2. Idiopathic Interstitial Pneumonias
• Subset of diffuse interstitial lung diseases of
unknown etiology characterized by expansion of
the interstitial compartment w/an infiltrate of
inflammatory cells sometimes accompanied by
fibrosis, either in the form of abnormal collagen
deposition or proliferation of fibroblasts capable
of collagen synthesis
• All under umbrella of IPF? Or separated based
on histological appearance? Matter of debate
3. Averill Liebow
• Pioneered the notion that morphologic characteristics are useful in
separating idiopathic interstitial pneumonias into clinically and
histologically distinct groups
• These processes were histological patterns rather than free standing
diagnostic entities, and that each could occur in a variety of clinical
contexts
• Maintained that precise histological classification of interstitial
pneumonias provides clues to etiology, pathogenesis, natural
history, and prognosis (helps limit differential dx and lead to
treatment options and response)
• The biopsy is intended not only to confirm the suspicion of an
interstitial pneumonia, but also to exclude various IPF mimics such
as sarcoidosis, hypersensitivity pneumonitis, and pulmonary
Langerhans' cell histiocytosis
4. UIP-Usual Interstitial Pneumonia
• IPF - a specific form of chronic fibrosing interstitial
pneumonia limited to the lung and associated with the
histologic appearance of usual interstitial pneumonia
(UIP) based on surgical biopsy
• IPF has an estimated prevalence of 14 to 43 per 100,000
• Most cases are sporadic and present with slowly
progressive dyspnea and nonproductive cough
• Prevalence and incidence increase with age
• HRCT demonstrates a characteristic pattern of peripheral
(subpleural) and bibasilar reticulonodular opacities
associated with architectural distortion, including
honeycomb changes and traction bronchiectasis
5. Histo
• Histologic hallmark and chief diagnostic criterion is a
heterogeneous appearance with alternating areas of normal lung,
interstitial inflammation, fibroblast foci, and honeycomb change
• The tissue is stained with hematoxylin (purple dye) and eosin
(pink dye) to make it visible. The pink areas in this picture
represent lung fibrosis (patchwork fibrosis)
7. RB-ILD Respiratory bronchiolitis-
associated interstitial lung disease
• Also uncommon, accounting for only 2 percent of
biopsied Mayo Clinic patients who were suspected of
having IPF
• DIP and RB-ILD show significant clinical, radiologic and
histologic overlap, and in some patients the distinction is
arbitrary and of uncertain clinical significance
• Clinical features are non-specific, usually males,
smokers, 30+ pk year hx, symptoms are usually mild
and not disabling
• Chest radiographs are abnormal in 80 percent of patients
and show diffuse fine reticular or reticulonodular
opacities in a bibasilar distribution
8. Histo
• The main feature that distinguishes DIP from RB-ILD is
that DIP affects the lung in a more uniform and diffuse
manner, lacking the bronchiolocentric distribution of
macrophages seen in RB-ILD
• It is likely that DIP and RB-ILD are highly related if not
identical lesions, differing only in the severity and extent
of the abnormality (ie, RB-ILD = mild/early DIP).
• Pertinent NEG findings: Lack of diffuse macrophage
accumulation, and interstitial fibrosis and/or honeycomb
fibrosis
9. • Diffuse ground glass
abnormality, with some
associated cystic changes
• Bronchial wall thickening
(arrow-thickened
interlobular septa)
10. DIP-Desquamative Interstitial
Pneumonia
• It is relatively uncommon, comprising 8 percent of biopsied Mayo Clinic
patients suspected of having IPF
• The vast majority (>90 percent) of patients with DIP are smokers, a small
percentage of cases are associated with connective tissue diseases
• Glucocorticoids are beneficial in the majority of patients, and the overall
survival is about 70 percent after 10 years
• Radiographic abnormalities: less severe than UIP, HRCT shows ground
glass opacities without the peripheral reticular and reticulonodular opacities
characteristic of UIP
• One review of HRCT findings found no evidence of progression from DIP to
UIP, further supporting the concept that DIP and UIP are separate and
distinct entities (Chest, 1996)
• DIP differs histologically from UIP in that the changes tend to be much
more uniform at low magnification
• The most striking feature is the presence of numerous mononuclear cells
within most of the distal air spaces. These mononuclear cells represent
smokers' macrophages rather than desquamated pneumocytes, as had
been originally proposed
11. Histo
• The alveoli are filled
with macrophages
containing brown
pigment in this
disease of smokers.
