loss, CP, arthralgia Crackles and lymphadenopathy Associated RA, SLE, Sjögren, Hashimoto Idiopathic LIP rarely progresses to fibrosis Corticosteroids improve symptoms

Lymphoid Interstitial Pneumonia BAL • BAL fluid shows lymphocytes

Lymphoid Interstitial Pneumonia Histology • Infiltrate of lymphocytes, plasma cells and histiocytes • Associated with type II cell hyperplasia and a mild increase in alveolar macrophages • Lymphoid follicles in pulmonary lymphatics

Lymphoid Interstitial Pneumonia Radiologic Features • Chest radiograph: two patterns – basilar with alveolar component – diffuse with associated honeycombing • CT: – ground glass is dominant – cysts or honeycombing can also be seen – reticular abnormality in 50% – nodules and widespread consolidation

Mueller-Mang C. et al. RadioGraphics 2007;27:595-615

Mueller-Mang C. et al. RadioGraphics 2007;27:595-615

Mueller-Mang C. et al. RadioGraphics 2007;27:595-615

Mueller-Mang C. et al. RadioGraphics 2007;27:595-615

Mueller-Mang C. et al. RadioGraphics 2007;27:595-615

Mueller-Mang C. et al. RadioGraphics 2007;27:595-615

Mueller-Mang C. et al. RadioGraphics 2007;27:595-615

Mueller-Mang C. et al. RadioGraphics 2007;27:595-615

Thank you!!