9/16- Pathology of Interstitial Lung Diseases Flashcards
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
The pulmonary interstitium is derived from what embryologic feature?
Splanchnic mesenchyme
What is the composition of the pulmonary interstitium? Function?
Supporting framework of the lung
- Fine elastic fibers
- Few fibroblasts
- Inflammatory cells
- Lymphovascular spaces
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
Again, which ILDs are in the fibrotic pattern?
- UIP
- NSIP
- Pneumoconioses
- Asbestosis
- Silicosis
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)
What may cause usual interstitial pneumonia?
- Drug toxicity
- Collagen vascular diseases
- Unknown
(idiopathic UIP=idiopathic pulmonary fibrosis, IPF)
What is seen here?
HRCT of UIP (usual interstitial pneumonia)
- Subpleural disease with honeycomb cysts
What is seen here?
Gross image of IUP
- Cobble-stone pleural surface due to scarring
- Subpleural process, patchy
- Primarily lower lobes
- Fibrosis, honeycomb
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
What is seen here?
Microscopic findings in UIP
- Patchy fibrosis
- Subpleural distribution
What is seen here?
Microscopic findings in UIP
What is seen here?
Microscopic findings in UIP
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
What is nonspecific interstitial pneumonia?
- Histology does not conform to other ILD’s
- Temporally uniform
- Cellular (inflammatory) pattern
- Fibrosing pattern
What causes nonspecific interstitial pneumonia?
- Most idiopathic
- Connective tissue diseases
- Occupational and environmental exposures
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
What is seen here?
NSIP: cellular pattern
- Infiltrate on left
- Normal lung on right
What is seen here?
NSIP: cellular pattern
- Interstitial infiltrate
- Architecture preserved
What is seen here?
NSIP: cellular pattern
- Lymphoplasmacytic infiltrate
- Type II pneumocyte hyperplasia
What is seen here?
NSIP: fibrosing pattern
- Temporally uniform fibrosis
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
What is asbestos?
Hydrated silicate fibers
- Amphiboles: straight fibers; association with mesothelioma
- Chrysotile: serpentine/curved fibers: primary form used in industry
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)
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
What are gross features of asbestosis?
- Subpleural and parenchymal fibrosis
+/- honeycomb change (lower lobe disease)
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
What is seen here?
Gross asbestosis
- Honeycomb changes and fibrosis seen in lower lobes
What is seen here?
Microscopic Asbestosis
- Thickening of pleura
- Fibrosis (?)
Looks a lot like UIP
What is seen here?
Asbestosis
- Interstitial fibrosis
- Asbestos bodies!
What is seen here?
Pleural plaques
- Parietal pleura and domes of diaphragm
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
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
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
What is seen here?
Silicosis
- Early: black nodules (upper lobe disease)
- Late: dense nodules and parenchymal fibrosis
What is seen here?
Silicosis
- Early lesions (dust filled macules)
- Peribronchiole/lymphovascular routes
What is seen here?
Silicosis
- Silicotic collagenous nodules
- Birefringent silica particles
What are granulomatous ILDs?
- HP
- Sarcoidosis
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
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
What is seen here?
Hypersensitivity pneumonitis (HP)
- Bronchiolocentric lymphoplasmacytic infiltrate (seen in 100%)
What is seen here?
Hypersensitivity pneumonitis (HP)
- Giant cells; ill-defined granulomas (seen in 67%)
What is seen here?
Hypersensitivity pneumonitis (HP)
- Organizing pneumonia (60%)
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
What is seen here?
Sarcoidosis
- Well formed granulomas (much more so than HP)
- Coalescing of nodules along bronchovascular channels
What is seen here?
Sarcoidosis
- Coalescing of nodules along interlobular septum (left) and bronchovascular structure (right)
What is seen here?
Sarcoidosis
- Well defined granulomas
- No necrosis
- Multinucleated giant cells, histiocytes, various inflammatory cells
What is seen here?
Top left: Asteroid bodies
Top right and bottom: Schaumann bodies (70%)
NOT specific for sarcoidosis
What are ILDs included in alveolar filling category?
- COP
Smoking-related ILDs:
- RB-ILD
- DIP
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
What causes cryptogenic organizing pneumonia (COP)?
Idiopathic
What is seen here?
COP
- Patchy foci of nodular consolidation
What is seen here?
COP
- Granulation tissue in airways
- Overall lung architecture preserved
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)
What is seen here?
COP
- Organizing granulation tissue within alveolar space
What is seen here?
COP
- Myxoid appearance: fibroblasts, histiocytes, chronic inflammatory cells
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
What is seen here?
Respiratory bronchiolitis (RB)
- Nodular collections of macrophages in bronchioles and surrounding alveoli
What is seen here?
Respiratory bronchiolitis (RB)
- Collection of macrophages in interstitium and adjacent alveolar tissue
What is seen here?
Respiratory bronchiolitis (RB)
- Very fine, dusty brown pigment
- Overall lung architecture preserved
What is seen here?
Respiratory bronchiolitis (RB): BAL specimen
- Left: fine smoker’s pigment
- Right: hemosiderin (bulkier pigment)
What is seen here?
Respiratory bronchiolitis (RB)
- Left: peribronchiolar fibrosis
- Right: metaplastic bornchiole epithelium
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
What is seen here?
Desquamative interstitial pneumonia (DIP)
- Some type II pneumocyte hyperplasia
- Chronic inflammation
What is seen here?
Desquamative interstitial pneumonia (DIP)
- Some fibrosis
- Chronic inflammation
- Macrophages within alveolar spaces
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
