** Histopath 7: Respiratory Pathology Flashcards
What does this show?
normal lung
- The airways are lined by ciliated respiratory epithelium (responsible for moving up mucus and pathogens)
- Alveoli are characterised by very fine capillaries lined by type 1 pneumocytes (short diffusion distance)
What does this show?
Pulmonary Oedema
What is pulmonary oedema? What are its causes?
- Often associated with heart failure (acute or chronic)
- VERY COMMON cause of acute and chronic respiratory failure
- Common finding at post-mortem
- Defined by the accumulation of fluid in the alveolar spaces either due to leaky capillaries or backpressure from a failing left ventricle
- This leads to poor gas exchange
What are the causes and pathology of pulmonary oedema?
-
Causes
- Left heart failure
- Alveolar injury (drug, inhalation, pancreatitis)
- Neurogenic following head injury
- High altitude
-
Pathology
- Heavy watery lungs
- Intra-alveolar fluid on histology
What does this CXR show?
Acute Lung Injury Pattern/Diffuse Alveolar Damage
What can Acute Lung Injury Pattern/Diffuse Alveolar Damage cause?
- Important cause of RAPID onset respiratory failure
- ADULTS - Acute Respiratory Distress Syndrome
- NEONATES - Hyaline Membrane Disease of the Newborn
What are the causes of ARDS?
Causes
- Infection
- Aspiration
- Trauma
- Inhaled irritant gases
- Shock
- Blood transfusion
- DIC
- Drug overdose
What is NEONATES - Hyaline Membrane Disease of the Newborn?
- Insufficient surfactant production
- Premature babies
What is Acute Lung Injury Pattern/Diffuse Alveolar Damage?
- This is acute respiratory failure NOT due to pulmonary oedema
- It is caused by acute damage to the endothelium and/or alveolar epithelium
- Basic pathology is the same in all cases: DIFFUSE ALVEOLAR DAMAGE
- The lungs are expanded and firm
- On post-mortem examination, the lungs are plum-coloured, heavy (> 1 kg) and airless
What is the pathophysiology of Acute Lung Injury Pattern/Diffuse Alveolar Damage?
- The lungs become congested and then they become leaky (exudative phase)
- They will then develop hyaline membranes (this is serum protein that has leaked out and ended up lining the alveolar spaces)
- Eventually, you get organisation of the exudates to form granulation tissue sitting within the alveolar spaces (organising pneumonia)
What is the prognosis of Prognosis of Diffuse Alveolar Damage?
- Death (40%)
- Superimposed infection
- Resolution (in some) - lung function returns to normal
- Residual fibrosis - leads to chronic respiratory impairment
What is asthma?
- DEFINITION: chronic inflammatory airway disorder with recurrent episodes of widespread narrowing of the airways that changes in severity over short periods of time.
What is status asthmaticus?
- In a SEVERE attack, patients develop status asthmaticus
What are some non-atopic triggers of asthma?
- Non-atopic triggers: air pollution, occupational, diet, physical exertion
What are the changes seen in asthma physiology-wise?
-
Acute Changes
- Bronchospasm
- Oedema
- Hyperaemia
- Inflammation
-
Chronic Change
- Muscular hypertrophy
- Airway narrowing
- Mucus plugging
NOTE: once you’ve plugged a large airway, the distal lung will collapse
Describe the histological features of asthma
- There are a lot of eosinophils and mast cells
- You will also see goblet cell hyperplasia
- Mucus plugs can be seen within the airway
- The bronchial smooth muscle becomes thick and the blood vessels become dilated
What are the 2 types of COPD?
- Chronic Bronchitis
- Emphysema
What are the 2 types of COPD?
- Chronic Bronchitis
- Emphysema
What are the 2 types of COPD?
- Chronic Bronchitis
- Emphysema
What is COPD?
Very common cause of chronic respiratory failure
- May present with acute exacerbations
- 80% are smokers
- Smoking causes inflammation leading to secondary damage to the airways and interstitium
- There is a mix of airway and alveolar pathology (chronic bronchitis and emphysema), resulting in progressive airway obstruction
Which condition does this show?
chronic bronchitis
What is the definition of chronic bronchitis?
