Interstitial, diffuse and inhalational lung disease Flashcards
1
Q
Acute Respiratory Distress Syndrome
A
Pathology:
-
Eitiology :
- Pulmonary injury: infection, aspiration, trauma, inhalational injury
- Extra-pulmonary injury: sepsis, nonthoracic trauma
-
Micro: diffuse alveolar damage
-
Early exudative stage (hours):
- endothelial cell oedema
- capillary congestion
- minimal interstitial hemorrhage/oedema
-
Late exudative stage (1 day - 1 week):
- necrosis of type 1 pneumocytes
- pulmonary oedema and hemorrhage
-
Proliferative/reparatives stage (1 week - 1 month):
- proliferation of type 2 pneumocytes + fibroblasts
- Collagen deposition
- Fibrotic stages (months): interstitial fibrosis –> squamous metaplasia –> honey combing
-
Early exudative stage (hours):
Clinical:
- SOB, tachycardia, hypoxia
- Complications: infection, fibrosis
- Rx: mechanical ventilation with high end-expiratory pressure
Imaging: CXR for monitoring, CT for problem solving
- Hours: may be normal 12-24 hours after injury
-
Days:
- Bilateral GGO + consolidations (within 24 hours)
- Pulmonary injury: more asymmetrical and similar GGO/consolidation
- Extra-pulmonary injury: more symmetric, GGO > consolidation
- Dependent atelectasis
- Interlobular septal thickening + pleural effusions less common (think heart failure)
- Bilateral GGO + consolidations (within 24 hours)
-
Weeks:
- Reducing conslidation
- Patchy airspace/GGO/reticular opacities
-
Months:
- Subpleural reticular opacities + honey combing
- May exhibit anterior predominance
- Atelectasis/consolidation may protect posterior lungs from effects of mechanical ventilation
DDx:
- Pulmonary oedema (cardiogenic and non-cardiogenic)
- Pulmonary hemorrhage
- Actue interstitial penumonia: idiopathic ARDS. Imaging is indistinguishable to ARDS.
2
Q
USUAL INTERSTITIAL PNEUMONIA PATTERN
A
Pathology:
- Histopathologic + radiologic pattern of ILD
-
Etiology of UIP pattern:
- Unknown –> Idiopathic Pulmonary Fibrosis
-
Secondary:
- CTD: RA, Scleroderma, Polymyositis/dermatomyositis
- Asestosis
- Chronic hypersensitivity pneumonitis
- Radiation
- Drug toxicity: amiodarone
- Vasculitis: ANCA positive
- Hermansky-Pudlak syndrome
- Key features: patchy fibrosis and architectural distortion
-
Gross:
-
SPATIAL AND TEMPROAL HETEROGENEITY
- identification of fibrotic lesions at different stages within same specimen
- eg: fibrolastic infiltrates, mature fibrosis, honeycombing within the sa
- Fibrosis, inflammation, honey combing with interspersed normal lung.
-
SPATIAL AND TEMPROAL HETEROGENEITY
-
Micro:
- Fibrosis: subpleural predominant
- Intersitial inflammation: histiocytes, plasma cells, lymphocytes, T2 pneumocyte hyperplasia
- Honey combing
- Regions of normal lung
ClinicaL ;
- 55-70 (increases with AGE)
- M > F (2:1)
- Prevalence: 4.5/100000
- Prognosis:
- inexorable progression
- mean survival 3.5 years from diagnosis.
- Lung cancer 10%
- Rx: none proven to improve survival.
