Histopathology - Lung

Question 1

What are

o Curschmann’s spiral
o Charcot Leyden crystals

and where are they seen?

Answer 1

o Curschmann’s spiral – spiral-shaped mucous plugs/ whorls of shed epithelium
o Charcot Leyden crystals – found in oesinophils/basophil granules

seen in asthma

Question 2

Define chronic bronchitis (COPD)

Answer 2

o Chronic cough productive of sputum, most days for >=3 months over >=2 consecutive years

Question 3

Histology of COPD

Answer 3

Goblet cell hyperplasia
Hypertrophy of mucous glands
Dilation of airways

Question 4

Histology of asthma

Answer 4

Hyperaemia 
Mucous plugging and inflammation 
Eosinophilic inflammation
Goblet cell hyperplasia
Hypertrophied constricted muscle 

Curschmann spirals
Charcot Leyden crystals

Question 5

Complications of chronic bronchitis (COPD)

Answer 5

Repeated infections - most common cause of hospital admission + death

Chronic hypoxia:

• reduced exercise tolerance
• pulmonary HTN
• cor pulmonale
• RHF

Lung cancer (independent of smoking)

Question 6

Bronchiectasis complications

Answer 6

Recurrent infections
Pulmonary HTN + RHF

Haemoptysis
Amyloidosis

Question 7

Which gene is responsible for CF?

Answer 7

CFTR (CF transmembrane conductance regulator) gene on Chr 7

Question 8

Histology of emphysema

Answer 8

Loss of alveolar parenchyma distal to the terminal bronchiole

Question 9

Where are iron-laden macrophages found?

Answer 9

Pulmonary oedema

Question 10

How does diffuse alveolar damage present in adults vs neonates?

Answer 10

Adults - ARDS

Neonated - RDS (=hyaline membrane disease of the newborn)

Question 11

Diffuse alveolar damage changes

Answer 11

Capillary congestion –> Exudative phase –> Hyaline membranes –> organising phase

Question 12

Histology of bronchopneumonia

Answer 12

Patchy bronchial and peribronchial distribution

Inflammation surrounding bronchioles themselves + is within the alveoli

Lower lobes

Question 13

Causes of bronchopneumonia vs lobar pneumonia

Answer 13

Bronchopneumonia –> Low virulence organisms

Staph
Strep
Haemophilus
Pneumococcus

Lobar pneumonia –> high virulence organisms
Pneumococcus

Question 14

Histology of lobar pneumonia

Answer 14

Widespread fibrinosuppurative consolidation

Question 15

Stages of lobar pneumonia

Answer 15

Congestion of the lungs - hyperaemia, intra-alveolar fluid

Red hepatisation - intra-alveolar neutrophils, hyperaemia (neutrophilia)

Grey hepatisation - intra-alveolar connective tissue (fibrosis)

Resolution
Complications - abscess, pleuritis, pleural effusion, empyema, fibrosis, sepsis

Question 16

What is atypical pneumonitis?

Answer 16

Interstitial inflammation without the accumulation of intra-alveolar inflammatory cells

Question 17

How does cigarette smoke cause emphysema

Answer 17

Activates neutrophils + macrophages

These in turn activate proteases (Elastase) which leads to tissue damage

alpha 1 antitrypsin normally inhibits these proteases but in A1AT deficiency these proteases cannot be inhibited

Question 18

Emphysema damage

Smoking vs A1AT deficiency

Answer 18

Smoking - loss centered around bronchiole = centrilobular

A1AT deficiency - diffuse loss of aleveolae = panacinar

Question 19

Causes of lung granulomas

Answer 19

TB - caseating
Sarcoid - non caseating
Occupational lung disease (extrinsic allergic alveolitis)

Question 20

Extrinsic allergic alveolitis histology

Answer 20

Polypoid plugs of loose connective tissue within alveoli/bronchioles
Granuloma formation
Organising pneumonia

Question 21

Extrinsic allergic alveolitis acute vs chronic presentation

Answer 21

• Acute presentation
o Inhalation of antigenic dust in sensitised individual – systemic symptoms (fever, chills, chest pain, SOB) within hours of exposure
o Usually settle by the following day

• Chronic presentation
o Progressive persistent productive cough + SOB
o Finger clubbing
o Severe weight loss

Question 22

What is interstitial lung disease?