• Tx: smoking
cessation, steroids
12. AIP-Acute Interstitial Pneumonia
• Etiology: neutrophil mediated lung injury
• Initial stage: inc capillary permeability, leads to organizing stage
with fibroblast prolif (can progress to severe fibrosis)
• Presents with the explosive onset of respiratory symptoms and is
characterized by rapidly progressive respiratory failure associated
with diffuse infiltrates on chest radiographs (versus chronic nature
of others)
• This acute variant is analogous to the acute respiratory distress
syndrome (ARDS), differing only in that it is not preceded by a
catastrophic event, it is idiopathic
• Other terms have been proposed: including Hamman-Rich syndrome
and accelerated interstitial pneumonia
• AIP has the same poor prognosis as ARDS, and the majority of
patients die of respiratory failure
• Digital clubbing is limited to patients with acute exacerbation of
underlying fibrotic lung disease and serves as a helpful clue to
separate such patients from those with AIP
13. Histo
• AIP is identical to the organizing or
proliferative stage of diffuse alveolar
damage (DAD)
• The main finding is extensive interstitial
fibroblast proliferation within an
edematous-appearing stroma
14. • Classical histopathology of DAD is evident with prominent hyaline
membranes (hm) lining alveolar spaces.
• Note that the interstitium of the lung is thickened and hypercellular. While
hyaline membranes are still present, 1-4 days after the acute injury event,
the interstitium is edematous and has sparse inflammatory cells
15. HRCT
• Characteristics are diffuse or
patchy consolidation
• HRCT findings in AIP are
indistinguishable from ARDS
• Sometimes bilateral areas of
airspace consolidation in a
predominantly subpleural
distribution. Mild honeycombing,
usually affecting < 10% of the
lung, may be present
• Traction bronchiectasis is often
seen as a delayed manifestation in
the areas of air-space consolidation
or ground-glass attenuation
16. NSIP-Nonspecific Interstitial
Pneumonia
• Chronic interstitial pneumonia that lacks the histopathologic features
typical of UIP, DIP, RB-ILD or AIP
• In studies of idiopathic pulmonary fibrosis, NSIP has been described
as "early" or "cellular" UIP (“fibrosing” NSIP behaves like IPF-more
fibrotic foci, worse outcome)
• The most important clinical characteristics that distinguish NSIP
from UIP are a subacute rather than insidious onset of symptoms,
associated fever in about one-third of patients, lack of a strong male
predominance, relative absence of clubbing in NSIP, and increased
frequency of features suggestive of connective tissue disease
• As the name implies, the histological findings in patients with NSIP
are variable
• The main change in all cases is an interstitial pneumonia
characterized by expansion of alveolar septa by a variably dense
infiltrate of predominantly mononuclear inflammatory cells with or
without associated fibrosis
17. HRCT
• HRCT findings include
bilateral patchy ground-
glass attenuation, bilateral
areas of consolidation,
irregular lines, and bronchial
dilatation. Ground-glass
attenuation is the
predominant finding in most
cases and is the sole
abnormality in about 1/3 of
cases
• Bilateral subpleural ground-
glass opacities (arrowhead)
and irregular linear opacities
(arrow)
18. NSIP contd
• Groups: I, II: majority of patients had a
prominent inflammatory component either
without (Group I) or with (Group II)
concomitant fibrosis; biopsies showing
predominantly fibrosis (Group III) were the least
common
• As noted in other studies, the most compelling
distinction between NSIP and UIP was related to
outcome: NSIP had a significantly better
prognosis than UIP
19. Treatment and Prognosis of
Idiopathic Interstitial Pneumonias
• Idiopathic pulmonary fibrosis: Possibly lung
transplantation, Mortality rate: 50–70% in 3 yr
• NS-IP: Corticosteroids, Mortality rate: < 10%
5yr
• RB-ILD: Smoking cessation, Mortality: rare
• DIP: Smoking cessation, Mortality rate: 5% in 5
yr
• AIP: Best tx unknown, Mortality rate: 60% in <6
mo (Corticosteroid therapy is generally used, but
efficacy has not been established)
20. BOOP/COP?
• Cryptogenic organizing pneumonitis
(COP), which is the name applied to the
idiopathic form of organizing pneumonia
(idiopathic BOOP), is a distinct clinical
entity with features of a pneumonia rather
than a primary airway disorder
21. Approach
• History, family history, occupational hx, exposures, syms, labs, rads, PFTs,
etc.
• Role of lung biopsy: Not possible to make a definitive diagnosis or to stage
the disease without careful examination of lung tissue
• Indications for performing a lung biopsy:
– To provide a specific diagnosis, especially in a patient with atypical or
progressive symptoms and signs, or rapid clinical deterioration or sudden change
in radiographic appearance
– To assess disease activity
– To exclude neoplastic and infectious processes that occasionally mimic chronic,
progressive interstitial disease
– To identify a more treatable process than originally suspected
– To establish a definitive diagnosis and predict prognosis before proceeding with
therapies which may have serious side effects
• Transbronchial lung biopsy: Normal tissue or nonspecific changes on
transbronchial lung biopsy may result from a sampling error, need larger
sample (VATS preferred method)
