Lung
Interstitial lung diseases associated with smoking
Desquamative interstitial pneumonitis
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Last author update: 1 March 2018
Last staff update: 8 September 2023
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PubMed Search: Desquamative interstitial pneumonitis [title]
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology description | Positive stains | Electron microscopy images | Videos | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Yoshikawa A. Desquamative interstitial pneumonitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungnontumordip.html. Accessed December 19th, 2024.
Definition / general
- In 1965, Liebow et al reported a series of cases with interstitial pneumonia characterized by massive proliferation and desquamation of epithelial cells and coined the term "desquamative interstitial pneumonia" (DIP) (Am J Med 1965;39:369)
- In 1977, Tubbs et al determined, based on electron microscopy, that most cells within alveolar spaces were macrophages (Chest 1977;72:159)
- In 2013, American Thoracic Society / European Respiratory Society (ATS / ERS) categorized DIP as a smoking related interstitial pneumonia, as well as respiratory bronchiolitis related interstitial lung disease (Am J Respir Crit Care Med 2002;165:277, Am J Respir Crit Care Med 2013;188:733)
Essential features
- A rare but characteristic type of smoking related lung disease
- Histologically, massive accumulation of intra-alveolar macrophages is the key finding
Terminology
- Although “desquamated cells” are now recognized as intra-alveolar macrophages and ATS / ERS once considered to change the name of this entity to “alveolar macrophage pneumonia”, it is still officially called “desquamative interstitial pneumonia” (Am J Respir Crit Care Med 2002;165:277)
ICD coding
- Desquamative interstitial pneumonia: J84.117
Epidemiology
- Rare, < 1% of cases with interstitial lung disease
- Common age at onset is 40 - 60 years (Eur Respir Rev 2013;22:117)
- Rarely occurs in neonates or children due to ABCA3 mutations (N Engl J Med 2004;350:1296, Am J Respir Crit Care Med 2005;172:1026, Mod Pathol 2007;20:1009, Thorax 2008;63:366)
- M:F = 2:1 (Eur Respir Rev 2013;22:117)
Sites
- Bilateral (or sometimes unilateral) lobes of the lung
Pathophysiology
- Respiratory bronchiolitis, respiratory bronchiolitis associated interstitial lung disease (RB-ILD) and DIP are now considered on a spectrum and it can be difficult in some cases to separate these diseases clearly (Histopathology 2011;58:509)
- Deaths are somewhat common in DIP (6 - 30%) but rare in respiratory bronchiolitis and RB-ILD
- Studies with mouse models suggest a two hit development (Chest 2015;148:1307, Antiviral Res 2011;92:319)
- Primary smoking exposure induces GM-CSF secretion from airway epithelial cells
- Subsequent infection provokes macrophage activation and accumulation
Etiology
- Majority (60 - 90%) of adult patients are current or ex smokers (Eur Respir Rev 2013;22:117, Histopathology 2011;58:509, Chest 2017;3692:33197)
- Nonsmoking patients often have a history of exposure to dust, fumes or second hand smoke (passive smoking)
- Mutation related to surfactant protein causes pediatric DIP
- Surfactant protein C (Pediatr Pulmonol 2014;49:1097, N Engl J Med 2001;344:573)
- ATP-binding cassette protein A3 (ABCA3) (Am J Respir Crit Care Med 2005;172:1026, Mod Pathol 2007;20:1009, Thorax 2008;63:366)
- Other causes
- Idiopathic
- Drugs (Respiration 2007;74:237, Pediatr Infect Dis J 2011;30:363)
- Connective tissue disease (rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus) (Intern Med 2009;48:827, Can Respir J 2012;19:50, J Clin Rheumatol 2010;16:284)
- Infection (Cytomegalovirus, aspergillus, hepatitis C virus) (Nephrol Dial Transplant 2005;20:635)
Clinical features
- Slight to mild chronic respiratory failure
- Dyspnea on exertion
- Dry cough
- Digital clubbing
- Abnormal chest auscultation
- End inspiratory fine crackles in bibasilar lung
- Mild systemic symptoms may accompany
- Fever
- Fatigue
- Weight loss
- Normal or slightly abnormal pulmonary function tests (restrictive, obstructive or mixed pattern)
- Decreased forced vital capacity (FVC)
- Decreased diffusing capacity of the lung for carbon monoxide (DLCO)
- See details in review (Eur Respir Rev 2013;22:117, Histopathology 2011;58:509, Chest 2017;3692:33197)
Diagnosis
- Based on clinical features, radiology and histopathology (Am J Respir Crit Care Med 2002;165:277)
- Lung biopsy is required to establish a firm diagnosis since the clinical and radiological findings are often not specific
- However, a biopsy may not be necessary if the clinical and radiological features are suggestive enough (Radiology 1999;211:555)
Laboratory
- Increased serum KL-6
Radiology description
- Simple chest radiograph (Clin Radiol 2003;58:259)
- Variable and nonspecific, including ground glass opacity and reticulonodular shadow
- High resolution CT (Clin Radiol 2003;58:259, Chest 2017;3692:33197)
- Bilateral and subpleural ground glass opacity
- Middle to lower zones are affected predominantly; however, the upper zone can be involved
- Linear shadow, cystic spaces, emphysema, traction bronchiectasis and honeycombing can be accompanied
Radiology images
Images hosted on other servers:
High resolution CT
Prognostic factors
- Generally a favorable prognosis with good response to treatment: overall survival rate is 70 - 90% at 10 years (Am J Respir Crit Care Med 2005;172:268, Chest 2017;S0012:33197, Histopathology 2011;58:509)
- Disease can be persistent, especially in cases with marked fibrosis (Chest 1977;72:159)
