Lung nontumor
Other interstitial pneumonitis / fibrosis
Desquamative interstitial pneumonia

Author: Akira Yoshikawa, M.D. (see Authors page)
Editor: Andrey Bychkov, M.D., Ph.D.
Deputy Editor in Chief: Debra Zynger, M.D.

Revised: 24 March 2018, last major update March 2018

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Desquamative interstitial pneumonitis [title]

Cite this page: Yoshikawa, A. Desquamative interstitial pneumonitis (DIP). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lungnontumorDIP.html. Accessed October 16th, 2018.
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-10 coding
  • Desquamative interstitial pneumonia: J84.117
Epidemiology
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
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

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High resolution CT

Prognostic factors
Case reports
Treatment
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

Images hosted on PathOut server:

Images contributed by Akira Yoshikawa, M.D.
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Case 1 (above): 68 year old man, ex-smoker (60 pack-years),
presented with persistent cough - Biopsy from S5


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Case 2: 61 year old man, ex-smoker (40 pack-years), presented with mild dyspnea - Biopsy from lower lobe



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Trichrome staining

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H&E and IHC of CD68


Virtual slides

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Dr. Rosai’s collection
- Desquamative interstitial
pneumonitis
Cytology description
  • Increased eosinophil or neutrophil ratio in bronchoalveolar lavage fluid
Positive stains
Electron microscopy images

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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
Board review question #1
    Which clinical and morphological finding is NOT suggestive for DIP?

  1. A history of passive smoking
  2. Bilateral ground glass opacity
  3. Intra-alveolar cells positive for M. tuberculosis
  4. Intra-alveolar cells positive for Prussian blue
  5. Intra-alveolar giant cells
Board review 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.