- Defined as:
- Chronic cough productive of sputum
- Most days for at least 3 months over 2 consecutive years
- Chronic injury to airways elicits reactive changes which predispose to further damage
Describe the pathology of chronic bronchitis
- Dilated airways
- Mucus gland hyperplasia
- Goblet cell hyperplasia
- Mild inflammation
What are the complications of chronic bronchitis?
- Recurrent infections (most common cause of admission and death)
- Chronic respiratory failure (with hypoxia and reduced exercise tolerance)
- Chronic hypoxia results in pulmonary hypertension and right heart failure (cor pulmonale)
- Increased risk of lung cancer (independent of smoking)
What does this show?
- Emphysema
What is the definition of emphysema?
Defined as a permanent loss of the alveolar parenchyma distal to the terminal bronchiole
- Damage to alveolar epithelium is secondary to inflammation, inflammation could be caused by:
- Smoking
- Alpha-1 antitrypsin deficiency
- RARE: cadmium exposure, IVDU, connective tissue disorder
How does smoking cause emphysema?
- Neutrophils and macrophages that are activated by smoking, will release proteases which degrade tissues
Describe the pathophysiology of emphysema?
- Smoking tends to cause centrilobular damage to the alveolar tissue
- Patients with alpha-1 antitrypsin deficiency tend to have damage throughout the lung (panacinar)
What are the complications of emphysema?
- Bullae (large air spaces)
- Can rupture and cause pneumothorax
- Respiratory failure
- Pulmonary hypertension and right heart failure
What does this show?
Bronchiectasis
What is the definition of bronchiectasis?
- permanent abnormal dilation of the bronchi with inflammation and fibrosis extending into adjacent parenchyma
- Varies in site depending on the cause (idiopathic often involves the lower lobe)
- Leads to inflamed and scarred lungs with dilated airways
What are the causes of bronchiectasis?
-
Infection (most common cause)
- Post-infectious (cystic fibrosis)
- Abnormal host defence (can be primary (e.g. hypogammaglobulinaemia) or secondary (e.g. chemotherapy))
- Ciliary dyskinesia
- Obstruction
- Post-inflammatory (aspiration)
- Secondary to bronchiolar disease and interstitial disease (e.g. sarcoidosis)
- Systemic disease (connective tissue disorders)
- Asthma
- Congenital
What are the complications of bronchiectasis?
- Recurrent infections
- Haemoptysis
- Pulmonary hypertension and right sided heart failure
- Amyloidosis
How is cystic fibrosis inherited?
- Autosomal recessive (approximately 1/20 are carriers)
-
Chromosome 7q3 = CFTR gene
- Chloride ion transporter protein
- 1400+ mutations
- Delta F508 is the MOST COMMON mutation
- → Abnormality leads to defective ion transport across cell membranes due to excessive resorption of water from secretions of exocrine glands
Which organ systems does CF affect?
- It is a generalised disorder of the exocrine glands resulting in abnormally thick mucus secretion - affects ALL organ systems
- GI = meconium ileus, malabsorption
- Pancreas = pancreatitis, malabsorption
- Liver = cirrhosis
- Male reproductive system = infertility
-
Lung
- Involved in 90% of cases
- Recurrent infections (S. pneumoniae, H. influenzae, P. aeruginosa and B. cepacia)
- Manifestations
- Haemoptysis
- Pneumothorax
- Chronic respiratory failure
- Cor pulmonale
- ABPA
- Atelectasis
- Bronchiectasis
What is the life expectancy of CF?
- Improved treatment means that most will survive 35-40 years
- Lung transplantation will prolong survival
What is the classification of bacterial pneumonia?
-
Community-Acquired
- Streptococcus pneumoniae
- Haemophilus influenzae
- Mycoplasma
-
Hospital-Acquired
- Gram-negatives (Klebsiella, Pseudomonas)
-
Aspiration
- Mixed aerobic and anaerobic
What are the main patterns of bacterial pneumonia?
- There are a variety of PATTERNS of lung involvement depending on the organism and other co-factors:
- Bronchopneumonia
- Lobar pneumonia
What is Bronchopneumonia?
