9/16- Pathology of Interstitial Lung Diseases Flashcards Preview

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Flashcards in 9/16- Pathology of Interstitial Lung Diseases Deck (66):
1

What are some of the shared clinical and radiological manifestations of ILDs?

Symptoms:

- Progressive dyspnea

- Tachypnea

- Persistent, non-productive cough

Diffuse abnormalities in lung mechanics and gas transfer (restrictive pattern, PFTs)

Imaging (HRCT):

- Nodules

- Irregular lines

- Ground-glass opacities

2

The pulmonary interstitium is derived from what embryologic feature?

Splanchnic mesenchyme

3

What is the composition of the pulmonary interstitium? Function?

Supporting framework of the lung

- Fine elastic fibers

- Few fibroblasts

- Inflammatory cells

- Lymphovascular spaces

4

What are the ILD pattern-based categories?

What are the ILDs within each?

Fibrotic

- UIP

- NSIP (also cellular component)

- Pneumoconiosis (macrophage nodules in silicosis)

Granulomatous

- Sarcoidosis

- HP (also cellular component)

Alveolar filling

- COP

- DIP

- RB-ILD

5

Again, which ILDs are in the fibrotic pattern?

- UIP

- NSIP

- Pneumoconioses

  • Asbestosis
  • Silicosis

6

What is the definition of usual interstitial pneumonia?

- Subpleural/interlobular septal location

- Patchy, temporally heterogenous interstitial fibrosis

  •  Dense fibrotic scars
  •  Fibroblastic foci

Honeycombing (end stage lung disease)

7

What may cause usual interstitial pneumonia?

- Drug toxicity

- Collagen vascular diseases

- Unknown

(idiopathic UIP=idiopathic pulmonary fibrosis, IPF)

8

What is seen here? 

HRCT of UIP (usual interstitial pneumonia)

- Subpleural disease with honeycomb cysts

9

What is seen here? 

Gross image of IUP

- Cobble-stone pleural surface due to scarring

- Subpleural process, patchy

- Primarily lower lobes

- Fibrosis, honeycomb

10

What are the major pathologic findings of UIP?

- Patchy interstitial fibrosis, remodeling

- Fibrosis subpleural, paraseptal and temporally heterogenous

  • Dense fibrosis with remodeling/honeycombing
  • Fibroblastic foci

- Chronic interstitial inflammation, mild-moderate

- Honeycombing

- Inflamed cystic spaces filled with mucin

- Lined by metaplastic bronchial cells

11

What is seen here? 

Microscopic findings in UIP

- Patchy fibrosis

- Subpleural distribution

12

What is seen here?

Microscopic findings in UIP

13

What is seen here?

Microscopic findings in UIP

14

What is honeycombing?

End stage lung disease

- Dense collagenous scars result in lung remodeling

- Collapse of alveolar walls

- Formation of cystic spaces lined by epithelial cells, filled with mucus and inflammatory cells

15

What is nonspecific interstitial pneumonia?

- Histology does not conform to other ILD’s

- Temporally uniform

  • Cellular (inflammatory) pattern
  • Fibrosing pattern

16

What causes nonspecific interstitial pneumonia?

- Most idiopathic

- Connective tissue diseases

- Occupational and environmental exposures

17

What are the major pathologic findings in NIP?

2 patterns, prognostically different

Cellular pattern

- Mild to moderate interstitial lymphoplasmacytic infiltrate (uniform distribution)

- Infiltrate involves alveolar interstitium

- Type II pneumocyte hyperplasia

- Lung architecture preserved

Fibrosing pattern

- Temporally uniform, diffuse (NO fibroblastic foci)

- Lung architecture preserved (NO honeycombing)

- Can see some chronic inflammatory cells

18

What is seen here? 

NSIP: cellular pattern

- Infiltrate on left

- Normal lung on right

19

What is seen here? 

NSIP: cellular pattern

- Interstitial infiltrate

- Architecture preserved

20

What is seen here?

NSIP: cellular pattern

- Lymphoplasmacytic infiltrate

- Type II pneumocyte hyperplasia

21

What is seen here? 

NSIP: fibrosing pattern

- Temporally uniform fibrosis

22

What is Pneumoconiosis?

Non-neoplastic lung reaction to inhalation of dust particles, chemical fumes, and vapors (occupational lung disease)

2 forms:

- Asbestos-related diseases

- Silicosis

23

What is asbestos?

Hydrated silicate fibers

- Amphiboles: straight fibers; association with mesothelioma

- Chrysotile: serpentine/curved fibers: primary form used in industry

24

What are some asbestos-related diseases?