Case reports
- Female infant with DIP related to ABCA3 and hydroxychloroquine treatment for 10 years (Pediatr Pulmonol 2014;49:299)
- 30 month old girl with DIP and multiple organ disorders (BMC Res Notes 2014;7:383)
- 8 year old boy with DIP due to passive smoking (Pediatr Pulmonol 2014;49:E56)
- 45 year old man with DIP due to waterproofing spray (Intern Med 2014;53:2107)
- 65 year old man with DIP and IgG4-related lung disease (Intern Med 2017;56:1553)
Treatment
- Smoking cessation or avoidance of etiological factors (including passive smoking) often improves the symptoms and prognosis (Histopathology 2011;58:509, Chest 2017;3692:33197, Eur Respir Rev 2013;22:117)
- Long term corticosteroid therapy is also effective
- Lung transplantation may be performed for progressive disease but recurrence of the disease was reported (Am J Respir Crit Care Med 1998;157:1349)
- Treatment for pediatric DIP includes corticosteroids, immunosuppressors (hydroxychloroquine) and lung transplantation (Pediatr Pulmonol 2014;49:1097, N Engl J Med 1993;329:1797, Pediatr Pulmonol 2014;49:299)
Gross description
- Diffuse bronchocentric multinodular change with lower lobe predominance
- Firm and consolidated
- Pale gray to white
- Mild to moderate increase in weight of the lung
- Honeycomb change can be seen but sparsely
Microscopic (histologic) description
- Diffuse and massive accumulation of intra-alveolar macrophages (smoker's macrophages)
- Brown pigments, more finely granular than hemosiderin, are seen in the eosinophilic cytoplasm (smoker's pigments)
- Giant cells can be also seen
- Mild to moderate interstitial fibrosis or cellular change
- Diffuse and homogeneous involvement (similar to NSIP) along with alveolar macrophages
- Lymphoid follicles and eosinophils are often present
- Marked dense fibrosis, architectural distortion, fibroblastic focus or presence of intact alveolar walls in the area of accumulated macrophages should suggest another diagnosis
- See details (Histopathology 2011;58:509, Chest 2017;3692:33197, Chest 2015;148:1307, Eur Respir Rev 2013;22:117)
Microscopic (histologic) images
Contributed by Akira Yoshikawa, M.D.
Low power
Middle power
Smoker's macrophages
Giant cells
Lymphoid follicles
Low power
Middle power
Smoker's macrophages and interstitial fibrosis
Images hosted on other servers:
Trichrome staining
H&E and IHC of CD68
Virtual slides
Images hosted on other servers:
Dr. Rosai's collection
- Desquamative interstitial
pneumonitis
Cytology description
- Increased eosinophil or neutrophil ratio in bronchoalveolar lavage fluid
Positive stains
- Prussian blue stains iron pigments in smoker’s macrophages
- Macrophages are positive for CD68 (Histopathology 1998;33:129)
Electron microscopy images
Images hosted on other servers:
Numerous lysosomes in macrophages
Videos
Histopathology Lung - Desquamative interstitial pneumonia
Differential diagnosis
- Alveolar hemorrhage
- Hemosiderin laden macrophages are seen
- Hemosiderin is positive for Prussian blue but more coarse and larger
- Eosinophilic pneumonia
- Marked interstitial eosinophils and edema, organizing pneumonia, mucus plugs and fibrin deposition are seen
- Hypersensitivity pneumonitis
- Clinically, smoking history is less common
- Patinets have a history of exposure to antigens such as spores of fungi, animal proteins and chemicals
- Positive for serum antibody to causative antigens
- Airway centered change, interstitial cellular infiltration and granuloma are seen
- Nonspecific interstitial pneumonias
- Accumulation of intra-alveolar macrophages may be seen but focal or mild (DIP-like reaction)
- Clinically, patients with NSIP often associated with collagen tissue disease
- Pneumoconiosis
- Clinically, the patients usually have a history of occupational exposure
- Macrophages, giant cells and causative particles (e.g. asbestos body, anthrosilicotic dust) are seen especially in interstitium
- Pulmonary Langerhans cell histiocytosis
- Bronchocentric nodules of Langerhans cells
- Positive for CD1a, S100 and Langerin
- Respiratory bronchiolitis
- Most common lung disease in smokers
- Clinical manifestation is slight or absent
- Macrophage accumulation in bronchocentric predominance is seen on histology
- Interstitial pneumonia, lymphoid follicles, giant cells and eosinophils are absent
- Respiratory bronchiolitis-associated interstitial lung disease
- Less common lung disease in smokers
- Physical deterioration, including respiratory symptoms and abnormal pulmonary function, is significant enough to diagnose as interstitial lung disease
- Almost identical to respiratory bronchiolitis on histology
- Usual interstitial pneumonia
- Marked dense fibrosis, architectural distortion and fibroblastic focus are seen
- Clinically, UIP / IPF is more progressive and not responding to corticosteroid therapy
Additional references
Board review style question #1
- Which clinical and morphological finding is NOT suggestive for DIP?
- A history of passive smoking
- Bilateral ground glass opacity
- Intra-alveolar cells positive for M. tuberculosis
- Intra-alveolar cells positive for Prussian blue
- Intra-alveolar giant cells
Board review style answer #1
C. Accumulated intra-alveolar cells of DIP are called smoker’s macrophages, which harbor aspirated particles in the cytoplasm. DIP is not related to mycobacterial infection.
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Reference: Desquamative interstitial pneumonitis
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Reference: Desquamative interstitial pneumonitis