Infection is centred around the airways
- Compromised host defence (elderly)
- Often LOW virulence organisms (Staphylococcus, Haemophilus, Streptococcus, Pneumococcus)
- Patchy bronchial and peribronchial distribution often involving the lower lobes
- There is acute inflammation surrounding airways and within alveoli
What is Lobar pneumonia?
- The infection is focused in a lobe of the lung
- Infrequent because of antibiotics
- 90-95% are S. pneumoniae
- Widespread fibrinosuppurative consolidation
- Histopathology
- Congestion (hyperaemia and intra-alveolar fluid)
- Red hepatisation (hyperaemia, intra-alveolar neutrophils)
- Grey hepatisation (intra-alveolar connective tissue)
- Resolution (restoration or normal tissue architecture)
- Abscess formation
- Granulomatous inflammation
What are the complications of bacterial pneumonia?
- Abscess formation
- Pleuritis and pleural effusion
- Infected pleural effusion (empyema)
- Fibrous scarring
- Septicaemia
What is a granuloma?
- A granuloma is a collection of macrophages and multi-nucleate giant cells
- It can be necrotising or non-necrotising
- Must think of TUBERCULOSIS + exclude
- Other causes include fungi and parasites (travel history is important)
What does this show?
- Atypical Pneumonia
Describe atypical pneumonia
- Mycoplasma, viruses (e.g. CMV, influenza), Coxiella and Chlamydia
- Interstitial inflammation (pneumonitis) without accumulation of intra-alveolar inflammatory cells
- Chronic inflammatory cells within alveolar septa with oedema with or without viral inclusions
What is Pulmonary Thromboembolism?
- Occlusion of pulmonary artery by thromboembolus
- Deep leg veins is a common site for clot formation (95%)
- May present with a painful, swollen leg
- Effect depends on the SIZE of the thrombus
What is Virchow’s triad?
How might a patient present with a small PTE?
- Patients with small emboli may present with pleuritic chest pain or chronic progressive shortness of breath due to pulmonary hypertension
- Repeated emboli cause increasing occlusion of the pulmonary vascular bed and pulmonary hypertension
How might a patient present with a large PTE?
- hypertension
- Large emboli may occlude the main pulmonary trunk (saddle embolus)
- This may present with sudden death, acute right heart failure or cardiogenic shock
- 30% will develop a second embolus
Name some non-thrombotic emboli
- Bone marrow
- Amniotic fluid
- Trophoblast
- Tumour
- Foreign body
- Air
- Fat
Which cell types do lung tumours arise from?
- Tumours can arise from a variety of cell types (epithelial, mesenchymal and lymphoid)
- Can arise in different sites
- Airways (mainly squamous cell carcinoma)
- Peripheral alveolar spaces (mainly adenocarcinoma)
- Small cell carcinoma can arise either centrally or peripherally
- Mesothelioma is a tumour of the pleura
Describe benign lung tumours
- Do NOT metastasise
- Can cause local complications (e.g. obstruction)
- Example: chondroma
Describe and name the types of malignant lung tumours
- Potential to metastasise
- Most common are epithelial (90-95%)
-
Non-Small Cell Carcinoma
- Squamous cell carcinoma (30%)
- Adenocarcinoma (30%)
- Large cell carcinoma (20%)
- Small Cell Carcinoma (20%)
- NOTE: incidence of lung cancer in men is dropping and in women is rising (because women took longer to quit smoking)
What is the aetiology of lung tumours?
