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PRESENTED IN RADIOLOGICAL-PATHOLOGICAL CONFERENCE
14 JULY 2015
BY T.CHAYOVAN
Hypersensitivity Pneumonitis: Essential Radiologic and
Pathologic Findings
Teri J. Franks, MD, Jeffrey R. Galvin, MD
Surgical Pathology Clinics
Volume 3, Issue 1, Pages 187-198 (March 2010) DOI: 10.1016/j.path.2010.03.005
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Hypersensitivity pneumonitis
Diffuse granulomatous interstitial lung disease
Caused by an immunologic response to repeated aerosol
inhalation
Clinical, radiologic, and histologic findings are quite variable
Diagnosis depends on a constellation of findings rather than a single defining feature
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Hypersensitivity pneumonitis
Acute, subacute, or chronic
Significant overlap
Active versus residual
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Hypersensitivity pneumonitis
Radiologic triad
Centrilobular nodules, multifocal ground glass opacities, air trapping
Characteristic histologic triad
Airway-centered chronic interstitial inflammation
Interstitial poorly formed non-necrotizing granulomas
Organizing pneumonia
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The recommendation of Schulyer
Symptoms compatible with hypersensitivity pneumonitis
Evidence of exposure to appropriate antigen
History or detection of serum and/or bronchoalveolar lavage (BAL) fluid
antibody
Findings compatible with hypersensitivity pneumonitis on chest
radiograph or HRCT
BAL fluid lymphocytosis
Histologic lung changes compatible with hypersensitivity pneumonitis
Positive natural challenge, which is reproduction of symptoms and
laboratory abnormalities after exposure to the suspected environment
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Gross features
Gross specimens of large size are not often encountered
BAL, transbronchial biopsy, or surgical lung biopsy
Radiologic studies, particularly HRCT, as their in vivo gross lung
examination
Distribution of disease
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Gross features
HRCT > plain chest radiograph
Sensitivity and specificity
Small, indistinct, centrilobular nodules
Multifocal ground glass opacities
Air trapping in the expiratory phase of respiration
Highly suggestive of hypersensitivity pneumonitis
Not specific: respiratory bronchiolitis, follicular bronchitis, and asthma
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Fig. 1
Surgical Pathology Clinics 2010 3, 187-198DOI: (10.1016/j.path.2010.03.005)
Copyright © 2010 Elsevier Inc. Terms and Conditions
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Fig. 3
Surgical Pathology Clinics 2010 3, 187-198DOI: (10.1016/j.path.2010.03.005)
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Residual phase of hypersensitivity pneumonitis
Fibrosis
Reticular pattern, honeycombing, and traction bronchiectasis
Associated with reduced survival
These findings are most severe in the upper and middle lungs
Fibrosis similar to idiopathic pulmonary fibrosis (IPF)
Strikingly lower lobe predominance
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Fig. 4
Surgical Pathology Clinics 2010 3, 187-198DOI: (10.1016/j.path.2010.03.005)
Copyright © 2010 Elsevier Inc. Terms and Conditions
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Fig. 5
Surgical Pathology Clinics 2010 3, 187-198DOI: (10.1016/j.path.2010.03.005)
Copyright © 2010 Elsevier Inc. Terms and Conditions
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Fig. 6
Surgical Pathology Clinics 2010 3, 187-198DOI: (10.1016/j.path.2010.03.005)
Copyright © 2010 Elsevier Inc. Terms and Conditions
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HP VS infection
Care for an infectious etiology
Focal or unilateral abnormalities
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Fig. 7
Surgical Pathology Clinics 2010 3, 187-198DOI: (10.1016/j.path.2010.03.005)
Copyright © 2010 Elsevier Inc. Terms and Conditions
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Microscopic features
Not an atopic disease and is not associated with increased
eosinophils
Surgical lung biopsy > transbronchial biopsy
To appreciate the distribution of histologic findings of hypersensitivity pneumonitis
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Microscopic features: Triad of active disease
Airway-centered chronic interstitial inflammation
Poorly circumscribed interstitial non-necrotizing granulomas
Organizing pneumonia
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Microscopic features: Triad of active disease
Airway-centered chronic interstitial inflammation
From an airway-centered to diffuse distribution
Lymphocytes > plasma cells
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Microscopic features: Triad of active disease
Interstitial non-necrotizing granulomas
Loose, poorly circumscribed interstitial collections of epithelioid histiocytes
admixed with variable numbers of multinucleated giant cells and
lymphocytes
Epithelioid histiocytes often present in the peribronchiolar interstitium
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Microscopic features: Triad of active disease
Organizing pneumonia
Plugs of pale staining, loose fibroblastic tissue filling
Distal bronchioles (bronchiolitis obliterans)
Alveolar ducts
Contiguous alveolar spaces
Foamy macrophages, fibrinous exudate, and neutrophils in alveolar
spaces secondary to bronchiolar obstruction
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Microscopic features
Continued exposure can lead to fibrotic residua in the
histologic patterns of fibrotic NSIP or UIP
Absent lymphoid follicles with germinal centers, interstitial eosinophils and neutrophils, and vasculitis
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Fig. 9
Surgical Pathology Clinics 2010 3, 187-198DOI: (10.1016/j.path.2010.03.005)
Copyright © 2010 Elsevier Inc. Terms and Conditions
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Fig. 10
Surgical Pathology Clinics 2010 3, 187-198DOI: (10.1016/j.path.2010.03.005)
Copyright © 2010 Elsevier Inc. Terms and Conditions
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Fig. 11
Surgical Pathology Clinics 2010 3, 187-198DOI: (10.1016/j.path.2010.03.005)
Copyright © 2010 Elsevier Inc. Terms and Conditions
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Fig. 12
Surgical Pathology Clinics 2010 3, 187-198DOI: (10.1016/j.path.2010.03.005)
Copyright © 2010 Elsevier Inc. Terms and Conditions
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Differential diagnosis
Organized into two groups:
Noninfectious interstitial lung disease, primarily sarcoidosis,
lymphoid interstitial pneumonia (LIP), NSIP, and UIP
Granulomatous infection
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Sarcoidosis Morphology and distribution of the granulomas
Degree and distribution of the chronic interstitial
inflammation.
