Histopathology - Lung Flashcards
What are
o Curschmann’s spiral
o Charcot Leyden crystals
and where are they seen?
o Curschmann’s spiral – spiral-shaped mucous plugs/ whorls of shed epithelium
o Charcot Leyden crystals – found in oesinophils/basophil granules
seen in asthma
Define chronic bronchitis (COPD)
o Chronic cough productive of sputum, most days for >=3 months over >=2 consecutive years
Histology of COPD
Goblet cell hyperplasia
Hypertrophy of mucous glands
Dilation of airways
Histology of asthma
Hyperaemia Mucous plugging and inflammation Eosinophilic inflammation Goblet cell hyperplasia Hypertrophied constricted muscle
Curschmann spirals
Charcot Leyden crystals
Complications of chronic bronchitis (COPD)
Repeated infections - most common cause of hospital admission + death
Chronic hypoxia:
- reduced exercise tolerance
- pulmonary HTN
- cor pulmonale
- RHF
Lung cancer (independent of smoking)
Bronchiectasis complications
Recurrent infections
Pulmonary HTN + RHF
Haemoptysis
Amyloidosis
Which gene is responsible for CF?
CFTR (CF transmembrane conductance regulator) gene on Chr 7
Histology of emphysema
Loss of alveolar parenchyma distal to the terminal bronchiole
Where are iron-laden macrophages found?
Pulmonary oedema
How does diffuse alveolar damage present in adults vs neonates?
Adults - ARDS
Neonated - RDS (=hyaline membrane disease of the newborn)
Diffuse alveolar damage changes
Capillary congestion –> Exudative phase –> Hyaline membranes –> organising phase
Histology of bronchopneumonia
Patchy bronchial and peribronchial distribution
Inflammation surrounding bronchioles themselves + is within the alveoli
Lower lobes
Causes of bronchopneumonia vs lobar pneumonia
Bronchopneumonia –> Low virulence organisms
Staph
Strep
Haemophilus
Pneumococcus
Lobar pneumonia –> high virulence organisms
Pneumococcus
Histology of lobar pneumonia
Widespread fibrinosuppurative consolidation
Stages of lobar pneumonia
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
What is atypical pneumonitis?
Interstitial inflammation without the accumulation of intra-alveolar inflammatory cells
How does cigarette smoke cause emphysema
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
Emphysema damage
Smoking vs A1AT deficiency
Smoking - loss centered around bronchiole = centrilobular
A1AT deficiency - diffuse loss of aleveolae = panacinar
Causes of lung granulomas
TB - caseating
Sarcoid - non caseating
Occupational lung disease (extrinsic allergic alveolitis)
Extrinsic allergic alveolitis histology
Polypoid plugs of loose connective tissue within alveoli/bronchioles
Granuloma formation
Organising pneumonia
Extrinsic allergic alveolitis acute vs chronic presentation
• 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
What is interstitial lung disease?
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
Pneumoconiosis vs extrinsic allergic aleveolitis
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)
Idiopathic pulmonary fibrosis/ cryptogenic fibrosing alveolitis histopathology
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
Define pulmonary HTN
Mean pulmonary arterial pressure >25mmHg at rest
Causes + classes of pulmonary HTN
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
Where is nutmeg liver found?
RHF
can be caused by a large pulmonary embolus (saddle embolus)
Complications of small emboli
Localised haemorrhagic infarct
Repeated small emboli –> increasing occlusion of the pulmonary vascular bed –> pulmonary HTN
Commonest type of cell from which lung cancers arise
Endothelial
Types of malignant tumours
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
Adenocarcinoma precursor lesion
AAH
Atypical adenomatous hyperplasia
Adenocarcinoma progression
Atypical adenomatous hyperplasia –> non-mucinous adenocarcinoma in situ –> mixed pattern invasive adenocarcinoma
histology –> glandular differentiation
Large cell carcinoma histology
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
Small cell lung cancer - which cells do they arise from?
Neuroendocrine cells
Small cell lung cancer histology
– Small poorly differentiated cells
– p53 and RB1 mutations common
Biopsy of central vs peripheral tumours
Central
- Biopsy at bronchoscopy
Peripheral
- Percutaneous CT guided biopsy
Molecular treatments in lung cancer
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)