- Steroid, immunosuppresion, antifibrotics
Imaging: HRCT
-
UIP pattern:
- Distribution: subpleural + basal predominance (lateral creep)
- Honey combing +/- traction bronchiectasis
- Reticular opacities
- Absence of features inconsistent with UIP
-
Probable UIP:
- UIP Pattern with NO HONEY COMBING
- GGO super imposed on reticular opacities (less extensive than reticulations)
-
Indeterminate for UIP:
- Distribution: variable and not specific to any etiology
- Evidence of fibrosis with some inconspicuous features suggestive of a non-UIP pattern (eg: Subtle reticular abnormalities +/- GGO)
-
Features most consistent with non-IPF/Alternative diagnosis:
- Distribution: upper/mid lung predominance, peribronchovascular, peri-lymphatic, subpleural sparing
- Mosaic attenuation + air trapping
- GGO or consolidation predominant (> reticular opacities)
- Profuse micronodules
- cysts
- Pleural changes: effusion/thickening/plaques
- Other: Dilated eosphagus (CTD), distal clavicular erosions (RA), Extensive lymphadenopathy
-
UIP pattern more suggestive of CTD:
- straight edge sign
- Anterior upper lobe sign (still has basal involvement)
- Exuberant honeycombing sign: >70% of fibrotic lung
DDX:
- NSIP
- Chronic hypersensitivity pneumonitis
- Connective tissue disease: Rheumatoid arthritis, systemic sclerosis
- Sarcoidosis
- Drug reaction: amiodarone
- Asbestosis
3
Q
Nonspecific Interstitial Pneumonia
A
Pathology:
-
Eitiology:
- Idiopathic
-
Secondary:
- Systemic disease: systemic sclerosis, Sjorgen syndrome, RA, polymyositits/dermatomyositis
- Hypersensitivity pneumonitis
- Drug induced lung disease
- Radiation toxicity
- NOT associated with cigges
-
Micro:
- Spatial and temporal homogeneity - distinguishing NSIP from UIP
- Interstitial inflammation/fibrosis
-
2 subtypes:
- Cellular (less common): interstitial infiltration/thickening by inflammatory cells, hyperplasia of type 2 pneumocytes, minimal fibrosis
- Fibrotic: interstitial collagen depostion (fibrosis), alveolar septal thickening, +/- distortion of lung architecture (may be difficult to distinguish from UIP)
Epi: age ~45, M=F
Clinical:
- gradual symptoms: cough, SOB, malaise, fatigue, weightloss
- Symptoms 6-18 months prior to presentation
- Diagnosis: Radiological + clinical +/- open lung biopsy (definitive)
- Prognosis: complete recovery (45%) > stable or improvement (42%) > mortality (11%)
- Rx: steroids
Imaging (HRCT)
- Distribution: Bilateral + lower lobe predominant + peribronchovascular + subpleural sparing.
- GGO: usually dominant feature
-
Reticular opacities (fibrotic types)
- +/- Thickening of peribronchovascular bundles
- +/- traction bronchiectasis/bronchiectasis
- Absent/sparse honey combing
- Consolidation: often in association with bronchiectasis
- Things that should prompt other differentials:
- Centrilobular nodules
- Mosaic attenuation
- Thin-walled cysts
DDx:
- UIP
- COP
- Hypersensitivity neumonitis
- DIP
- Pulmonary alverolar proteinosis
- Sarcoidosis
- Lipoid pneumonia
4
Q
Organising Pneumonia
A
Pathology:
- Characterized by polypoid plugs of granulation tissue within air spaces
-
Causes
- Idiopathic (cryptogenic)
- infection : bacteria, fungal, virus, parasitic
- Drugs : amiodarone, bleomycin, busulphan, gold salts, sulfasalazine, tacrolimus, cocaine
- Connective tissue disease : RA, sjogren syndrome, PMR, dematomyositis
- Transplantation
- IBD
- Hematological disorder: leukemia, myelodysplastic syndrome
- Immunologica/inflammatory disorder: Behcet disease
- Radiation
- Aspiration
- Macro: no fibrosis, granulation tissue extending into lumen
- Micro: buds of loosely organized granulation tissue extend through pores of Kohn to next alveolus (butterfly pattern). Mononuclear cell interstitial infitltration admixed with other inflammatory cells (non-specific)
Epid: ~55, M=F, non-smoker/ex-smokers
Rx: steroids (good prognosis), relapse (50%)
HRCT:
- Location: subpleural +/- bronchovascular, mid and lower zone predominant
- Consolidation
- GGO +/- crazy paving
-
Reverse Halo (atoll sign): central ground-glass opacity + surrounding rim of consolidation (suggestive but not pathognomonic)
- Also seen in fungal/TB infections, Wegeners/sarcoid, infarct
- Perilobular pattern: linear opacities along interlobular septa
- Nodules (variable)
- Reticular opacities
- Other: bronchial wall thickening, bronchiectasis, solitary pulmonary mass simulating malignancy
DDx:
- Lymphoma
- Adenocarcinoma
- Sarcoidosis
- Chronic eosinophlic pneumonia
- Lipoid pneumonia
5
Q
Sarcoidosis
A
Pathology:
- Systemic granulomatous disease of unknown etiology
-
Micro:
- Non-caseating epithelioid granulomas
- Fibrosis
- Exclude: infection, neoplasm, pneumoconiosis, HP
Epidemiology:
- peak age 25
- African americans/scandinavians/Japanese
Clinical:
- Asymptomatic 40%
- Profiles:
- Lofgren syndrome (acute): bilateral hilar lymphadenopathy, erythema nodosum, fever, arthralgia
- Heerfordt syndrome: uveitis, parotitis, fever
- Lupus pernio: chronic cutaneous induration, purple discoloration of central face/hand
- Chronic: uveitis, hypercalcaemia/nephrocalcinosis, nasal mucosa, neurosarcoid, cardiac sarcoid, cystic skeletal lesions
- Lab: elevated ACE, lysozyme
- PFT: restriction, reduced DLCO
- Rx: immunosuppresion, monoclonal antibodies, steroids
Imaging: Abnormal CXR 90%
- Lymphadenopathy (80%): symmetric. Garland triad (both hilar + right paratracheal)
- Upper/mid zone predominant + bilateral
-
Perilymphatic micronodules:
- peribronchovascular + subpleural/fissural/interlobular septal nodules or thickening
- 90-100% with lung involvement
-
Nodular sarcoid:
- nodular/mass-like opacities –> can form conglomerate masses
- Consolidations +/- bronchograms
- Galaxy sign: large nodules with irregualr borders formed by satelitte micronodules
- Reverse halo sign
- Patchy GGO
-
Airway invovlement:
- nodular thickening of airway wall
- mosaic attenuation
- Expiratory air-trapping
- Complications:
- Fibrosis (20%)
- Mycetoma
- Pulmonary artery hypertension
- Cystic changes
- Rare: solitary/dominant nodule or mass. Pleural effusions/thicekning/pneumothorax.
DDx:
- Lymphangitis carcinomatosis
- Lymphocytic intersitial pneumonia
- Silicosis
- Berylliosis
- Chronic hypersensitivity pneumonitis
6
Q
Respiratory Bronchiolitis
Respiratory Bronchiolitis-associated intersitital lung disease (RB-ILD)
A
Pathology:
-
Etiology:
- airflow dynamics for small particulate material such that they preferentially imapct into small airways rather than larger airways.
- Ciggies (most common) >> other inhaled fumes
- Gross: bronchial wall thickening, associated centrilobular empysema
-
Micro:
- Bronchioles filled with pigmented macrophages (may spill into surroudning alveoli)
- +/- Hyperplasia/metaplasia of bronchial epithelium
Epid: ~36, SMOKERS
Clinical
- RB: CT/histological findings + asymptomatic
- RB-ILD: CT/Histological findings + symptomatic
- PFT tends to be normal or mixed restrictive/obstructive.
- Thought ot be prescursor to centrilobular nodules/emphysema
- Rx: smoke cessation.
HRCT:
- Centrilobular GGO/micronodules
- Bronchial wall thickening
- Upper lobe predominance ( inhalational)
- No evidence of fibrosis
- Co-existing emphysema (smoking related)
DDx:
- Desquamative interstitial pneumonia (DIP): thought to be a specturm of RB-ILD
- Hypersensitivity pneumonitis
- Pulmonary LCH
- Pneumonia
7
Q
Pulmonary Langerhans Cell Histiocytosis
A
Pathology:
-
Eitiology:
- Pathogenesis not completely understood
- Child: clonal cellular process unrelated to smoking
- Adults: immune-mediated nonclonal proliferation related to smoking
-
Gross:
- Cellular and fibrotic lesions + variable cyst formation.
- Endstage: fibrosis/honeycombing/emphysema.
-
Micro:
- Bronchiolocentric proliferation of langerhan cells (Birbeck granules on electron microscopy is pathognomonic.)
