Pathology of Lung Cancer and Spread of Cancers Flashcards
1
Q
What 2 diseases constitute COPD?
A
- Emphysema
- Destruction of lung resulting in increased air spaces.
- Chronic bronchitis
- Inflammatory - asociated with muscular spasm in the bronchus and increased production of mucus.
2
Q
Describe the difference between centrilobular emphysema and panacinar emphysema.
A
- Normal acinus = gas exchange area.
-
Centrilobular emphysema = damage before the branching.
- Tends to be associated with deposition of e.g. cigarette smoke / pollution particles. They get trapped and cause damage, inflammation, fibrosis etc.
-
Panacinar emphysema = the whole acinus is affected.
- Can sometimes be associated with cigarette smoke or pollution, but the other condition it is strongly associated with is genetic deficiency of alpha1 anti-trypsin.
- Heterozygote state is quite common – can present as lung or liver injury if suitably stressed.
- Alpha1 anti-trypsin is an anti-protease enzyme and is present in plasma. It therefore can counteract the effects of activated neutrophils where there has been damage. Patients with homozygous deletion of alpha1 anti-trypsin tend to get a pattern and smokers get it too.
3
Q
Describe cor pulmonale.
A
- Emphysema - instead of fine holes with normal alveolar spaces there are enlarged holes, fibrous septa replacing the destroyed terminal bronchioles and acini. No gas exchange can take place here.
- This means that blood moving through from the right heart → pulmonary circulation → left heart cannot be oxygenated because the blood is being shunted through larger blood vessels.
- This might result in increased pulmonary pressure which can increase workload on the right side of the heart.
- So, one of the pathologies associated with severe chronic emphysema is increased right heart workload resulting in hypertrophy which can give rise to heart failure (congestive heart failure – build up on the venous side) and the condition (constellation) is called Cor pulmonale.
4
Q
Describe this histological slide.
A
- Chronic bronchitis.
- Arrow – muscle fibres which are thickened. This is why patients with bronchitis can get muscle spasm.
- Many blue cells infiltrating – predominantly lymphocytes with some neutrophils because there is a tendency to infection.
- Chronic inflammation.
- Mucous glands (yellow arrow) which are grossly hypertrophied producing more mucous.
- Condition is inflammatory, too much mucous production, potential for muscle spasm and the whole bronchus is constricted and therefore this is obstructive to the flow of air (patients typically have obstructive pattern).
5
Q
What are the common interstitial lung diseases?
A
- Hypersensitivity pneumonitis
- Sarcoidosis
- Idiopathic pulmonary fibrosis
- Asbestosis
6
Q
Describe hypersensitivity pneumonitis (extrinsic allergic alveolitis).
A
- Disease of the lungs in which your lungs become inflamed as an allergic reaction to inhaled dust, fungus, molds or chemicals.
- Type III and IV
- III - immune complex formation
- IV - cell-mediated
- The antigen which triggers the immune response is an antigen present in e.g. grain in bird feathers:
- Bird fancier
- Farmer’s lung
- Hypersensitivity reaction:
- Inflammation
- Presents as acute illness - dyspnoea and inability for sufficient gas exchange.
7
Q
Describe sarcoidosis.
A
- Multi-system granulomatous disorder of unknown cause.
- In 20-40%, disease is an incidental finding on CXR (thus is asymptomatic).
- African-Caribbeans are affected more frequently and more severely than Caucasians.
- It can cause lung damage, skin rashes, and eye disease and can affect other organs of the body.
- Presentation of acute sarcoidosis:
- Fever
- Erythema nodosum
- Polyarthralgia
- Bilateral hilar lymphadenopathy
- Cell-mediated.
- Causes raised angiotensin-converting enzyme.
- Rather than the diffuse lymphocytic picture as before – there are ill-defined areas (granulomas). Granulomas containing cytokine-producing macrophages and a multi-nucleated giant cells thicken the wall of the airway (thicken alveolar walls) and reducing gas exchange.
- Parts of the lung are normal so this condition may not present with breathlessness; it may be an incidental finding on CXR or because there are skin lesions. Can go on to scarring which causes subsequent problems with gas exchange. CXR will often show enlarged lymph nodes at the lung hilum. Biomarker used for diagnosis is raised ACE.
8
Q
Describe idiopathic pulmonary fibrosis.
A
- Disease that causes scarring (fibrosis) of the lungs.
- Scarring causes stiffness in the lungs and makes it difficult to breathe. Lower parts of the lung are turned into fibrous tissue.
- Lung damage from IPF is irreversible and progressive.
- Triggers:
- Post-viral?
- Can be part of other systemic disease
- Part of a spectrum?
- ‘Honeycomb lung’.
- Once this disease is established, the oucome and survival is not too different to that of lung cancer.
9
Q
What is a mesenchymoma?
A
- Benign tumour
- Papilloma
- Inflammatory myoblastic tumour
- There are glandular parts at the edge but most is cartilage.
- There is a very distinct boundary which is encouraging because it shows it is not invasive (and is therefore benign).
- Classically large shadow on CXR with no enlarged lymph nodes.
10
Q
Where can primary malignant tumours of the lung arise from?
A
- Can arise from:
- Epithelium
- Most arise from epithelium.
- Epithelial derived = carcinoma.