Sarcoidosis HP
Granulomas compact, well circumscribed,
sometimes hyalinized,
distributed in a lymphangitic pattern
along bronchovascular bundles, pleura, and interlobular septae
Loose, poorly circumscribed,
lack hyalinization,
confined to a peribronchiolardistribution
Chronic interstitial inflammation
accompanies the distribution of
granulomas
without significant extension into the adjacent parenchyma
greater degree of interstitial
inflammation
with more extensive
involvement of the surrounding parenchyma
Organizing pneumonia
- +
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Fig. 13
Surgical Pathology Clinics 2010 3, 187-198DOI: (10.1016/j.path.2010.03.005)
Copyright © 2010 Elsevier Inc. Terms and Conditions
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Fig. 11
Surgical Pathology Clinics 2010 3, 187-198DOI: (10.1016/j.path.2010.03.005)
Copyright © 2010 Elsevier Inc. Terms and Conditions
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LIP
Densely cellular interstitial infiltrates of lymphocytes, plasma cells,
and histiocytes that markedly expand and distort alveolar walls.
LIP diffusely involves the lung parenchyma and lacks airway-
centered distribution
Lymphoid aggregates with reactive germinal centers
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http://www.scielo.br/scielo.php?pid=S0482-50042014000400326&script=sci_arttext&tlng=en
http://library.med.utah.edu/WebPath/TUTORIAL/AIDS/AIDS071.html
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Residual HP VS UIP VS Fibrotic NSIP
HP UIP NSIP
upper lobe lower lobe lower lobe
airway-centered
subpleural airway-centered
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Granulomatous infections
Special stains for microorganisms in all biopsies with granulomas
Culture correlation
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Hot tub lung
Controversially represents a hypersensitivity reaction or infection
Characterized by airway-centered non-necrotizing granulomas, organizing pneumonia, and chronic interstitial inflammation
Hot tub lung HP
Granulomas well-formed
distributed in both the interstitium and alveolar spaces
Loose, poorly circumscribed,
confined to a peribronchiolardistribution
Chronic interstitial inflammation
Tends to associated with the granulomas
More diffusely distributed in the lung parenchyma
Organizing pneumonia
++ +
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An approach to biopsy diagnosis
Interpretation of biopsies in this setting is difficult since
granulomas occur in a wide array of disease processes
Multidisciplinary triangle of clinical, radiologic, and pathologic information
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An approach to biopsy diagnosis
Active disease
Airway-centered chronic interstitial inflammation, poorly-formed
granulomas, and organizing pneumonia on biopsy
Widespread mosaic ground glass attenuation and centrilobular
nodules on chest CT
Rresidual disease
Presence of epithelioid histocytes and granulomas
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An approach to biopsy diagnosis
Lung injury caused by infection > HP
Chest CT plays a critical role in identifying esp. mycobacterial infections
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Treatment
Avoiding contact with the offending antigen is the cornerstone of
hypersensitivity pneumonitis treatment
Active disease typically resolves without sequelae
Oral corticosteroids serve to control symptoms but do not appear
to effect long-term outcome
The presence of fibrosis on histology or CT portents a poor
prognosis
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Points in Histologic Evaluation of Hypersensitivity Pneumonitis
Interpreting biopsies with clinical and radiologic findings
Perform special stains for microorganisms and correlate with
cultures when granulomas are present on biopsy
Negative special stains do not exclude infection