Respiratory bronchiolitis-associated interstitial lung disease is commonly seen in heavy smokers and characterized by: 1) Intraluminal accumulation of pigmented macrophages in respiratory bronchioles, alveolar ducts, and surrounding alveoli in a patchy distribution. 2) Mild interstitial chronic inflammation and fibrosis mainly around bronchioles that may extend to alveolar septa. 3) It can be diagnosed when the above microscopic findings are present along with clinical evidence such as abnormal pulmonary function tests and CT findings showing centrilobular nodules and ground glass opacity, but no honeycombing.

1. FLASHPATH
H A Z E M A L I

2. RESPIRATORY
BRONCHIOLITIS
H A Z E M A L I

3. CLINICAL
• Common in heavy smokers
• Incidental finding
• Called respiratory bronchiolitis-associated interstitial lung disease
when:
– Abnormal pulmonary functions: mild restrictive or mixed
restrictive/obstructive
– Abnormal CT: centrilobular nodules with patchy ground-glass opacity
• But no honeycombing
• Good response to smoking cessation

4. GROSS
• No specific gross features
• Smoking related gross features
– Anthracosis
– Emphysema
– Dilated bronchi with increased mucus secretions

5. MICROSCOPY
• Intraluminal accumulation of pigmented macrophages
– Distribution: respiratory bronchioles, alveolar ducts
and surrounding alveoli
• The term “ membranous bronchiolitis” applied when pigmented macrophages
accumulate mainly within the terminal “membranous” bronchioles
– Pattern: patchy (not diffuse)
– Macrophages: finely granular, yellow/brown pigments
• Called “smokers macrophages”

6. MICROSCOPY
• Mild interstitial chronic inflammation / fibrosis
– Distribution: mainly peri-bronchiolar – may extend to
surrounding alveolar septa
– Alveolar lining: may show type II pneumocytes hyperplasia
or bronchiolar epithelial metaplasia (lambertosis)
Lambertosis:
• Appearance of bronchiolar type epithelium on the surface of fibrotic
alveoli next to a scarred bronchiole
• It refers to an older concept that this epithelium grew onto the alveolar
surface from the bronchiolar lumen via the canals of Lambert
• It differs from those of atypical adenomatous hyperplasia in that the
cells are mainly of ciliated type, closely abut each other and there is no
atypia

7. MICROSCOPY
• Other Smoking-related conditions:
– Anthracosis
– Emphysema
– Chronic Bronchitis
– Desquamative interstitial pneumonia
– Pulmonary eosinophilic granuloma
• “Langerhans cell histiocytosis”
– Usual interstitial pneumonia

8. SPECIAL STUDIES
• Smokers macrophages stain positive with iron stains
• How to differentiate them from Hemosiderin laden macrophages
– Hemosiderin laden macrophages (coarse granular)
– Smokers macrophages (fine granular)

9. DIFFERENTIAL DIAGNOSIS
• Usual interstitial pneumonia
• Desquamative interstitial pneumonia
• Langerhans cell histiocytosis
• Hypersensitivity pneumonitis
• Other interstitial pneumonias and processes
– Acute interstitial pneumonia (diffuse alveolar damage)
– Acute fibrinous and organizng pneumonia
– Cryptogenic organizing pneumonia (BOOP)
– Lymphocytic interstitial pneumonitis
– Nonspecific interstitial pneumonia
Respiratory bronchiolitis associated
interstitial lung disease can be diagnosed
only in the presence of clinical disease
(Pulmonary functions and CT) and in the
absence of patterns of other interstitial lung
diseases

10. DIFFERENTIAL DIAGNOSIS
• Usual interstitial pneumonia
– Disturbed architecture (honeycombing)
– Frequent fibroblastic foci
– No intraluminal accumulation of macrophages
• Desquamative interstitial pneumonia
– Intra-alveolar accumulation of macrophages
– Diffuse pattern
– Prominent pneumocyte hyperplasia
– Mild interstitial fibrosis may be seen

11. DIFFERENTIAL DIAGNOSIS
• Langerhans cell histiocytosis
– Frequent cystic changes (imaging – gross)
– Mainly interstitial process (not intraluminal)
– Aggregates of Langerhans histiocytes
• Convoluted / folded / grooved / kidney-shaped nuclei
• Positive CD1a
– Increased eosinophils
• Hypersensitivity pneumonitis
– History of exposure to organic dust
– Poorly formed granulomas – giant cells

12. DIFFERENTIAL DIAGNOSIS
• Other interstitial pneumonias and processes
– Acute and nonspecific interstitial lung diseases are diffuse processes
– Cryptogenic organizing pneumonia is also bronchiolocentric
• but is characterized by intraluminal organization (rather than intraluminal
macrophages)

13. WWW.
DO NOT FORGET TO SEARCH FOR MORE PICS
AND VIRTUAL SLIDES

14. THANK YOU
H a z e m A l i