- Bronchiolocentric nodules +/- cavities +/- lung cysts
- DIP/COP/RB may occur in adjacent lung
Epi: 20-40, M=F, white people. Adults associated with smokers.
Clinical:
- cough, SOB, fatigue, chest pain, fever, weight loss
- Asymptomatic (25%)
- pneumothorax 25%
- Young adult (Hand-Schuller-Christian) vs infantile (Letterer Siwe)
HRCT:
- Upper and mid lung predominance (generalised in younger children/infants)
-
Nodules:
- stellate morphology
- centrilobular, peri bronchial, peri bronchiloar
- +/- cavitation or cyst formation
-
Cysts (more common than nodules):
- variable shape ( may be bizarre)
- Thin or thick nodular/irregular walls.
- Other: GGO, reticular opacities, septal lines, irregular bronchovascular bundles
- Late stage: coalescent cysts, fibrosis, honey comb
- Pneumothorax common
DDx:
- LAM
- PJP
- Silicosis/Coalworker’s pneumoconiosis
- Sarcoid
- Larygneal papillomatosis
- Hypersensitivity pneumonitis
- Bullous emphysema
8
Q
Asbestosis
A
Pathology:
- Asbestos: serpentine vs amphibole
- Increased deposition of fibres in lower lung zones from gravitational ventilatory gradient
- No lymphatic removal
- Fibrosis + asbestos bodies = asbestosis
- Tends to be occupational exposure
Associations
- Pleural disease: plaques, effusions, thickening
- Rounded atelectasis
- Mesothelioma
- Lung cancer
Imaging:
-
Fibrosis:
- Early: peripheral posterior basilar reticulations, centrilobular nodules, bronching opacities
- Late: Severe reticulations, traction bronchiectasis, honey comb (similar to UIP)
- Pleural plaques (80%) +/- calcificaitons
- Subpleural curvilinear line
- Parenchymal bands projected from pleura
- Mosaic attenuation + air trapping
DDx:
- Pulmonary fibrosis: UIP/NSIP
- Hypersensitivity pneumonitis
- Lymphangitis carcinomatosis
- Drug reaction
9
Q
Silicosis and Coal Worker’s Pneumoconiosis
A
Pathology:
- Eitiology: inhaleld silica/sicilicondioxide/coal dust desposited into respiratory bronchioles, removed by macrophages and lymphatics.
- Fibrogenic: silica>>> coal
- Gross: upper lung predominant (inhalational) fibrosis
-
Micro:
- Silica: birefringent silicate crystals, centered within concentric lamaella of collagen along bronchial walls or withiin macrophages/granulomas. Silicoproteinosis (high silica + lipoprotienaceous material within alveoli.
- Coal: Coal macule (stellate collection of macropohages containing black particles)
Clinical:
- SImple pneumoconiosis: normal PFT
- Complicated pneumoconiosis: restrictive PFT (can be mixed due to smoking related disease)
- Exposure usually > 20 years
- Acute silicoproteinosis: death 2-3 years.
Imaging:
- location: upper lung predominant + subpleural
- Small solid centrilobular nodules
- PMF (aggregation of nodules into larger conglomerate masses) +/- calcifications (differentiates from sarcoid)
- Hilar/mediastinal lymphadenopathy +/- calcification (egg shell in 5%)
- Uncommon: intralobular or interlobular lines.
DDx:
- Sarcoidosis
- TB
- LCH
- Hypersensitivity pneumonitis
10
Q
Hypersensitivity Pneumonitis
A
Pathology;
-
Eitiology:
- Animal protein (birds)
- Microbes (bacterial, yeast)
- Chemicals
- Other
- Pathophysiology: small particales deposit in bronchioles –> elicits type 3/4 hypersensitivity allergic reactions (allergic granulomatous inflammatory reaction )
- Associations: 90% non-smokers
-
Micro:
- TRIAD: Cellular bronchiolitis, non-caseating granulomas, bronchiolocentric intersitital lyphocytis pneumonitis
-
Cluster 1: ‘
- Neutorphil/eosinophil in alvolear spaces + small vessel vasculitis
- Lymphocytic interstitial infiltration
- Non-necrotising granulomas
- Cellular bronchiolitis
-
Cluster 2:
- Non-caseating granulomas +/- granulomas
- Bronchiolocentric lymphocytic and plasmatic alveolar wall infiltration
- Fibrosis: UIP (40%), NSIP (50%), OP (10%)
-
2 Clusters:
- Cluster 1: symptoms occur hours after exposure
- Cluster 2: chronic
Epidemiology:
- Acute: sudden onset flu-like symptoms
- Subacute: insiduous, non-specific
- Chronic: dyspnoea
- PFT: restrictive pattern with reduced DLCO
- Prognosis: may retrun to normal if acute. May progress even after exposure for chronic/subacute.