Answer 22

Inflammation + fibrosis of the pulmonary connective tissue

Can be
- Fibrosing
Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis)
Pneumoconiosis (industrial lung disease)

• Granulomatous
  Sarcoid
  Extrinsic Allergic alveolitis

Question 23

Pneumoconiosis vs extrinsic allergic aleveolitis

Answer 23

Pneumoconiosis - occupational lung disease caused by inhalation of mineral dusts or inorganic particles (fibrosing interstitial lung disease)

Extrinsic allergic alveolitis - intense/prolonged exposure to organic antigens (granulomatous interstitial lung disease)

Question 24

Idiopathic pulmonary fibrosis/ cryptogenic fibrosing alveolitis histopathology

Answer 24

Interstitial pneumonia (required for dx)
Interstitial fibrosis 
Honeycomb fibrosis
Loss of normal lung architecture 
Usually sub-pleural

Hypertrophy of type II pneumocytes –> cyst formation

diagnosis by HRCT +/- biopsy

Question 25

Define pulmonary HTN

Answer 25

Mean pulmonary arterial pressure >25mmHg at rest

Question 26

Causes + classes of pulmonary HTN

Answer 26

Pre-capillary - Vasoconstriction due to chronic hypoxia - Thromboembolism (class 4) ``` Capillary - Widespread pulmonary fibrosis (class 3) ``` Post-capillary - LHF (class 2) - Veno-occlusve disease ``` class 1 - primary PAH, idiopathic, hereditary, drugs/toxins Class 5 - pulmonary HTN with unclear multifactorial mechanisms ```

Question 27

Where is nutmeg liver found?

Answer 27

RHF can be caused by a large pulmonary embolus (saddle embolus)

Question 28

Complications of small emboli

Answer 28

Localised haemorrhagic infarct | Repeated small emboli --> increasing occlusion of the pulmonary vascular bed --> pulmonary HTN

Question 29

Commonest type of cell from which lung cancers arise

Answer 29

Endothelial

Question 30

Types of malignant tumours

Answer 30

 Non-small cell carcinoma - less chemosensitive * SCC (30%) – smokers, central (airways), spread locally, late metastasis, PTHrP, cavitation * Adenocarcinoma (30%) – non-smokers, females, peripheral (peripheral alveolar spaces), early metastasis, extra thoracic metastases common and early * Large cell carcinoma (20%)  Small cell carcinoma- chemoradiotherapy • SCLC (20%) – smokers, central, SIADH, ACTH, Lamber-Eaton Myasthenic syndrome (LEMS) • poor prognosis

Question 31

Adenocarcinoma precursor lesion

Answer 31

AAH Atypical adenomatous hyperplasia

Question 32

Adenocarcinoma progression

Answer 32

Atypical adenomatous hyperplasia --> non-mucinous adenocarcinoma in situ --> mixed pattern invasive adenocarcinoma histology --> glandular differentiation

Question 33

Large cell carcinoma histology

Answer 33

No histological evidence of glandular/ squamous differentiation BUT on electron microscopy many show some evidence of glandular, squamous or neuroendocrine differentiation – i.e are probably very poorly differentiated adeno/squamous cell carcinomas

Question 34

Small cell lung cancer - which cells do they arise from?

Answer 34

Neuroendocrine cells

Question 35

Small cell lung cancer histology

Answer 35

– Small poorly differentiated cells | – p53 and RB1 mutations common

Question 36

Biopsy of central vs peripheral tumours

Answer 36

Central - Biopsy at bronchoscopy Peripheral - Percutaneous CT guided biopsy

Question 37

Molecular treatments in lung cancer

Answer 37

EGFR mutation - TKI inhibitor - cetuximab ALK translocation - crizotinib Ros1 translocation - crizotinib PDL1 expression inhibition (high levels of PD1 or PDL1 protein expression may inhibit immune response- inhibit cytotoxic T cells)