1. Interstitial Lung Diseases
Dr. C. Lai

2. Objectives
Describe the normal interstitium & the pathological changes in cells & lung architecture that may occur in interstitial lung disease.
Describe the key pathological features of the common idiopathic interstitial lung diseases.
Describe the pathological features of common secondary interstitial lung diseases (pneumoconiosis & collagen vascular disease) & compare & contrast their pathological features.
Describe the key pathological features of pulmonary vascular diseases.

3. Air Exchange Diseases Infectious pneumonias Interstitial lung diseases
Bacterial, mycobacterial, viral, fungal
Interstitial lung diseases
Pneumoconiosis, sarcoidosis, idiopathic interstitial fibrosis
Pulmonary “vascular” diseases
Pulmonary embolism, pulmonary edema, ARDS

4. Interstitial Lung Diseases
Pulmonologist, radiologist, & pathologist have different approaches to ILDs
Each approach provides unique insight, but can be confusing due to use of own terminology
Clinician: disease causing dyspnea, tachypnea, & restrictive lung disease
Radiologist: disease producing irregular lines, small nodules (dots), or ground glass shadows on CXRs
Pathologist: disease characterized predominantly by inflammation & fibrosis of pulmonary interstitium

5. Pulmonary Interstitium

6. Axial Interstitium

7. Peripheral Interstitium
Pleural Interstitium
Interlobular Interstitium

8. Septal Interstitium

9. Pathophysiology Impaired lung mechanics Impaired gas exchange
Reduces lung compliance
Increases work of breathing
Reduces lung volumes
Impaired gas exchange
Smaller lung volumes results in less surface area for gas exchange
Interstitial thickening impedes transfer of oxygen from alveoli to pulmonary capillaries

10. Interstitial lung diseases
Acute vs chronic
Known vs unknown etiology
Primary vs secondary
Pathologic patterns 10

11. Interstitial Lung Diseases
Primary
Sarcoidosis (20%)
Idiopathic pulmonary fibrosis - IPF (15%)
Secondary
Congestive heart failure/pulmonary edema
Infection (pneumonia)
Malignancy (lymphangitic carcinomatosis)
Pneumoconiosis (25%)
Connective tissue disease (10%)
Hypersensitivity pneumonitis (5%)
Drugs/radiation (5%)

12. Secondary ILDs

13. Pneumoconioses
Nonneoplastic lung reaction to inhalation of mostly inorganic particulate matter (mineral dusts) encountered in the workplace
Usually fibrogenic:
Silica
Asbestos
Usually non-fibrogenic
Coal
Beryllium (granulomatous)

14. Silicosis
Common lung disease caused by inhalation of crystalline proinflammatory silicon dioxide (silica)
Quartz most commonly implicated
Subacute presentation (rare)
Heavy exposure over months to few years
Intra-alveolar accumulation of lipoproteinaceous material
Chronic presentation (most common)
Usually presents after decades of exposure
Slowly progressive, nodular, fibrosing interstitial lung disease 14

15. Pulmonary Silicosis Early stage Later stage Advanced stage
Tiny, barely palpable, discrete pale to blackened nodules in hilar lymph nodes & upper lung zones
Later stage
Coalescence of nodules into hard, collagenous scars
Advanced stage
Expansion and coalescence of lesions to produce progressive massive fibrosis

16. Silicotic Nodule
Central area of whorled collagen fibers (arrow) with peripheral zone of dust-laden macrophages
Intra-histiocytic, short, needle- shaped, birefringent silicate particles
Histiocytic aggregates along lymphatic routes & within lymph nodes

17. Asbestosis Asbestos Asbestosis
Pro-inflammatory crystalline hydrated silicates
Asbestosis
Asbestos-related disease
Chronic presentation (20 to 30 yrs after first exposure)
Progressive peribronchiolar & alveolar septal fibrosis
Presence of multiple asbestos bodies (long slender fibers coated by iron, AKA ferruginous bodies)
Predominantly involves lung bases & subpleural lung 17

18. Asbestos Body

19. Pulmonary Fibrosis
Septal thickening

20. Pleural Plaques

21. Collagen Vascular Diseases
Autoimmune diseases can involve the lungs & cause interstitial pneumonitis at some point in their course
Rheumatoid arthritis, progressive systemic sclerosis (scleroderma), systemic lupus erythematosus, Sjögren syndrome, dermatomyositis-polymyositis, mixed connective tissue disease
Histological features are indistinguishable from idiopathic forms of interstitial lung diseases
Most have better prognoses than idiopathic pulmonary fibrosis

22. Hypersensitivity Pneumonitis
Immune-mediated interstitial lung disease due to exposure to inhaled organic antigens
Thermophilic bacteria, fungi, animal proteins (birds)
Acute, subacute or chronic presentation
Peribronchiolar interstitial pneumonitis (centrilobular lymphoplasmacytic inflammation)
Presence of poorly-formed, nonnecrotizing granulomas
Interstitial fibrosis in chronic presentation (late stages) 22