- 25% of lung cancer in non-smokers is attributed to passive smoking
- Smoke contains
- Tumour initiators (polycyclic aromatic hydrocarbons)
- Tumour promoters (nicotine)
- Complete carcinogens (nickel, arsenic)
- Strongest association with:
- Squamous cell carcinoma
- Small cell carcinoma
- NOTE: adenocarcinoma is more common in non-smokers
-
Other Risk Factors
- 25% of lung cancers are in non-smokers
- Asbestos
- Radiation (radon exposure)
- Air pollution
- Heavy metals
- Genetics (familial lung cancers are rare)
- Susceptibility genes
- Chemical modification of carcinogens
- Susceptibility to chromosomal damage
- Nicotine addiction
Describe the development process of a carcinoma
- Multistep pathway includes:
- Metaplasia
- Dysplasia
- Carcinoma in situ
- Invasive carcinoma
- Due to an accumulation of gene mutations
- There are different pathways for different tumour types
Describe SCC (lung)
- Squamous epithelium is much more resilient but it does NOT have cilia
- This leads to a build up of mucus
- Within this mucus, you will get loads of carcinogens
- This leads to more mutations
- Invasive squamous carcinoma is responsible for about 35% of lung cancers
- Closely associated with smoking
- Traditionally centrally located arising from bronchial epithelium
- Increasing incidence of peripheral squamous cell carcinomas (possibly because modern cigarette smoke can be inhaled more deeply)
- Spreads locally
- Metastasises late
What does this show?
SCC (lung)
Where does adenocarcinoma of the lung tend to arise?
- Tend to arise in the periphery of the lung (often around the terminal airways)
What is the common precursor lesion for adenocarcinoma of the lung?
- Precursor lesion: atypical adenomatous hyperplasia
- This is proliferation of atypical cells lining the alveolar walls
- This will increase in size and eventually become invasive
Name the Molecular Pathways in the Development of Adenocarcinoma
- In smokers, the main mutations are K ras, issues with DNA methylation and p53
- In non-smokers, EGFR mutations are very important (these are drug targets)
Describe the epidemiology of adenocarcinoma of the lung
- Incidence is INCREASING
- More common in females, far East and non-smokers
- Tends to occur peripherally and are often multi-centric (lots of little tumours at different stages of development)
- Extra-thoracic metastases are COMMON and occur EARLY (80% present with metastases)
- Histology will show evidence of glandular differentiation
What does this show
cytology of adenocarcinoma of the lung
What does this show?
Large Cell Carcinoma of the lung
Describe the histopathology of large cell carcinoma of the lung
- Poorly differentiated tumours composed of large cells
- There is NO histological evidence of glandular or squamous differentiation
- NOTE: on electron microscopy, there may be some evidence of glandular, squamous or neuroendocrine differentiation
What is the prognosis of large cell carcinoma of the lung vs other types?
- POORER prognosis
What does this show?
Small cell carcinoma of the lung
Describe small cell carcinoma of the lung
- 20% of lung tumours
- Very close association with SMOKING
- Often CENTRAL and near the bronchi
- 80% will present with advanced disease
- Very chemosensitive but VERY POOR PROGNOSIS
- May cause paraneoplastic syndromes
Describe the histology of small cell carcinoma
- Small poorly differentiated cells
- Common mutations
- P53
- RB1
What does this show?
What is the survival for small cell cancer?
- Survival 2-4 months if untreated
- Survival 10-20 months on current treatment
- Chemoradiotherapy is the mainstay (surgery is rarely performed because most cases would have spread by the time of diagnosis)
What is the survival for non-small cell lung cancer?
- Early stage 1 tumours have 60% 5-year survival
- LESS chemosensitive
Why are molecular changes important to know in adenocarcinoma? Which are these?
- Molecular changes are important for adenocarcinoma because they can be targeted using specific therapies
- Main molecular changes:
- EGFR mutation (responder or resistance)
- ALK translocation
- Ros1 translocation
Why is it important to know the type of lung cancer?
- It is important to know the type of cancer because, for example, in some patients with squamous cell carcinoma, they can develop fatal haemorrhage with some new chemotherapeutic drugs (bevacizumab)
What is the role of the pathologist in lung cancer?
What are the Tx types for lung cancer?
-
Curative
- Surgery +/- radical radiotherapy +/- immunemodulatory therapy
-
Palliative
- Chemoradiotherapy, immunemodulatory, targeted therapy
What does this show?
Describe mesothelioma
- Malignant tumour of the pleura
- < 1% of cancer deaths but increasing incidence with a peak predicted in around 2010-2020
- Associated with asbestos exposure
- There is a long lag (tumour may develop decades after exposure)
- More common in males
- 50-70 years
- Essentially FATAL
- Medicolegal implications because of compensation
- POOR prognosis
- Several histological types