- Asbestosis: bilateral diffuse interstitial fibrosis

- Fibrous pleural plaques

- Pleural effusions

- Mesothelioma: cancer of mesothelium (1000x’s compared to non-exposed)

- Lung cancer: 55 fold increase in lung ca (Asb + smoking) vs 5 fold increase (Asb alone)

25

What are some features of asbestosis (broadly)?

- Bilateral diffuse interstitial fibrosis caused by inhalation of asbestos fibers

- Pattern of fibrosis is indistinguishable from other forms of ILD’s (need to see asbestos bodies)

- Primarily involves lower lobes

26

What are gross features of asbestosis?

- Subpleural and parenchymal fibrosis

+/- honeycomb change (lower lobe disease)

27

What are microscopic features of asbestosis?

Patchy interstitial and subpleural fibrosis (fibers stimulate release of mediators leading to repeated cycles of inflammation/fibrosis)

- Starts around respiratory bronchioles and alveolar ducts, proceeds distally

- Fibrosis similar to UIP Asbestos bodies (asbestos fiber + iron-protein coat

28

What is seen here? 

Gross asbestosis

- Honeycomb changes and fibrosis seen in lower lobes

29

What is seen here? 

Microscopic Asbestosis

- Thickening of pleura

- Fibrosis (?)

Looks a lot like UIP

30

What is seen here?

Asbestosis

- Interstitial fibrosis

- Asbestos bodies!

31

What is seen here? 

Pleural plaques

- Parietal pleura and domes of diaphragm

32

What is silicosis? What causes it?

- Most prevalent chronic occupational lung disease worldwide

- Long exposure, slowly progressing nodular/fibrosing pneumoconiosis

Caused by: inhalation of crystalline silicon dioxide (silica)

- Sandblasting, coal mining, stone masonry, ceramic/pottery manufacture, etc

33

What is silica? What form causes silicosis?

Has amorphous and crystalline forms

- Crystalline is more fibrogenic vs amorphous

- Quartz, most abundant form of crystalline silica and therefore most frequently implicated in silicosis

- Silica causes activation of macrophage mediators including fibrogenic cytokines

34

What are features of early and late lesions in silicosis?

Other pathogenic features?

- Early lesions: dust-filled macrophages, lymphatic/bronchovascular distribution

- Later lesions: silicotic nodules (lamellar fibrosis with birefringent silica particles)

- Uniform fibrosis begins around bronchioles, can get honeycombing

- Upper lobe disease

35

What is seen here? 

Silicosis

- Early: black nodules (upper lobe disease)

- Late: dense nodules and parenchymal fibrosis

36

What is seen here? 

Silicosis

- Early lesions (dust filled macules)

- Peribronchiole/lymphovascular routes

37

What is seen here?

Silicosis

- Silicotic collagenous nodules

- Birefringent silica particles

38

What are granulomatous ILDs?

- HP

- Sarcoidosis

39

What is hypersensitivity penumonitis (HP)?

- Immune mediated ILD; prolonged exposure to inhaled organic antigens (AKA extrinsic allergic alveolitis)

- Interstitial inflammatory and granulomatous reaction

- Inhale dust with antigens from bacterial spores, fungi or animal proteins

Examples:

- Farmer’s lung

- Bird fancier’s lung

- Humidifier/air conditioner lung

- Maple bark stripper’s disease

40

What are microscopic findings in HP? (acute and subacute/chronic findings)

Acute phase: Neutrophils in alveoli and respiratory bronchioles (last 1-2 days)

Subacute/chronic:

- Interstitial lymphoplasmacytic infiltrate, begins around bronchioles (~100%)

- Ill-defined, random, non-caseating granulomas (~67%)

- Patchy organizing pneumonia (60%) (granulation type tissue in alveolar spaces)

* Can see fibrosis in late stage disease; can mimic UIP

41

What is seen here? 

Hypersensitivity pneumonitis (HP)

- Bronchiolocentric lymphoplasmacytic infiltrate (seen in 100%)

42

What is seen here? 

Hypersensitivity pneumonitis (HP)

- Giant cells; ill-defined granulomas (seen in 67%)

43

What is seen here?

Hypersensitivity pneumonitis (HP)

- Organizing pneumonia (60%)

44

What is sarcoidosis? Pathologic findings?

- Systemic disease of unknown cause

- Non-caseating granulomas involving lungs, lymph nodes, liver, spleen, bone marrow, skin, eyes, etc

  • Hilar lymph nodes or lung involvement (90%)

- Disordered immune reaction in genetically predispose individuals

Pathologic findings:

- Multiple nodules; pleura, interlobular septa, bronchovascular structures

- Well-formed granulomas

  • Epithelioid histiocytes
  • Multinucleated giant cells
  • Chronic inflammatory cells
  • Usually no necrosis (noncaseating)
  • Lung architecture preserved

Still need to rule out infection

45

What is seen here?