- Rx: avoid exposure to antigen + steroids
Imaging:
-
Cluster 1: (acute/subacute)
- Locaiton: usually diffuse and random but may be upper/mid zone predominant
- Diffuse ground-glass opacities
- Centrilobular ground glass nodules
- Mosaic attenuation, air trapping (lobular)
-
Head Cheese Sign:
- GGO (high attenuation) + mosaic attenuation/air trappng (low attenuation) + normal lung (normal attenuation)
- Other: interlobular septal thickeing + pleural effusion
-
Cluster 2: (chronic)
- Location: upper/mid zone predominant, peribronchovascular/subpleural
- Reticulations: peribronchovascular/subpleural
- Fibrosis: honey combing, Architectural distortion. traction bronchiectasis
- Centrilobular/peribronchiolar nodules
- Superimposed findings of cluster 1 HP
DDx:
- Acute interstitial pneumonia
- Respiratory Bronchiolitis
- UIP/NSIP
11
Q
Aspiration
A
-
Location (dependent)
- Erect: lower lobe basal segments
- Recumbent patients: posterior upper lobe segments, posterior/superior lower lobe segments.
- Focal/multifocal consolidation (dependent location)
- atelectasis (endobronchial material)
- Centrilobular nodules +/- tree in bud opacities
- Pneumatoceles
DDx:
- Multifocal consolidation
- Atelectasis
- Focal mass
12
Q
Chronic eosinoiphilic pneumonia
A
Pathology:
- Eitiology: unknown pathogenesis, thought to be hypersensitivity reaciton to unknown antigen
- Must excluded eosinophilic response to drug reactions/parasitic infections
- Associations:
- Asthma/atopy (50%)
- Non-smokers (90%)
- Other: RA, cutaneous T-cell lymphoma, radiation therapy for breast Ca
- Micro: Inflammatory infiltrate containing eosiniophils in alveolar space/septa/perivascular spaces
- Lab: Blood eosinophilia, increased eosinophils in bronchioalveolar lavage fluid
Epid: 18-80 yr, F>M (2:1)
Clinical:
- Insidious symptoms: fever, malaise, weight loss, dyspnea, cough
- Average duration of 7.7 months prior to diagnosis
- Rx: steroids –> rapid response with high relapse rate once stopped
Imaging:
-
Location: Bilateral (75%) + peripheral (outer 2/3) + upper lobe
- may have subpleural sparring
- Homogenous conslidations (100%)/GGO (90%)
- Nodular consolidation (40%)
- Interlobular septal thickening (20%)
- Crazy paving (8%)
- Rare: cavitation, emphysema (usually non-smokers)
- Associations:
- Small pleural effusions
- Mediastinal lymphadenopathy
-
EVOLUTION:
- Migratory consolidation with waxing/waning in different lung regions simultaenously
- Early (<1 month): peripheral
- Late (>1month): patchy and may spare lung
- Resolution: tends to occur lateral –> medial, leaving bands/lines of conslidated lung that parallel chest wall (wisp of smoke)
- Relapse: same place/size/shape
DDx:
- COP
- Pulmonary eosinophilia
- Churg-Strauss syndrome
- pneumonia
- Malignancy
- Sarcoid
- Pulmonary infarcts
- Pulmonary alveolar proteinosis
13
Q
Acute Eosniophilic Pneumonia
A
Pathology:
- Unknown pathogenesis, thought to be hypersensitivity reaciton to environmental agents
- Associated with recent onset of smoking/binge smoking
- Must rule out other causes of eosinophilic lugn disease
- Life of eosinophils deribed from marrow: 13-18hrs
Imaging: VERY SIMILAR TO PULMONARY OEDEMA
- location: variable
- GGO (100%) + smooth interlobular septal thickeing (90%)
