Pathology of Interstitial Lung Disease Flashcards
In interstitial lung diseases, what typically happens to the lung compliance, FVC, and FEV1:FVC ratio?
Restrictive pattern:
Reduced lung compliance
Reduced FVC
Normal FEV1:FVC ratio
What can be seen generally in pathology in all interstitial lung diseases?
- Chronic inflammatory infiltrate
- Cyst formation from coalescence of alveoli
- Interstitial fibrosis
- Honeycomb lung
What is honeycomb lung?
End stage scarred lung
- > dilated airspaces from destroyed lung alternating with fibrous scars
- > septae are extremely thick with poor gas exchange due to fibrosis of interstitium
What are the two names for the most common ILD and what is the prognosis?
Usual Interstitial Pneumonitis (UIP) or Idiopathic Pulmonary Fibrosis (IPF)
Prognosis: Poor - 3 year median survival
What are the common risk factors for UIP?
Smoking, wood dust inhalation, and therapy with EGFR TKI’s (mutations for fibrosis develop)
What is the common pathology of UIP?
Subpleural and bibasilar accentuation of tissue damage (extensive fibrosis)
->heterogeneity of tissue damage with “fibroblastic foci” - extensive fibroblast proliferation with ECM
What must not be present to make a UIP diagnosis?
Pertinent negative findings:
i.e. granulomas, Langerhans cells, asbestos bodies
-> thinks which would rule out idiopathic fibrosis
What is the inciting stimulus which begins fibrosis in UIP?
Damage to respiratory epithelium / basement membrane
- > activation of inflammation and coagulation pathways
- > eventual release of growth factors and TGF-beta, with tissue remodelling
What processes are responsible for an increase in fibroblasts in UIP?
- Transformation of pneumocytes into myofibroblasts (Epithelial-Mesenchymal-Transition)
- Migration from bone marrow
- Proliferation of native fibroblasts
What is DIP and how does it epidemiologically and prognostically differ from UIP?
DIP - Desquamating Interstitial Pneumonitis
Epidemiologically - happens in 40s and 50s vs 60s and 70s with UIP.
DIP is very associated with smoking and is made better by cessations - 90-100% survival
What is seen in the pathology of DIP?
Large numbers of alveolar macrophages in the alveoli
Interstitium is filled with lymphocytes, fibrosis is only mild and rarely progresses to honeycomb
What is the pathogenesis of DIP?
Similar to UIP, except more reliant on smoking as a stimulus for fibrosis and more reversible
What is NSIP and what are its two subtypes? Which has worse prognosis?
Nonspecific Interstitial Pneumonia -
Second most common interstitial lung disease, it is an IP that does not fit into any of the other histological categories
Subtypes:
Cellular - (closer to DIP)
Fibrotic - Worse prognosis (closer to UIP)
What does the pathology of NSIP look like / how does it differ from DIP / UIP?
Main difference is that the fibrosis and tissue damage is uniform across the lung rather than pleural or basilar (as in UIP), and there are no alveolar macrophage aggregates in alveoli (as in DIP)
What tends to aggregate in the cellular form of NSIP?
Lymphocytes tend to accumulate in the alveolar septae
How is diagnosis of hypersensitivity pneumonitis (HP) confirmed typically?
Clinical and CT findings will suggest the diagnosis
Lymphocytosis on bronchoalveolar lavage suggests it
Positive inhalation challenge / serum antibodies to allergen are near diagnostic
Biopsy is rarely required, only when clinical diagnosis cannot be reached
How are the tissue findings of subacute vs chronic phases of HP related?
Acute - may be no changes
Subacute - typical tissue findings
Chronic - subacute findings coexisting with fibrosis and restrictive lung pattern of disease
What are the classical tissue findings of HP?
Interstitial lymphocytes (like cellular NSIP) - worse in peribronchiolar areas like asthma
Mild interstitial fibrosis
Interstitial poorly formed non-necrotizing granulomas or single giant cells (from T4 hypersensitivity, as in Bosch’s lacture)
Why is it difficult to diagnose ILDs and what other things must be ruled out?
Because they have overlapping symptoms and pathologies with inter-observer disagreement
Must rule out toxic agents, infectious etiology, and co-morbid conditions w/ pulmonary manifestations
What is the role of the radiologist vs pathologist in diagnosis of Idiopathic Pulmonary Fibrosis?
Radiologist - sees CT scan, which is best to get the big picture of the lung
Pathologist - Can only confirm probable UIP, or definitely see features INCOMPATIBLE with UIP via pathology -> pathology can only rule out, but cannot make diagnosis
Sarcoidosis is a systemic disease. Where is it most commonly involved in the lung? What pattern does this make?
Mediastinal / hilar lymph nodes and lymph vessels (lymphangitic pattern) - makes sense because immune-mediated
Bilateral hilar lymphadenopathy causes “butterfly” pattern
What is the pathology of sarcoidosis? How can you diagnose based on this?
Noncaseating micro-granulomas with diffuse interstitial involvement and fibrosis
Focal necrosis of tissue may still be present, but rarer
Diagnosis can NOT be made on pathology alone
What levels are found to be elevated in diagnosis of sarcoidosis with bronchoalveolar lavage? What lab tests will be elevated?
Elevated CD4+:CD8+ T cell ratio (more CD4 cells due to activation of granulomas)
Noncaseating granulomas of sarcoidosis also elevated blood calcium (increased vitamin D levels due to 1-alpha-hydroxylase activity of macrophages) and elevated ACE (made in granuloma)
How are Langerhans cells identified pathologically?
Langerhans cells with grooved, irregular nuclei and cytoplasmic inclusions called “Birbeck granules” -> an endosomal inclusion.