Sarcoidosis

- Well formed granulomas (much more so than HP)

- Coalescing of nodules along bronchovascular channels

46

What is seen here?

Sarcoidosis

- Coalescing of nodules along interlobular septum (left) and bronchovascular structure (right)

47

What is seen here? 

Sarcoidosis

- Well defined granulomas

- No necrosis

- Multinucleated giant cells, histiocytes, various inflammatory cells

48

What is seen here?

Top left: Asteroid bodies

Top right and bottom: Schaumann bodies (70%)

NOT specific for sarcoidosis

49

What are ILDs included in alveolar filling category?

- COP

Smoking-related ILDs:

- RB-ILD

- DIP

50

What is cryptogenic organizing pneumonia (COP)?

Pathologic findings?

- Granulation tissue in distal airspaces

- OP associated many conditions: infections, collagen vascular diseases, HP, inhalation injuries, XRT

- COP = idiopathic OP (AKA BOOP, (bronchiolitis obliterans organizing pneumonia)

Pathologic findings:

- Intraluminal plugs of granulation tissue (Masson bodies) in distal airways (bronchioles, alveolar ducts, alveoli)

- Patchy distribution; temporally homogenous

- Lung architecture preserved, NO honeycombing

- Mild chronic interstitial inflammation

51

What causes cryptogenic organizing pneumonia (COP)?

Idiopathic

52

What is seen here? 

COP

- Patchy foci of nodular consolidation

53

What is seen here? 

COP

- Granulation tissue in airways

- Overall lung architecture preserved

54

What is seen here? 

Cryptogenic Organizing Pneumonia (COP)

- "Bronchiolitis obliterans"- granulation tissue looks to be obliterating alveoli (this entity also seen in pts with chronic rejection)

55

What is seen here? 

COP

- Organizing granulation tissue within alveolar space

56

What is seen here?

COP

- Myxoid appearance: fibroblasts, histiocytes, chronic inflammatory cells

57

What is respiratory bronchiolitis?

Microscopic findings?

- Exuberant form of RB (clinical/radiologic findings of diffuse “interstitial” LD)

- Primarily small airway disease (bronchioles/adjacent alveolar ducts, alveoli)

- Virtually all patients current or past heavy smokers (at least 30 pack-year)

Microscopic findings:

- Finely pigmented (dusty brown) macrophages in resp. bronchioles and adjacent alveolar ducts and alveoli

- Bronchiole wall may have chronic inflammation and fibrosis

- Metaplastic bronchiolar epithelium involves alveolar ducts

* Extensive RB + clinical and X-ray of ILD = RB-ILD

58

What is seen here? 

Respiratory bronchiolitis (RB)

- Nodular collections of macrophages in bronchioles and surrounding alveoli

59

What is seen here? 

Respiratory bronchiolitis (RB)

- Collection of macrophages in interstitium and adjacent alveolar tissue

60

What is seen here? 

Respiratory bronchiolitis (RB)

- Very fine, dusty brown pigment

- Overall lung architecture preserved

61

What is seen here?

Respiratory bronchiolitis (RB): BAL specimen

- Left: fine smoker's pigment

- Right: hemosiderin (bulkier pigment)

62

What is seen here? 

Respiratory bronchiolitis (RB)

- Left: peribronchiolar fibrosis

- Right: metaplastic bornchiole epithelium

63

What is Desquamative interstitial pneumonia (DIP)?

Major pathologic findings?

- Desquamative – “desquamated” cells (believed to be pneumocytes)

- Exclusively in current or former smokers

- Numerous alveolar macrophages

- Uniform fibrosis & chronic inflammation within interstitium

- NO honeycombing

Pathologic features:

- Diffuse involvement of lung parenchyma

- Large accumulation of alveolar macrophages

- Uniform fibrotic thickening of alveolar septa (mild-moderate)

- Chronic interstitial inflammation (mild)

- NO honeycombing, fibroblast foci, organizing pneumonia

64

What is seen here?

Desquamative interstitial pneumonia (DIP)

- Some type II pneumocyte hyperplasia

- Chronic inflammation

65

What is seen here? 

Desquamative interstitial pneumonia (DIP)

- Some fibrosis

- Chronic inflammation

- Macrophages within alveolar spaces

66

Summary of ILDs

Want to separate UIP from other ILDs

- Heterogeneous, FF, honeycombing = UIP

- Cellular and uniform fibrous patterns = NSIP

- Uniform, luminal granulation tissue = COP

- Hyaline membranes + interstital organization = DAD

- Pigment macrophages + smoking Hx = RB-ILD/DIP

- Granulomas + interstitial chronic infiltrate = HP

- Noncaseating granulomas + hilar adenopathy = Sarcoidosis

- Asbestos bodies + lower lobe disease = Asbestosis

- Nodules/birefringent particles + upper lobe disease = Silicosis