Respiratory System Pathology 3 - Galbraith

Question 1

Chronic diffuse interstitial lung diseases

Answer 1

Cause inflammation and fibrosis of the interstitial

Cause restrictive lung diseases. Interstitial fibrosis leads to:

• decreased diffusing capacity
• decreased lung volume
• decreased lung compliance

Advanced stages - difficult to differentiate due to extensive scarring - honeycomb lung

Categorized by:
Fibrosing
Granulomatous
Eosinophilic
Smoking-related
Other

Question 2

Idiopathic pulmonary fibrosis

Answer 2

progressive interstitial fibrosis and respiratory failure

Unknown cause
Secondary to repeated injury to alveolar epithelial cells with a pro-fibrotic response in genetically susceptible people

Question 3

Idiopathic pulmonary fibrosis incidence

Answer 3

older than 50

Injury due to:
tobacco smoke
occupational irritants - fumes, dusts
viruses
persistent GERD

Genetics:
Telomerase mutations - TERT, TERC
Surfactant mutations
MUC5B variant

Question 4

Idiopathic pulmonary fibrosis morphology

Answer 4

Usual Interstitial Pneumonia (UIP)

Sub pleural and interlobular septal fibrosis

Fibrosis patchy, variable in intensity and age
-Early lesion show cellular fibroblastic foci

“Honeycomb fibrosis” with spaces surrounded by dense collagen, line with hyper plastic type II pneumocytes and bronchial epithelium

Question 5

Idiopathic pulmonary fibrosis clinical course

Answer 5

gradual worsening dyspnea with exertion

Development of progressive hypoxemia, cyanosis, clubbing occurring late

Rate of deterioration is variable

Medial survival 3 yrs

Question 6

Nonspecific interstitial pneumonia

Answer 6

Diffuse interstitial disease with a better prognosis than diseases featuring UIP

Two histologic patterns:

• Cellular (interstitial chronic inflammation)
• Fibrosing (interstitial fibrosis, lesions are the same stage of development)

Women, 50s, no smoking association

Dyspnea, cough

Question 7

Cryptogenic organizing pneumonia (COP)

Answer 7

Tufts, balls or plugs of immature fibroblastic tissue (Masson bodies) found within terminal bronchioles, alveolar ducts, alveolar spaces

No interstitial fibrosis
Connective tissue plugs at same stage of development

Underlying lung architecture is normal

Arise in various infectious or inflammatory lung injuries

• present with cough, dyspnea
• resolve spontaneously or with steroid therapy

Question 8

Pneumoconioses

Answer 8

Exposure to mineral dusts, inorganic and organic particles, chemical fumes

Influenced by:

• partial size (1-5 um most pathogenic)
• Particle solubility
• Level and duration of exposure/effectiveness of clearance
• intensity of immune response

Question 9

Coal worker’s lung disease

Answer 9

inhaled carbon dust taken up by macrophages - accumulate in interstitial tissue along pulmonary lymphatic tissue

Anthracosis - black pigmented lesions formed by coal dust containing macrophages

Seen in smokers and urban dwellers

can cause centriacinar emphysema

Question 10

Complicated coal worker’s pneumoconiosis

Answer 10

Progressive massive fibrosis

Characterized by multiple anthracitic scars, when extensive lead to:
respiratory failure
pulmonary HTN
Cor pulmonale

Question 11

Silicosis

Answer 11

Inhaling crystalline silicon dioxide over long periods of time

Crystalline particles ingested by macrophages, then mounts inflammatory response

• slowly growing nodular collagenous scars
• over time coalesce –> progressive massive fibrosis

Question 12

Silicosis morphology

Answer 12

nodular scars in lungs or hilar LN
-calcified LN identified with CXR

Nodules: whorled balls of dense collagen fibers, surrounded by dust-containing macrophages
-more prominent apically

silica particles birefringent with plane-polarized light

Question 13

Silicosis - clinical course

Answer 13

Rate of onset and disease progression variable
-progress after exposure ceases

Increased susceptibility to TB

2x risk of lung CA

Question 14

Asbestos

Answer 14

fibrous hydrated silicate crystals

cause interstitial and pleural fibrosis –> lung carcinoma and malignant mesothelioma