- Crazy paving
- Consolidation (55%)
- centrilobular nodlues (30%)
- Peribronchovascular thickeining (67%)
- Pleural effusions (80%) - nearly always bilateral
- No lymphadenopathy/pericardial effusion
DDx:
- pulmonary oedema
- Acute interstitial pneumonia + ARDS
- Other causes of eosinophilic lung disease: drug induced/parasitic/ABPA/Churg-strauss syndrome
14
Q
Lymphangioleimyomatosis
A
Pathology:
- Low-grade malignant neoplasm of smooth muscle-like cells: characteriszed by interstitial proliferation of LAM cells that can obstruct venules/lymphatics/airways
-
2 phases:
- Early: proliferation of
- Late: cystic changes
- Sporadic (S-LAM) vs TSC associated (TSC-LAM)
-
Genetics: mutation in TSC1 (chromosome 9) or TSC2 (chromosome 16)
- S-LAM: acquired mutations in TSC2 gene confined to LAM lesions
- TSC-LAM: Genetic/acquired mutations in TSC1 (harmatin)/TSC2 (tuberin)
-
Associations:
- TSC
- Chylous ascites
- Renal/hepatic/splenic AML
- Abdominal/pelvic LAM
- Uterine leiomyomas, lymphaticoureteric/lymphaticovenous communicaitons
-
Gross:
- enlarged lungs
- numerous cysts along visceral pleura + homogenously throughout lung
- Enlarged thoracic duct/lymphatics
-
Micro:
- cysts + atypical smooth muscle cells (LAM CELLS)
- LAM cells: small, round, large and spindle shaped epitheloid
- LAM cells in cyst walls/lymphatics
- S-LAM/TS-LAM almost indistinguishable
- multifocal micronodular pneumocyte hyperplasia is pathopneumonic for TSC
Imaging:
- Radiograph: reticulonodular densities +/- hyperinflation/pneumothorax/chylothorax
-
Diffuse parenchymal Cysts + NORMAL INTERVENING LUNG
- Thin-walled
- 2-5mm
- Round, polygonal, ovoid
- Interlobular septal thickening
- Patchy GGO (hemorrhage)
- Mediastinal/hilar lymphadenopathy
- +/- thoraci duct dilatation
- Complications:
- pneumothorax
- Chylous plerual effusions
DDx:
- Centrilobular emphysema
- LCH
- Lymphocytic interstitial pneumonia
- Idiopathic pulmonary fibrosis
15
Q
Pulmonary Alveolar Proteinosis
A
Pathology:
- Alveolar accumulation of proteinaceous and lipid-rich surfactant like material
-
Eitiology :
- Autoimmune (90%). Granulocyte/Macrophage colony stimulating factor (GM-CSF) autoantibodies Strong association with smoking
- Secondary (5-10%): inhalational, hematological malignancy, immunodefiency
- Congential (minority): homozygous mutation of genes encoding surfactant protein SP-B/SP-C and ABCA3 transporter
- Gross: hard yellow lung
-
Micro:
- alveolar lipoproteinaceous material (periodic-acid Schiff positive
- Hyperplasia of type 2 pneumocytres
- Variable inflammation
Epid: ~40, smokers, m>f
Clinical:
- Asymptomatic (33%)
- Progressive SOB
- Dry cough
- Lab: raised lactate, GM-CSF autoantibodies (autoimmune type), Milk material in BAL, reduced DLCO, reduced lung volumes
- Complications: infections, fibrosis
- Rx: whole lung lavage
Imaging: Mimics pulmonary odema with no pleural effusion or cardiomegaly
- Random geographic distribution, widespread, bilateral
- Crazy paving (55%)
- GGO/Consolidation
- Mediastinal lymphadneopathy
- +/- fibrosis
DDx:
- Pulmonary oeedema
- PJP
- Diffuse alveolar hemorrhage
- INvasive mucinous adenocarcinoma
- other: sarcoid, OP, ARDS, lipoid pneumonia, non-specific interstitial pneumonia