- Vessels
- Sarcoma or angiosarcoma.
- Muscle
- Leioma sarcoma.
- Cartilage
- Chondrosarcoma or chondroma
- Lymphoid
- Lymphoma
- Pleura
- Mesothelioma
- Epithelium
11
Q
What is the difference between metaplasia and dysplasia?
A
- Metaplasia is not premalignant.
- Dysplasia is progressive disordered maturation and proliferation which ultimately can result in invasion which is malignant.
- Malignant epithelial tumours are carcinomas.
12
Q
Describe how normal epithelium of the lung can become a carcinoma.
A
- Normal epithelium of the lung is columnar which is a glandular type of epithelium.
- But, with the influence of cigarette smoke or other noxious agents, this can convert from one mature cell type to another (metaplasia) – in this case from pseudocolumnar to squamous (a more hardy surface).
- As a secondary change, there can be the beginnings of genetic changes and damage resulting in disordered proliferation and maturation (dysplasia).
13
Q
What are the common sites of origin of secondary metastatic disease in the lung?
A
- Sarcoma
- Renal carcinoma
- Lymphoma
- Secondary cancer in the lung is COMMON. Particularly in those with advanced disease. It is often not the presenting feature and by the time the lung looks like this they have extensive problems elsewhere.
- Some tumours (like carcinoma) preferentially spread by blood borne spread, but so also does renal carcinoma. So, the lung is frequently involved early in RCC and may be the first site of metastatic disease.
- Patients present with RCC as an incidental finding of a CXR with multiple regular lesions (cannonball lesions).
14
Q
What are cannonball lesions?
A
- Seen on the CXR of a patient with renal cell carcinoma.
- Often an incidental finding and first presentation of RCC.
- Multiple regular lesions in the lung.
15
Q
What are the different types of primary epithelial tumour?
A
- Squamous
- Adeno
- Arises from glandular epithelium.
- Small cell undifferentiated
- Arises from primitive neuroendocrine cells.
- They are in the bronchus with very little function excpet producing amines and various mediators.
- They grow very rapidly and can be very aggressive but paradoxically can respond very well to chemotherapy initially.
- Carcinoid
- On a spectrum from almost benign to fairly malignant.
- It is probably contiguous with small cell undifferentiated.
- Large cell undifferentiated
- Non-small cell.
- Probably squamous or adeno but is so undifferentiated that it is impossible to tell.
17
Q
Describe squamous NSCLC.
A
- ~30% of all cases of NSCLC.
- Triggers:
- Smoking
- Air pollution
- Asbestos
- Fibrosing lung disease.
- Image - huge peripheral tumour. Does not have smooth surface; there is focal necrosis and keratin prosuction. Histologically - ‘whorls’ of keratinisation, occasional single karatinocytes but many of the cells are undifferentiated.
19
Q
What is bronchoalveolar adenocarcinoma (NSCLC)?
A
- Variant of adenocarcinoma.
- Pattern of spread - intrapulmonary dissemination.
- Occasionally get unusual subtypes. Cancer cells essentially replace normal alveolar cells. One of the problems is that these cells are coughed up and you aspirate them so it spreads within the lung and to the opposite lung.
20
Q
Describe small cell undifferenciated lung tumours.
A
- Neuroendocrine.
-
Paraneoplastic effects
- One of the major cancer types to produce paraneoplastic syndrome.
- Not directly due to presence of the tumour, rather because of what it produces.
- May be productive bioactive amines or peptides e.g. ADH, PTH-like peptides, ACTH.
- Neurological - e.g. demyelination. These conditions may also have immunological basis.
- Very little cytoplasm. Frequent spontaneous cell death.
- Very aggressive tumours.
21
Q
Describe carcinoid lung tumours.
A
- Malignant spectrum.
- ‘Typical’ - less aggressive end of the spectrum.
- ‘Atypical’ - smoking-related, tends toward malignant end of the spectrum.
24
Q
Describe PD1 and PD-L1 checkpoint inhibition.
A
- These are immune checkpoints. T-lymphocyte has programmed death molecule which interacts with the PD ligand which is on the cancer cell.
- If this interaction happens, the T cell says “I’m not going to destroy this cell because I am being told to switch off”.
- Throw in an antibody either against PD1 or PD-L1 which means that the invisibility cloak of the cancer cell is destroyed, thereby allowing the patient’s immune system to attack and destroy the cancer cells.
- So, if a patient has an immunologically susceptible tumour (that is, there should be an immune response happening), these patients may be appropriate to treat with an immune checkpoint inhibitor.
- Side effects can be bad but can significantly change the overall life expectancy of a patient with lung cancer.
26
Q
Describe mesothelioma.
A
-
Asbestos
- Almost always associated with asbestos.
- Incidence rising.
- Long lag period of 20-40 years.
- Male:Female 5:1. Probably reflects industrial exposure.
- Significance of fibrous pleural plaques.
- In the pleura, the significant lesion is mesothelioma. It is MALIGNANT. Arises from the lining cells of the pleura.
- Nasty tumour – grows along the pleural cavity. It means patient cannot expand the lungs so they suffocate.
- If you stick a needle in the chest to make a tissue diagnosis this tumour has a habit of growing along the needle track and may appear and start growing out on the skin.
- The benign equivalent is pleural plaques which are visible on CXR.