Types: serpentine, amphibole

Question 15

Asbestos-related lung disease

Answer 15

asbestos fibers taken by macrophages, causes inflammatory response leading to interstitial fibrosis

interstitial fibrosis pattern –> honeycomb lung

Lung bases affected FIRST and progresses upwards

characterized by asbestos (or ferruginous) bodies within macrophages

Plaques of dense collagen, sometimes calcified, form on pleura, particularly parietal pleura
-may result in pleural effusion

predisposed to malignancy, exacerbated by smoking

Question 16

Asbestosis-related lung disease presentation

Answer 16

Present similar to pneumoconiosis or usual interstitial pneumonia (patchy areas of different ages)

symptoms appear decades after exposure

Pleural plaques asymptomatic

complicated by lung or pleural malignancy carries a poor prognosis

Question 17

Sarcoidosis

Answer 17

Multiorgan granulomatous disorder - unknown cause

Lung and/or hilar LN in 90% of cases

Dx of exclusion

arise from abnormal immune regulation

Question 18

incidence and genetic component of Sarcoidosis

Answer 18

younger than 40
10X higher in African-Americans
Females

Genetics:
Family/race clustering
HLA-A1 and HLA-B8

Question 19

Sarcoidosis morphology

Answer 19

small, noncaseating granulomas with multinucleate giant cells - naked granulomas

Lungs commonly involved with granulomas distributed along pulmonary lymphatics
-granulomas may coalesce forming grossly-apparent nodules up to 2 cm in diameter

Other sites involved: Liver, spleen, bone marrow, skin, eye

Question 20

Sarcoidosis clinical course

Answer 20

Constitutional symptoms: weight loss, fever, fatigue, night sweats

Pulmonary symptoms: dyspnea, hemoptysis, cough, pain

Resolution with or without steroids
-20% residual pulmonary impairment
10% develop progressive pulmonary fibrosis, PHTN, and cor pulmonale

Question 21

Hypersensitivity pneumonitis

Answer 21

Immunologic reaction to inhaled organic antigens causing:

• interstitial pneumonitis - lymphocytes, plasma cells, macrophage
• noncaseating granulomas
• Interstitial fibrosis

Continued antigen exposure –» progressive fibrotic lung disease

Question 22

Antigens implicated in hypersensitivity pneumonitis

Answer 22

Thermophilic bacteria - air conditioner lung

antigens from bird excretions or feathers - bird fancier’s disease

Various spore-forming fungi or bacteria - farmer’s lung

Question 23

Desquamative interstitial pneumonia

Answer 23

alveoli filled with numerous macrophages
-some with phagocytosed surfactant

Mild chronic inflammation and fibrosis

30s-40s

Persistent dry cough, dyspnea, clubbing

Responds to steroid therapy

Question 24

Respiratory bronchiolitis - associated interstitial lung disease

Answer 24

peribronchiolar fibrosis and chronic inflammation

associated with anthracotic macrophages in bronchiolar lumens

incidental finding in many smokers

cough, dyspnea in long term smokers

treated with smoking cessation

Question 25

Pulmonary Langerhans cell histiocytosis

Answer 25

Accumulation of Langerhans cells (dendritic cells) to form nodules, along with fibroblasts, macrophages, eosinophils

young smokers

lesions behave as reactive processes, others have shown BRAF mutations

Question 26

Pulmonary alveolar proteinosis (PAP)

Answer 26

Accumulation of surfactant within alveolar and bronchiolar spaces
-secondary to impeded or diminished pulmonary macrophage activity

Autoimmune (Ab to GM-CSF), secondary, or hereditary

Question 27

Pulmonary alveolar proteinosis morphology, presentation and treatment

Answer 27

Surfactant accumulates within lungs making them enlarged and heavy

alveoli filled with granular pink precipitate

Present with cough, producing sputum and gelatinous material

Progressive respiratory failure may occur, at risk for infection

Tx: whole lung lavage and GM-CSF