23. Hypersensitivity Pneumonitis
Septal thickening

24. Hypersensitivity Pneumonitis
Giant
cell

25. Primary ILDs

26. Sarcoidosis Systemic granulomatous disease of unknown etiology
Often involves lung & lymph nodes but can involve many other tissues & organs
Immune dysregulation in genetically predisposed individuals
Type IV hypersensitivity reaction to unidentified antigen with granulomatous inflammation along lymphatic routes
Unpredictable clinical course
65% to 70% recovery with minimal or no residual sequelae
20% permanent loss of some lung function or visual impairment
10% to 15% progressive pulmonary fibrosis and cor pulmonale

27. Sarcoidosis
Interlobular septum
Granulomata

28. Sarcoidosis
Artery
Bronchiole
Granulomata

29. Sarcoidal Granuloma
Granuloma
Histiocytes
Giant cell

30. Idiopathic Pulmonary Fibrosis
Clinicopathological syndrome of unknown etiology characterized by progressive interstitial pulmonary fibrosis & eventually respiratory failure
AKA cryptogenic fibrosing alveolitis (Europe)
Middle aged-to-elderly individuals (rare before 50 yrs old)
Insidious clinical course with gradually increasing exertional dyspnea & dry cough
Median survival is ~3 years after diagnosis
Lung transplantation is only definitive therapy

31. Idiopathic Pulmonary Fibrosis

32. End-Stage Lung (Honeycombing)
Fibrous septa
Honeycombing (circled areas)

33. Idiopathic Pulmonary Fibrosis
Cystic spaces (*)
Septal fibrosis *
Bronchioles

34. Idiopathic Pulmonary Fibrosis
Normal septum
Septal fibrosis
Inflammatory cells

35. Pulmonary Vascular Diseases

36. Types of Diseases
Obstruction to venous outflow (pulmonary congestion )
Congestive heart failure → pulmonary edema
Increase in pulmonary artery resistance (pulmonary hypertension)
Primary or secondary (e.g. systemic sclerosis)
Pulmonary artery obstruction (pulmonary thromboembolism)
Emboli (common) or thrombosis (uncommon)
Vascular inflammation (vasculitis)
Granulomatosis with polyangiitis (Wegener’s granulomatosis), Churg-Strauss syndrome

37. Pulmonary Thromboembolism
Pulmonary artery embolism (common)
More than 95% associated with deep venous thrombosis of lower limbs
Predisposing factors include bedridden, leg surgery, severe trauma, oral contraceptives, cancer, genetic hypercoagulability)
Pulmonary artery thrombosis (uncommon)
Large vessels: rare, associated with pulmonary hypertension, pulmonary atherosclerosis, heart failure
Small vessels: vasculitis, inflammation, diffuse intravascular coagulation (DIC)

38. Pulmonary Embolism Acute changes Chronic changes
Luminal obstruction with endothelial damage
Small vessels: alveolar hemorrhage in corresponding irrigated area & possible infarct (especially in those with compromised cardiovascular function)
Larger vessels: wedge-shaped, hemorrhagic infarction in center & hemorrhage in periphery
Chronic changes
Infarcted areas become fibrotic
Chronic pulmonary embolism (multiple small emboli) can lead to pulmonary hypertension and chronic cor pulmonale

39. Thrombosis

40. Pulmonary Embolism

41. Pulmonary Embolism
Artery
Embolus
Respiratory bronchiole

42. Pulmonary Infarct
PA thrombus
Infarct

43. Pulmonary Infarct
Alveolar septa *
Intra-alveolar hemorrhage (*)

44. Complete Obstruction Organized thrombus
Internal elastic layer (short arrows)

45. Recanalized Thrombus
New lumen
Organized thrombus

46. ARDS Acute Respiratory Distress Syndrome
Manifestation of severe acute lung injury (abrupt onset of significant hypoxemia & bilateral pulmonary infiltrates in absence of heart failure)
Diffuse alveolar damage is histologic manifestation of ARDS
Complication of diverse conditions
Sepsis, diffuse pulmonary infections, mechanical trauma (including head injuries), & gastric aspiration account for >50% of ARDS cases
Numerous other causes: extensive burns, ionizing radiation, fat embolism, pancreatitis, inhaled irritants (toxic fumes), chemical injury, uremia, cardiopulmonary bypass, etc.

47. Pathogenesis of ARDS
ARDS initiated by injury to alveolar septal pneumocytes & endothelial cells
Endothelial activation from pneumocyte injury or circulating inflammatory mediators (e.g. sepsis)
Adhesion & extravasation of neutrophils into interstitium & alveoli  degranulation & release of more inflammatory mediators  increased recruitment & adhesion of leukocytes  more endothelial injury
Increased vascular permeability  interstitial & intra-alveolar edema  fibrinous exudate & hyaline membrane formation
Difficult repair, frequently evolving to death or fibrosis

48. Diffuse Alveolar Damage

49. Diffuse Alveolar Damage
Hyaline membranes (small arrows)
Early septal fibrosis